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Biomedical subjects

P Martin

Publications and source records attributed to P Martin.

At least 685 records · Page 38Linked to original sources
PubMed1990

Long-term irreversibility of bone loss after surgery for primary hyperparathyroidism.

We reported previously that radial bone mineral content was decreased in patients with primary hyperparathyroidism and remained subnormal 1 year after surgery. In this study, we reviewed the results of sequential measurements of the radial bone mineral content, performed up to 107 months after removal of the parathyroid adenoma in 71 patients suffering from primary hyperparathyroidism. Bone mineral content increased during the first year after surgery. During the period 1 to 8 months after removal of the adenoma, the mean monthly increment was 0.009 +/- 0.0022 g/cm for the radial epiphysis and 0.0084 +/- 0.0023 g/cm for the shaft. However, in 39 patients seen at the end of 1 year after surgery, the bone mineral content of the epiphysis remained more than 1 SD below the normal mean in 61% (24) of the patients and more than 2 SDs in 36% (14) of the patients. For the shaft, those percentages were 59% (23) and 26% (10), respectively. Thereafter, the monthly increment rate of bone mineral content decreased rapidly with time, so that only minor further increase could be expected. Data show that patients with a low bone mineral content when diagnosed with primary hyperparathyroidism will conserve life long an irreversible loss of bone as compared with a matched control population.

Adenoma↗
PubMed1989

Reversal by apomorphine of the gabaculine-induced GABA accumulation in mouse cortex.

To test the assumption that in the mice cortex the rate of accumulation of gamma-aminobutyric acid (GABA) after irreversible inhibition of 4-aminobutyrate: 2-oxoglutarate aminotransferase (EC 2.6.1.19; GABA-T) represents an index of GABA turnover, we examined whether the reversal of the gabaculine-induced accumulation of GABA elicited by apomorphine was due to a decrease in GABA turnover or to a modulation of the activity of the GABA-T inhibitor. Therefore, we simultaneously measured the action of apomorphine on gabaculine-induced accumulation of GABA and on GABA-T activity. In vitro, apomorphine (3 and 30 microM) did not alter the concentration-dependent inhibition of GABA-T by gabaculine. Ex vivo, apomorphine (2 x 0.5 mg/kg s.c.) markedly decreased (69%) gabaculine-induced (150 mg/kg i.p.) accumulation of GABA. This drug had no direct effect on GABA-T activity, but significantly reduced from 83 to 71% the inhibition of GABA-T by gabaculine. The linear correlation found between GABA levels and GABA-T activity allowed the quantification of the decrease in GABA turnover elicited by apomorphine. The results showed that apomorphine decreased significantly (P less than 0.001) the rate of GABA synthesis from 7.48 to 3.36 micromol GABA/g per h, if the partial reversal of gabaculine-induced inhibition of GABA-T is considered and 2.44 micromol/g per h if not. Apomorphine effect on GABA accumulation is mainly due to a decrease of the rate of GABA synthesis and to a lesser extent to a reversal of the inhibitory activity of gabaculine. Thus, inhibition of GABA-T by gabaculine is a sensitive and reliable method for the estimation of the rate of synthesis.

4-Aminobutyrate Transaminase↗
PubMed1989

Recombinant interferon alfa therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial.

Infection with the hepatitis C virus may result in chronic liver disease for which no effective therapy is now available. We studied the effects of recombinant human interferon alfa in a prospective, randomized, double-blind, placebo-controlled trial in patients with well-documented chronic hepatitis C. Forty-one patients were enrolled in the trial, 37 of whom were later found to have antibody to hepatitis C virus. Twenty-one patients received interferon alfa (2 million units) subcutaneously three times weekly for six months, and 20 received placebo. The mean serum aminotransferase levels and the histologic features of the liver improved significantly in the patients treated with interferon but not in the patients given placebo. Ten patients treated with interferon (48 percent) had a complete response, defined as a decline in mean serum aminotransferase levels to the normal range during therapy; three others had a decrease in mean aminotransferase levels of more than 50 percent. After treatment ended, however, serum aminotransferases usually returned to pretreatment levels; 6 to 12 months after the discontinuation of interferon therapy, only two patients (10 percent) still had normal values. We conclude that interferon alfa therapy is beneficial in reducing disease activity in chronic hepatitis C; however, the beneficial responses are often transient.

Adult↗
PubMed1989

The bovine papillomavirus E5 transforming protein can stimulate the transforming activity of EGF and CSF-1 receptors.

The bovine papillomavirus E5 transforming gene encodes a 44 amino acid protein product that is localized to cytoplasmic membranes, including the plasma membrane. We now report that E5 can cooperate with human EGF receptors and with human CSF-1 receptors to induce cellular transformation of NIH 3T3 cells. Cooperation occurred in the absence of receptor stimulation by ligand, and it was further augmented by treatment with ligand. Cooperation was not seen between E5 and either c-fes or c-src. The cooperation between E5 and high levels of EGF receptors was associated with inhibition of receptor degradation and persistence of activated receptors on the cell surface. We conclude that E5 may enhance the receptor activity via inhibition of receptor down-modulation.

Animals↗
PubMed1989

Secondary cancers after bone marrow transplantation for leukemia or aplastic anemia.

To determine the incidence of secondary cancers after bone marrow transplantation, we reviewed the records of all patients at our center who received allogeneic, syngeneic, or autologous transplants for leukemia (n = 1926) or aplastic anemia (n = 320). Thirty-five patients were given a diagnosis of secondary cancer between 1.5 months and 13.9 years (median, 1.0 year) after transplantation. Sixteen patients had non-Hodgkin's lymphomas, 6 had leukemias, and 13 had solid tumors (including 3 each with glioblastoma, melanoma, and squamous-cell carcinoma). There were 1.2 secondary cancers per 100 exposure-years during the first year after transplantation (95 percent confidence interval, 0.7 to 2.0). The rate declined to 0.4 (95 percent confidence interval, 0.2 to 0.7) after one year. The age-adjusted incidence of secondary cancer was 6.69 times higher than that of primary cancer in the general population. In a multivariate model, the predictors (and relative risks) of any type of secondary cancer were acute graft-versus-host disease treated with either antithymocyte globulin (relative risk, 4.2) or an anti-CD3 monoclonal antibody (13.6) and total-body irradiation (3.9). Two additional factors were associated with secondary non-Hodgkin's lymphomas: T-lymphocyte depletion of donor marrow (12.4) and HLA mismatch (3.8). We conclude that recipients of bone marrow transplantation have a low but significant risk of a secondary cancer, particularly non-Hodgkin's lymphoma.

Adolescent↗
PubMed1989

Glomerulonephritis caused by chronic hepatitis B virus infection: treatment with recombinant human alpha-interferon.

STUDY OBJECTIVES: To assess the efficacy of alpha-interferon therapy in patients with hepatitis B virus (HBV)-related glomerulonephritis. DESIGN: Prospective, nonrandomized study. PATIENTS: Five patients with persistence of hepatitis B surface antigen, hepatitis B e antigen (HBeAg) and HBV DNA in serum for at least 6 months and histologic changes of chronic hepatitis on liver biopsy as well as persistent proteinuria of greater than 2 g/d and histologic changes of glomerulonephritis on renal biopsy. INTERVENTIONS: Patients received a 4-month course of recombinant human alpha-interferon (alfa-2b) beginning at a dose of 5 million units administered subcutaneously each day. RESULTS: Serum levels of HBV DNA decreased in all patients and fell to undetectable levels during treatment in four of five patients. In the four responding patients, serum HBeAg disappeared, aminotransferases fell into the normal range, and a follow-up liver biopsy showed an improvement in the hepatocyte necrosis and inflammation. Urine protein excretion also decreased during treatment. In the four responding patients, urine protein excretion gradually fell to less than 1 g/d and serum albumin levels rose into the normal range. Resolution of the biochemical and serologic evidence of chronic hepatitis and glomerulonephritis was accompanied by disappearance of signs and symptoms of liver and kidney disease. CONCLUSIONS: A high proportion of patients with HBV-related glomerulonephritis will respond to a 4-month course of alpha-interferon with a clinical, biochemical, and serologic remission.

Adult↗
PubMed1989

Effects of dihydropyridine drugs on reversal by imipramine of helpless behavior in rats.

The present study was undertaken in order to determine the effects of the dihydropyridine calcium channel blocker, nimodipine and the dihydropyridine calcium channel activator BAY k 8644, in the learned helplessness test in the rat. Nimodipine dose dependently (0.5-2 mg/kg per day) reversed the behavioral deficit induced by inescapable shocks. The reversal of helpless behavior by imipramine (32 mg/kg per day) was antagonized by BAY k 8644 (0.5 and 1 mg/kg per day), and the effects of imipramine 8 and 16 mg/kg per day) were potentiated by a subeffective dose (0.5 mg/kg per day) of nimodipine. These results suggest that central dihydropyridine binding sites may be specifically involved in the modulation of the imipramine reversal of helpless behavior and favor a physiological role for dihydropyridine binding sites in the brain.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Gonadotropin-releasing hormone (GnRH) as antidepressant: a psychopharmacological animal study.

Because the secretion of gonadotrophic hormones is disturbed in some depressive states, it has been hypothesized that gonadotropin-releasing hormone (GnRH) has antidepressant properties in humans, but no clear information has emerged from clinical trials. The lack of experimental psychopharmacological data prompted us to investigate the effects of GnRH on the 'learned helplessness' behavioral model of depression in rats. GnRH was injected i.p. at doses of 0.06, 0.25, 0.50, 1 and 2 mg/kg per day. GnRH significantly reduced the number of escape failures at doses of 1 mg/kg per day or higher during the first shuttle-box session and at doses of 0.25 mg/kg per day onwards during the third shuttle-box session. These antidepressant-like effects of GnRH were similar to those observed with the tricyclic antidepressants imipramine (32 mg/kg per day) or clomipramine (32 mg/kg per day) in the same model. Moreover, while the induction of learned helplessness behaviour resulted in a fall in the plasma levels of FSH and LH, normal values of these hormones could be restored by a behaviorally effective GnRH regimen. From these data it can be suggested that GnRH exhibits an interesting antidepressant-like activity in rats.

Animals↗
PubMed1989

Analysis of Adh gene regulation in Drosophila: studies using somatic transformation.

We have used in vitro mutagenesis and somatic transformation [Sofer and Martin, 1987a; Martin et al., 1986] to investigate the role of cis-acting sequences in the control of alcohol dehydrogenase gene expression in larvae of Drosophila melanogaster. Two sets of experiments were carried out. In the first, a series of deletions were constructed in the region upstream of the proximal transcriptional start site. In the second, one or both introns were removed from within the structural gene. These constructs (on circular plasmids) were injected into Adh-null embryos and ADH activity was assayed in third instar larvae of the injected generation. The first set of experiments indicated that there are at least three distinct regulatory regions essential for larval activity located in the 5' flanking region of the gene. One, in an area that includes the TATA box, was found to be necessary but not sufficient for larval ADH activity. Two others, further upstream, seemed to have enhancer-like properties because their absence could be compensated by a second copy of the Adh gene on the same plasmid molecule. The second set of experiments showed that neither the tissue distribution nor amount of ADH activity was affected by the removal of one or both introns from the Adh gene.

Alcohol Dehydrogenase↗
PubMed1989

300 mg/m2 carboplatin (Cb), adriamycin (A) cyclophosphamide (C) (CACb-300) combination in advanced ovarian carcinoma: a feasibility study.

Carboplatin (Cb) is an active drug in ovarian carcinoma that has fewer visceral side effects than cisplatin (CDDP) but higher myelotoxicity, which makes it difficult to combine at efficient doses with other myelotoxic drugs. In a preliminary study in advanced ovarian carcinoma, Rosso et al. showed the maximum tolerated dose of Cb given in combination with cyclophosphamide (C) and adriamycin (A) to be 200 mg/m2. Since the efficacy of Cb may be dose-dependent, as is that of CDDP, we started a feasibility study of a CACb-300 regimen, that is, using Cb at 300 mg/m2 with lower C and A doses. Our data shows that the CACb-300 combination can safely be given in previously untreated patients for at least six 28-day cycles.

Adenocarcinoma↗
PubMed1989

Rapidly progressive non-A, non-B hepatitis in patients with human immunodeficiency virus infection.

No information is available on the role of non-A, non-B hepatitis in the various hepatic abnormalities described in patients with the acquired immune deficiency syndrome. Of 97 patients referred with suspected non-A, non-B hepatitis, 3 were found to have antibody to the human immunodeficiency virus. These latter 3 patients all developed symptomatic cirrhosis within 3 yr of onset of hepatitis. Such a rapid progression of liver disease was rare in patients with non-A, non-B hepatitis who did not have simultaneous human immunodeficiency infection. These findings suggest that human immunodeficiency virus infection may potentiate the liver injury of chronic non-A, non-B hepatitis.

HIV Seropositivity↗