Interactions between cyclosporin A, indomethacin and 16,16-dimethyl prostaglandin E2: effects on renal, hepatic and gastrointestinal toxicity in the rat

Rats were treated for 3 or 14 days with cyclosporin A (CsA, 50 mg/kg) or indomethacin (2 or 5 mg/kg) either alone or in combination, or with CsA plus 16,16-dimethylprostaglandin E2 (DMPGE2, 0.25 mg/kg). Hepatic and renal function were unaffected by treatment with indomethacin at either dose and only at the higher dose was severe intestinal ulceration observed. CsA caused renal and hepatic toxicity, evidenced by increased urine N-acetyl-beta-D-glucosaminidase activity, serum urea, creatinine and bilirubin and decreased serum albumin and total protein. In rats cotreated with CsA and either dose of indomethacin the increases in serum urea and creatinine and decreases in serum albumin and total protein were accentuated, but serum bilirubin was not further increased. Intestinal lesions were present in rats treated for 14 days with CsA plus the lower dose of indomethacin, but not in rats treated with either drug alone. In rats treated with DMPGE2 plus CsA, serum urea and creatinine were normal and urine N-acetyl-beta-D-glucosaminidase activity was reduced compared to rats treated with CsA alone, but DMPGE2 cotreatment had no effect on the CsA induced hyperbilirubinaemia. Hepatic microsomal cytochrome P-450 concentration and aminopyrine N-demethylase activity were lower in rats treated with CsA plus indomethacin than in untreated rats or those treated with either drug alone. Coadministration of indomethacin or DMPGE2 had no effect on serum trough CsA levels. The results are interpreted as showing an exacerbation by CsA of the intestinal toxicity of indomethacin, an increase by indomethacin in the renal toxicity of CsA and a protection by DMPGE2 against CsA renal toxicity. Possible mechanisms involving drug interactions and either hepatic cytochrome P-450, renal cyclooxygenase or other renal sites are discussed.     

Production of chick interferon by reactivating chick erythrocytes

When chick erythrocytes were fused with mouse L929 or A9 cells and the heterokaryons induced for interferon production on consecutive days, considerable amounts of mouse interferon were produced every day. Small amounts of chick interferon were produced 2 to 3 days after fusion, coincident with the appearance of a chick enzyme, appearance of nucleoli and increase in chick cell nuclear diameter.     

Adult cellular rhabdomyoma of the heart: a report of 3 cases

We present 3 adults with cardiac rhabdomyomas, 2 in the atria and 1 in the right ventricle. One atrial tumor was discovered incidentally, and 1 resulted in supraventricular tachycardia. The ventricular lesion caused ventricular tachycardia. Compared with congenital rhabdomyomas, the tumors are relatively cellular, the cells are smaller, there are few spider cells, and there is evidence of cell proliferation. Two of the 3 tumors demonstrated spindling in contrast to adult rhabdomyomas of the head and neck. Although surgical excision was possible in all patients, long-term follow-up will be required to determine the true biologic behavior of these neoplasms.     

A springtime olympics demands special consideration for allergic athletes

BACKGROUND: The Sydney Olympic and Paralympic Games will be held in September-October 2000, which is early to mid-spring in the southern hemisphere. Pollen-sensitive athletes may encounter problems with allergic symptoms triggered by pollen exposure, thus compromising their ability to attain peak performance. OBJECTIVE: We sought to monitor pollen levels at the major Olympic venues to provide information for allergic athletes and their team doctors in order to adequately prepare them for Olympic competition. METHODS: We performed aerobiologic monitoring of the major Olympic venues to provide a profile of the most prevalent pollen species appearing during the spring. In the second part of this study, we surveyed a population of elite Australian athletes from Olympic sports to ascertain the prevalence of allergic rhinoconjunctivitis, to investigate the major allergens involved in sensitization, and to conduct a pilot study to assess the effect of allergic rhinoconjunctivitis on quality of life. RESULTS: The pollen counts obtained at the 3 major sites were high over the period of Olympic competition. Tree pollens appeared from July, and grasses appeared from early September and peaked in the second week of October, the beginning of Paralympic competition. A relatively small number of pollen varieties comprise the majority of the total pollen count. Two hundred fourteen athletes (61% male; mean age, 21 +/- 16 years) representing 12 Olympic sports participated in the study. Fifty-six percent gave a symptom history consistent with allergic rhinoconjunctivitis, 41% had symptoms of allergic rhinoconjunctivitis and a positive test response to any one allergen, and 29% had seasonal allergic rhinoconjunctivitis (a positive history and at least one positive skin prick test response to a seasonal allergen). Athletes from aquatic sports were more likely to have symptoms than those from other sports. Symptom scores were higher and quality of life ratings were poorer in allergic compared with nonallergic athletes over the spring period. CONCLUSION: Olympic team managers and medical officers need to adequately prepare Olympic athletes for the possibility of exposure to high pollen levels in the weeks leading up to this most important sporting event. Symptoms of pollen sensitivity, such as rhinoconjunctivitis and exacerbation of asthma, could be devastating to athletes expecting peak performance. Potential Olympic athletes should be screened for the possibility of pollen allergy and have medical programs with permitted medication tailored to meet their needs. This may involve preventative therapy with medication, such as intranasal corticosteroid sprays or immunotherapy programs, if symptoms are particularly severe. The newer nonsedating antihistamines are the treatment of choice for acute intermittent symptoms. Appropriate management will ensure that the allergic athlete will safely perform to maximum ability with permitted medication during the Spring 2000 Olympic Games in Sydney.     

Clinical impact of a 2-week psychotropic medication washout in unipolar depressed inpatients

BACKGROUND: Short-term discontinuation of psychiatric medications is required in many types of research studies. Yet there are few studies of the clinical impact of psychotropic discontinuation. We studied the impact of a short-term medication washout in unipolar depressed patients consecutively admitted to hospital for neuroimaging and cerebrospinal fluid (CSF) studies. METHOD: Patients (n=51) with unipolar depression who were taking antidepressant or mood stabilizing medication at or within 1 week of admission, and who had not been responding satisfactorily, were assessed for severity of psychopathology within 1 week of hospital admission and 41 of the group were reassessed following an approximately 2-week medication washout. RESULTS: On average, patients remained stable during the washout or improved on clinical measures. No serious adverse clinical changes were observed. LIMITATIONS: Potential sample bias, small sample size. CONCLUSION: The results suggest that similar studies can be conducted without causing undue worsening of symptoms. The benefit of medication washout may be related to the fact that many of the patients had been responding poorly to the medication they were taking. There is a need for further research on the effects of medication washout, for example in outpatients or those who are responding well to treatment, but have intolerable side-effects.     

Inflammatory smears--is there a correlation between microbiology and cytology findings?

Cervical smear results reporting the presence of inflammation are regularly encountered by smeartakers, yet the significance of this finding is not clear. We wished to evaluate whether the presence of inflammation on smear test was associated with a higher incidence of lower genital tract infection. A retrospective review was carried out on women attending our colposcopy unit for their first visit during 2001. Results of 256 women were available for analysis. Evidence of inflammation was found in 9.7% of smears. Genital tract infection was found in 29.2% of women overall. Infection with more than one micro-organism was present in 8.9 percent. Forty eight percent of women having inflammatory changes on smear test had genital tract infection. This compared with 27.3% of women whose smear tests showed no evidence of inflammation. Prevalence of infection with Chlamydia trachomatis, Candida, Bacteroides and Gardnerella vaginalis was higher in the inflammatory smear group. This study shows that women with an inflammatory smear are more likely to harbour genital tract infection than women whose smear shows no evidence of inflammation. Chlamydia infection in particular has long-term fertility consequences through its potential to cause asymptomatic tubal damage: it was present in a substantial proportion of women with inflammation on smear (20%). Screening for lower genital tract infection via high vaginal swab and either intracervical swab or urinary screening for Chlamydia infection should be carried out in all women with smear tests reporting the presence of inflammation.     

Somatic cell genetics of human interferon production in human-rodent cell hybrids.

Forty-two primary human-mouse cell hybrids, derived in two separate experiments, were treated with Newcastle disease virus (NDV): eight hybrids were found to produce human interferon and this was shown in every case to be predominantly of the fibroblast type. An extensive analysis was made in terms of karyotype and marker enzymes on all the eight hybrids producing interferon and also on five hybrids which did not produce interferon, five randomly selected hybrids and eleven subclones resistant to diphtheria toxin. The results suggest that, contrary to previous reports, a gene on chromosome 5 is not involved in production of human interferon. Its production was however correlated with the presence of chromosome 9 in the hybrids. Analyses of two sets of human-Chinese hamster hybrid subclones from two different crosses were also consistent with the assignment of a human interferon gene to chromosome 9.     

Diffuse malignant lymphoma with cerebriform nuclei: A B-cell lymphoma studied with monoclonal antibodies

A lymph node biopsy performed on a 55-year-old woman with asymptomatic generalized lymphadenopathy revealed a diffuse, malignant lymphoma composed of small to intermediate-sized lymphocytes with cerebriform-shaped nuclei; electron microscopy confirmed the nuclear complexity. The cerebriform nuclear configuration, coupled with an interfollicular pattern of nodal involvement with encroachment upon residual germinal centers, was presumptive of either mycosis fungoides or a peripheral T-cell lymphoma. Immunologic evaluation, however, indicated that the cerebriform lymphocytes represented a monoclonal B-cell population (IgM-IgD, lambda). Staining with monoclonal antibodies disclosed a phenotype of Ia+, B1+, BA-1+, BA-2+, Leu-1+; the neoplastic cells were unreactive with T-cell, lineage-specific antibodies (anti-Leu-2a, -3a, -4, -5) and with J5 (CALLA). In light of the immunophenotype and the distributional pattern, the cerebriform-shaped lymphocytes may represent an extreme morphologic variant of intermediate lymphocytic lymphoma.     

Outwardly rectifying deflections in threshold electrotonus due to K+ conductances

A transient decrease in excitability occurs regularly during the S1 phase of threshold electrotonus to depolarizing conditioning stimuli for sensory and, less frequently, motor axons. This has been attributed to the outwardly rectifying action of fast K⁺ channels, at least in patients with demyelinating diseases. This study investigates the genesis of this notch in healthy axons. Threshold electrotonus was recorded for sensory and motor axons in the median nerve at the wrist in response to test stimuli of different width. The notch occurred more frequently the briefer the test stimulus, and more frequently in sensory studies. In studies on motor axons, the notch decreased in latency and increased in amplitude as the conditioning stimulus increased or the limb was cooled. Low-threshold axons displayed profound changes in strength–duration time constant even though the threshold electrotonus curves contained no detectable notch. When a 1.0 ms current was added to subthreshold conditioning stimuli to trigger EMG, the notch varied with the timing and intensity of the brief current pulse. This study finds no evidence for an outwardly rectifying deflection due to K⁺ channels, other than the slow accommodation attributable to slow K⁺ currents. In normal motor axons, a depolarization-induced notch during the S1 phase of threshold electrotonus is the result of the conditioning stimulus exceeding threshold for some axons. The notch is more apparent in sensory axons probably because of the lower slope of the stimulus–response curve and their longer strength–duration time constant rather than a difference in K⁺ conductances. This may also explain the notch in demyelinating diseases.