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Biomedical subjects

J M Wright

Publications and source records attributed to J M Wright.

At least 217 records · Page 12Linked to original sources
PubMed1982

A double-blind clinical trial of isoniazid in Huntington disease.

Isoniazid (INH) was given to nine patients with Huntington disease (HD) in a double-blind, placebo-controlled crossover trial. In an earlier open trial, three of six patients had improved, and one of them remained improved after 7 years on INH. Only one patient benefited in the present trial. All patients excreted small amounts of hydrazine in their urine while taking INH, and it is this INH metabolic that elevates GABA content in brain. GABA concentrations were markedly increased in CSF during INH therapy. Lack of clinical improvement in most HD patients despite elevation of brain GABA content suggests that in the minority who are benefited, INH may be acting by some mechanism other than increase of GABAergic neuronal function.

Adult↗
PubMed1981

The odontogenic keratocyst: orthokeratinized variant.

The histopathologic and clinical features of sixty cases of orthokeratinized odontogenic cysts were compared with those of odontogenic keratocysts (typically parakeratinized). According to the results of this study, the orthokeratinized odontogenic cyst appears to be a distinct clinicopathologic entity. This cyst is histologically characterized by a thin, uniform, epithelial lining with orthokeratinization and a subjacent granular cell layer. The basal cells are usually cuboidal or flattened. Clinically, the orthokeratinized cyst is a single cyst, shows a predilection for males, and is most often found in the second to the fifth decade, it appears most commonly as a dentigerous cyst in the posterior mandible. The orthokeratinized cyst shows little clinical aggressiveness. Follow-up of twenty-four patients revealed only one recurrence; of nineteen patients evaluated, none had features of the basal cell nevus-bifid rib syndrome. It is suggested that this cyst be called odontogenic keratocyst, orthokeratinized variant.

Adolescent↗
PubMed1981

Non-surgical embryo transfer in cattle embryo-recipient interactions.

Results from 2286 non-surgical embryo transfers were analyzed to find relationships between embryo factors and recipient factors that affect pregnancy. Pregnancy rates from morulae (44%) and advanced morulae (53%) were reduced (P < .05) when compared to early blastocysts (65%), blastocysts (65%), blastocysts (66%) and advanced blastocysts (64%). Pregnancy rates from good quality Grade 1 embryos (64%) were higher (P < .05) than from Grade 2 (45%) or Grade 3 (33%) embryos. Pregnancy rates related to synchronization of estrus between donor and recipients are: -36 hrs. (before donor) (59%), -24 hrs. (61%), -12 hrs. (68%), 0 hr. (59%), +12 hrs. (61%), +24 hrs. (58%) and +36 hrs. (41%). Differences in pregnancy rate were significant for -12 hrs. (P < .01) and +36 hrs. (P < .01) recipients. Overall pregnancy rates in recipients on day 5 (48%), 5 1/2 (50%) and 6 (53%) were reduced (P < .02) when compared to day 6 1/2 (62%), 7 (63%), and 7 1/2 (66%) and 8 (62%). Pregnancy rates within each embryo stage of development were not related to synchronization with the donor cow (-36 hrs. to +36 hrs.) or the day of the recipient cycle (day 5 to 8).

Journal Article↗
PubMed1981

Fetal alcohol syndrome: the social work connection.

It is crucial that social workers have some knowledge of fetal alcohol syndrome so that they can play a significant role in its prevention. The author suggests several kinds of intervention and describes techniques for helping the affected infant and members of the family.

Alcoholic Beverages↗
PubMed1981

Elevation of brain GABA content by chronic low-dosage administration of hydrazine, a metabolite of isoniazid.

When gamma-aminobutyric acid aminotransferase (GABA-T) activity was measured in vitro in rat brain, neither isoniazid (INH) nor for of its known metabolites (isonicotinic acid, acetylisoniazid, acetylhydrazine, diacetylhydrazine) inhibited the enzyme in concentrations (5 mM) far higher than those likely to be achieved when INH is administered to man. In contrast, hydrazine (5 micrometers) caused a 50% inhibition of GABA-T without inhibiting glutamic acid decarboxylase (GAD). Rats were injected daily for 109 days with hydrazine (0.08 or 0.16 mmol/kg/day), after which amino acid contents and enzyme activities were measured in their brains. Both hydrazine doses caused significant elevations of whole brain GABA content and reductions of GABA-T activity, but did not affect GAD activity. Chronic administration of hydrazine at these doses did not reduce weight gain or alter rat behavior, nor did it produce any irreversible pathologic changes in liver or alterations in hepatic aryl hydrocarbon hydroxylase activity. However, hydrazine treatment caused changes in the contents of many brain amino acids besides GABA, and markedly increased concentrations of ornithine, tyrosine, and alpha-aminoadipic acid in rat plasma. Inhibition of GABA-T activity and the other biochemical alterations observed in patients given high doses of INH probably result from hydrazine formed in the metabolic degradation of INH. Thus administration of hydrazine might be a more direct means of elevating brain GABA content in patients where this seems indicated, and might not entail a greater risk of adverse effects.

4-Aminobutyrate Transaminase↗
PubMed1980

Failure of aminooxyacetic acid therapy in Huntington disease.

Seven patients with Huntington disease were treated with aminooxyacetic acid (AOAA), an inhibitor of gamma-aminobutyric acid aminotransferase (GABA-T), in an effort to alleviate symptoms by increasing brain GABA content. AOAA was given orally in a placebo-controlled crossover trial in which patients, relatives, and three of the evaluating physicians remained blind. Toxic symptoms occurred in all seven patients when AOAA dosage was increased beyond 2 mg per kilogram per day, and included drowsiness, ataxia, seizures, and psychotic behavior. In five patients who took AOAA for 4 months, no clinical improvement was observed. Biochemical monitoring showed that less inhibition of hepatic GABA-T enzyme activity was achieved than in patients treated with large doses of isoniazid. Results of this trial neither support nor exclude the possible therapeutic usefulness of increasing brain GABA content in Huntington disease.

Acetates↗
PubMed1980

Use of the progestogen challenge test to reduce the risk of endometrial cancer.

In contrast to several retrospective studies reporting an increased risk of endometrial cancer during the mid-1970s, especially in estrogens.gen-treated postmenopausal women, the number of cancers at Wilford Hall USAF Medical Center has steadily declined despite continued estrogen use. In a 4-year study from 1975 to 1978, there were 17 adenocarcinomas of the endometrium during 10,872 patient-years of observation, for an overall annual incidence of 156.4:100,000 women. The highest incidence of endometrial cancer (359.1:100,000) was found in those women using estrogens alone. The lowest incidence of cancer was observed in the estrogen-progestogen users (56.4:100,000) and was significantly lower (P less than .01) than that found in the estrogen users. The incidence of corpus malignancy in the estrogen-progestogen users was also significantly lower (P less than .05) than that observed in the untreated women (248.3:1000,000). The progestogen challenge test has been devised to identify postmenopausal women at greatest risk for adenocarcinoma of the endometrium. It is concluded that the use of this test will reduce the risk of endometrial cancer in both estrogen-treated postmenopausal women and women with increased endogenous estrogens.

Adenocarcinoma↗
PubMed1979

Squamous odontogenic tumorlike proliferations in odontogenic cysts.

Five cases of squamous odontogenic tumorlike proliferations occurring in the walls of odontogenic cysts are presented. These lesions showed no more aggressive potential than the cysts, if taken alone, in which they occurred. The lesions showed no tendency to develop into solid tumors and, on the basis of this limited series of cases, conservative surgery appears to be the treatment of choice.

Adult↗
PubMed1979

Isoniazid therapy of Huntington disease.

We describe clinical and biochemical changes in seven patients with Huntington disease given isoniazid (INH) in dosages three to five greater than normally used in tuberculosis. Because INH inhibits the enzyme gamma-aminobutyric acid aminotransferase (GABA-T), and increases GABA content in the brains of experimental animals, it might correct the brain GABA deficiency characteristic of Huntington disease. Of six patients treated long enough to be clinically evaluated, one showed marked and two others showed signifciant improvement. High-dose INH therapy carries serious toxic risks, which are influenced by patients' acetylator phenotypes. Nevertheless, results are sufficiently promising to warrant further controlled trials of INH or other GABA-T inhibitors in Huntington disease.

4-Aminobutyrate Transaminase↗
PubMed1978

Interaction of human blood platelets with the 2',3'-dialdehyde and 2',3'-dialcohol derivatives of adenosine 5'-diphosphate and adenosine 5'-triphosphate.

1. The 2',3'-dialdehyde derivative of ADP (oADP) at concentrations approaching the millimolar range induces human blood platelets to undergo the transition from discoid to globular morphology (the 'shape change') but is incapable of inducing aggregation. 2. When incubated with platelets for 1 min before addition of the agonist, oADP acts as a competitive inhibitor of shape change and aggregation induced by ADP. Under these conditions secretion and hence aggregation induced by low concentrations of collagen; and secretion and hence secondary aggregation induced by adrenaline, thrombin and vasopressin are also inhibited by this analogue. In addition, oADP stimulates the rate of primary aggregation induced by adrenaline and causes partial inhibition of primary aggregation induced by thrombin or vasopressin. When longer preincubation times are employed the extent of inhibition with respect to all agonists, except for high concentrations of collagen, is increased and the competitive character of the inhibition with respect to ADP is no longer apparent. 3. Incubation of human platelets with the 2',3'-dialdehyde derivative of ATP (oATP) causes effects similar to those described for oADP except that the analogue neither induces platelet shape change, nor stimulates the rate of primary aggregation induced by adrenaline. In addition oATP fails to cause significant inhibition of platelet shape change induced by serotonin. The extent and character of inhibition caused by addition of oATP is not a function of the time of incubation. 4. The 2',3'-dialcohol derivatives of ADP and ATP and orATP) effect the aggregation properties of human blood platelets in a manner generally resembling those observed for the 2',3'-dialdehyde analogues. However, orADP is only weakly effective in causing platelet shape change and stimulating the rate of primary aggregation induced by adrenaline and does not inhibit secretion induced by adrenaline, collagen, thrombin and vasopressin. The extent of inhibition by orADP increases only slightly with increased time of incubation. 5. The data suggest that oADP acts as a partial agonist, and oATP as an antagonist, at the platelet ADP receptor, but that platelet membrane stabilisation also results from interaction with these dialdehyde analogues. Such membrane stabilisation does not complicate the interaction of platelets with orADP, which appears to act as a classical antagonist for the ADP receptor.

Adenosine Diphosphate↗
PubMed1978

Microchromatographic methods for hemoglobin A2 quantitation compared.

On 20 consecutive work days during four weeks, one technologist performed 24 microchromatographic determinations of hemoglobin A2 (Hb A2) by each of four methods: the Efremov procedure requiring Tris/HCl buffer, the original Huisman technique with use of glycine developer, and two commercial test kits in which a modified glycine developer is used. The bloood samples tested were obtained from 12 adults with no hematological abnormality and from 12 beta-thalassemia carriers previously diagnosed by familial and hematologic studies. Results by the first method and the two commercial kits (one from Helena Laboratories and one from Isolab, Inc.) did not differ significantly in precision for either the normal or beta-thalassemia trait samples. For both sample types, the second method yielded larger coefficients of variation than those obtained with the other methods. Moreover, the second method was the only one with which values overlapped for normal samples and samples with above-normal Hb A2 concentrations.

Chromatography, Ion Exchange↗
PubMed1977

Determination of hydrazine metabolites of isoniazid in human urine by gas chromatography.

A method is described for the determination of isoniazid, acetylisoniazid, acetylhydrazine, diacetylhydrazine and hydrazine in urine. Isoniazid, acetylhydrazine and hydrazine are reacted in aqueous solution with p-chlorobenzaldehyde to form hydrazones. Following the addition of appropriate internal standards, these hydrazones are then extracted into an organic solvent and determined by gas chromatography using a nitrogen-sensitive detector. Acetylisoniazid and diacetylhydrazine are determined similarly after hydrolysis to isoniazid and acetylhydrazine, respectively.

Acetylation↗