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Biomedical subjects

R C Bell

Publications and source records attributed to R C Bell.

At least 19 recordsLinked to original sources

Long-term consequences in offspring of diabetes in pregnancy: studies with syngeneic islet-transplanted streptozotocin-diabetic rats.

To study the long-term effects of exposure to maternal hyperglycemia and insulin deficiency in utero, we used the syngeneic islet transplanted streptozotocin-diabetic rat model of diabetes in pregnancy and examined insulin secretion and action in 6-month-old offspring. Female rats were rendered diabetic with streptozotocin and then transplanted with 2500, 750, or 500 islets. Control animals were also studied, and one group whose islet transplants failed remained diabetic. During pregnancy, plasma glucose levels in the diabetic rats and the groups receiving 500 and 750 islets were 24.7 +/- 1.0, 15.3 +/- 1.4, and 7.9 +/- 0.5 mmol/liter, respectively, all significantly greater than the control value (5.6 +/- 0.3 mmol/liter; P < 0.05). The plasma glucose level in the 2500 islet group was 6.2 +/- 0.2 mmol/liter, which was not significantly higher than the control value. When the offspring were studied at 6 months, there was no significant difference between groups in either glucose or insulin levels after iv glucose, although acute insulin secretion tended to be higher in the offspring of the diabetic animals. A study of insulin action with the euglycemic clamp at two insulin levels showed that insulin sensitivity was reduced in the offspring of diabetic animals vs. controls (1.97 +/- 0.24 vs. 7.58 +/- 0.95 mumol/liter x 100/kg/min.pmol/liter; P < 0.05). Insulin sensitivity was also significantly reduced in the 2500, 750, and 500 islet group offspring (4.81 +/- 0.57, 4.82 +/- 0.64, and 4.01 +/- 0.63 mumol/liter x 100/kg/min.pmol/liter; P < 0.05) compared to that in the control. There were no differences in insulin sensitivity between male and female animals. In summary, animals displaying maternal insulin deficiency have offspring who are insulin resistant without any evidence of iv glucose intolerance or diminished insulin secretion.

Animals

Pathologic changes induced by phospholipase A2 isolated from the venom of Collett's snake, Pseudechis colletti: a light and electron microscopic study.

Pseudechis colletti is an Australian elapid snake with a range limited to central Queensland, Australia. The venom of this snake, as well as that of several other Australian elapids, has been shown to contain a phospholipase A2 (PLA2) which can cause a marked myoglobinuria in mice. Few studies have described the histopathologic and ultrastructural changes that result from myotoxic PLA2-induced damage. Our investigation demonstrated that the isolated PLA2 induced myodegeneration and necrosis in myocardium in a dose-related manner, with subsequent myoglobinuria and myoglobinuric nephropathy.

Animals

Prediction of employability in schizophrenic patients.

This study, the third of a series of reports on employability and schizophrenia, investigated the effects of both interview and non-interview variables on employability. Data on 46 chronic schizophrenic inpatients included demographic and illness-related variables, measures of psychopathology and interview-based ratings of employment skill. Latent class analysis using linear structural relations (LISREL) modelling generated the main finding namely, that interview-based measures are the strongest determinants of employability. However, other variables pertaining to illness, prior functioning and negative symptoms, exert an effect on interview performance and hence indirectly influence employability ratings and judgements.

Activities of Daily Living

Relative usefulness of the WMS and WMS-R: a comment on D'Elia et al. (1989)

In a previous commentary, D'Elia and colleagues reflected on the relative adequacy of normative data for the original Wechsler Memory Scale (WMS) and the Wechsler Memory Scale-Revised (WMS-R). They concluded that, for some age groups, the original version of the test is preferred. We discuss further the crux of the D'Elia and colleagues criticism of the WMS-R, namely the issue of interpolation in tables of normative data. We also consider two additional criteria: the sampling techniques used to obtain the normative samples, and the respective standard errors of measurement and scaling properties of scores on the two tests. We conclude that on each of these criteria the WMS-R is preferable.

Adolescent

The structure of personality disorders in DSM-III.

In DSM-III it is proposed that there are 11 personality disorders (PDs) that fall into 3 superordinate clusters: cluster A, labelled the odd or eccentric; cluster B, labelled the emotional, dramatic or erratic; and cluster C, described as the anxious or fearful. To check this proposal, data were obtained from a sample of 112 state hospital psychiatric inpatients via the Structured Interview for DSM-III Personality (SIDP). Various statistical techniques were applied to the data, ranging from the least constrained method of multidimensional scaling to the most constrained and statistically rigorous approach of confirmatory factor analysis. In the latter approach, the models suggested by the various statistical approaches were contrasted directly. A 3-cluster solution was accepted as the best representation of the data, although PD membership of the 3 clusters varied in some ways from those suggested by DSM-III. An exploratory correlation analysis showed that many of the items were more strongly correlated with PDs other than the ones specified by DSM-III, but generally items clustered within the 3 superordinate clusters. This issue deserves further investigation.

Adult

A prospective study of incisional time, blood loss, pain, and healing with carbon dioxide laser, scalpel, and electrosurgery.

Carbon dioxide laser incisions are reported to be less painful, less bloody, and less prone to seroma formation and to heal better than scalpel or electrosurgical incisions. We compared all three modalities in a prospective randomized study of cholecystectomy incisions. Time required for the incision and incisional blood loss was less with electrosurgery than with the carbon dioxide laser or scalpel. Postoperative pain and wound healing, however, were the same for all three techniques. The carbon dioxide laser appears to offer no advantage over conventional means of making a standard incision.

Adult

Lethal potency and fractionation of Duvernoy's secretion from the brown tree snake, Boiga irregularis.

The liquid secretion contained only 15% protein and had relatively low proteolytic activity. The reconstituted crude secretion had a murine i.p. LD50 of 10.33 mg/kg and was not hemorrhagic in doses up to 200 micrograms. Fast Protein Liquid Chromatographic (FPLC) cation exchange analysis of reconstituted crude secretion resulted in resolution of 16 peaks. Lethal activity was identified in three peaks. The major lethal fraction was 12.5% of the secretion protein and had a murine i.p. LD50 of 7.3 mg/kg. A pooled fraction containing two lethal peaks which comprised 9.4% of secretion protein had moderate proteolytic activity and produced myoglobinuria in mice. The fraction had an approximate murine i.p. LD50 of 3.7 mg/kg. Microscopic examination of muscle tissue from mice succumbing to this fraction revealed multifocal myofiber degeneration and necrosis. SDS-PAGE indicated that the major lethal fraction contained three proteins with mol. wts of 12,500, 18,000 and 52,000 and the myotoxic fraction contained two proteins with mol. wts of 14,500 and 17,000. While B. irregularis Duvernoy's secretion has a low lethal index, it does contain a myotoxic fraction with moderate lethal potency. These observations and recent data describing clinical envenomation of several infant patients suggest that large specimens may pose a hazard to infants and small children.

Animals

Thermogenesis, low-protein diets, and decreased development of AFB1-induced preneoplastic foci in rat liver.

The development of hepatocellular, putatively preneoplastic, gamma-glutamyl transpeptidase positive (GGT+) foci and tumors induced by aflatoxin B1 (AFB1) has been shown to be reduced in male F344 rats fed a diet containing 6% protein (as casein). This reduction occurs despite increased energy intake, when compared with animals fed a diet containing 22% protein. Among its many effects, low protein intake is known to increase the proportion of energy intake expended in the form of heat (thermogenesis); thus, this investigation examined the association between the development of GGT+ foci and alterations in indices of thermogenesis induced by feeding varying levels of dietary protein. Five days following the completion of AFB1 dosing, animals were assigned to groups fed 4%, 8%, 12%, 16%, or 22% dietary protein for 6 weeks. Foci development (% liver volume occupied) was markedly reduced in animals fed the low-protein diet (4%, 8%), yet calorie consumption per 100 g body wt was greater. A modest negative linear trend was observed in oxygen consumption with increasing levels of dietary protein intake. Urinary norepinephrine levels were elevated in the groups fed 4% and 8% protein; urinary dopamine and norepinephrine turnover rates in brown adipose tissue were highest in animals fed 4% protein. These results suggest that GGT+ foci development occurs when a "critical level" (approx 12%) of dietary protein intake is reached. Inhibition of foci development at lower levels of protein intake is associated with several indicators of increased thermogenesis.

Aflatoxin B1

Radiographic findings in a group of elderly patients at a Canadian dental school.

The panoramic and intraoral radiographs of 154 elderly dental patients aged 65 years and older were assessed at the College of Dentistry, University of Saskatchewan, Saskatoon. Thirty-seven per cent of the patients were completely edentulous, and 61% were partially edentulous. In the dentate group, 87% had evidence of at least one carious tooth, and all had radiographic evidence of alveolar bone loss. The incidence of periapical inflammatory lesions and root remnants was relatively high.

Aged

Decision for surgical management of perforation following endoscopic sphincterotomy.

Duodenal perforation resulting from endoscopic sphincterotomy (ES) is a serious complication with a high mortality. Diagnosis is often problematic and the optimum treatment is controversial. Eight proven perforations occurred following 441 ES at University of Colorado Hospital, a rate of 1.8 per cent. Physical and laboratory findings were of little diagnostic value, whereas plain abdominal radiographs showed evidence of perforation in 86 per cent. All patients were operated on promptly after diagnosis of perforation. Delay in diagnosis of perforation beyond 24 hours in six patients was associated with a high morbidity and two deaths. Analysis of published series confirmed that delay in diagnosis and delay in operation after perforation were associated with a higher mortality rate than early diagnosis with or without operation. We recommend operative intervention in all patients with clinical evidence of perforation following ES.

Adult

Clinical determinants of abnormalities in pulmonary functions in survivors of the adult respiratory distress syndrome.

Pulmonary function tests (PFTs) were performed in 39 survivors of the adult respiratory distress syndrome (ARDS) in whom clinical data had been prospectively collected during the acute episode. PFTs stabilized within 6 months of the episode and had returned to normal in most survivors. Persistent abnormalities were found after 6 months in diffusing capacity (14 of 23 patients, 61%), vital capacity (10 of 23 patients, 43%), and total lung capacity (five of 24 patients, 21%). To clarify the mechanisms underlying these persistent abnormalities, we attempted to correlate long-term PFT outcomes with estimates of the severity of initial lung injury as assessed from clinical data and with other features of the patient's course. The severity of lung function impairment during the first 3 days of ARDS was not related to long-term PFT values. However, a lower DLCO was related to a higher AaDO2, higher pulmonary artery pressure, and worse radiographic appearance on Days 4 through 7 and to the occurrence of sepsis. A lower FVC was related to higher pulmonary vascular resistance in Days 4 through 7 of ARDS. Long-term values for FVC and TLC were directly related to increasing levels of PEEP applied from Days 4 through 7 of ARDS in patients with peak airway pressures less than 50 cm H2O. Long-term abnormalities of pulmonary function of survivors of ARDS were not related to initial lung impairment but were directly related to persistence of impaired lung function during the acute episode. Recovery of lung function may also have been directly related to therapeutic modalities such as PEEP and impaired by the occurrence of sepsis.

Adolescent

C-reactive protein, leukocytes, and fever after central IL 1 and alpha-MSH in aged rabbits.

Aged and young unanesthetized rabbits with intracerebroventricular cannulas were tested in experiments designed to determine whether increases in plasma C-reactive protein (CRP) level and leukocytosis can be rapidly induced by central administration of crude buffy-coat supernatant commonly called endogenous pyrogen or interleukin 1 (IL 1). The results indicate that both acute-phase responses occur during fever caused by central administration of this supernatant and that they are generally detectable within 2 h. Although the febrile response was smaller in aged female rabbits, there was no decline in CRP or leukocyte responses, an observation that was not predicted. The antipyretic neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) reduced fever caused by central IL 1 more effectively in the aged rabbits. alpha-MSH likewise inhibited the CRP and leukocyte responses to central IL 1. The results confirm that CRP and leukocyte responses can be driven by a central IL 1 signal and further indicate that the response can occur rapidly, consistent with direct central nervous system control of the acute-phase responses. The findings indicate that the acute-phase responses depend in part on the age of the host and that the responses can be modulated by an endogenous central nervous system peptide with known antipyretic and immune modulatory properties.

Acute-Phase Reaction

Pulsatile release of antipyretic neuropeptide alpha-MSH from septum of rabbit during fever.

The effects on fever of central administration of alpha-melanocyte-stimulating hormone (alpha-MSH) and its antiserum, the specific increase in central concentration of alpha-MSH during fever, and related results indicate that this neuropeptide is important to central nervous system (CNS) regulation of the febrile response. The present experiments were designed to establish whether alpha-MSH is released from septal tissue during fever and, if so, in what temporal course relative to the febrile response. alpha-MSH release at localized push-pull perfusion sites within the septum during fever induced by intravenous interlukin-1 occurred in two basic patterns: prolonged or repeated release over sequential 10-min sample periods or a more discrete pulse largely confined to a single 10-min period. The greatest increases in concentration and the greatest number of increases occurred during the chill phase of fever, when temperature was rising rapidly, rather than during the plateau phase. Such episodic release is similar to that known to occur in neuroendocrine and other physiological systems, and it provides further support for a physiological role of alpha-MSH in CNS control of fever.

Animals

Incidence, site, and outcome of infections in patients with the adult respiratory distress syndrome.

Bacterial infection in the adult respiratory distress syndrome (ARDS) is associated with the occurrence of multiple organ failures and death. We studied 108 infections in 129 patients with ARDS and evaluated the organisms responsible, the body sites involved, and the outcomes of therapy. Gram-negative bacilli represented 57% of the microbial pathogens and gram-positive cocci 36%. Only 7% of infections were caused by other organisms (fungi, viruses, Pneumocystis, Legionella). Gram-negative organisms were more common in the lung, abdomen, and pleura. Bacteremia was more common in abdominal infections (11 of 17, 67%) than in infections at other sites (18 of 65, 28%), (p less than 0.01); ;9 patients were bacteremic from clinically undetected sites. Ten of 17 (59%) patients with abdominal infections survived compared with 7 of 56 (13%) patients with lung infections (p less than 0.001). A retrospective review of in vitro organism susceptibility and the antibiotics administered revealed that the patients who received adequate antibiotic therapy did not have a higher survival rate (20 of 69, 29%) than those who received inadequate antibiotic therapy (3 of 13, 23%). These data suggest that further investigation of infections in patients with ARDS is required and that emphasis should be placed on pathogenesis, prevention, and host responses.

Adult