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Biomedical subjects

J Maher

Publications and source records attributed to J Maher.

At least 55 records · Page 3Linked to original sources
PubMed1994

Retroviral-mediated gene transfer of a mutant H-ras gene into normal human bone marrow alters myeloid cell proliferation and differentiation.

To investigate the effects of mutant ras expression on the growth and differentiation of normal human bone marrow, we used retrovirus-mediated gene transfer. A retrovirus (HR-1) containing a mutant ras gene (H12-ras) in addition to the selectable neo gene was transferred by cocultivation of a packaging cell line with long-term cultures of normal human bone marrow. Controls were established by cocultivating aliquots of the same bone marrow with a retrovirus (VSN-2) containing only neo. The efficiency of gene transfer, as determined by the percentage of G418-resistant colony-forming units-granulocyte/macrophage (CFU-GM) immediately after termination of cocultivation, was similar: 8 +/- 4% with HR-1 and 5 +/- 3% with VSN-2. After a further week in long-term culture, there was an increase in the number and percentage of G418-resistant CFU-GM in both the HR-1-infected and VSN-2-infected marrows. Thereafter, the numbers of G418-resistant CFU-GM declined, becoming undetectable at 4 weeks. The time course of the production of G418-resistant colonies was not significantly different in HR-1- and VSN-2-infected marrows, indicating that H12-ras did not alter the proliferation of normal CFU-GM. However, the total cellularity of HR-1-infected marrow cultures was significantly greater than that of VSN-2-infected marrow cultures. This was due to increased cellular proliferation of HR-1-infected cultured cells, since differential counts showed a significant increase in myeloid blast cells together with a slight reduction in mature myeloid cells in HR-1-infected marrow compared to baseline and to VSN-2-infected marrow. No leukemic blast cell colonies were grown from HR-1-infected marrows or control marrows, and HR-1 infection did not confer serum independence. These data show successful retroviral infection of normal bone marrow progenitor cells and suggest that expression of mutant H12-ras in such cells results in enhanced proliferation of early myeloid cells at the expense of differentiation.

Animals↗
PubMed1993

A circadian distribution to febrile episodes in neutropenic patients.

Four-hourly temperature charts relating to 63 febrile neutropenic episodes in 32 patients were assessed for a circadian distribution to the onset of fever (> 37.5 degrees C) using the Edward's test. A highly significant distribution was found with the maximum incidence of febrile events between the hours of 5 p.m. and midnight (acrophase 9.30 p.m.). Patients were 5.53 times more likely to develop fever at 9.30 p.m. that 9.30 a.m.

Adolescent↗
PubMed1993

Severe bleomycin lung toxicity: reversal with high dose corticosteroids.

A 42 year old man, treated for testicular carcinoma with combination chemotherapy that included bleomycin, developed life threatening interstitial pneumonitis. He recovered successfully after treatment with very high doses of corticosteroids and azathioprine. This report suggests that bleomycin lung toxicity may be reversible if treated aggressively.

Adult↗
PubMed1993

Pneumothorax and palliative pleural aspiration--an audit of technique.

The incidence of pneumothorax following a review of 55 single-sitting bedside pleural aspirations of malignant effusions over an 18-month period in the clinical oncology departments of the Middlesex and Mount Vernon Hospitals was assessed and two groups were compared. Group 1 (29 aspirations in 16 patients) involved a technique using an 8 ch (French) gauge trocar and cannula, a three-way tap and a sealed bag system, resulting in no pneumothoraces. Group 2 (26 aspirations in 18 patients) involved a variety of other techniques with a pneumothorax rate of 19.2% (p = 0.0189 using Fisher's Exact Test). The small trocar/sealed bag system was complication-free, relatively painless, quick to perform, cheap, gave the option of draining to dryness and was easily learnt by the junior doctors who most often perform this procedure at the bedside. This technique is described in detail in the text. A reduction in the risk of pneumothorax minimizes the need for a postaspiration chest radiograph, facilitating aspiration in an outpatient, hospice or domiciliary setting. A domiciliary study is to be planned using the procedural standard described.

Chest Tubes↗
PubMed1993

Hypothermia as a potential treatment for cerebral ischemia.

Experimentally, focal and global cerebral ischemia are markedly affected by small changes in brain temperature. Mild hypothermia greatly ameliorates and mild hyperthermia markedly exacerbates ischemic-induced neuronal injury. Mild hypothermia not only protects against neuronal injury but also improves clinical outcome. This effect depends on the temperature of the brain both during and after the ischemic episode. Clinical and laboratory evidence concerning the value of hypothermia and the danger of hyperthermia in acute ischemia are presented. Potential mechanisms of action of hypo- and hyperthermia in ischemic injury are also addressed. The need to treat fever in acute cerebral ischemia, even if evidence is only empiric, and the intriguing possibility of using mild hypothermia to treat acute cerebral infarction are discussed.

Animals↗
PubMed1993

Maternal uniparental disomy for human chromosome 14, due to loss of a chromosome 14 from somatic cells with t(13;14) trisomy 14.

Uniparental disomy (UPD) for particular chromosomes is increasingly recognized as a cause of abnormal phenotypes in humans. We recently studied a 9-year-old female with a de novo Robertsonian translocation t(13;14), short stature, mild developmental delay, scoliosis, hyperextensible joints, hydrocephalus that resolved spontaneously during the first year of life, and hypercholesterolemia. To determine the parental origin of chromosomes 13 and 14 in the proband, we have studied the genotypes of DNA polymorphic markers due to (GT)n repeats in the patient and her parents' blood DNA. The genotypes of markers D14S43, D14S45, D14S49, and D14S54 indicated maternal UPD for chromosome 14. There was isodisomy for proximal markers and heterodisomy for distal markers, suggesting a recombination event on maternal chromosomes 14. In addition, DNA analysis first revealed--and subsequent cytogenetic analysis confirmed--that there was mosaic trisomy 14 in 5% of blood lymphocytes. There was normal (biparental) inheritance for chromosome 13, and there was no evidence of false paternity in genotypes of 11 highly polymorphic markers on human chromosome 21. Two cases of maternal UPD for chromosome 14 have previously been reported, one with a familial rob t(13;14) and the other with a t(14;14). There are several similarities among these patients, and a "maternal UPD chromosome 14 syndrome" is emerging; however, the contribution of the mosaic trisomy 14 to the phenotype cannot be evaluated. The study of de novo Robertsonian translocations of the type reported here should reveal both the extent of UPD in these events and the contribution of particular chromosomes involved in certain phenotypes.

Abnormalities, Multiple↗
PubMed1992

Academic and environmental effects of small group arrangements in classrooms for students with autism and other developmental disabilities.

The use of small group instructional formats with children who have autism and developmental disabilities has received mixed results in the research literature (Reid & Favell, 1984). The purpose of the two studies reported herein was to address this controversy by comparing the performance of students in one-to-one instruction to those transitioned to small groups for a variety of teachers, students, settings, and under different training circumstances. In the first study, 41 students, ranging in age from 5 to 21 years old, from six classrooms, participated; and 25 students from six classrooms participated in the second study. Measures of environmental effects included academic gains via pre- and posttests, on-task and self-stimulatory behavior levels, correct responding, and frequencies of teacher behaviors during both one-to-one and small group formats. Results of both experiments indicated that students were able to successfully transition to small group formats across several curriculum areas including language, math, readiness, and shopping. Further, experienced teachers and administrators were able to train a second group of staff to use the small group procedures effectively. The successful application for this number of students and teachers within natural learning environments is unprecedented and provides important documentation for both the utility and practicality of small group instruction with students who have developmental disabilities.

Achievement↗
PubMed1992

Skin anergy and tuberculosis.

In our experience tuberculin skin anergy (negative response to 10 TU Mantoux) occurs in 8% of patients with tuberculosis. In this study we compare 81 patients with skin anergy and proven tuberculosis with a background reactive population of patients with tuberculosis. Patients with skin anergy and tuberculosis were older and had fewer symptoms--less cough, less sputum production, less haemoptysis, less malaise, less chest pain--than patients with skin reactivity. There was no difference with respect to male/female ratio, marital status, smoking habits, coexistent major illness, prescribed medications at diagnosis, nor the proportion of patients with extrapulmonary tuberculosis, previous history of BCG vaccination or past history of tuberculosis. Comparison of chest radiographs showed more advanced, more bilateral and more miliary disease in the anergic patients. Pyrexia and elevated ESR at diagnosis were also more common in this group. Fewer of the anergic group of patients were consistently culture negative after 1 month's treatment compared to the background population. Mortality was higher in the anergic group, but this excess mortality occurred from causes other than tuberculosis. Repeat Mantoux testing was performed in 20 of the 81 anergic patients, after a minimum of 3 months of antituberculous chemotherapy, and 14 had become tuberculin positive, suggesting that tuberculin skin anergy may be a temporary phenomenon.

Adult↗
PubMed1991

A prospective study to evaluate the dose of vitamin D required to correct low 25-hydroxyvitamin D levels, calcium, and alkaline phosphatase in patients at risk of developing antiepileptic drug-induced osteomalacia.

The dose of vitamin D3 required to maintain normal serum 25-hydroxyvitamin D levels in epileptic patients was evaluated in a prospective study. Patients were divided into two groups, comprising 14 institutionalized and 18 non-institutionalized subjects; they were taking carbamazepine, phenytoin and phenobarbitone, alone or in combination. The study was divided into a dose titration stage and a further period of assessment on a fixed dose after attainment of normal serum 25-hydroxyvitamin D levels. Seventeen of the 18 non-institutionalized patients achieved normal levels over a period of 12 months; the remaining patient became normal after 15 months. The dose required to achieve normal levels ranged from 400 to 4000 IU/day; three patients required less than 2400 IU vitamin D3, 12 required 2400 IU and three required greater than 2400 IU. All institutionalized patients achieved normal levels over a period of 12 months; six patients required less than 2400 IU, six required 2400 IU and two required greater than 2400 IU vitamin D3. Raised alkaline phosphatase levels occurred in 11 patients, and reverted to normal in six patients during the initial return of 25-hydroxyvitamin D levels to normal. During the second 12 months, when patients were taking a fixed dose of vitamin D3, alkaline phosphatase increased in five patients who had achieved normal levels. During this phase normal 25-hydroxyvitamin D levels were not maintained in five patients. There was a significant seasonal variation of 25-hydroxyvitamin D levels institutionalized patients, being highest in June and lowest in December. Our findings show that while there was a wide range in the dose required to achieve normal serum 25-hydroxyvitamin D levels--between 400 and 4000 IU/day--78 per cent of patients responded to a dose of 2400 IU/day.

Adolescent↗
PubMed1988

Radiotherapy employing three fractions on each of twelve consecutive days.

In order to achieve the greatest advantage of accelerated hyperfractionated radiotherapy, treatment has been given 3 times each day for 12 consecutive days without a rest period. A total tumour dose of 50.4 Gy was well tolerated in a series of 38 patients with bronchial, head and neck and oesophageal carcinomas. A further 14 patients have now received an elevated dose of 54 Gy, again with satisfactory tolerance. The tumour responses at all these sites have been very promising and further work is proceeding.

Bronchial Neoplasms↗