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Biomedical subjects

D May

Publications and source records attributed to D May.

At least 37 records · Page 2Linked to original sources
PubMed1995

5 alpha-Reductase type 1 is localized to the outer nuclear membrane.

The subcellular distribution of the two isozymes of 5 alpha-reductase has been controversial. To resolve this issue which could provide clues about the respective functions of the two isozymes, two antisera were generated, one which was specific for the Type 1 5 alpha-reductase and one which recognized both isozymes. In COS cells transfected separately with the Type 1 or Type 2 cDNA, both isozymes were detected on Western blots at an M(r) of 26,000. Subfractionation of the COS cells resulted in the partitioning of both isozymes between the crude nuclear and cytosolic fractions, while cytoimmunofluorescence localized both reductases to the nuclear periphery. In rat liver homogenate, the 5 alpha-reductase was also detected at M(r) 26,000. The 5 alpha-reductase immunoreactivity was increased after castration of the animals with no further effect when castrated animals were treated with androgens. Although the rat liver expresses only the Type 1 5 alpha-reductase, the 5 alpha-reductase was distributed about equally between crude nuclear and cytosolic subfractions; this distribution could be shifted to the cytosolic fractions with harsher homogenization procedures. Further extensive subfractionation and extraction studies identified the rat liver Type 1 5 alpha-reductase as an integral membrane protein present in the outer nuclear membrane of the nuclear envelope and in rough endoplasmic reticulum. Thus, the subfractionation and cytoimmunofluorescence studies are consistent with the localization of the Type 1 5 alpha-reductase to the outer nuclear membrane of the nuclear envelope which is continuous with and indistinguishable from the endoplasmic reticulum. This study is the first to localize rat liver Type 1 5 alpha-reductase to the nuclear envelope to which the prostatic 5 alpha-reductase activity previously had been localized. We conclude that, contrary to previous tissue distribution studies, but consistent with investigations in transfected cells, both isozymes are similarly localized to the nuclear periphery.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1992

[Refractory anemia with 5q--anomaly. Clinical picture and follow-up of seven patients].

The clinical picture and the course of the disease of seven patients with the 5q-syndrome are described. Examination of peripheral blood revealed refractory anaemia with macrocytosis, anisocytosis, poikilocytosis of erythrocytes, and platelet anisocytosis with some giant platelets. Characteristic bone marrow findings are megaloblastic dyserythropoiesis and micromegakaryocytes with hypolobulated nuclei. Cytogenetically, an interstitial deletion of the long arm of chromosome 5 is always found, associated with a haploid loss of the genes for the growth factors GM-CSF, M-CSF and IL-3. The disease is usually chronic, and only in the case of clonal evolution is there a considerable risk of leukemic transformation occurring. In the chronic phase, infusion of packed red cells as required individually has proved a reliable form of treatment. The results of chemotherapy have disappointed both in the chronic and acute phases of the disease.

Adult↗
PubMed1992

Juvenile granulosa cell tumor of an intraabdominal testis.

Juvenile granulosa cell tumor of the testis is a distinct form of sex cord-stromal tumor of neonates and infants [1]. This tumor comprises a significant percentage of testicular tumors in baby boys. We present a patient who had preoperative imaging studies.

Cryptorchidism↗
PubMed1992

Lupus-like autoimmune disease induced by interferon therapy for myeloproliferative disorders.

Symptoms of autoimmune disease were evaluated in 125 patients with chronic myelogenous leukemia (CML) and in 12 patients with essential thrombocythemia undergoing treatment with recombinant interferon (IFN)-alpha-2b plus/minus low-dose recombinant IFN-gamma. Twenty-seven of 137 patients (20%) developed rheumatoid symptoms. Furthermore, the incidence of antinuclear antibody (ANA) formation was studied. Elevated ANA titers were found in 5/19 (26%) of CML patients at the time of diagnosis and in 3/18 (17%) of patients treated with hydroxyurea or busulfan. During IFN treatment, 18 of 25 tested patients (72%) had elevated ANA titers. In 15 of these ANA-positive patients, clinical signs of autoimmune disease appeared. All these patients were under long-term IFN treatment and were in remission of disease. In three patients criteria for systemic lupus erythematosus were fulfilled. Severity of side effects had led to the discontinuation of IFN treatment in these patients. The data indicate that IFN-alpha and IFN-gamma can induce ANA associated with autoimmune disease in patients with myeloproliferative disorders.

Adult↗
PubMed1992

The spread of multiply resistant Streptococcus pneumoniae at a day care center in Ohio.

Streptococcus pneumoniae, type 23F, resistant to penicillin (MIC, 2 micrograms/mL) and multiple other antimicrobic agents, was isolated from middle ear fluid of a child with otitis media attending a day care center in Ohio. To determine the extent of spread of this strain, nasopharyngeal culture surveys were done, and 52 carriers were identified among 250 children attending the index day care center. No carriers were found among 121 children at two other day care centers in the same urban area. Use of prophylactic doses of antibiotics (P < .001) and frequent use of antibiotics (P < 0.001) were risk factors for nasopharyngeal carriage. Carriers were more likely to have had frequent otitis media episodes (P < .02) and otitis media not responsive to antimicrobial therapy (P < .001). Strategies to limit the spread of highly resistant pneumococcal strains should include encouraging judicious use of antimicrobic agents and reevaluating indications for prophylactic use of antimicrobic agents.

Adult↗
PubMed1992

[Cervical meningocele and meningomyelocystocele. Apropos of 4 cases].

Published cases of cervical dysraphic lesions are rare. Their estimated proportion is about 5% of the entire group of spinal dysraphism. Four cases are reported, representing 2 types of lesion: 2 meningoceles with a simple fibrous band fixing the posterior aspect of the cord to the skin and 2 meningomyelocystoceles with other associated anomalies (hydromyelia, hydrocephalus, Chiari II, Peter's ocular anomaly). The clinical presentation is that of a soft posterior cervical mass without marked neurological impairement. The surgical treatment is simple, consisting in the resection of the lesion, intradural exploration to untighten the cord if fixed by a fibrous band, and drainage of the hydrocephalus. Neurological outcome is generally good immediately but may need sometimes secondary surgical exploration.

Abnormalities, Multiple↗
PubMed1992

[The basic ideas for evaluating diagnostic tests in medicine and periodontics].

In the medical literature, and in particular in the field of periodontology, one could observe since several years an increasing interest in diagnostic tests. However, these are often difficult to comprehend. Indeed, understanding the value of these tests implies mastering the meaning of certain basic notions such as sensitivity, specificity and predictive value. The aim of this paper is to present these essential theoretical notions in a simple way and to illustrate them using clinical examples. Finally, several applications of these tests in the field of periodontology will be discussed.

Diagnostic Tests, Routine↗
PubMed1991

Interferon alfa-2b in acute- and chronic-phase chronic myelogenous leukaemia: initial response and long-term results in 54 patients.

Fifty-four patients with Ph1-positive chronic myelogenous leukaemia (CML) (48 with chronic-phase and six acute-phase disease) were treated with interferon alfa-2b subcutaneously (s.c.). The starting dose was 4 million units (MU)/m2 body surface area daily. It was reduced in parallel with serially determined leucocyte counts, and minimal effective doses were given as maintenance after achieving remission. Haematological remissions were induced in 22 of the 48 patients (46%) with chronic-phase disease. Thirteen patients (27%) revealed partial haematological remission and another 13 no response to treatment. No complete remission could be induced, although minor or partial cytogenetic responses were seen in 16 patients (33%). Moreover, a bcr-abl reduction was detected on Southern blot analysis in two patients. In chronic-phase disease, results of treatment were influenced by elapsed time after diagnosis, extent of previous treatment and interferon dosage. No beneficial effects of interferon were detected in the six patients with acute-phase disease. Principal acute side effects were fever and flu-like symptoms at the beginning of the therapy, which usually subsided within 3-7 days. Chronic side effects, especially weakness and neuropathy, were less frequent but more severe and necessitated discontinuation of treatment in 10 patients. In summary, interferon alfa-2b seems to be an effective treatment in early chronic-phase CML. Long-term effects on the course of the disease, however, must be determined.

Adolescent↗
PubMed1991

Cholinergic dependence of gallbladder response to cholecystokinin in the guinea pig in vivo.

The physiological mechanism responsible for cholecystokinin (CCK)-induced gallbladder (GB) contraction is unclear. We investigated the relative roles of direct muscle stimulation and neural activation at physiological and supraphysiological levels of CCK-octapeptide (CCK-8) using an in vivo guinea pig model. GB pressure was measured by a pressure transducer inserted into the GB lumen. Infusion of CCK-8 (2.5-40 ng.kg-1.min-1) increased GB pressure in a dose-dependent fashion. Pretreatment with atropine or hexamethonium antagonized GB responses to low doses of CCK-8 (2.5-5 ng.kg-1.min-1) but had no effect on doses greater than 10 ng.kg-1.min-1. Bilateral truncal vagotomy also significantly reduced GB responses to low doses of CCK-8 (2.5-5 ng.kg-1.min-1) but did not affect responses to high doses (10-40 ng.kg-1.min-1). Atropine or hexamethonium had no further inhibitory effects on guinea pigs that had undergone truncal vagotomy. Fasted guinea pigs that were fed ad libitum produced a postprandial peak plasma CCK level of 7.8 +/- 1.8 pM. This level was most closely approximated by infusion of 5 ng.kg-1.min-1 of CCK-8 (8.4 +/- 2.6 pM). CCK-8 infusion at greater than or equal to 10 ng.kg-1.min-1 gave supraphysiological plasma CCK levels. These observations indicate that CCK stimulated GB contraction via both a neural and a direct smooth muscle effect. Doses of CCK-8 that produce physiological plasma CCK levels act via stimulation of presynaptic cholinergic neurons in a vagally mediated pathway, whereas doses of CCK-8 that produce supraphysiological CCK levels act directly on GB smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Ifosfamide, methotrexate and 5-fluorouracil for pretreated advanced breast cancer.

A total of 51 fully evaluable patients with advanced and intensively pretreated breast cancer were treated with a combination chemotherapy of ifosfamide plus mesna, methotrexate and 5-fluorouracil. All patients had received at least one series of combined chemotherapy, 30 patients had received more than one combination and 41 patients had had anthracyclines before. Metastatic lesions in more than one site were found in 42 patients, and 24 patients had metastatic liver lesions. Partial remission was achieved in 10 patients (20%) and no change in 16 patients (31%). Survival was almost identical in both groups of responding patients and significantly shorter in treatment failures. Response was favorable in patients without pretreatment with anthracyclines. Two patients who received this protocol directly after progression with cyclophosphamide, methotrexate and 5-fluorouracil (CMF protocol) responded with a partial remission. Median time to progression was 7 months for partial responders and 4.5 months for patients achieving a no-change status. Median survival was 8 months for all patients. Toxicity was tolerable. Leukocytopenia and thrombocytopenia were treatment-limiting parameters. Overall, this protocol is well tolerable and effective in breast cancer patients with advanced disease and in intensively pretreated patients.

Adult↗
PubMed1991

Teaching mental handicap to medical students.

An innovative approach to the teaching of mental handicap to pre-clinical medical students as part of their Behavioural Sciences course is first described. The teaching is organized around a number of extended placements which allow students to interact with people with a mental handicap on a basis of equality and reciprocity. Students respond positively to the seminar, regarding it as enjoyable, interesting and relevant to their future work as doctors. Questionnaires administered to students participating in the seminar suggest that they have a generally positive image of mentally handicapped people and hold vaguely liberal views as to how they should be treated by Society. Few, however, wish to work in the mental handicap area. There is no evidence that the experience of the seminar leads to any significant change in these attitudes.

Behavioral Sciences↗
PubMed1991

Low levels of cryofibrinogenaemia and peripheral circulatory dysfunction.

Over 12 months of general internal medicine practice in a small community, three premenopausal women, and a man presented with peripheral circulatory complaints. All were found to have cryofibrinogen, a cold-precipitable abnormal fibrinogen complex, in their blood. None had cryofibrinogen levels above 100mg per 100ml. The plasma of 195 other patients were screened. Cryofibrinogen was found in only one of these samples, that of a 23 year old women with active lupus erythematosis. These case reports suggest a relationship between low levels of cryofibrinogenaemia and mild circulatory disorders.

Adolescent↗
PubMed1990

[Cardiac side effects of 5-fluorouracil].

In four patients (a 54-year-old man and three women aged 57, 60 and 65 years, respectively) with colorectal carcinoma and no obvious cardiac abnormality anginal symptoms and ECG changes occurred during chemotherapy with 5-fluorouracil at a dose of 400 and 600 mg/m2. The ECG changes consisted of descending ST depressions with preterminally negative T waves, terminally negative T waves, ventricular extrasystoles and sinus tachycardia with intermittent atrial fibrillation. The signs first appeared between the second and fourth day of treatment; in two patients they improved with glyceryl trinitrate. A few days after 5-fluorouracil had last been administered all ECG changes had disappeared. The causes of cardiotoxicity of the drug remain unknown.

Aged↗
PubMed1990

Treatment of chronic myelogenous leukemia with interferons alpha and gamma.

A 23-year-old male patient with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) was treated with both IFN alpha and IFN gamma. Normalization of leukocyte counts was reached after 3 months of treatment. Southern blot analysis failed to detect the neoplastic cell clone after 19 months of therapy. Cytogenetically, complete suppression of Ph positive cells in the patient's bone marrow and blood was observed after 20 months and 25 months, respectively. This response was achieved with doses of IFN alpha and IFN gamma which were considerably lower than the dosage of IFN used in single agent therapy of CML.

Adult↗
PubMed1990

DNA-flow cytometry studies in blood and marrow cells from chronic myelogenous leukemia patients treated with interferon alpha-2b.

Cell cycle distribution in bone marrow and peripheral blood mononucleated cells was studied in patients with chronic myelogenous leukemia (CML) before and during treatment with interferon (IFN) alpha-2b. DNA-flow cytometry with ethidium bromide fluorescence was used. Highly significant differences between mononucleated cells from CML patients and normal controls were seen in peripheral blood but not in bone marrow specimens. Patients achieving hematologic remission during IFN treatment showed a cell cycle distribution in bone marrow cells and peripheral blood cells similar to normal controls.

Bone Marrow↗
PubMed1990

Intracellular mechanism responsible for reduced enzyme secretion from camostate-induced hypertrophied pancreas.

Chornic exogenous administration of cholecystokinin octapeptide (CCK8) to rats led to a reduced sensitivity of pancreatic acinar cells to both CCK8 and carbachol stimulation without changes in affinity or number of CCK or muscarinic receptors. In addition, repeated feeding of camostate, a synthetic protease inhibitor which stimulates endogenous CCK release, desensitized the response of the acini to caerulein. This study investigates whether an altered postreceptor signal transduction mechanism is responsible for the reduced amylase secretion. Four days of camostate treatment significantly increased pancreatic weight, protein and amylase, but not DNA content, indicating organ hypertrophy, CCK8 and carbachol stimulated amylase release from acini, isolated from camostate-treated rats, was significantly reduced without shifting the dose response curve compared to controls. There was no difference in total phosphoinositide turnover between the groups. In addition, CCK8 and carbachol stimulated 45Ca efflux and calcium ionophore stimulated amylase release were similar in both groups. These results indicate that the release of calcium from intracellular stores and the utilization of intracellular calcium to drive amylase secretion is not affected in the hypertrophied pancreas. In contrast, incubation of acini from camostate-treated rats with TPA (a phorbol ester which directly stimulates protein kinase C) showed a 48% reduction in amylase secretion. This suggests that a regulatory mechanism is present at the level of protein kinase C or beyond, which is responsible for the decrease in amylase release in the hypertrophied pancreas.

Amylases↗