[Diagnostic value of ultrasonographic evaluation of thoracic and cervical organs in lymphogranulomatosis and lymphosarcoma].
Examinations of 65 patients with Hodgkin's disease (n = 61) and with non-Hodgkin's (n = 4) by x-ray method, computer-aided tomography, and sonography were carried out and the potentialities of sonography in detection of the lymph node lesions in lymph collectors above the level of the diaphragm analyzed. Sonography helped detect signs of envolopment of small palpated and nonpalpated lymph nodes, differentiate individual nodes, conglomerations, specify the volume an localization of changes in the mediastinal lymph nodes and in the adjacent anatomical structures, and choose an approach to collection of material for morphologic examination. Ultrasonic examination is informative as a method for monitoring the treatment results and for disease recurrences during the period of postirradiation changes in the mediastinum.


Hurdles to asepsis, universal literacy, and chronobiology-all to be overcome.
A joining of chronobiology and endocrinology was achieved in 1974 at a symposium focusing on the critical role of the hypothalamic-pituitary-adrenal network on the basic side and on the first drug to carry timing in its name. The next step is a section on chronobiology in this neuroendocrinology journal. An account of the problems encountered before both asepsis and universal literacy became the law of the profession and of the land serves here as background to endeavors in behalf of chronobiologic literacy. A step toward the latter goal is the use of systematically collected measurements of heart rate and blood pressure evaluated by computer against reference standards from peers of corresponding age, gender and ethnicity. Thereby, an illustrative, clinically relevant aspect of everyday physiology is resolved within the otherwise neglected normal range, and disease risk syndromes are detected so that preventive treatment can be instituted before catastrophic disease occurs. The scope of this chronobiology section of the Neuroendocrinology Letters is to map the time-qualified feedsideward interactions within the neuroendocrines, in the rest of an organism and in the environment. Thereby, we replace time-unqualified feedbacks and feedforwards, along imaginary axes, by neuroendocrine and cellular networks operating predictably insofar as rhythmically within the range of everyday physiology. Subtle effects are thus found that are otherwise covered by the curtain of ignorance drawn over the normal range. More important, feedsidewards account for opposite effects that recur rhythmically, and thus help clarify mechanisms that may underlie the difference between stimulating or inhibiting a malignancy and thus shortening or lengthening the lifespan.


[CT manifestations of schizencephaly].
Schizencephaly is a variety of neuron migration anomalies which are caused by insults to the migration of subependymal neuroblasts during the third to fifth gestational months. It has characteristic CT findings including a hemispheric cleft, either unilateral or bilateral, in the parasylvian region lined with heterotopic gray matter and extending from the pial to the ependymal surface. In type I the lips of the cleft are fused, whereas in type II, these are separated. Polymicrogyria and malformations of septum pellucidum and corpus callosum are common associated findings. Seventeen cases of schizencephaly with only two cases of bilateral clefts were presented in this paper.


Germline mutations in RAD51, RAD51AP1, RAD51B, RAD51C,RAD51D, RAD52 and RAD54L do not contribute to familial chronic lymphocytic leukemia.
While familial predisposition to B-cell chronic lymphocytic leukemia (CLL) is well recognized no gene which when mutated in the germline has been unambiguously shown to confer susceptibility to the disease. An approach based on mutation screening methods targeted to coding regions of candidate genes offers an attractive strategy for the identification of rare disease-causing alleles. The RAD genes participate in the cellular response to DNA double strand breaks, detecting DNA damage, activating cell cycle checkpoints and apoptosis. Defects in members of these genes are linked to increased chromosomal instability and in lymphoma predisposition, thereby representing strong candidate susceptibility genes a priori. To examine this proposition we screened 75 familial CLL probands for germline mutations in this set of genes. No overt pathogenic mutations were identified. These findings indicate that germline mutations in RAD51, RAD51AP1, RAD51L1, RAD51L3, RAD52 and RAD54L are unlikely to be causal of an inherited predisposition to CLL.


Antibodies to chlamydia trachomatis in semen and relationship with parameters of male fertility.
To screen for infection with Chlamydia trachomatis in semen samples from asymptomatic men in couples consulting for infertility and to determine the relationship of seminal chlamydial antibodies with clinically relevant parameters of male fertility, 197 randomly chosen patients were enrolled in a prospective study. The median duration of infertility was 4 years (range 1-18). Screening for C. trachomatis and chlamydial antibodies of the immunoglobulin (Ig) A and IgG classes were performed in ejaculates and, in parallel, endocervical material from the partners of the patients and serum samples from both partners were evaluated. A comprehensive examination of semen quality included sperm analyses, semen cultures, local antisperm antibody (ASA) testing, the determination of potential infection markers, and sperm-cervical mucus interaction testing in vitro (SCMPT) and in vivo (post-coital testing). Chlamydial IgA antibodies were found in the semen samples of 18.8% (37/197) of the patients, while chlamydial IgG antibodies were found in 8.1% (16/197) of the patients. Screening for C. trachomatis was negative in all semen and cervical specimens. Only 5.5% of men remembered a past genital infection. Chlamydia antibodies (IgA/Ig/G) in semen were significantly correlated with chlamydia IgG antibodies in serum samples (P < 0.001). No marked relationship was found between the presence of seminal chlamydial antibodies and the major parameters of sperm analysis, semen cultures, local ASA and sperm penetration testing as an indicator of functional capacity. Seminal chlamydial antibodies were not significantly associated with potential infection or inflammation markers in aliquots of the same ejaculates. However, a significant relationship of chlamydial antibodies in patients' semen with past genital infections of their female partners was found with clinical relevance for a tubal infertility factor. The results indicate that in asymptomatic patients the presence of chlamydial antibody IgA or IgG in semen is not associated with reduced semen quality, potential seminal infection markers or impaired functional capacity as important determinants of male fertility; however, seminal chlamydial antibodies suggesting a previous sexually transmitted disease are significantly related to a tubal infertility factor of female partners.


Acute pancreatitis in chickens due to non-virulent Newcastle disease virus.
A non-virulent Newcastle disease virus (strain APMV-1 96/89 VB) was isolated from a broiler chicken from a backyard flock. Using monoclonal antibodies, the virus was shown to be different from the vaccinal virus strains Hitchner, La Sota and Ulster. The virus was shown to replicate in the pancreas of one-day-old specific pathogen-free chickens infected orally, and the histological lesions observed in the pancreas of chickens inoculated with the fourth chicken passage of the virus five to nine days after infection were consistent with an acute pancreatitis.


[The nutritional status and immune function of patients with chronic obstructive pulmonary disease].
The nutritional status and immune function of 14 patients with exacerbation of chronic obstructive pulmonary disease (COPD) were assessed and were studied again one week after the patients had recovered. The results showed that the nutritional status of the patients was poorer on admission, the level of some kinds of serum free amino acid was significantly lower than the normal value, the value of branch-chain amino acid (BCAA) was significantly lower than that in healthy people (P < 0.01), but the level of aromatic amino acid (AAA) was higher than the normal value. Level of serum free fatty acid was significantly lower during admission and in recovery period (P < 0.01). It is suggested that shortage of essential fatty acid in the patients is obvious. The results also showed that the patients identified as malnourished had a lower cellular immune function, but the humoral immune function was not significant between the patients group and control group. Immune function was improved with the recovery nutritional status of the patients. The results suggest that malnutrition and hypoimmunity may play a very important role in the pathogenesis of COPD.


Age, geographic, and temporal distribution of fecal shedding of Cryptosporidium parvum oocysts in cow-calf herds.
To evaluate fecal shedding of Cryptosporidium parvum from California cow-calf herds with respect to age, geographic region, temporal effects, and association with watery feces. Cows and calves from 38 beef cow-calf operations. Fecal specimens were collected and examined for C parvum oocysts, using immunofluorescent microscopy. Associations between age, geographic region, month of collection, watery feces, and likelihood of shedding C parvum were evaluated. 3.9% of cattle were shedding C parvum oocysts. Prevalence of shedding among calves ranged from 0 to 13%, and was 0.6% among cattle > or = 12 months old. The odds of shedding C parvum among 2-month-old calves were 41 times greater than among cattle > 4 months old. The odds of shedding C parvum among cattle tested in May were 8.7 times greater than among cattle tested during June, July, or August. The odds of infected individuals having watery feces were 3 to 4 times greater than for noninfected individuals, but the etiologic fraction was only 8 to 9%. Substantial fecal shedding of C parvum by cow-calf herds was limited to calves 1 to 4 months old, with low prevalence detected in older animals. Risk of contamination of watersheds with C parvum was limited to those periods when young calves were in the herd. Although the odds of having watery feces were greater for animals infected with C parvum than for noninfected animals, the low etiologic fraction suggests that most calves with watery feces were not infected with C parvum.


Understanding the instrumental profile of synchrotron radiation X-ray powder diffraction beamlines.
A Monte Carlo algorithm has been developed to calculate the instrumental profile function of a powder diffraction synchrotron beamline. Realistic models of all optical elements are implemented in a ray-tracing software. The proposed approach and the emerging paradigm have been investigated and verified for several existing X-ray powder diffraction beamlines. The results, which can be extended to further facilities, show a new and general way of assessing the contribution of instrumental broadening to synchrotron radiation data, based on ab initio simulations.


Small animal SPECT and its place in the matrix of molecular imaging technologies.
Molecular imaging refers to the use of non-invasive imaging techniques to detect signals that originate from molecules, often in the form of an injected tracer, and observe their interaction with a specific cellular target in vivo. Differences in the underlying physical principles of these measurement techniques determine the sensitivity, specificity and length of possible observation of the signal, characteristics that have to be traded off according to the biological question under study. Here, we describe the specific characteristics of single photon emission computed tomography (SPECT) relative to other molecular imaging technologies. SPECT is based on the tracer principle and external radiation detection. It is capable of measuring the biodistribution of minute (<10(-10) molar) concentrations of radio-labelled biomolecules in vivo with sub-millimetre resolution and quantifying the molecular kinetic processes in which they participate. Like some other imaging techniques, SPECT was originally developed for human use and was subsequently adapted for imaging small laboratory animals at high spatial resolution for basic and translational research. Its unique capabilities include (i) the ability to image endogenous ligands such as peptides and antibodies due to the relative ease of labelling these molecules with technetium or iodine, (ii) the ability to measure relatively slow kinetic processes (compared with positron emission tomography, for example) due to the long half-life of the commonly used isotopes and (iii) the ability to probe two or more molecular pathways simultaneously by detecting isotopes with different emission energies. In this paper, we review the technology developments and design tradeoffs that led to the current state-of-the-art in SPECT small animal scanning and describe the position SPECT occupies within the matrix of molecular imaging technologies.


Control of coherence resonance by self-induced stochastic resonance in a multiplex neural network.
We consider a two-layer multiplex network of diffusively coupled FitzHugh-Nagumo (FHN) neurons in the excitable regime. We show that the phenomenon of coherence resonance (CR) in one layer can not only be controlled by the network topology, the intra- and interlayer time-delayed couplings, but also by another phenomenon, namely, self-induced stochastic resonance (SISR) in the other layer. Numerical computations show that when the layers are isolated, each of these noise-induced phenomena is weakened (strengthened) by a sparser (denser) ring network topology, stronger (weaker) intralayer coupling forces, and longer (shorter) intralayer time delays. However, CR shows a much higher sensitivity than SISR to changes in these control parameters. It is also shown, in contrast to SISR in a single isolated FHN neuron, that the maximum noise amplitude at which SISR occurs in the network of coupled FHN neurons is controllable, especially in the regime of strong coupling forces and long time delays. In order to use SISR in the first layer of the multiplex network to control CR in the second layer, we first choose the control parameters of the second layer in isolation such that in one case CR is poor and in another case, nonexistent. It is then shown that a pronounced SISR can not only significantly improve a poor CR, but can also induce a pronounced CR, which was nonexistent in the isolated second layer. In contrast to strong intralayer coupling forces, strong interlayer coupling forces are found to enhance CR, while long interlayer time delays, just as long intralayer time delays, deteriorate CR. Most importantly, we find that in a strong interlayer coupling regime, SISR in the first layer performs better than CR in enhancing CR in the second layer. But in a weak interlayer coupling regime, CR in the first layer performs better than SISR in enhancing CR in the second layer. Our results could find novel applications in noisy neural network dynamics and engineering.


Performance of a four-element Si drift detector for X-ray absorption fine-structure spectroscopy: resolution, maximum count rate, and dead-time correction with incorporation into the ATHENA data analysis software.
The performance of a four-element Si drift detector for energy-dispersive fluorescence-yield X-ray absorption fine-structure measurements is reported, operating at the National Institute of Standards and Technology beamline X23A2 at the National Synchrotron Light Source. The detector can acquire X-ray absorption fine-structure spectra with a throughput exceeding 4 x 10(5) counts per second per detector element (>1.6 x 10(6) total counts per second summed over all four channels). At this count rate the resolution at 6 keV is approximately 220 eV, which adequately resolves the Mn Kalpha and Kbeta fluorescence lines. Accurate dead-time correction is demonstrated, and it has been incorporated into the ATHENA data analysis program. To maintain counting efficiency and high signal to background, it is suggested that the incoming count rate should not exceed approximately 70% of the maximum throughput.


[Lower extremity varicose veins in childhood and at a young age: Mechanism of development and specific features].
In Russia more than 125,000 patients with various venous diseases, lower extremity varicose veins (LEVV) being predominant, were annually operated on. In recent years, there has been a trend toward younger patients with signs of LEVV. Screening studies have revealed the signs of the disease in 10-15% of high-school children. The high prevalence of LEVV as a whole and its younger onset in recent decades cause more attention to an investigation of the relationship between the development of varicose veins, in childhood and adolescence in particular, and genomic changes. Patients with varicose veins have been noted to have a genetically reduced capacity for contraction of the smooth muscle cells of the vein walls, their remodeling due to the increased synthesis of matrix Gla protein, overproduction of TGF-β1, a matrix metalloproteinase inhibitor, hyperhomocysteinemia, and mutations in the genes encoding the synthesis of thrombomodulin. Varicose vein transformation is considered to be a minor phenomenon of undifferentiated connective tissue dysplasia (UCTD) leading to failure of their walls due to abnormalities in the fibrous structures and extracellular matrix. Confirmation of the role of UCTD in the development of varicose veins will be able to provide an individual approach to treating patients and to choosing adequate postoperative therapy aimed at preventing a disease recurrence.


Vitamin D insufficiency and bone fractures in patients on maintenance hemodialysis.
The incidence of fractures is substantially increased in patients with chronic kidney disease (CKD) compared to the general population. The factors associated with increased bone fracture in this population are not well understood. Vitamin D deficiency has been associated with decreased bone mass and higher incidence of fractures in the general population. In this study, we aimed to assess the association between fracture and vitamin D status and other factors potentially associated with fracture in patients on maintenance hemodialysis. One hundred and forty-four patients were assessed and interviewed about previous low-trauma fractures. Evidence of fracture was obtained from medical records and also through patient interviews. Routine laboratory results were collected from medical records. Serum intact PTH (iPTH) and 25(OH) vitamin D(3) were measured. All patients underwent bone densitometry of the lumbar spine, femoral neck and distal radius. Bone quality was also assessed with quantitative bone ultrasound (QUS). Descriptive statistics, logistic regression models were used to analyze factors associated with fractures. One hundred and thirty patients were included in the final analysis. Patients with fractures (n = 21) had lower 25(OH) vitamin D(3) levels (15.8 nmol/l (interquartile range, IQR: 27) vs. 30.0 nmol/l (IQR: 28.5), P = 0.029), were more likely females, had longer duration of end-stage kidney disease, and lower bone mineral density (BMD) at the distal radius. QUS parameters were not associated with fractures. Multivariate analyses revealed that serum 25(OH) vitamin D(3) concentration, BMD at the radius, iPTH less than 100 pg/ml and history of fractures were independent predictors of new bone fracture after the initiation of dialysis therapy. Increased bone fragility in dialysis patients is associated with vitamin D deficiency and relative hypoparathyroidism in addition to reduced BMD at the radius. Further studies are needed to determine whether patients with vitamin D deficiency benefit from vitamin D supplementation to reduce fracture risk.


Giant cerebral aneurysms: endovascular challenges.
Giant (>or=25 mm in diameter) cerebral aneurysms have a poor natural history, with high risks of subarachnoid hemorrhage or progressive disability or death caused by mass effect or stroke. Surgical treatment may be effective but carries a high burden of morbidity and mortality. Thus, attempts at endovascular solutions to these complex lesions have been developed to offer therapy at reduced risk. The authors reviewed their clinical experience and the current body of literature concerning giant cerebral aneurysms and present their perspective on the current state of the art in endovascular therapy for these aneurysms. A variety of techniques are described that can be used in an attempt to provide a solution to the wide variety of clinical dilemmas associated with the management of these difficult lesions. Preprocedural planning and periprocedural considerations are discussed briefly. The use of intracranial balloons and stents are described in conjunction with the use of detachable platinum coils. The developing concept of using stents alone to treat aneurysms is discussed. Alternative methods of treating giant aneurysms are discussed. Current endovascular approaches, when properly selected and applied, can provide lower-risk therapies than conventional microsurgical approaches for patients harboring giant cerebral aneurysms. However, endovascular approaches do not, at present, provide results that are as durable as current surgical techniques for giant cerebral aneurysms. Treatment of giant cerebral aneurysms via endovascular therapeutics requires the interventionist to possess an extensive armamentarium. Meticulous preprocedure evaluation, patient selection, and execution of the treatment plan enable safe and effective management. Current therapies do not provide an ideal solution for every patient, so one must consider creative and evolving solutions to these difficult clinical challenges. The procedural morbidity of open surgery versus the decreased durability of current endovascular techniques must be assessed carefully.


[Influence of arteriovenous hemofiltration on teicoplanin pharmacokinetics].
To assess the pharmacokinetics of a single dose of teicoplanin in critically ill patients treated with continuous arteriovenous haemofiltration (CAVH). Prospective open clinical study. Eleven patients with acute renal insufficiency and suspected of a Gram negative infection. After injection of teicoplanin, 6 mg.kg-1 over 30 minutes the plasma and haemofiltrate concentrations were measured over 24 hours with high power liquid chromatography (HPLC). In plasma, the mean half-life of the first phase was 0.6 +/- 0.2 hour and terminal half-life was 16.4 +/- 5 8 hours, total clearance 30.4 +/- 7.1 mL.h-1.kg-1, volume of distribution was 0.7 +/- 0.3 L.kg-1 and the mean resident time 19.2 +/- 7.4 hours. In the haemofiltrate, the amount of teicoplanin eliminated after 24 hours was less than 1% in seven patients, between 1.8 and 3.7% in three and reached 7% in one patient. During CAVH, the elimination of a single dose of teicoplanin in the haemofiltrate is low.


Increased velocity and induction of chemotactic response in mouse spermatozoa by follicular and oviductal fluids.
The dynamic parameters of mouse sperm cells exposed to follicular and oviductal fluids were assessed. Spermatozoa were tracked on a chemotactic Zigmond chamber and recorded using a videomicroscopy system. The results were evaluated with computer-supported image analysis. Follicular fluid at a dilution of 10(-4) markedly increased the proportion of spermatozoa with high velocity, and stimulated chemotactic behaviour. The highest velocities were observed in sperm cells exposed to oviductal fluid, and a greater proportion of these cells had high velocity compared with those exposed to follicular fluid. Chemotaxis was induced in spermatozoa exposed to oviductal fluid at dilutions of 10(-3) and 10(-5). These results suggest the presence of temporal subpopulations of responsive spermatozoa, considering the distance travelled towards both follicular and oviductal fluids and the proportion of sperm cells migrating towards the gradient in the highest distance ranges. This is the first report on the effect of isolated follicular and oviductal fluids on dynamic parameters and chemotaxis of mouse spermatozoa. The findings support previous work showing that the motility and directionality of mouse sperm cells is increased by factors in the microenvironment of the egg. Although the significance of these factors in vivo is unknown, it is possible that there is a relay mechanism involving sequential activity of both oviductal and follicular fluids to direct the male gametes towards the egg.


Earlier Hospital Discharge With Prospectively Designated Discharge Time in the Electronic Health Record.
Hospital discharge requires multidisciplinary coordination. Insufficient coordination impacts patient flow, resource use, and postdischarge outcomes. Our objectives were to (1) implement a prospective, multidisciplinary discharge timing designation in the electronic health record (EHR) and (2) evaluate its association with discharge timing. This quality-improvement study evaluated the implementation of confirmed discharge time (CDT), an EHR designation representing specific discharge timing developed jointly by a patient's family and the health care team. CDT was intended to support task management and coordination of multidisciplinary discharge processes and could be entered and viewed by all team members. Four plan-do-study-act improvement phases were studied: (1) baseline, (2) provider education, (3) provider feedback, and (4) EHR modification. Statistical process control charts tracked CDT use and the proportion of discharges before noon. Length of stay was used as a balancing measure. During the study period from April 2013 through March 2017, 20 133 pediatric discharges occurred, with similar demographics observed throughout all phases. Mean CDT use increased from 0% to 62%, with special cause variations being detected after the provider education and EHR modification phases. Over the course of the study, the proportion of discharges before noon increased by 6.2 percentage points, from 19.9% to 26.1%, whereas length of stay decreased from 47 (interquartile range: 25-95) to 43 (interquartile range: 24-88) hours (both P < .001). The implementation of a prospective, multidisciplinary EHR discharge time designation was associated with more before-noon discharges. Next steps include replicating results in other settings and determining populations that are most responsive to discharge coordination efforts.


Multicenter case-control study of risk factors for histoplasmosis in human immunodeficiency virus-infected persons.
We conducted a multicenter case-control study to identify risk factors for histoplasmosis among persons with acquired immunodeficiency syndrome (AIDS) and to evaluate predictors of a poor outcome (defined as death or admission to the intensive care unit). Patients with histoplasmosis were each matched by age, sex, and CD4 lymphocyte count to 3 controls. From 1996 through 1999, 92 case patients and 252 controls were enrolled. Of the case patients, 81 (89%) were men, 50 (55%) were black, 78 (85%) had a CD4 lymphocyte count of <100 cells/microL, 80 (87%) were hospitalized, and 11 (12%) died. Multivariable analysis found that receipt of antiretroviral therapy and of triazole drugs were independently associated with a decreased risk of histoplasmosis. Chronic medical conditions and a history of infections with herpes simplex virus were associated with poor outcome. Triazoles should be considered for chemoprophylaxis for persons with AIDS, especially those who take part in high-risk activities that involve frequent exposure to soil, who have CD4 lymphocyte counts of <100 cells/microL, and who live in areas where histoplasmosis is endemic.


Oxidation of urea-derived nitrogen by thaumarchaeota-dominated marine nitrifying communities.
Urea nitrogen has been proposed to contribute significantly to nitrification by marine thaumarchaeotes. These inferences are based on distributions of thaumarchaeote urease genes rather than activity measurements. We found that ammonia oxidation rates were always higher than oxidation rates of urea-derived N in samples from coastal Georgia, USA (means ± SEM: 382 ± 35 versus 73 ± 24 nmol L-1 d-1 , Mann-Whitney U-test p < 0.0001), and the South Atlantic Bight (20 ± 8.8 versus 2.2 ± 1.7 nmol L-1 d-1 , p = 0.026) but not the Gulf of Alaska (8.8 ± 4.0 versus 1.5 ± 0.6, p > 0.05). Urea-derived N was relatively more important in samples from Antarctic continental shelf waters, though the difference was not statistically significant (19.4 ± 4.8 versus 12.0 ± 2.7 nmol L-1 d-1 , p > 0.05). We found only weak correlations between oxidation rates of urea-derived N and the abundance or transcription of putative Thaumarchaeota ureC genes. Dependence on urea-derived N does not appear to be directly related to pH or ammonium concentrations. Competition experiments and release of 15 NH3 suggest that urea is hydrolyzed to ammonia intracellularly, then a portion is lost to the dissolved pool. The contribution of urea-derived N to nitrification appears to be minor in temperate coastal waters, but may represent a significant portion of the nitrification flux in Antarctic coastal waters.


[Lumbar hernia. Case report and literature review].
Lumbar hernia is a rare abdominal wall defect that usually presents spontaneously after trauma or lumbar surgery or, less frequently, during infancy (congenital). Few reports have been published in the literature describing congenital lumbar hernia. We present the case of a patient with congenital lumbar hernia and a review describing the regional anatomy, laparoscopic techniques as a surgical alternative, and the impact of modern imagenology in diagnosis, confirmation and demarcation of the aponeurotic defect, in order to update information and to provide the surgeon with the tools for optimal perioperative preparation and the best operative technique for this rare disease. We describe here the case of a 5-month-old Mexican female infant with a right lumbar bulging. Ultrasonographic findings showed an aponeurotic defect and an ipsilateral renal agenesia. Open surgical repair was carried out with identification of the defect in the superior or Grynfellt-Lesshaft's triangle and the inferior triangle as well, and a polypropylene mesh was placed below the posterior abdominal sheath. Congenital lumbar hernia usually originates in the superior triangle or Grynfellt-Lesshaft's triangle and is frequently associated with the lumbocostovertebral syndrome. Surgery is always indicated, with utilization of prosthetic material or muscular flaps as the best repair technique.


Effect of simultaneous administration of betamethasone and triiodothyronine (T3) on the development of functional pulmonary maturation in fetal rabbit.
Recent experimental evidence suggests that a combination of glucocorticoid and thyroid hormone may be more effective than either hormone alone in accelerating morphologic as well as biochemical mammalian fetal lung maturation. We have demonstrated that IM administration of T3 to the rabbit doe is associated with enhanced functional fetal lung maturation. We investigated the effect of simultaneous administration of T3 and betamethasone on the development of functional fetal lung maturation and the duration of survival after premature delivery. On day 25 and 26 of pregnancy, T3 (175 micrograms/kg/dose) betamethasone (85 micrograms/kg/dose), T3 plus betamethasone or the appropriate amount of the vehicles were injected. The functional fetal pulmonary maturity and the duration of survival after premature delivery were assessed on day 27 of gestation. Although enhanced functional fetal lung maturation was observed after T3 or betamethasone administration, there was no additive effect after simultaneous administration of both. The duration of survival on premature delivery was enhanced in betamethasone but not T3 or T3 plus betamethasone group when compared to control. Further animal experimentation seems necessary before a clinical trial of T3 plus betamethasone therapy is considered.


Bold age.
The debate about epidurals has long raged in midwifery circles. But now the question is being tackled in research which should help to point the way for future practice.


Actinomycosis of the jaws. 2 case reports.
The diagnosis of actinomycosis is not always straightforward. It has been described as a masquerader, and 2 cases are presented which exemplify this. Their mode of presentation and natural history are contrasted.


Influence of age on the stereoselective disposition and metabolism of ibuprofen in humans.
Ibuprofen is widely used in the treatment of pain and inflammatory disorders. Metabolic events that occur within the pharmacokinetic behavior of ibuprofen enantiomers create problems for patients, particularly the elderly and those with conditions where the maintenance of renal function is prostaglandin-dependent. Eighteen healthy volunteers of two different age groups received an oral dose of 800 mg of racemic ibuprofen, and the pharmacokinetic profiles of (R)- and (S)-ibuprofen metabolism were examined. The results showed reduced ibuprofen clearance in the older group, as indicated by elevated values of T1/2 (R), AUC(R) and AUC(S), as well as reduced clearance/fraction of absorption (R). Clearly, age is a risk factor for ibuprofen-related renal failure. The aging process, functional changes in drug metabolism and disposition contribute to the increased incidence of ibuprofen-related toxicity in the elderly.


Characterization of HbEREBP1, a wound-responsive transcription factor gene in laticifers of Hevea brasiliensis Muell. Arg.
AP2/ERF transcription factors play an important role in regulation of the cross-talk between ethylene and jasmonate signaling pathways mediating defense responses of plants to biotic and abiotic stresses. In this study, an AP2/ERF transcription factor gene was isolated and characterized from laticifers of rubber tree by using RACE and real time PCR. The full length cDNA, referred to as HbEREBP1, was 1,095 bp in length and contained a 732 bp open reading frame encoding a putative protein of 243 amino acid residues. The molecular mass of the putative protein is 26.4 kDa with a pI of 9.46. The deduced amino acid sequence had a specific domain of AP2 superfamily and an ethylene-responsive element binding factor-associated amphiphilic repression motif, sharing 42.4, 39.1, and 38.0% identity with that of AtERF11, AtERF4, and AtERF8 in Arabidopsis, respectively. HbEREBP1 expression was down-regulated by tapping and mechanical wounding in the laticifers of adult trees. It was also down-regulated at early stage while up-regulated at late stage upon treatment with exogenous ethephon or methyl jasmonate, which was reverse to the case of defense genes in laticifers of epicormic shoots of rubber tree. Our results suggest that HbEREBP1 may be a negative regulator of defense genes in laticifers.


Eighteen years' experience with a community-based vocational rehabilitation programme.
Eighteen years' experience in the development of an innovative community-based regional vocational rehabilitation service has been described. The programme continues to develop with the recent introduction of a vocational consulting service offering employee assistive programmes to local employers, and with funding from the Solicitor General's Department to provide vocational assessment and retraining to women in conflict with the law. The success of this programme is due to the co-operative melding of the contributions of the university, the regional rehabilitation centre and broadly based community participation by employers and a variety of agencies.


Locally advanced colorectal cancer in pregnancy.
To highlight the issue of diagnostics and treatment management in colorectal cancer of pregnant women. Case report. Department of Obstetrics and Gynaecology, Pardubice Hospital. We present a case of a 24-year-old secundigravida, diagnosed as colorectal cancer in week 34 of pregnancy, manifesting as a diarrhoea and a stomach ache. The diagnosis was made in an advanced stage due to underestimation of clinical symptoms. The diagnosis of the colorectal cancer in pregnancy can be difficult because the presenting symptoms are easily attributable to pregnancy. Therefore the advanced disease is diagnosed more frequently in pregnant patients than in the general population. Colorectal cancer should be managed by multidisciplinary team with regard to gestation.


Adenoid cystic carcinoma of the head and neck: a clinical study of 37 cases.
Thirty-seven cases of adenoid cystic carcinoma treated at the Otolaryngologic Clinic of the University of Florence between 1962 and 1979 were studied. The patients were treated with radical surgical excision (20), non-radical surgery associated with radiotherapy (13), or with palliative treatment (4). The aim of this study is to evaluate the course of the disease according to the site and type of operation. Our results show that non-radical surgical treatment associated with radiotherapy seems to give results comparable to those obtained with radical surgery alone.


Magnitude and orientation of Zernike terms in patients with keratoconus.
To measure the magnitude and orientation of the Zernike terms in keratoconic eyes, with and without rigid gas-permeable (RGP) contact lenses. A total of 76 eyes with keratoconus, 58 eyes with keratoconus suspect, and 105 normal eyes were studied. To determine the effect of RGP lenses, 19 eyes with keratoconus, 9 eyes with keratoconus suspect, and 17 normal eyes, with and without an RGP lenses, were compared. Ocular higher-order aberrations (HOAs) were measured with a wavefront sensor for a 4-mm-diameter pupil, and the magnitudes, axes of trefoil, and coma were calculated by vector analysis. Zernike vector analysis showed prominent vertical coma with an inferior slow pattern, with mean axes of 82.5 degrees or 91.0 degrees in the patients with keratoconus or keratoconus suspect, respectively. The mean axes of trefoil in patients with keratoconus (93.8 degrees ) and keratoconus suspect (100.6 degrees ) differed from that in normal subjects (35.4 degrees ), indicating that keratoconus has a reverse trefoil pattern from that of normal eyes. Although the total HOAs were significantly (keratoconus and keratoconus suspect, P < 0.001 and P = 0.012, respectively) reduced with an RGP lens, the patterns of the axes of coma and trefoil were reversed with the lens. In addition to the larger amount of trefoil, coma, tetrafoil, and secondary astigmatism, keratoconic eyes tend to have a reverse coma pattern and reverse trefoil aberrations compared with normal eyes. Although RGP lenses correct the irregular astigmatism, smaller comet-like retinal images in the opposite direction remain due to residual vertical coma.


Odontometrics of the permanent teeth in cleft lip and palate: systemic size reduction and amplified asymmetry.
Mesiodistal diameters of the permanent teeth of 70 isolated cleft lip and palate cases were analyzed. Subjects with unilateral cleft lip and palate (CLP) exhibit significantly smaller crown sizes than controls. Size reduction averages 2.3 percent, which translates to a 5.2-mm mean difference summed across all 28 permanent teeth. Bilateral cases are twice as affected, with a 4.2 percent reduction (9.3 mm). The baseline level of left-right asymmetry is significantly amplified across the whole dentition, encompassing both early- and late-forming teeth and constituting a 30-percent increase in overall asymmetry. Also, there is a localized peak of disproportionately high asymmetry centered on the upper lateral incisor but extending to both the central incisor and canine. The consistency of these differences across all tooth types and among early- and late-forming teeth implies that isolated CLP is a sequelae of a systemic, generalized restriction of these individuals' growth potential.


Thin molecular films of supramolecular porphyrins.
A relevant series of symmetric supramolecular porphyrins has been obtained by attaching four [RuII(bipy)2Cl] groups to the pyridyl substituents of meso-tetra(4-pyridyl)porphyrin and its metallated derivatives. These compounds display a rich electrochemistry and versatile catalytic, electrocatalytic and photochemical properties, associated with the ruthenium-bipyridine and the porphyrin complexes. These properties can be transferred to the electrodes by attaching thin molecular films of the compounds, by dip-coating, electrostatic assembly or electropolymerization. In this way, the interesting properties of those supermolecules and supramolecular assemblies can be used to prepare molecular devices and sensors.


Interactive effect of the p53 gene and cigarette smoking on coronary artery disease.
p53 is a tumour suppressor protein involved in the control of cell growth and has an established role in carcinogenesis, particularly in relation to smoking. It may also be related to arteriosclerosis by affecting smooth muscle cell proliferation, a feature of atherogenesis. We explored a role for p53 in atherogenesis by assessing the association between two DNA polymorphisms of the p53 gene (MspI at intron 6 and HaeIII at intron 1) and angiographically documented coronary artery disease (CAD) in 654 Australian Caucasian patients. There was a significant interactive effect of the two polymorphisms and cigarette smoking on CAD in a logistic regression analysis (P = 0.0039) but no association between CAD and either individual p53 polymorphic marker. CAD occurrence was more frequent in non-smoking patients with rare alleles at both sites (85.0%) compared to those homozygous for common alleles at both sites (70.4%). However, this was not seen in smokers (85.7 vs 82.8%). In all 654 patients cigarette smoking remained a significant predictor of CAD irrespective of p53 genotypes (P = 0.0065). Our findings identify an interactive effect of both p53 polymorphisms and cigarette smoking on the occurrence of coronary artery disease in that non-smoking patients with rare alleles at both sites had increased incidence of CAD. They illustrate the relevance of genotype-specific and environment-dependent enhanced cardiovascular risk and foreshadow a need for further studies to establish functional changes.


Innate cellular defenses of APOBEC3 cytidine deaminases and viral counter-defenses.
The APOBEC3 cytidine deaminases, which are unique to mammals, have been identified as potent innate cellular defenses against both endogenous retroelements and diverse retroviruses. To evade such host defenses, retroviruses have developed multiple strategies. This article reviews several proposed mechanisms of these viral counter-defenses. Primate lentiviruses encode a virion-infectivity factor that induces targeted destruction of APOBEC3 proteins by hijacking the cellular ubiquitin-proteasome pathway. Virion-infectivity factor molecules of HIV-1 and SIV are newly identified substrate receptor proteins that assemble with Cul5, ElonginB, ElonginC, and Rbx1 to form an E3 ubiquitin ligase and target selected APOBEC3 proteins for polyubiquitination. Foamy viruses use a different viral protein, BET, which binds and sequesters APOBEC3 away from the assembling virions. Simple retroviruses such as murine leukemia virus may avoid virion packaging of cognate APOBEC3 protein through yet another novel mechanism, in the absence of a viral regulatory factor. APOBEC3 cytidine deaminases target broad retroelements. Contemporary retroviruses have developed multiple unique strategies to combat this powerful host defense system. As a result, these retroviruses and APOBEC3 proteins maintain an equilibrium that allows regulated viral replication. These viral counter-defenses thus represent vulnerable targets for the design of new classes of antiviral inhibitors.


A rapid, simple enzyme immunoassay for detection of antibody to individual epitopes in the serodiagnosis of tuberculosis.
The antibody response to individual epitopes has previously been analysed by competition assay using 125I- or enzyme labelled monoclonal antibodies. A modification of the test is described in which competition of human sera with unlabelled mouse monoclonal antibodies at the limiting dilution is revealed by peroxidase labelled antimouse IgG conjugate. Analysis of 54 sera from patients with pulmonary (36) and extra-pulmonary (18) tuberculosis and 31 controls indicated that the modified test compares favourably with the test based upon directly labelled antibodies. Diagnostic sensitivity for five monoclonal antibodies evaluated was 11.1% (TB78), 35.2% (TB23 and TB68), 37.0% (TB71) and 61.1% (TB72) at 97.5% specificity. For TB72, sensitivity was highest for pulmonary disease (69.7%). The modified assay is also easier to standardise for screening new monoclonal antibodies using a single enzyme-labelled conjugate.


Versatile strategy to access fully functionalized benzodifurans: redox-active chromophores for the construction of extended pi-conjugated materials.
An efficient synthetic approach to construct a fully substituted benzo[1,2-b:4,5-b']difuran (BDF) 2a via base-catalyzed double annulations is presented. Compound 2a can readily undergo Suzuki, Heck, and Sonogashira coupling reactions to afford in good yields a manifold of extended pi-conjugated BDF derivatives, e.g., with pyridine termini (4-6) and with different spacers. These are highly luminescent materials that undergo two reversible one-electron oxidations. Remarkably, their photophysical and electrochemical properties can be largely tuned by methylation or protonation. Consequently, they can function as pH-dependent fluorescence switches. Finally, the observed electronic properties are explained on the basis of density functional theory.


Effect of Temperature, Relative Humidity, and Suspending Menstrua on the Resistance of Listeria monocytogenes to Drying.
The ability of Listeria monocytogenes to survive dehydrated storage at different temperatures (5 vs. 25°C) and relative humidities (75, 59, 35, 14, and 1%) when suspended in different menstrua was studied. L. monocytogenes survived longer when held at 5°C compared to 25°C, and when suspended in beef extract, glycerol, Karo syrup, skim milk, and canned milk compared to distilled water. The contribution of relative humidity to survival was less clear, though survival tended to be longer at the lower relative humidities. At 5°C when suspended in beef extract and held at relative humidities of 59% and below, there was less than a 2 log10 decline in the viable population (starting count ca. 105/coverslip). L. monocytogenes was not injured during drying or storage at the various relative humidities. In addition, based on the Listeria selective media evaluated, these Listeria media permitted quantitative recovery of the organism dried on surfaces. These results suggested that once L. monocytogenes has contaminated a food processing plant, it can persist for long periods in the plant environment if the temperature is low and the organism is protected by various food components.


A score using left ventricular diastolic dysfunction to predict 90-day mortality in acute ischemic stroke: The DONE score.
The aim of this study was to identify whether diastolic dysfunction predicts death at 90 days after acute ischemic stroke. We retrospectively analyzed patients with ischemic stroke. All patients underwent transthoracic echocardiography to evaluate systolic function and diastolic function by means of assessing ejection fraction and septal E/e'. We evaluated the initial National Institute of Health Stroke Scale (NIHSS) score, arterial occlusion, and laboratory data. We used multivariate regression models to identify independent predictors of 90-day mortality. Among 1208 patients, the overall 90-day mortality rate was 8%. In multivariate logistic regression analysis, a higher initial NIHSS score, plasma D-dimer level and E/e', and occlusion of internal carotid artery or basilar artery were independent predictors of 90-day mortality. The DONE score derived from these valuables showed good discrimination with area under the curve (AUC) value of 0.82 (95% confidence interval [CI], 0.78-0.87) to predict 90-day mortality. The DONE score also predicted poor outcome (modified Rankin scale score, 4-6) at 90 days (AUC, 0.82; 95% CI 0.80-0.85). Higher E/e', indicating diastolic dysfunction, may be associated with 90-day mortality in patients with acute ischemic stroke. The DONE score could readily predict poor outcome after acute ischemic stroke.


The ciliary pocket.
Cilia are fascinating highly conserved organelles shared by very different organisms from unicellular eukaryotes to vertebrates where they are involved in motility and sensory functions. In vertebrates, the function of the primary cilium, a unique nonmotile cilium found at the surface of most cell types during development, remained mysterious during 40 years until its crucial function in the control of key signaling cascades during development and its involvement in complex genetic disorders now called ciliopathies were uncovered. Recent studies have focused on a specific membrane domain found at the base of primary cilia in most cell types which was already mentioned in the first descriptions of these cilia but did not raise much interest during 50 years. This membrane domain, the 'ciliary pocket', also found at the base of some motile cilia, may act as a platform for cilia-associated vesicular trafficking and as an interface with the actin cytoskeleton but also likely in additional important functions which remain to be discovered.


[Symptomatic therapy of pruritus (author's transl)].
The symptomatic therapy of generalized primary pruritus is reviewed. The topical therapy consists of skin care measures; more or less greasy ointments or creams should be used depending on the degree of dryness of the skin. It is to be noted that tenside-containing bath additives may promote drying of the skin, in pruritus patients they should be replaced with oil-based bath additives. Antihistamines have proved valuable in systemic therapy. The pharmacological effects of these H2 receptor antagonists is dealt with. The principles for selection of individual preparations from the vast number of substances available are commented on; combination therapy is gone into and also possible side-effects, particularly of ethylenediamine and piperazine antihistaminics. Glucocorticoids and antiphlogistics have no place in the treatment of generalized primary pruritus.


Effect of different extracting methods on quality of Chrysanthemum Morifolium Ramat. Infusion.
The flower of Chrysanthemum Morifolium Ramat. (CM) is a useful food and folk medicine in China. Effects of Chrysanthemum Morifolium extracting (CME) conditions, including extraction temperature, extraction time and the ratio of flower to water on infusion quality were investigated. The extractability, liquor color differences and the major flavonoids of luteolin-7-O-beta-D-glucoside and luteolin of various CME methods were evaluated. The results indicated that CME temperature was the most important factors affecting quality of CM infusion. Based on the extractability and chemical compositions, the best CME conditions were the 90 to approximately 100 degrees C, 20-30 min and the ratio of flower to water of 1:40 (w/v). High-performance liquid chromatography (HPLC) of Chrysanthemum Morifolium chemical compositions including luteolin-7-O-beta-D-glucoside and luteolin was also discussed in the present paper.


Multiple signaling pathways of human interleukin-8 receptor A. Independent regulation by phosphorylation.
Interleukin-8 (IL-8) receptor A (CXCR1) couples to a pertussis toxin-sensitive G protein to mediate phospholipase Cbeta (PLCbeta) activation and cellular responses. Responses to CXCR1 are attenuated by prior exposure of neutrophils to either IL-8, a cleavage product of the fifth component of complement (C5a) or n-formylated peptides (formylmethionylleucylphenylalanine, fMLP). To characterize the role of receptor phosphorylation in the regulation of the CXCR1, a phosphorylation-deficient mutant, M2CXCR1, was constructed. This receptor, stably expressed in RBL-2H3 cells, coupled more efficiently to G protein and stimulated enhanced phosphoinositide hydrolysis, cAMP production, exocytosis, and phospholipase D activation, and was resistant to IL-8-induced receptor internalization. The rate and total amount of ligand stimulated actin polymerization remained unchanged, but interestingly, chemotaxis was decreased by approximately 30% compared with the wild type receptor. To study the role of receptor phosphorylation in cross-desensitization of chemoattractant receptors, M2CXCR1 was coexpressed with cDNAs encoding receptors for either fMLP (FR), C5a (C5aR), or platelet-activating factor (PAFR). Both C5aR and PAFR were cross-phosphorylated upon M2CXCR1 activation, resulting in attenuated guanosine 5'-3'-O-(thio)triphosphate (GTPgammaS) binding in membranes. In contrast, FR and M2CXCR1 were resistant to cross-phosphorylation and cross-inhibition of GTPgammaS binding by other receptors. Despite the resistance of M2CXCR1 to cross-phosphorylation and receptor/G protein uncoupling, its susceptibility to cross-desensitization of its Ca2+ response by fMLP and C5a, was equivalent to CXCR1. Regardless of the enhancement in certain receptor functions in M2CXCR1 compared with the wild type CXCR1, the mutated receptors mediated equivalent PLCbeta3 phosphorylation and cross-desensitization of Ca2+ mobilization by FR, C5aR, and PAFR. The results herein indicate that phosphorylation of CXCR1 regulates some, but not all of the receptors functions. While receptor phosphorylation inhibits G protein turnover, PLC activation, Ca2+ mobilization and secretion, it is required for normal chemotaxis and receptor internalization. Since phosphorylation of CXCR1 had no effect on its ability to induce phosphorylation of PLCbeta3 or to mediate class-desensitization, these activities may be mediated by independently regulated pathways.


[Bleeding gastric and duodenal varicose veins: endoscopic embolisation using tissue adhesives].
Endoscopically guided intravascular injections of the tissue glue N-butyl-2-cyanoacrylate have since 1990 been performed in eight patients (seven men, one woman; median age 59.5 [40-72] years) with cirrhosis of the liver (alcoholic: n = 6, posthepatic, n = 2), decreased haemoglobin (6-10 g/dl) and transient shock symptoms (n = 5) due to gastric (n = 7) or duodenal varices (n = 1). Gastric acid production was suppressed with omeprazole. Neither balloon catheters nor drugs were used to lower portal vein pressure. Initial haemostasis was achieved in all patients. One patient with consumption coagulopathy died of recurrent bleeding from varices in the body of the stomach which could be only temporarily arrested. Another patient had a recurrence of bleeding from varices in the cardia 3 months after the initial treatment: it was again controlled by endoscopic sclerotherapy with tissue glue. All other patients remain free of bleeding after a mean observation time of 8.4 months.


New treatments for erectile dysfunction.
Erectile dysfunction (ED) is an increasingly common problem, affecting up to 30 million American men. This largely results from increased risk factors and an aging population. ED is now also recognized as a marker for cardiovascular disease. The ED patient should be thoroughly evaluated for coexisting vascular disease. The pathophysiology of ED is becoming better understood, largely as a result of the development of new therapies. Once the underlying processes are known, more selective targeting of these will lead to novel "designer drugs."


[Inflammatory colitis and chronic granulomatous disease, a steroid-dependent case report].
Chronic granulomatous disease may lead to inflammatory bowel disease with endoscopic and histological aspects similar to that observed in patients with Crohn's disease. Inflammatory symptoms are generally controlled by steroids, but resistant forms may need total colectomy. Therapeutic strategy in steroid-dependent cases is not yet established. We report here the case of a patient with chronic granulomatous enteritis dependent on steroids at a daily dose of 20 mg. Azathioprine made it possible to withdraw steroid therapy without relapse over twenty Months and without infectious complication during the follow up.


Mimicking somatic hypermutation: affinity maturation of antibodies displayed on bacteriophage using a bacterial mutator strain.
Human antibodies can now be isolated from antibody repertoires displayed on the surface of filamentous bacteriophage in a process that mimics the primary immune response. Here we have attempted to mimic the secondary response, the natural process of affinity maturation of antibodies occurring in germinal centres, by multiple cycles of random mutation and selection. Phage displaying a human antibody fragment recognising the hapten 2-phenyl-5-oxazolone were grown in a mutator strain of bacteria (Escherichia coli: mutD5) to generate a large repertoire of antibodies that should include the majority of possible single nucleotide point mutations. The repertoire of phage antibody mutants was then selected by binding to hapten. By multiple rounds of growth in the mutator strain, and increasingly stringent selection, we succeeded in isolating mutants with improved binding affinities; furthermore, the distribution of mutations and nucleotide substitution preferences strongly resembled those of somatic hypermutation. We then constructed a genealogical tree from the sequences of mutants taken at different rounds, and identified four sequentially acquired mutations that together improve the binding affinity of the antibody by a factor of 100-fold (from Kd 320 nM to 3.2 nM).


Borelli's lactritmel agar induces conidiation in rare-macroconidia producing dermatophytic fungi.
Macroconidia are among the most important indicators used to identify dermatophytic fungi, but several do not usually sporulate and/or produce macroconidia on Sabouraud glucose agar. Specifically, Microsporum audouinii, M. ferrugineum, Trichophyton concentricum, T. schoenleinii, T. verrucosum, and T. violaceum (including T. soudanense and T. yaoundei) rarely form macroconidia and, therefore, cannot be easily identified. In this study, we investigated the production of macroconidia on nine common laboratory media, including Borelli's lactritmel agar (BLA), modified Borelli's lactritmel agar (MBLA), brain heart infusion agar (BHIA), Christensen's urease agar in Petri dishes (UPA), cornmeal dextrose agar (CMDA), Lowenstein-Jensen agar (LJA), malt extract agar (MEA), oatmeal agar (OA), and potato dextrose agar (PDA). The performance of these media was evaluated using 18 rare-macroconidia producing isolates, including representative of the six species mentioned above. All cultures in this study were incubated at 26°C on the bench, and conidia formation on each was investigated at 5, 10, 15, 20, 25, and 30 days of incubation. BLA apparently improved macroconidia production after 15 days and was the most useful nutrient agar medium to induce these phenotypic characters in daily practice, closely followed by OA, PDA, and MBLA.


Motor and non-motor symptoms in old-age onset Parkinson's disease patients.
Advancing age is a well-known risk factor for Parkinson's disease (PD). With population ageing it is expected that the total number of patients with PD onset at oldage increases. Information on the motor but particularly on non-motor phenotype of this late-onset population is lacking. We recruited 24 patients with PD onset at or over 75 years. Each patient was matched with 1 control patient with PD onset between the ages of 40 and 65 and matched for disease duration. Both groups were assessed with the UPDRS, the Non-motor symptoms scale (NMSS) and other scales to assess non-motor symptoms. Groups were compared with conditional logistic regression analysis. Old-age onset PD was, on average, 80 years at the time of PD onset while middle-age onset were 59. Disease duration was approximately 5 years in both groups. While no difference was observed in the total UPDRS-III scores, old-age onset PD was associated with higher axial symptoms (7.42 vs. 4.63, p = 0.011) and a higher frequency of dementia (7/24 vs. 0/24, p = 0.009). While no difference in the total number of non-motor symptoms was observed (6.79 vs. 6.22, p = 0.310), old-age onset patients had a higher prevalence of gastrointestinal symptoms (20/24 vs. 12/24, p = 0.037). For the same disease duration, older age onset is associated with worse axial motor dysfunction and dementia in PD patients. Beside gastrointestinal symptoms, non-motor symptoms are not associated with age.


Asymmetric hybrids formed with hemoglobin British Columbia (alpha 2 beta 2101Glu----Lys).
Whole blood and purified hemoglobins from a patient heterozygous for Hb British Columbia were studied with various types of electrophoresis. Isoelectric focusing of whole blood in cylindrical polyacrylamide gels showed 3 major hemoglobin species at equilibrium: Hb A, Hb British Columbia, and an unidentified Hb with an isoelectric point of 7.15. In addition, a transient asymmetric hybrid band was observed between Hb A and Hb British Columbia; it had disappeared at equilibrium. Hb A2 was never present. Isoelectric focusing of purified Hbs A2 and British Columbia in various proportions, and gel permeation chromatography of them in equal amounts, indicated that the pI 7.15 component was a very stable hybrid. This hybrid was recovered from thin-layer isoelectric focusing in agarose. Electrophoresis on agar at pH 6.0 showed 3 hemoglobins: A2, British Columbia, and one of intermediate migration. On cellulose acetate at pH 9.2, only the 2 parent Hb components, A2 and British Columbia were seen. Thus, the single Hb recovered from agarose is probably the asymmetric hybrid alpha 2 delta beta British Columbia.


Molecular events in radiation transformation.
Studies of human tumor cell lines have revealed alterations in the regulation of a number of cell cycle-related genes, associated in some cases with a TP53-independent loss of the radiation-induced G(1)-phase arrest. It is not clear, however, whether these are early or late events in tumor development, or they arise in tumor cell lines during growth in culture. Since the oncogenic transformation of an individual cell is thought to be an early event in tumor development, we have used a model system of normal and radiation-transformed C3H 10T(1/2) mouse fibroblast cell clones to address this issue. Transformed clones derived from type III foci were compared with clones derived from parental, wild-type cells. Approximately 25% of transformed clones showed Trp53 mutations in exon 5; however, preliminary results based on in situ immunofluorescence studies with an antibody recognizing mutant Trp53 indicate that the appearance of such mutations in transformed clones occurs late in the process of transformation and is unlikely to represent an initiating event. The remaining transformed clones and all clones derived from parental cells expressed wild-type Trp53. Radiation-induced G(1)-phase arrest was either absent or significantly reduced in all of the transformed clones, independent of Trp53 status. Constitutive expression of Cdkn1a protein was significantly increased in most of the transformed clones. Also, the majority of transformed clones showed elevated levels of cyclin D1, and two clones overexpressed cyclin E. These results indicate that loss of G(1)-phase checkpoint control, independent of Trp53 status, and altered expression of cell cycle regulatory proteins may represent early events in the process of radiation-induced carcinogenesis that are associated with the malignant transformation of individual cells.


Cholangiocarcinoma with a background of hepatitis B virus-associated cirrhosis.
Recently, hepatitis virus-associated chronic hepatitis or cirrhosis has been suggested to be involved in the pathogenesis of cholangiocarcinoma (CC). A 52-year-old man was diagnosed as CC with a background of hepatitis B virus (HBV)-dependent cirrhosis. A minute hepatic tumor was found during the follow-up, and was diagnosed as CC on percutaneous biopsy. The patient died of hepatic failure and an autopsy revealed the tumor to be a well to moderately differentiated adenocarcinoma. An immunohistological analysis of HBV X gene-encoded protein (HBX) was neither detected in the cancerous nor in the noncancerous tissue. No oncogenic role of the virus was verified in this case.


Assessment of antihyperlipidemic therapy in US patients with coronary heart disease.
Knowledge of the trends and possible differences in the use of antihyperlipidemic medications in US patients with coronary heart disease (CHD) is vital in order to stimulate a positive change in the health of society. To assess, in the ambulatory setting, the frequency of antihyperlipidemic medication use in US patients with CHD. Retrospective, national, cross-sectional study using data from the 2004 National Ambulatory Medical Care Survey (NAMCS). Ambulatory medical visits surveyed by the 2004 NAMCS associated with select ICD-9-CM CHD-related diagnoses were included. Use of antihyperlipidemic medications was captured by searching the database for drug names. Demographics assessed for association with antihyperlipidemic therapy included region of the country in which care was provided; patient age group, sex, ethnicity, and race; physician medical degree; and payment type. Statistical analyses used sample weights to determine national estimates. A weighted national estimate of nearly 16 million ambulatory medical care visits was made in the United States in 2004 of patients with one of the selected CHD diagnoses. Use of any form of lipid-lowering therapy was associated with 40.4% of the CHD patients seeking ambulatory-based medical care in 2004. Non-Hispanic/Latino patients with CHD were more than 4.5 times more likely to be receiving lipid-lowering therapy (odds ratio [OR], 4.59; 95% CI, 1.28-16.37). Patients with CHD who had Medicare as their form of payment for healthcare were less likely to be receiving lipid-lowering therapy (OR, 0.50; 95% CI, 0.28-0.91), as were those receiving medical care in the South region of the United States (OR, 0.36; 95% CI, 0.14-0.89). Similar differences in medication use were noted with the statin medication class. In 2004, less than half of the ambulatory medical visits by US patients with CHD were associated with antihyperlipidemic treatment, and most of these patients were treated with one medication (a statin). A CHD patient's reported ethnicity, primary method of payment, and area of the United States in which care was received all demonstrated differences. On the basis of the growing evidence-based medical literature, it is imperative to continue this research to assess changes in future trends and to work with healthcare and policy advocates to strike a positive change for all patients.


ADAPT, a Novel Scaffold Protein-Based Probe for Radionuclide Imaging of Molecular Targets That Are Expressed in Disseminated Cancers.
Small engineered scaffold proteins have attracted attention as probes for radionuclide-based molecular imaging. One class of these imaging probes, termed ABD-Derived Affinity Proteins (ADAPT), has been created using the albumin-binding domain (ABD) of streptococcal protein G as a stable protein scaffold. In this study, we report the development of a clinical lead probe termed ADAPT6 that binds HER2, an oncoprotein overexpressed in many breast cancers that serves as a theranostic biomarker for several approved targeting therapies. Surface-exposed amino acids of ABD were randomized to create a combinatorial library enabling selection of high-affinity binders to various proteins. Furthermore, ABD was engineered to enable rapid purification, to eradicate its binding to albumin, and to enable rapid blood clearance. Incorporation of a unique cysteine allowed site-specific conjugation to a maleimido derivative of a DOTA chelator, enabling radionuclide labeling, ¹¹¹In for SPECT imaging and ⁶⁸Ga for PET imaging. Pharmacologic studies in mice demonstrated that the fully engineered molecule (111)In/⁶⁸Ga-DOTA-(HE)3-ADAPT6 was specifically bound and taken up by HER2-expressing tumors, with a high tumor-to-normal tissue ratio in xenograft models of human cancer. Unbound tracer underwent rapid renal clearance followed by high renal reabsorption. HER2-expressing xenografts were visualized by gamma-camera or PET at 1 hour after infusion. PET experiments demonstrated feasibility for discrimination of xenografts with high or low HER2 expression. Our results offer a preclinical proof of concept for the use of ADAPT probes for noninvasive in vivo imaging.


Managing food allergies in schools.
Food allergies are estimated to affect as many as 8 % of children with 2.5 % being allergic to peanut products. Based on the results of recent surveys, this prevalence has been increasing over the last few decades for unknown reasons. As children with food allergies reach school age, the issue is becoming more common in schools. For that reason, schools are now required to be prepared to take responsibility for the safety of food-allergic students. This review discusses the common problems surrounding management of food allergies in the school setting along with reasonable recommendations for addressing those problems. The most important component of food allergy management is for the student to get an accurate diagnosis and to then discuss development of an anaphylaxis action plan with their health-care provider. Each school should insist that a copy of such a plan be provided for each student with food allergy and that epinephrine is readily available should a student have an anaphylactic reaction. In addition to epinephrine, it is essential that school personnel be properly trained to recognize and treat allergic reactions should they occur. Known deficiencies in school preparedness have been documented in previous literature, and consequently, both state and the federal government have begun to implement policies to help with school preparedness.


Toxic effects of two brominated flame retardants BDE-47 and BDE-183 on the survival and protein expression of the tubificid Monopylephorus limosus.
The toxic effects of two brominated diphenyl ethers (BDE), BDE-47, and BDE-183, on a benthic oligochaete tubificid, Monopylephorus limosus were studied under laboratory conditions. Investigated responses included survival, growth, and protein expression profiles, at BDE concentrations of 1, 10, 100, and 700 ng/g on a dry soil weight basis, with isooctane as the carrier solvent. Body weight losses among treatments were insignificant after 8 weeks of exposure. The 8-wk LC(50) of BDE-47 and -183 were 2311 and 169 ng/g, respectively. By applying multivariate analysis techniques, protein expression patterns were compared and correlated with stressful sources of long-term culture, carrier solvent, BDE-47 and -183. The treatment of 8-wk 100 ng/g BDE-47 was most closely clustered to the 10 ng/g BDE-183 treatment, based on the 40 examined protein spots. This indicated that BDE-183 was more potent to M. limosus, than was BDE-47. The 2-wk and 8-wk controls clustered into different groups indicating the occurrence of physiological changes due to long-term laboratory culture. Additionally, solvent effect was shown by grouping the isooctane carrier to different clusters. With further characterization by principle component analysis, it was found that the separation was mainly contributed by the 2nd principal-component. And, the primarily inhibitory variation was at spots 2 (UMP-CMP kinase) and 40 (plasma retinol-binding protein precursor) in the 8-wk groups. On the contrary, protein spots 16 (cell division control protein 2 homolog) and 24 (mitochondrial DNA mismatch repair protein) showed stimulatory variation. In all, the observed proteomic responses suggest that BDEs disrupted metabolic function in M. limosus and multivariate analysis tool offers significant potential for the assessment of various stress sources at biochemical level.


Energy-dependent calcium sequestration activity in a Golgi apparatus fraction derived from lactating rat mammary glands.
A fraction isolated from lactating rat mammary glands was shown by marker enzyme assays to be rich in Golgi apparatus vesicles. This Golgi apparatus-rich fraction was shown to accumulate calcium in the presence of ATP but not in its absence. Other nucleoside triphosphates were only partially effective in promoting calcium transport. Mg2+ was required for the uptake which was also temperature and pH dependent. The uptake was sustained by the use of oxalate and phosphate as intravesicular trapping agents. In the presence of 10 mM oxalate the apparent Km for calcium uptake was 0.24 muM ionized calcium. The V was 4.45 nmol calcium/min per mg protein. Preloaded calcium could be rapidly released by the addition of the ionophore A23187 indicating an intravesicular location for the sequestered ion. Addition of ethylene glycol bis(beta-aminoethylether)-N,N'-tetraacetic acid resulted in a slower release of preaccumulated calcium, indicating the existence of one or more efflux routes by which calcium leaves the vesicles in the presence of MgATP. Ruthenium red partially inhibited the uptake but lanthanum and particularly the sulphydryl inhibitor p-hydroxy-mercuribenzoate were much more effective. The properties of the calcium-sequestering system in the Golgi apparatus-rich fraction were similar to those reported for other non-muscular tissues and lend support to the hypothesis that calcium is secreted into milk via the Golgi apparatus of the mammary gland secretory gland.


An autistic dimension: a proposed subtype of obsessive-compulsive disorder.
This article focuses on the possibility that autism spectrum disorder (ASD: Asperger syndrome, autism and atypical autism) in its milder forms may be clinically important among a substantial proportion of patients with obsessive-compulsive disorder (OCD), and discusses OCD subtypes based on this proposition. The hypothesis derives from extensive clinical experience of OCD and ASD, and literature searches on MEDLINE. Neuropsychological deficits are more common in OCD than in panic disorder and depression. Moreover, obsessive-compulsive and schizotypal personality disorders are over-represented in OCD. These may constitute mis-perceived clinical manifestations of ASD. Furthermore, repetitive behaviours and hoarding are common in Asperger syndrome. It is suggested that the comorbidity results in a more severe and treatment resistant form of OCD. OCD with comorbid ASD should be recognized as a valid OCD subtype, analogous to OCD with comorbid tics. An odd personality, with paranoid, schizotypal, avoidant or obsessive-compulsive traits, may indicate these autistic dimensions in OCD patients.


Carbon-Based Catalyst Synthesized and Immobilized under Calcium Salt Assistance To Boost Singlet Oxygen Evolution for Pollutant Degradation.
Carbon-based materials are recognized as promising candidates for pollutant degradation because of their environmental benignity. Massive and cost-effective production and efficient recovery of carbon-based catalysts are crucial to apply this technology. However, various nanostructured carbons with different dimensions are usually utilized as precursors while not considering their complex preparation procedures and the high costs of ingredients. Moreover, catalyst separation and recovery are not given sufficient attention. In this work, a calcium salt-assisted pyrolysis strategy is proposed to tune the catalytic site formation of carbon-based catalysts. Results show that blending equal amounts of Ca2+ (calcium chloride) and organic precursors could greatly improve the catalytic activity of the carbonated product to activate peroxymonosulfate for pollutant degradation. In addition, the proposed synthetic strategy is universal to most of the readily accessed and cost-effective organic precursors. Singlet oxygen is identified as the main reactive oxidant for pollutant removal in the catalytic reaction. By cross-linking calcium ions and alginate as a hydrogel to immobilize the catalyst, the carbon material could be readily recovered. Furthermore, a long-term continuous-flow reactor test is conducted to validate the effectiveness of applying the immobilized catalyst to treat a synthetic wastewater with 0.5 mM bisphenol A. As a result, a green synthesis and immobilization strategy for persulfate catalysts is successfully established, and the prepared catalyst might be applied for wastewater treatment through using calcium salt in two purposes.


An integrated system to represent and manage medical knowledge.
This paper describes an integrated system in Prolog that permits the creation of a personal Knowledge Base to express and formalize specialist knowledge in medicine. Formalisms used are production rules and frames. The integrated system is able to manage data and knowledge stored in a database built in M Technology (MUMPS).


[Dynamic changes in the hemostatic indices of diabetics during biostator control].
In 25 patients with insulin-dependent diabetes and without microangiopathic complications the main hemostatic inhibitors antithrombin III, alpha-2-macroglobulin, and alpha-2-antiplasmin were examined before and after an optimal compensation of the carbohydrate metabolism was achieved. The patients were treated for 24 hours with the help of an artificial endocrine pancreas--biostator. The initial mean value of hyperglycemia of 15.61 mmol/l fell significantly to a mean value of 5.67 mmol/l at the end of the 24 hour treatment. During this 24 hour period the levels of the indices followed up did not change significantly. They were as follows: antithrombin III--98.48%, alpha-2-macroglobulin--112.25%, alpha-2-antiplasmin--110.68%. The lack of changes in the hemostatic inhibitors is explained by the short term biostator treatment.


The effects of estrogen on osteoarthritis.
The prevalence of osteoarthritis is higher in women than men, and in women it increases dramatically in the years after menopause. These observations and others reporting a painful form of hand osteoarthritis after the menopause suggest that loss of estrogen at the time of menopause increases a woman's risk of getting osteoarthritis. This article reviews biologic evidence for hormone sensitivity of cartilage, animal studies testing the effect of estrogen on the joints of ovariectomized animals, and human epidemiologic and clinical studies evaluating endogenous estrogen levels and estrogen replacement therapy and their relation to the occurrence of osteoarthritis. Overall the evidence for a role of estrogen in osteoarthritis is conflicting. Epidemiologic studies of women who take estrogen replacement therapy, however, consistently report that these women have a lower prevalence of osteoarthritis than women not taking estrogen, suggesting a possible therapeutic role for estrogen in osteoarthritis.


[The contribution of Academician L. A. Orbeli to the theory of higher nervous activity].
In the paper are discussed the main directions of the investigation of the higher nervous activity, fruitfully developed by academician L. A. Orbeli and his school. These directions are the following: the evolutionary approach, the study of the influence of the sympathetic nervous and endocrine systems, of the role of the extracortical brain structures, especially the hypothalamus and the cerebellum, and the significance of pain and efferent systems for the higher nervous activity.


Factors Associated With Accidental Injuries in Children With ADHD-Combined Type: More Than a Motor Problem?
Objective: We explored the relationship between accidental injuries, motor impairment, and co-occurring autism spectrum disorder (ASD) symptoms in children with ADHD-combined type (ADHD-CT). Method: Participants were 32 male children diagnosed with ADHD-CT and 23 typically developing male children (7-12 years, full scale IQ [FSIQ] > 80). Parents completed a customized questionnaire on the occurrence of accidental injuries (e.g., bruises, cuts) their child experienced in the past 12 months. Motor proficiency was assessed using the Movement ABC-2 (MABC-2). Parents rated motor, ADHD-CT, ASD, and anxiety symptoms. Results: Children with ADHD-CT had significantly increased parent-reported accidental injuries compared with typically developing children. Among children with ADHD-CT, Spearman's rho rank correlations revealed no association between increased accidental injuries and MABC-2 score, but significant associations with increased hyperactivity/impulsivity, ASD, and anxiety symptoms. Conclusion: Although these findings require validation, they suggest a need for further research investigating the contribution of co-occurring ASD and anxiety symptoms to accidental injuries in children with ADHD-CT.


The role of interventional radiology for complications of cholecystectomy.
This report summarizes diagnostic and therapeutic radiologic procedures in 45 patients who suffered major complications from cholecystectomy. Complications were divided into (1) bile duct injury or ligation and (2) a variety of pathologic fluid collections. Specific lesions were bile duct injury (n = 6), accidental bile duct ligation (n = 12), ductal stricture (n = 12), abscess (n = 11), biloma (n = 7), hematoma (n = 5), infected pancreatic pseudocyst (n = 3), and stones (n = 2). Presenting problems were sepsis, jaundice, and intermittent cholangitis. The patients underwent 104 interventional radiologic procedures including 29 percutaneous transhepatic cholangiograms, 21 percutaneous biliary drainages, 12 balloon dilatations of strictures, drainage of 11 abscesses, 8 bilomas, 5 hematomas, and 3 pancreatic pseudocysts. Stones were removed by baskets in 2 patients; 12 pressure and perfusion studies were performed. One hundred of 104 procedures were successful; there was one failed biliary drainage, one unsuccessful stricture dilatation, one unsuccessful hematoma drainage, and one recurrent biloma. Thirty patients were spared another operation. The percutaneous procedures were beneficial although not curative in 14 of 15 patients who underwent reoperation; in those patients the procedures helped to establish a diagnosis, improve the patient's preoperative status, or serve as a landmark for the surgeon to locate and repair the ligated or injured duct. One patient died after reoperation, a 2.2% mortality rate. Sectional imaging studies combined with interventional radiologic procedures help to diagnose promptly and effectively treat major complications of cholecystectomy. These interventional procedures either cure the complication and obviate reoperation or aid the surgeon by relieving sepsis and jaundice before reoperation and providing an intraoperative guide for bile duct reconstruction.


Morphological deformities of benthic foraminifera in response to nearshore pollution of the Red Sea, Egypt.
The Red Sea encompasses a wide range of tropical marine habitats that are stressed due to anthropogenic activities. The main anthropogenic activities are hydrocarbon exploration and important trading harbors. This work aims to assess the influence of the Red Sea coastal heavy metal contamination on the marine meiofauna along three sites (Ras Gharib, Safaga, and Quseir). Eight heavy metal (Cu, Cd, Zn, Pb, Cr, Co, Ni, and Mn) contents are considered in four benthic foraminiferal species (Elphidium striatopunctatum, Amphistegina lobifera, Amphisorus hemprichii, and Ammonia beccarii). Quseir Harbor showed the highest level of pollution followed by Safaga and Ras Gharib sites. The analyzed benthic foraminiferal tests displayed noteworthy high concentrations of Cd, Zn, and Pb in Quseir Harbor which could be attributed to the anthropogenic activities in the nearshore areas. Some foraminiferal tests exhibited abnormalities in their apertures, coiling, and shape of chambers. A comparison between normal and deformed foraminiferal tests revealed that the deformed ones are highly contaminated with elevated heavy metal contents such as Fe, Mn, Ni, and Cd. Statistics in addition to geo-accumulation and pollution load indices reveal a whistling alarm for the Quseir harbor. The present data are necessary to improve conservation and management of the Red Sea ecosystem in the near future.


Hypoxia response in asthma: differential modulation on inflammation and epithelial injury.
Oxygen-sensing prolyl-hydroxylase (PHD)-2 negatively regulates hypoxia-inducible factor (HIF)1-α and suppresses the hypoxic response. Hypoxia signaling is thought to be proinflammatory but also attenuates cellular injury and apoptosis. Although increased hypoxic response has been noted in asthma, its functional relevance is unknown. The objectives of this study were to dissect the mechanisms and role of the hypoxic response in asthma pathophysiology. Experimental studies were conducted in mice using acute and chronic allergic models of asthma. The hypoxic response in allergically inflamed lungs was modulated by using pharmacologic PHD inhibitors (ethyl-3-4-dihydroxybenzoic acid [DHB], 1-10 mg/kg) or siRNA-mediated genetic knockdowns. Increased hypoxia response led to exacerbation of the asthma phenotype, with HIF-1α knockdown being beneficial. Chronically inflamed lungs from mice treated with 10 mg/kg DHB showed diffuse up-regulation of the hypoxia response, severe airway remodeling, and inflammation. Fatal asphyxiation during methacholine challenge was noted. However, bronchial epithelium restricted up-regulation of the hypoxia response seen with low-dose DHB (1 mg/kg) reduced epithelial injury and attenuated the asthmatic phenotype. Up-regulation of the hypoxia response was associated with increased expression of CX3CR1, a lymphocyte survival factor, and increased inflammatory cell infiltrate. This study shows that an exaggerated hypoxia response may contribute to airway inflammation, remodeling, and the development of asthma. However, the hypoxia response may also be protective of epithelial apoptosis at lower levels, and the net effects of modulating the hypoxia response may vary based on the context.


Errors in Moral Forecasting: Perceptions of Affect Shape the Gap Between Moral Behaviors and Moral Forecasts.
Research in moral decision making has shown that there may not be a one-to-one relationship between peoples' moral forecasts and behaviors. Although past work suggests that physiological arousal may account for part of the behavior-forecasting discrepancy, whether or not perceptions of affect play an important determinant remains unclear. Here, we investigate whether this discrepancy may arise because people fail to anticipate how they will feel in morally significant situations. In Study 1, forecasters predicted cheating significantly more on a test than participants in a behavior condition actually cheated. Importantly, forecasters who received false somatic feedback, indicative of high arousal, produced forecasts that aligned more closely with behaviors. In Study 2, forecasters who misattributed their arousal to an extraneous source forecasted cheating significantly more. In Study 3, higher dispositional emotional awareness was related to less forecasted cheating. These findings suggest that perceptions of affect play a key role in the behavior-forecasting dissociation.


Effects of repeated oral doses of fenflumizole on platelet aggregation and thromboxane formation in man ex vivo.
Anti-platelet effects of fenflumizole, a new cyclo-oxygenase inhibitor, were studied in man ex vivo. Fenflumizole was given to male volunteers at the oral doses of 25, 50 or 100 mg per day, each dose for a period of seven days. The formation of thromboxane B2 (TXB2) during whole blood clotting, platelet aggregation induced by arachidonic acid and ADP, the formation of TXB2 during aggregation as well as serum concentration of fenflumizole were measured repeatedly during drug administration and for a fortnight after drug discontinuation. TXB2 formation during whole blood clotting was decreased dose-dependently by fenflumizole. The degree of inhibition of TXB2 formation was proportional to fenflumizole concentration in serum within each individual. The lag phase of platelet aggregation induced by arachidonic acid was prolonged and the formation of TXB2 during aggregation decreased by fenflumizole. No total inhibition of either TXB2 synthesis or platelet aggregation was caused by the fenflumizole doses used. The results show that the degree of inhibition of platelet thromboxane forming capacity by repeated doses of fenflumizole is closely related to the concentration of the drug in blood. Platelet aggregation however is less sensitive to changes in fenflumizole levels and cannot be assessed solely on the basis of cyclo-oxygenase activity.


Genetic engineering of virus-specific T cells with T-cell receptors recognizing minor histocompatibility antigens for clinical application.
Donor lymphocyte infusion is an effective form of adoptive immunotherapy for hematologic malignancies after allogeneic stem cell transplantation. Graft-versus-host disease, however, often develops due to recognition of ubiquitously-expressed minor histocompatibility antigens. Transfer of T-cell receptors recognizing hematopoiesis-restricted minor histocompatibility antigens to virus-specific T cells may be a powerful anti-tumor therapy with a low risk of graft-versus-host disease. The purpose of this study was to develop an optimal T-cell receptors-encoding multi-cistronic retroviral vector and an efficient method for generating T-cell receptors-engineered virus-specific T cells. Retroviral vectors encoding the T-cell receptors for the hematopoiesis-restricted minor histocompatibility antigen HA-2 with and without selection markers were compared for T-cell receptors surface expression and HA-2-specific lysis. In addition, two different methods, i.e. peptide stimulation of CD8(+) cells and Pro5 MHC pentamer-based isolation of antigen-specific T cells, were investigated for their efficiency to generate T-cell receptors-transduced virus-specific T cells. Bi-cistronic vectors without selection markers most efficiently mediated T-cell receptors surface expression and HA-2-specific lysis. Furthermore, both methods were useful for generating gene-modified cells, but the purity of virus-specific T cells was higher after pentamer isolation. Finally, the capacity of gene-modified cells to express the transgenic T-cell receptors at the cell surface markedly differed between virus-specific T cells and was correlated with lysis of relevant target cells. Our data support T-cell receptors gene transfer to pentamer-isolated virus-specific T cells using bi-cistronic retroviral vectors and illustrate the relevance of selection of gene-modified T cells with appropriate transgenic T-cell receptors surface expression for clinical gene therapy.


A new natural background radiation area on the southwest coast of India.
The systematic study of background radiation and the distribution of radionuclides in the environment of coastal Karnataka, South India, has been initiated with an objective of establishing reliable baseline data on the background radiation level of the region for future assessment of the impact of nuclear and thermal power stations that are being set up in the region. The ambient gamma radiation survey in the environment of Mangalore, a major industrial city of coastal Karnataka, revealed significantly high gamma dose in air in certain locations of the Mangalore beach area. Thermoluminescent dosimetric studies indicated conspicuously high gamma dose in air in these places. Gamma spectrometric analyses of the soil and sand samples of this high background area have been carried out. The measured gamma dose in air in high background area is in the range 44-2102 nGy h-1. The average activity of 232Th, 238U, and 40K in soil samples is 2,971 Bq kg-1, 546 Bq kg-1, and 268 Bq kg-1, respectively. In sand samples, the respective activities are 1,842 Bq kg-1, 374 Bq kg-1, and 158 Bq kg-1. Results of these systematic investigations which establish the existence of new patches of monazite in the Mangalore beach area, on the southwest coast of India, are presented in this paper.


Solute and mobile phase contributions to retention in hydrophobic interaction chromatography of proteins.
Hydrophobic interaction chromatography utilizes high salt concentrations mobile phases to induce an interaction between a weakly hydrophobic matrix and exposed hydrophobic amino acids of a native protein. Proteins with a hydrophilic exterior have shorter retention times on a hydrophobic interaction column than do proteins with more hydrophobic exteriors. To examine the effect of amino acid substitutions on protein retention, lysozyme isolated from related bird species was chromatographed on a hydrophobic interaction column at increasing ammonium sulfate concentrations. Chromatographic retention deviated only when amino acid substitutions occurred on the surface of lysozyme opposite the catalytic cleft. This area may constitute a contact surface area and extends from Residue 41 to 102 and from 75 to the alpha-helical region starting with Residue 89. Retention was analyzed by plotting log k' versus the molal concentration of ammonium sulfate. The slope did not deviate significantly for each of the bird lysozymes, indicating a similar contact surface area. However, there was significant deviation in the intercept of each of the lysozyme lines, which probably reflects the strength of the hydrophobic interaction. The intercept increased as the lysozyme became more hydrophobic. Hydrophilic amino acid substitutions affected retention as much as hydrophobic ones. The ionization state of histidine residues within the contact area between lysozyme and the column surface also influenced retention. An uncharged histidine residue increased retention, while a decrease in retention was seen with a charged histidine residue. The amino acid substitutions did not appear to affect the size of the hydrophobic contact surface area, but rather the strength of the hydrophobic interaction. The effect of salt composition on protein retention indicated that factors other than surface tension could influence retention. These factors appear to include protein hydration and specific interactions between the protein and the salt ions. Of these, the latter may or may not result in an alteration in protein structure. The magnitude of the effect of salt composition was found to be dependent upon the protein.


Teaching international nursing students: challenges and strategies.
Cross-cultural education presents many challenges and focuses attention on the significant differences in teaching and learning styles around the world. In 1995, the George Mason University College of Nursing and Health Science embarked on the Saudi-US University Project, an effort that brought these theoretical differences to life. The stark contrast between the Saudi Arabian and Western cultures provided administration, faculty, and students the opportunity to develop creative strategies to accommodate learning across cultures.


Repeated graft loss caused by recurrent hepatic artery thrombosis after liver transplantation.
Hepatic artery thrombosis (HAT) is a main cause of graft loss and patient mortality after orthotopic liver transplantation (OLT). Several surgical and nonsurgical risk factors have been associated with HAT. Retransplantation often is the only possible treatment for this complication; however, the incidence of recurrence of HAT after retransplantation and the underlying conditions of this occurrence have never been investigated. Of 629 consecutive recipients transplanted at a single institution, 24 underwent retransplantion for HAT: in 4 of them (16%), HAT recurred in the second graft; 3 of these patients lost their first graft because of late HAT, whereas another one lost 4 consecutive grafts for early HAT. Antiphospholipid syndrome and paroxysmal nocturnal hemoglobinuria were diagnosed in three and one of these patients, respectively. Recurrent HAT is an uncommon occurrence that, in our experience, was linked to specific thrombophilic conditions; careful screening of these disorders should be included in the pretransplant workup, and adequate prophylaxis is advisable.


Immunological phenotyping of fibroblast cultures from patients with a mitochondrial respiratory chain deficit.
Conventional approaches to the diagnosis of mitochondrial respiratory chain diseases, using enzyme assays and histochemistry, are laborious and give limited information concerning the genetic basis of a deficiency. We have evaluated the diagnostic value of 12 monoclonal antibodies to subunits of the four respiratory chain enzyme complexes and F(1)F(0)-ATP synthase. Antibodies were used in immunological studies with skin fibroblast cultures derived from patients with diverse mitochondrial diseases, including patients in which the disease was caused by a nuclear genetic defect and patients known to harbor a heteroplasmic mutation in a mitochondrial tRNA gene. Immunoblotting experiments permitted the identification of specific enzyme assembly deficits and immunocytochemical studies provided clues regarding the genetic origin of the disease. The immunological findings were in agreement with the biochemical and genetic data of the patients. Our study demonstrates that characterization of the fibroblast cultures with the monoclonal antibodies provides a convenient technique to complement biochemical assays and histochemistry in the diagnosis of mitochondrial respiratory chain disorders.