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Biomedical subjects

S Hall

Publications and source records attributed to S Hall.

At least 19 recordsLinked to original sources

Does activation of the TAL1 gene occur in a majority of patients with T-cell acute lymphoblastic leukemia? A pediatric oncology group study.

Almost 25% of patients with T-cell acute lymphoblastic leukemia (T-ALL) have tumor-specific rearrangements of the TAL1 gene. Although TAL1 expression has not been observed in normal lymphocytes, TAL1 gene products are readily detected in leukemic cells that harbor a rearranged TAL1 allele. Hence, it has been proposed that ectopic expression of TAL1 promotes the development of T-ALL. In this report, we show that TAL1 is expressed in the leukemic cells of most patients with T-ALL, including many that do not display an apparent TAL1 gene alteration. A polymorphic dinucleotide repeat in the transcribed sequences of TAL1 was used to determine the allele specificity of TAL1 transcription in primary T-ALL cells. Monoallelic expression of TAL1 was observed in the leukemic cells of all patients (8 of 8) bearing a TAL1 gene rearrangement. In the leukemic cells of patients without detectable TAL1 rearrangements, TAL1 transcription occurred in either a monoallelic (3 of 7 patients) or a biallelic (4 of 7 patients) fashion. Thus, TAL1 activation in these patients may result from subtle alterations in cis-acting regulatory sequences (affecting expression of a single TAL1 allele) or changes in trans-acting factors that control TAL1 transcription (affecting expression of both TAL1 alleles).

Alleles

Prenatal exclusion of the HHH syndrome.

Prenatal diagnosis of the hyperornithinaemia, hyperammonaemia, and homocitrullinuria syndrome is described by the analysis of ornithine incorporation in second-trimester cultured amniotic fluid cells. An unaffected fetus was predicted and confirmed in the newborn child. This is the third reported prenatal diagnosis for this disorder and the second predicting an unaffected fetus.

Amino Acid Metabolism, Inborn Errors

Different muscle graft denaturing methods and their use for nerve repair.

In an attempt to enhance recovery through denatured muscle grafts we have used different methods to denature muscle, either using dry heat in a microwave oven or by warming in sterile distilled water. Axonal regeneration was studied at intervals from day 5 to day 60 after insertion of the muscle grafts and compared to results found in frozen-thawed muscle grafts and in autologous nerve grafts used as controls. Axonal regeneration, Schwann cell behaviour and the degree of inflammation were quantified using immunohistochemical techniques and computerised image analysis. Autologous nerve grafts supported the highest rates and volumes of axonal regeneration until day 30 when the microwaved muscle grafts had the highest values for axonal immunostaining and at 60 days the highest level of Schwann cell immunoreactivity. We conclude that microwave heating is suitable as an alternative denaturing method for successful muscle grafts and has a potential clinical use.

Animals

The potencies of synthetic analogues of saxitoxin and the absolute stereoselectivity of decarbamoyl saxitoxin.

The potencies of synthetic saxitoxin (+/- STX) and six of its synthetic analogues, including the enantioselectively synthesized unnatural (-)enantiomer of decarbamoyl saxitoxin (dcSTX), were measured and compared to those of natural saxitoxin [(+)STX]. The analogues, all of which were racemic (+/-) mixtures except for dcSTX, varied in the substituents at the C6 position, the carbamoyl 'moeity', and the C12 position, the hydrated ketone. The ability of the toxins to inhibit the compound action potential (AP) and to displace radiolabeled natural saxitoxin (3H-STX) from nerve membranes at equilibrium were both used as potency assays. Biological activity of both (+)- and (-)dcSTX was analyzed by the kinetics of block of single Na+ channels reconstituted in planar lipid bilayer membranes, where it was demonstrated that only (+)dcSTX had biological activity. The potency of STX analogues fell markedly as the substituent at the C6 position became smaller; Ki values from the binding competition assay (at 4 degrees C) are: (+/-)6-methanolic-STX, 5 x 10(-10) M; (+/-)6-methyl-STX, 1 x 10(-6) M; (+/-)6-dihydro-STX, 3.5 x 10(-5) M. Replacement of the ketone at the C12 position by a methylene group was accomplished in two derivatives, although both also had substituents at the C6 position. The compound (+/-)6-methyl-12-deoxy-STX was about 0.03 as potent as (+/-)6-methyl-STX and only 10(-5) as potent as racemic (+/-)STX. In synthetic compounds where the benzyloxymethyl (-CH2OCH2C6H5) substituent occurred at the C6 position, the C12-methylene derivative still displayed some binding activity (Ki = 6 x 10(-4) M). However, when the same C6 derivatized compounds also contained a 6-membered heterocyclic group (-C3H8S2-) conjugated to carbon 12, the measured binding affinity was even further decreased (Ki = 2 x 10(-3) M). The findings show that substitutions on the carbon 6 position of STX have stronger effects on STX potency than previously believed, and that the toxin may form a hydrogen bond with the sodium channel at this site. Furthermore, the total removal of oxygen from the C12 position does not completely abolish the binding activity of the molecule.

Action Potentials

The experience of labour: a perspective from those receiving care in a midwife-led unit.

AIM: to elucidate the experience of labour for those receiving any aspect of care in a midwife-led unit. PARTICIPANTS: a total of 32 women and six partners who were interviewed during the postnatal period, either prior to discharge from the unit or between three and five months following delivery. METHOD: in-depth focused interviews were taped, transcribed, and analysed using a grounded theory approach to identify common categories of experience. FINDINGS: the core category to emerge was the balance of perceived control and perceived support. Sub-categories included feeling informed, having options and choices, a supportive environment and someone to trust and give confidence. Continuity of care was found not to be an option for those whose care was transferred during pregnancy or labour. CONCLUSIONS: staffing levels which provide immediate access to the support of the midwife throughout labour enhance personal control. Those with the greatest need for support and continuity of care and carer are among those least likely to receive it.

Female

Comparative clinical trial of granisetron and ondansetron in the prophylaxis of cisplatin-induced emesis. The Granisetron Study Group.

PURPOSE: To compare the efficacy and safety of granisetron and ondansetron, serotonin (5-HT3) receptor antagonists shown to be effective in the prevention of chemotherapy-induced emesis. PATIENTS AND METHODS: In a double-blind, randomized, stratified, parallel-group study, the efficacy and safety of granisetron and ondansetron were compared in 987 chemotherapy-naive patients who received cisplatin in doses > or = 60 mg/m2. Granisetron was administered as a single dose of 10 or 40 micrograms/kg before the start of chemotherapy. Ondansetron was administered in doses of 0.15 mg/kg before and 4 and 8 hours after the start of chemotherapy. The three treatment groups were well-matched with respect to demographic characteristics and the dose of cisplatin administered. RESULTS: For all evaluations, single doses of granisetron 10 or 40 micrograms/kg were as effective as three 0.15-mg/kg doses of ondansetron. Total control (no vomiting, no retching, no nausea, and no use of rescue) was attained by 38%, 41%, and 39% of all patients who received granisetron 10 microgram/kg, granisetron 40 micrograms/kg, and ondansetron, respectively. No vomiting or retching and no use of rescue antiemetics were reported in 47%, 48%, and 51% of patients who received granisetron 10 micrograms/kg, granisetron 40 micrograms/kg, and ondansetron, respectively; no nausea and no use of rescue antiemetics were reported in 39%, 42%, and 40% of patients, respectively. CONCLUSION: All three treatment regimens were well-tolerated. The results of this study indicate that a single dose of granisetron 10 or 40 micrograms/kg is as effective as three doses of ondansetron 0.15 mg/kg in the prevention of nausea and vomiting induced by cisplatin chemotherapy.

Adult

Use of dreams in therapy: a survey of clinicians in private practice.

A literature review indicated a dearth of research on how dreams are used in therapeutic settings so a questionnaire was sent to a random sample of 500 members of the Florida Psychological Association to assess (a) the extent of dream use in therapy, (b) theoretical approaches applied to dream interpretation, and (c) basis for experience and expertise in dream work. Of the 500 potential clinicians, 228 returned survey forms for a response rate of 46%. Analysis indicated that 83% of the respondents used dream material at least occasionally in their practice and that Freudian and Gestalt approaches were most often used in dream interpretation. Interestingly, most respondents gained their 'experience' in dream work through self-study and continuing education workshops and seminars.

Adult

Immunosuppressive therapy for vasculitis.

There are few controlled trials of immunosuppressive therapy for vasculitis, making the further study of long-term outcome of these diseases with contemporary modes of management necessary. Relapse is frequent in many forms of vasculitis. The consequences of immunosuppressive therapy, including opportunistic infection, have been emphasized. Novel forms of therapy have been described in small series and case reports, although the precise role of such therapies in the treatment of vasculitis in general is far from certain in the absence of collaborative, multicenter controlled studies. The relationship between vasculitis and hepatitis C virus has prompted the use of interferon therapy in the treatment of vasculitic complications resulting from this infection.

Cyclophosphamide

Glycosyl-phosphatidylinositol anchor synthesis in paroxysmal nocturnal hemoglobinuria: partial or complete defect in an early step.

The defect in the biosynthesis of the glycosyl-phosphatidyl inositol (GPI) anchor in paroxysmal nocturnal hemoglobinuria (PNH) appears to be in the initial steps. In biosynthetic studies using [3H]mannose, abnormal granulocytes of eight patients, and B lymphocytes transformed by Epstein-Barr virus of six different patients synthesized dolichyl phosphoryl mannose, but little or no later mannosylated intermediates. When fused with murine cell lines known to be deficient at different biosynthetic steps of the GPI anchor, the GPI-anchor-deficient granulocytes of 21/21 patients and lymphocytes from 6/6 patients complemented all murine cell lines except those of class A; cells of this class are not able to add N-acetylglucosamine to phosphatidylinositol. These studies indicate that the defect in GPI-anchor synthesis in PNH is early in the pathway, and is the same as that of class A mutants, but may be partial in some patients, resulting in the production of small amounts of mannosylated intermediates.

Antigens, CD

Defense style in women with eating disorders.

A relatively new instrument, the Defense Style Questionnaire (DSQ), represents an efficient method by which to quantify an individual's psychological defense style. We administered the DSQ to 66 women hospitalized for anorexia nervosa, bulimia nervosa, or concurrent anorexia and bulimia nervosa. Contrary to our expectations, there were no consistent patterns of identifiable defense styles specific to these groups in qualitative, univariate, and multivariate analyses. The failure of the DSQ to demonstrate specificity across eating disorder subgroups suggests it is not informative in regard to the pathogenesis of these specific syndromes. In contrast, in a previous study, we found temperamental measures to be informative.

Adult

Low-grade squamous intraepithelial lesions: cytologic predictors of biopsy confirmation.

One hundred and seven smears demonstrating a low-grade squamous intraepithelial lesion (LSIL) were analyzed for features predicting subsequent biopsy confirmation. Twelve (29%) of 41 smears showing few LSIL cells were biopsy confirmed compared to 33 (60%) of 55 containing an intermediate number of LSIL cells and 9 (82%) of 11 displaying many LSIL cells (P < 0.002). Thirty-seven (47%) of 78 smears showing mainly condylomatous atypia (CA), 7 (54%) of 13 revealing predominantly cervical intraepithelial neoplasia 1 (CIN 1), and 10 (63%) of 16 displaying both CA and CIN 1 were histologically confirmed (N.S.). Biopsy confirmation was obtained in 35 (65%) of 54 women whose repeat smears obtained at colposcopy demonstrated SIL compared to four (15%) of 26 patients whose repeat smears were normal or contained atypical squamous cells of undetermined significance (P < 0.001). These results suggest that the number of diagnostic cells in an LSIL smear predicts biopsy confirmation and affirm the validity of combining CA and CIN 1 under the category of LSIL in the Bethesda System.

Adult

Why do ambiguous figures reverse?

For much of this century the dominant theory of reversal of ambiguous figures has been neural satiation. We suggest a very different kind of theory based on the consequences of the typical instructions given to subjects in experiments on reversal. In analyzing these instructions in preliminary experiments we conclude that what matters is the subject's knowledge that the figure is reversible and specific knowledge of how its alternative construals appear. This leads to an intention to reverse the figure. In one experiment we demonstrate that recent experience with the ambiguous figure and its two modes of appearance does not lead to its reversal if the subject does not know the figure is reversible. In another experiment we demonstrate that when the subject does know the ambiguous figure is reversible, it nonetheless will not tend to reverse if the intention to do so is contravened by a different intention. We suggest that the intention to reverse cannot succeed unless the subject "knows" how to carry it out and, further, that the intention may become involuntary and automatic.

Female

Parvovirus B19 outbreak on an adult ward.

In November and December 1992, an outbreak of parvovirus B19 infection occurred among patients and staff on an adult mixed surgical ward at a large hospital in London. Three patients and 15 staff members were serologically confirmed as acute cases. The attack rate among susceptible members of staff was 47%. In those infected, arthralgia (80%) and rash (67%) were the most common symptoms. Of six susceptible in-patients on the ward, three became infected. One of the in-patients who had carcinoma of the mouth was viraemic for more than 10 days with marrow suppression resulting in the postponement of chemotherapy until intravenous immunoglobulin was given and he was no longer viraemic. Control measures taken included closure of the ward to new admissions, transfer of only immune staff to the ward, and restriction of the ward nursing staff to working only on that ward. Although no specific exposure was conclusively identified as a risk factor, there was a suggestion of an increased risk of acquiring parvovirus B19 infection among those staff who did not adopt strict hand washing procedures after each physical contact with a patient (RR = 2.33; P = 0.07). Knowledge of parvovirus B19 among interviewed health care workers was poor: only 42% reported knowing about parvovirus B19 and only 38% could name a patient category at risk of a severe outcome following infection. This is the first report of a nosocomial outbreak affecting an adult ward and of possible transmission of parvovirus B19 infection from staff to in-patients. Hospital control of infection teams should include parvovirus B19 in their outbreak containment plans.

Adult

Do young children reverse ambiguous figures?

Most adult observers tend not to reverse ambiguous figures if they are not informed about the ambiguity of the figure. The question was asked whether very young children who have rarely, if ever, seen any kinds of ambiguous figures will reverse if uninformed, and also how they will behave if they are informed. It was found that 3 and 4 year olds never reverse when presented with two different kinds of ambiguous figures when uninformed, and only some do even when informed; further, those that do reverse do so only once or twice over a 60 s inspection period. These results are interpreted as further confirmation of an earlier finding with adults--that reversal is not simply a matter of prolonged inspection of an ambiguous figure leading automatically to neural satiation. Instead, cognitive factors such as utilization of memory and intention are implicated.

Attention