Inhibition by melatonin of the pituitary response to luteinizing hormone releasing hormone in vivo.

The rate of secretion of 17-oxosteroids by the testes of anaesthetized dogs in vivo was used as an index of LH secretion. Intracarotid injection of luteinizing hormone releasing hormone (LH-RH, 1, 5 or 10 microgram/kg body wt) resulted in an increase in the testicular 17-oxosteroid secretion which was roughly proportional to the dose administered and which reached a maximum 60 min after the injection. Testicular output of 17-oxosteroids was unaffected by administration of melatonin (10 or 100 microgram/kg body wt) into the carotid artery. When LH-RH (5 microgram/kg) was injected into the carotid artery 3 h after intracarotid injection of melatonin (10 or 100 microgram/kg), the testicular response to LH-RH was considerably diminished. Pretreatment with melatonin (100 microgram/kg) did not alter the testicular response to human chorionic gonadotrophin (20 i.u./kg body wt) given i.v. Is is concluded that melatonin may act directly on the anterior pituitary gland in dogs to inhibit the LH-RH-induced release of LH.     

Bilirubin response to corticosteroids in severe alcoholic hepatitis

INTRODUCTION: There is little consensus on the management of alcoholic hepatitis, particularly with regard to corticosteroid therapy. We aimed to identify those patients who respond to corticosteroid therapy for alcoholic hepatitis. METHODS: We identified 37 patients with alcoholic hepatitis with a modified Maddrey's discriminant function of 32 or greater. We assessed their outcomes at 28 and 56 days treatment after admission relative to their response to corticosteroid treatment. RESULTS: Corticosteroid treated patients experienced a change in the serum bilirubin concentration after 6-9 days of -23.0+/-4.7%. Overall, the mortality was 18.9 and 35.1% at 28 and 56 days. Response to corticosteroids was defined as a 25% fall in serum bilirubin after 6-9 days of treatment. The mortality of the non-responders was 36.8% and 57.9% at 28 and 56 days compared with 0% (P=0.0148) and 11.1% (P=0.0084) for corticosteroid responders. CONCLUSIONS: Patients with a 25% fall in bilirubin after 6-9 days of corticosteroid therapy have a significant and sustained improvement in outcome.     

Atopic asthma: T-cell response to corticosteroids

Atopic asthma is associated with diminished cell-mediated immunity and elevated levels of IgE, both of which may be caused by imbalances of T-lymphocyte subsets. We analyzed the response of peripheral blood T-cell subsets to two commonly used corticosteroid preparations as a probe of T-cell subset regulation. We administered prednisone (P) 60 mg or 20 mg, beclomethasone dipropionate (BDP) aerosol, 336 micrograms, placebo, or BDP vehicle in a double-blind protocol to 15 atopic asthmatic patients and ten nonatopic subjects. No difference was found between the groups of the baseline number of T-cells with T4, T8, M1, and Ia antigens, nor the ratio of T4+ (helper) to T8+ (suppressor) cells. Five hours after administration of BDP aerosol, BDP vehicle, and oral placebo, there was no change of these values in either the atopic or in the nonatopic group. In contrast, P, 20 and 60 mg, caused a fall of T4/T8 ratio in the atopic, but not in the nonatopic population. Atopic asthma is not associated with baseline imbalances of peripheral blood T-cell subsets, but is associated with an abnormal response to systemic, but not inhaled corticosteroid.     

Lack of response to corticosteroids and pulse cyclophosphamide therapy in Cogan's syndrome

Summary A 17-year-old girl with Cogan's syndrome is described. Total and irreversible hearing loss occurred which was unresponsive to corticosteroids and immunosuppressive therapy. The girl died a year later from subarachnoid haemorrhage. The lethal prognosis in Cogan's syndrome despite the available treatment is emphasized.     

HLA-DR4 associated response to corticosteroids in Graves' ophthalmopathy patients

Fifty-seven patients with severe Graves' ophthalmopathy were treated with corticosteroids. Therapeutic outcome was assessed according to predetermined criteria as response (n = 37) or non-response (n = 20) to therapy. Patients were typed for HLA-A, -B, -C, -DR and -DQ. HLA-DR4 was completely absent in the 20 non-responder patients (corrected p value = 0.042). In the responder group 14 of the 37 patients were HLA-DR4 positive. This study shows that in Graves' ophthalmopathy patients the presence of HLA-DR4 is associated with a good response to corticosteroid therapy. The frequency of HLA-DR4 in the Graves' ophthalmopathy population as a whole, however, was not different from normal (25% versus 26%). But as reported previously, the frequency of HLA-DR3 was significantly increased in the Graves' ophthalmopathy patients when compared to healthy blood donors (47% versus 24%, corrected p value = 0.02). No significant deviations were found in the HLA-A, -B, or -C loci.     

Severe bleomycin-induced pneumonitis. Clinical features and response to corticosteroids

Ten (3 percent) of 287 patients receiving combination chemotherapy developed severe bleomycin-induced pneumonitis. The course and the response to therapy in these patients are summarized in this report. The dose of bleomycin received varied from 136 to 588 units, with toxic effects occurring in six patients who had received less than 200 units. Dyspnea and dry cough were the presenting symptoms in nine patients; one was asymptomatic. Roentgenograms were abnormal in nine cases, with five showing bilateral infiltrates. Four patients had asymmetric abnormalities, with radiographic involvement of only a single lung in two of these. Pulmonary function tests were abnormal, with a decreased diffusing capacity. Seven patients were treated with corticosteroid therapy, and significant clinical and radiographic improvement was noted; however, pulmonary function tests remained abnormal and could not be used to monitor the response. Prolonged therapy with corticosteroids was required over many months to maintain improvement. Tapering of the steroid dosage led to recurrence of clinical symptoms and radiographic infiltrates in five patients. Mortality was 60 percent, with three early deaths in untreated patients and three late deaths which occurred 12 to 15 months after diagnosis. In this study, patients with severe bleomycin-induced pneumonitis had symptomatic improvement and roentgenographic clearing following corticosteroid therapy.     

Neutropenia associated with large granular lymphocytes responsive to corticosteroids in vitro and in vivo

We describe a patient with neutropenia associated with increased circulating large granular lymphocytes (LGL). Absolute neutropenia was accompanied by the absence of myeloid precursor cells in the bone marrow. No myeloid progenitor cells (CFU-C) could be detected by in vitro colony culture. The peripheral blood was also remarkable for the presence of a population of large granular lymphocytes demonstrable by conventional staining. These cells in flow microfluorometry studies expressed antigens Leu 4 (T-cell antigen receptor), Leu 7 (natural killer cell marker), Leu 2 (suppressor cell marker), and HLA-DR (activation marker); they lacked Leu 1 (a pan-T cell antigen), Leu 3 (helper cell marker) and Tac (interleukin 2 receptor). Hematopoietic colony formation in vitro improved with addition of corticosteroids to the culture medium or elimination of the LGL population with complement-mediated cytotoxicity. Anti-neutrophil antibodies were present prior to and following therapy. Clinically, administration of prednisone resulted in a normalization of the total white blood cell count and absolute polymorphonuclear cell number, an increase into the normal range of the number of CFU-C, and elimination of the LGL population. In this case of steroid-responsive LGL-associated neutropenia, laboratory studies suggested direct suppression of myelopoiesis by steroid-responsive LGL.     

Rapid response to intravenous corticosteroids in osteitis pubis after Marshall-Marchetti-Krantz urethropexy

SIR, Osteitis pubis is a painful inflammatory condition thatinvolves the pubic bone, symphysis and surrounding structures[1]. It is an infrequent complication of pelvic surgery, parturitionor athletic activities [2, 3]. It occurs in only 0.74% of instancesafter Marshall–Marchetti–Krantz urethropexy [3]and its aetiology, pathogenesis and     

Role of corticosteroids in the management of chronic obstructive lung disease: factors predicting response.

A double-blind crossover trial of prednisolone was conducted in 70 patients of chronic obstructive lung disease (COLD). Emphysema dominated the clinical picture in 38, rest being chronic bronchitis with varying degrees of air trapping. None of the patients had clinical asthma. All the patients had obtained maximal benefit from an optimal dose of bronchodilators prior to entering the study. Prednisolone in a dose of 0.8 mg/kg was prescribed in a double blind crossover manner with identical appearing placebo tablets. Patients were evaluated on a weekly basis for an objective as well as a subjective response and side effects of therapy. Thirty-four patients demonstrated a statistically significant improvement in pulmonary functions. In 20 others only subjective response was observed. A good objective response was predicted by a pre-study variability in FEV1, disease duration of less than 10 years and a history of smoking less than 50 pack years.     

Growth hormone response to growth hormone releasing factor in Alzheimer's disease

Because of the well-established reduction in the concentration of somatostatin in several brain areas of patients with histologically verified Alzheimer's disease, we sought to determine if growth hormone (GH) secretion is altered in Alzheimer's disease. In order to study this, we assessed the GH response to growth hormone releasing factor (GRF) in 8 patients with Alzheimer's disease and 8 age-matched controls. Although there was no difference between the magnitude of the GRF-induced GH response (delta max GH response or area under the curve) between the Alzheimer's disease patients and the controls, the Alzheimer's patients exhibited a delayed GH response to GRF.