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Biomedical subjects

R Welch

Publications and source records attributed to R Welch.

At least 19 recordsLinked to original sources

Recombinant human erythropoietin in patients with ovarian carcinoma and anaemia secondary to cisplatin and carboplatin chemotherapy: preliminary results.

Preliminary results from the first 21 patients of a group of 30 with International Federation of Gynaecology and Obstetrics (FIGO) stage II-IV epithelial ovarian carcinoma and anaemia are reported. Patients entered this open-label, comparative-group, out-patient study and were randomized to receive conventional support alone (control patients) or recombinant human erythropoietin (r-HuEPO) in addition to conventional support for 6 months. The aim of the study was to determine the effects of r-HuEPO on the anaemia induced by platinum-based chemotherapy. Patients randomized to r-HuEPO therapy received 300 U/kg subcutaneously 3 times weekly in addition to conventional chemotherapy. All patients underwent regular haematological monitoring. One patient developed a deep venous thrombosis after 17 doses of r-HuEPO; it was thought that this event may have been related to therapy and the patient was withdrawn from the study. Three other withdrawals occurred after 11, 15 and 40 doses of r-HuEPO because of progressive anaemia, metoclopramide-induced skin rash and change of chemotherapy, respectively. In the 21 patients analysed to date, there was a notable reduction in blood transfusion requirements during the 6 months of chemotherapy and an improvement in mean serial haemoglobin concentrations in patients on r-HuEPO compared with the control group. In conclusion, r-HuEPO has the potential for reducing haematological toxicity in patients with ovarian carcinoma receiving platinum-based chemotherapy. Also, r-HuEPO may allow modest dosage increments in chemotherapy or the addition of abdominopelvic radiotherapy.

Adult

High-performance liquid chromatographic analysis of doxacurium, a new long-acting neuromuscular blocker.

A rapid and sensitive high-performance liquid chromatographic procedure was developed for the analysis of the new, long-acting neuromuscular blocker doxacurium in the plasma and urine of dog and man and in the bile of dog. Samples were prepared on solid-phase extraction cartridges containing a methyl (C1) bonded phase and were chromatographed on a 15 cm reversed-phase column (C1) using a mobile phase of 0.05 M monobasic potassium phosphate-acetonitrile (30:70, v/v). The compound was detected at 210 nm with a lower limit of quantitation of 10 ng/ml. An inter-assay accuracy of 90-92% was obtained for the analysis of the drug from biological fluids. The method was applied to studies of doxacurium after intravenous administration to dog and man.

Animals

Serial magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy.

We prospectively performed magnetic resonance imaging (MRI) studies during the neonatal period, and at 4 and 8 months of age, on 15 term infants with hypoxic-ischemic encephalopathy, and compared the results with their neurodevelopmental outcome at 18 months of age. Cerebral palsy developed in nine infants, two infants were classified as having abnormalities of tone and delayed motor milestones that were suggestive of cerebral palsy, and four infants were normal. Structural abnormalities, delayed myelination, or a combination of the two were detected with MRI at 8 months of age in all nine infants with later development of cerebral palsy. Three of the four normal infants and one infant with suggestive abnormalities had normal serial MRI findings. Each of the remaining two infants (one normal, one with suggestive abnormalities) had isolated persistent ventricular dilation on all three MRI studies. Our results suggest that 8 months appears to be the earliest time at which MRI findings correlate well with later adverse neurodevelopmental outcome in this population.

Age Factors

Mental health needs of the chronically mentally ill elderly.

The treatment histories and current social, financial, and clinical status of 111 chronically mentally ill (CMI) persons over the age of 60 were examined. Information was obtained from Ss, family, mental health records, and mental health professionals familiar with Ss. Psychiatric symptoms were observed in 74% of Ss. Many Ss experienced long periods without acute episodes of illness. Recurring episodes eventually appeared in most Ss, however, and ongoing deficits in daily functioning and social contacts were prototypical. Two thirds of the Ss were living in the community, relying heavily on family contacts; the rest lived primarily in nursing homes (23.4%) or psychiatric hospitals (7.2%). Social support was the best predictor of level of functioning. Findings suggest that failure of CMI elderly to use mental health services is not due to lack of need. Mental health services currently do not appear to be meeting the needs of this population.

Activities of Daily Living

Determinants of polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), and dichlorodiphenyl trichloroethane (DDT) levels in the sera of young children.

Serum samples from 285 4-year-old Michigan children were evaluated for levels of 11 environmental contaminants. Polychlorinated biphenyls (PCBs) were found in half the samples tested; polybrominated biphenyls (PBBs) in 13-21 percent; dichlorodiphenyl trichloroethane (DDT), in more than 70 percent. Nursing (Mothers' milk) was the principal source of these exposures. Congener-specific analysis documented the presence of at least one highly toxic PCB congener, 2,3',4,4',5-pentachlorobiphenyl. The data demonstrate the multigenerational impact of female exposure to persistent organic environmental contaminants.

Body Burden

Validity of messages from quadriplegic persons with cerebral palsy.

Interpreting gestures from retarded, nonvocal subjects is scientifically risky. Investigators must construe the subject's meaning without reference to an external validity measure. A procedure was devised in which message content was provided to nonvocal, severely palsied quadriplegic subjects in advance. Subjects' responses were limited to yes/no gestures. Another investigator elicited the messages without prior knowledge of their content. Results, which indicated reasonably high correspondence between stimulus messages and messages elicited, suggest that such subjects can present the content of their own phenomenal field accurately and that investigators' interpretations need not be considered imaginary.

Adult

Toluidine blue in the corroboration of rape in the adult victim.

Objective physical evidence to corroborate a claim of rape is frequently absent. Genital lacerations are considered evidence that rape has occurred. In this study, toluidine blue dye, a nuclear stain, was used to detect vaginal lacerations. The detection of vaginal lacerations in reported rape victims increased from one in 24 to 14 in 24 with toluidine application. Toluidine blue increases the detection of perineal lacerations in adult rape victims and the presence of lacerations is supportive of the documentation of rape.

Adult

Mechanism of Escherichia coli alpha-hemolysin-induced injury to isolated renal tubular cells.

Alpha-hemolysin (AH) is a 110,000-dalton protein secreted extracellularly by certain Escherichia coli. This protein is an acknowledged virulence factor for E coli and recently has been implicated as an important determinant in the pathogenesis of E coli pyelonephritis. Recombinant engineered strains of E coli were used that varied only in their ability to secrete AH extracellularly. The effect of AH on vital dye exclusion, oxygen consumption rate (QO2) adenosine triphosphate (ATP) levels, superoxide (O2-) and hydrogen peroxide (H2O2) production in preparations of isolated rat cortical renal tubular cells (RTCs) was assessed. Approximately 5-10 pg of AH dramatically stimulated QO2 by nearly 150%. This was associated with a marked increase in production of O2- and H2O2, to 13.9 +/- 1.7 and 13.2 +/- 2.1 nM/mg cell protein, respectively (P less than 0.05), as well as a 38% decrease in cellular ATP. These biochemical effects were all seen after a 30-minute exposure to AH and by 120 minutes were associated with 15.7% +/- 1.1% of RTCs that were unable to exclude vital dye. The effect of AH on QO2 and O2- formation was prevented by pretreatment of RTCs with ouabain, which indicates that the effect of AH on oxygen metabolism is linked to Na-K ATPase activity. However, when ouabain-treated RTCs were exposed to AH, ATP remained depressed despite the inhibition of QO2 and O2- production. In contrast, in ouabain-pretreated RTCs, cell membrane integrity was dramatically protected, because only 2.4% +/- 0.4% of RTCs were not unable to exclude vital dye. Thus, the data demonstrate that E coli AH provokes at least two biochemical events that may be injurious to RTC: increased oxygen intermediates (O2- and H2O2 and ATP depletion. These findings with ouabain suggest that the first mechanism of injury may be a more proximate cause of cell death. Moreover, the data suggest that endogenous production of reactive oxygen molecules may be critical modulators of RTC membrane injury.

Adenosine Triphosphate

Generalization gradients following differential intradimensional autoshaping.

Three pigeons were trained on a differential, intradimensional autoshaped discrimination. A 45 degrees line tilt was always paired with food whereas a 15 degrees line tilt was never paired with food. All subjects learned the discrimination within 17 sessions. The pigeons were then given generalization tests in extinction over seven line tilts (0 degrees, 15 degrees, 30 degrees, 45 degrees, 60 degrees, 75 degrees and 90 degrees). The subjects yielded generalization gradients with maxima at 45 degrees and minima at 15 degrees. An area shift, but no peak shift, was found for each subject.

Animals

Methadone maintenance: an assessment of potential fluctuations in behavior between doses.

Thirty methadone maintenance outpatients were measured 1 and 25 hours after ingestion of methadone on auditory threshold, distance perception, simple and differential reaction time, time perception, attention span, and short-term memory. The results revealed a small but statistically significant difference between the two tests for distance perception. In addition, treatment interacted with preparatory interval on differential reaction time and with sex on attention span.

Adolescent

Controlled trials of aluminum hydroxide gels for peptic ulcer.

Relief of duodenal ulcer pain by aluminum hydroxide gel (AG) was compared with that obtained by a dummy gel (DG) in randomized trials. In 44 individual pain episodes, complete relief was obtained by 15-ml doses of AG in 79% and by DG in 45% (P less than 0.05). In 48 identical blind trials replicated at another hospital the difference was not significant. The gels were also tested against ulcer pain induced by intragastric acid instillation (Palmer test) in 35 patients; pain was relieved by AG in 63% and by DG in 62%. Presumed effectiveness in terminating ulcer episodes was studied in 65 patients admitted for pain; 37 received milk and cream hourly and 28 did not. All were treated with 15 ml of AG or DG during waking hours. Median time for complete disappearance of spontaneous pain was 3 days for AG and 7 days for DG, the same in both groups. In all patients the acid instillation test was repeated every few days. For the milk and cream group it became negative after 4 days with AG and after 6 days with DG. In 18 patients with gastric ulcer treated for 4 weeks AG led to greater reductions in size than did DG. A number of these trials indicate AG to be more effective than DG, but sampling and other methodological problems limit the certainty of any conclusions.

Aluminum Hydroxide