Clastogenicity of diepoxybutane in bone marrow cells and male germ cells of mice

The bifunctional metabolite of 1,3-butadiene, 1,2:3,4-diepoxybutane(DEB), was tested in the mouse bone marrow micronucleus assayand in male mouse germ cell tests, namely the analysis of firstcleavage divisions and the dominant lethal assay. All experimentswere performed with single intraperitoneal treatment of theanimals. In the micronucleus test, DEB doses of 4.5, 9.0, 18.0and 36.0 mg/ kg body weight were tested at a sampling intervalof 24 h for bone marrow. The dose response for the inductionof micronuclei in polychromatic erythrocytes was linear withthe lowest effective dose of 9.0 mg/kg body weight No sensitivitydifference was observed between male and female mice. The cytogeneticanalysis of first cleavage division chromosomes was performedafter treatment of male mice with 17, 26, 34, 43 and 52 mg/kgbody weight of DEB and mating the males to hormonally stimulatedfemales on days 7, 14, 21 and 28 after treatment The two higherdoses caused general toxicity evidenced by the poor mating behaviorof the males. Only 13 and 20% of the mated females were fertilizedon day 7 after treatment of the males with 43 and 52 mg/kg bodyweight of DEB, respectively. An increased number of unfertilizedoocytes was obtained from fertilized females on day 7 aftertreatment of the males with 34 mg/kg body weight of DEB. Witha dose of 26 mg/kg body weight, it was demonstrated that chromosomalaberrations were only induced in spermatozoa (mating on day7 after treatment) while spermatids (mating on days 14 and 21)and spermatocytes (mating on day 28) were not susceptible tothe clastogenic effect of DEB. The response in spermatozoa inthe dose range 17–34 mg/kg body weight was linear up to26 mg/kg body weight and reached a plateau thereafter. The resultsof the dominant lethal experiments performed in the dose range18–54 mg/kg body weight gave results similar to the cytogeneticstudy. With the highest dose tested, the toxicity and cytotoxicityduring the first 8 mating days after treatment dramaticallyreduced the number of pregnant females and, consequently, thetotal implantations, so that no significant dominant lethaleffect could be assessed. During mating days 9–12 (treatedlate spermatids), a significant dominant lethal effect was observed.With the two lower doses (18 and 36 mg/kg body weight), thedominant lethal effect was restricted to spermatozoa. The goodcorrelation of the chromosomal aberrations with dominant lethalmutations confirms the chromosomal origin of dominant lethaleffects. The clastogenic effect of DEB in somatic cells andin germ cells of mice was of the same order of magnitude. ³To whom correspondence should be addressed     

Diagnostic value of sialochemistry. Results of an albumin study

In 196 patients suffering from disease of the cephalic salivary glands and in 57 healthy controls the concentration of albumin in parotid and submandibular saliva was measured by the immunodiffusion technique. To summarize the results, albumin seems to be a reliable marker of inflammations of the salivary glands even in the early stages and is therefore recommended for the primary diagnostic and the follow-up of acute and chronic inflammatory conditions of the major cephalic salivary glands. In combination with the evaluation of the flow rate, other sialochemic parameters like phosphohexose isomerase and kallikrein activity, B-mode sonography and fine needle aspiration biopsy the frequency of x-ray examination of the radiosensitive salivary glands may be reduced.     

Diagnosis and evaluation of adults with attention-deficit/hyperactivity disorder.

Although some areas of adult ADHD knowledge remain unclear, there isa strong sense of how to proceed with diagnosis using current DSM-IV criteria as a guide. Thorough clinical interview, aided by the use of rating scales for current symptoms and collateral information about childhood from parents or siblings, forms the backbone of the assessment. The poor psychosocial outcomes of patients with ADHD. often a consequence of unrecognized,untreated disorder manifestation, also can serve as a diagnostic indicator. Diagnostic and symptom assessment scales also can be a significant helpin diagnosing and establishing the symptoms of ADHD in adults. It is important to remember that according to DSM-IV, the cardinal criteria for making the diagnosis are the presence of sufficient current symptoms and impairment in two realms (home, school/work, and social interactions). Accordingly, adult ADHD remains a clinical diagnosis, and the clinician-administered interview remains the cornerstone of diagnostic evaluation.     

In vivo and in vitro rat model for cyclosporine-induced proximal tubular toxicity

Cyclosporine is used widely to prevent transplant rejection. Unfortunately, this drug causes both renal glomerular and tubular damage. To develop a stable reproducible noncatabolic animal model of cyclosporine nephrotoxicity, rats were fed a special liquid diet and daily administered 7.5 mg/kg of cyclosporine intramuscularly. Twenty-one days after this regimen was started, the body weight of cyclosporine-treated rats had increased 15%, a value only 38% less than the increase in pair-fed controls. After 21 days, glomerular filtration rate fell 34% in cyclosporine-treated rats (p less than 0.001) compared with the pair-fed controls. Simultaneously, citrate and N-acetylglucosaminidase excretion increased significantly. When isolated proximal tubules obtained after 21 days from the cyclosporine and pair-fed rats were incubated by using 1.0 mmol/L glutamine and 1.0 mmol/L citrate substrates, ammonia production was reduced 40% and glucose production reduced 20% (p less than 0.001) in the cyclosporine-treated rats. Discontinuing cyclosporine for 7 days partially reversed all these changes. The glomerular filtration rate in cyclosporine-treated rats now was only 15% below that in controls (p less than 0.05), N-acetylglucosaminidase excretion was the same in both groups, and urinary citrate excretion in the cyclosporine-treated rats fell from 122% to 62% above that in controls. In vitro differences in tubular ammonia and glucose production also narrowed. In summary, these experiments describe a stable reproducible noncatabolic and at least partially reversible rat model for studying cyclosporine nephrotoxicity.     

Codistribution of a sensory gating deficit and schizophrenia in multi-affected families.

Because the clinical diagnosis of schizophrenia has not generally been an adequate phenotypic marker to detect the genes that convey risk for schizophrenia, efforts have been directed toward the identification of more elementary neuronal dysfunctions in schizophrenic patients and their families. Psychophysiological studies of sensory gating and selective attention suggest that defects in these brain functions are present in schizophrenic patients and some of their relatives. This study examines one of these defects in sensory gating, failure to suppress the P50 evoked response to repeated auditory stimuli. Six pedigrees, chosen because of the presence of large sibships containing several cases of schizophrenia, were studied. A mathematical model was developed to assess the familial association of the P50 defect with schizophrenia. The model preserves the quantitative nature of the data and is suitable for use in a sample with small numbers of pedigrees comprising many individuals. It is thus suitable for the evaluation of putative phenotypes in families to be studied by linkage analysis with polymorphic genetic markers. The results suggest that the P50 defect is familially associated with schizophrenia.     

Early Intervention for Trauma: Current Status and Future Directions

Although psychological debriefing (PD) represents the most common form of early intervention for recently traumatized people, there is little evidence supporting its continued use with individuals who experience severe trauma. This review identifies the core issues in early intervention that need to be addressed in resolving the debate over PD. It critiques the available evidence for PD and the early provision of cognitive-behavioral therapy (CBT). Based on available evidence, we propose that psychological first aid is an appropriate initial intervention, but that it does not serve a therapeutic or preventive function. When feasible, initial screening is required so that preventive interventions can be used for those individuals who may have difficulty recovering on their own. Evidence-based CBT approaches are indicated for people who are at risk of developing posttraumatic psychopathology. Guidelines for managing acutely traumatized people are suggested and standards are proposed to direct future research that may advance our understanding of the role of early intervention in facilitating adaptation to trauma.     

Gating of the Auditory Evoked Potential in Children and Adults

Auditory evoked potentials were recorded from 163 subjects, aged IS months to 55 years. A conditioning-testing paradigm was used to assess sensory gating. In this paradigm, click stimuli are presented in pairs to the subjects with a 0.5-second intrapair interval. In normal adults, the first stimulus activates or “conditions” sensory gating mechanisms. The strength of these mechanisms is “tested” by the second stimulus, which produces a response whose amplitude is significantly suppressed. This aspect of sensory gating was not reliably observed in our subjects until age 18 years. Younger subjects varied widely in their ability to demonstrate sensory gating. Mean levels of suppression increased during late childhood and adolescence, with no relationship to other changes in evoked potential amplitude and latency. Sensory gating would appear to be a late developing aspect of human sensory physiology.     

Time trends of haemologbin levels and anaemia prevalence in infancy in a total community

In order to determine the trends in haemoglobin (Hb) levels and the prevalence of anaemia in infancy in an entire community, 3,147 infants aged 9-11 months attending the Mother and Child Health Clinics of the teaching and research Health Center in Kiryat Hayovel, Jerusalem, were examined. From 1971 to 1979 infants diagnosed as anaemic were given treatment. From 1980 to 1988 supplement was given to all infants from the age of 3 to 12 months. There was a mean increase of 0.6 g/dlHb between the two periods, with a larger increase in the Hb levels in 1980-88 as compared to 1971-79 (P = .0001). The prevalence of anaemia less than 11 g/dlHb decreased from 36% in 1971 to 27% in 1979 and to 19% in 1988. The prevalence of anaemia less than 10 g/dlHb decreased from 13.7% in 1971 to 8.7% in 1979 and to 3.6% in 1988. The time trend is probably due to changes in the socio-demographic characteristics of the population, an overall change in infant feeding practices in relation to iron source and the supplementation programme.     

Clinical impact of CCM mutation detection in familial cavernous angioma

Introduction and background A 3-year-old Bosnian girl with a large symptomatic brainstem and multiple supratentorial cavernous angiomas, who underwent neurosurgical treatment, is presented. As multiple cavernomas are more common in familial cases, genetic analyses and neuroradiological imaging were performed in the patient and her parents to see whether there was any evidence for inheritance. This information is important for genetic counseling and provision of medical care for at-risk relatives. Currently, no recommendation is available on how to manage these cases.Results Genetic analyses demonstrated a novel CCM1 frameshift mutation (c.1683_1684insA; p.V562SfsX6) in the child and the asymptomatic 27-year-old mother. Sensitive gradient-echo magnetic resonance imaging of the mother revealed multiple supratentorial lesions, whereas analogous imaging of the father showed no pathological findings.Conclusion This case exemplifies that seemingly sporadic cases with multiple lesions might well be hereditary and that presymptomatic genetic testing of family members may identify relatives for whom clinical and neuroradiological monitoring is indicated.     

Sirolimus and mycophenolate mofetil as calcineurin inhibitor-free immunosuppression in a cardiac transplant patient with chronic renal failure.

Chronic renal failure triggered by calcineurin inhibitor (CNI)-based immunosuppression is a common complication after cardiac transplantation. Sirolimus and mycophenolate mofetil (MMF) are 2 newer immunosuppressive agents with no documented nephrotoxic side effects. This case report describes a patient with ongoing chronic renal failure 10 months after cardiac transplantation on cyclosporine-based immunosuppressive therapy. Conversion of the immunosuppressive regimen from cyclosporine to sirolimus and MMF resulted in freedom from acute rejection, excellent cardiac graft function and consistently improved renal function. This case illustrates the beneficial potential of sirolimus and MMF as CNI-free and safe long-term immunosuppression in a patient with chronic renal failure after heart transplantation.