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Biomedical subjects

M Robinson

Publications and source records attributed to M Robinson.

At least 289 records · Page 16Linked to original sources

Genetic control of the immune response to Trichinella spiralis: recognition of muscle larval antigens.

Host antibody recognition of muscle larval (ML) antigens of Trichinella spiralis was examined. Monoclonal antibodies (MoAbs) to known host protective ML antigens have been produced in order to aid this examination. Eleven strains of mice with independent MHC haplotypes and seventeen T. spiralis infected human patients were all found to recognize the same three major antigens as the monoclonal antibodies; i.e., of mw 41, 46 and 55 kD. However all serum samples tested also recognized further ML antigens and this recognition varied with the individual or strain. This variation in antigen recognition also applied to the MoAb. Mutual inhibition studies demonstrated that even where the MoAb apparently recognized the same antigens, specific epitope recognition was disparate. Hence some of the major antigens recognized by hosts of T. spiralis, regardless of whether vaccinated or infected, correspond with antigens which have considerable host protective properties. There also appear to be a number of epitopes upon these antigens and the biological implications of this are discussed.

Animals↗

Evaluating FACES III and the Circumplex Model: 2,440 families.

Previous evaluations of the Circumplex Model's curvilinear hypothesis using FACES instruments have yielded conflicting results. A review of the different research procedures and samples used in those investigations revealed that none of the studies had samples large and/or heterogenous enough to test the curvilinear hypothesis adequately. The present study evaluates the curvilinear hypothesis of family functioning and the concurrent validity of FACES III with a sample of optimal size (N = 2,440 families) and diversity. The lack of support for the curvilinear hypothesis in this "greenhouse" sample is explained by different findings for the two FACES III subscales. There was no relationship between the study's measures of well-being and the adaptability subscale and a linear relationship between these measures and the cohesion subscale. Implications of these findings for the continuing use of the FACES III and for the Circumplex Model of Marital and Family Systems are discussed.

Adolescent↗

The effects of diet on the incidence of periodontitis in rats.

Four groups of 60 male Alpk:APfSD rats were fed different nutritionally comparable diets for 107 weeks with interim sacrifices at 26, 53 and 77 weeks in order to compare the effect of diet on the incidence of oral disease. Changes in the oral and nasal cavities were assessed by histopathology. Oro-nasal fistulation and severe periodontitis were associated with diets containing fibres originating from oats and barley. An expanded ground diet induced the most severe lesions. Aspects of the pathogenesis of the lesions observed are discussed.

Animal Nutritional Physiological Phenomena↗

Ten- and ninety-day toxicity studies of 1,2-dichlorobenzene administered by oral gavage to Sprague-Dawley rats.

Ten- and ninety-day toxicity studies of 1,2-dichlorobenzene (DCB) were conducted in male and female Sprague-Dawley rats to meet the needs of the U.S. Environmental Protection Agency for toxicity data on this chemical for use in their determination of possible health risks related to human exposure. 1,2-Dichlorobenzene was administered at doses of 37.5, 75, 150, and 300 mg/kg/day (10-day), and 25, 100, and 400 mg/kg/day (90-day) in corn oil by oral gavage; control animals received corn oil. At time of sacrifice, gross necropsies were performed and selected tissues were weighed and prepared for histological evaluation. Blood was taken for hematology and clinical chemistries. In the 10-day study, exposure of 300 mg DCB/kg body weight to male rats resulted in a statistically significant decrease in final body weight, organ weights (heart, kidneys, spleen, testes, and thymus), and relative organ weights (spleen and thymus). A significant increase in absolute and relative liver weights was also noted in this dose group. Males also displayed significant increases in water consumption (300 mg/kg group), ALT (300 mg/kg) and leukocyte count (150 and 300 mg/kg). A significant increase in the incidence of hepatocellular necrosis was seen in the 300 mg/kg group of males compared to controls. In the 90-day study, male rats exposed to 400 mg DCB/kg displayed a statistically significant decrease in body weight, organ weight (spleen), and relative organ weight (spleen). The absolute weights of kidney and liver and the relative weights for heart, kidney, liver, lung, brain, and testes were increased significantly for this dose group. The absolute and relative weights of both the kidney and liver were significantly increased in the female 400 mg/kg dose group. The only clinical chemistry parameters statistically different than control were increased ALT (100 and 400 mg/kg groups), BUN and total bilirubin in the male 400 mg/kg group and total bilirubin in the 400 mg/kg female group. Histopathological evaluation showed hepatocellular lesions associated with DCB treatment which included centrolobular degeneration and hypertrophy, and single cell necrosis in male and females receiving 400 mg DCB/kg. The NOAEL observed in this study is 25 mg/kg/day.

Administration, Oral↗

Total androgen ablation: European experience. The EORTC GU Group.

Zoladex plus flutamide significantly delays the time to progression (subjective, objective, first progression) compared with orchiectomy, but no difference in survival (death from all causes or from malignant disease) could be detected. Thus, a delay in the appearance of progression has not improved survival. In fact, the duration of survival after progression tends to be shorter on Zoladex plus flutamide. There is thus no evidence to suggest any survival benefit with Zoladex plus flutamide. The quality control of our data revealed acknowledged problems in defining responses in patients with advanced prostate cancer. The review of the Bone Scan Committee provided the data for Tables 5 to 7. These data must provoke some reflections and emphasize once again the heterogeneity of the studied patient population. Table 4 on pain response after 4 weeks is just one of the many items to be analyzed by the committees for response criteria and quality of life. We expect that the other trials face similar problems. More work and patience are needed to obtain a firm answer to this clinical problem. These efforts will never be wasted, however, because the combined results of these trials will increase our knowledge of the treated history of prostate cancer and will, we hope, indicate a net treatment benefit in some subsets of patients. An individually tailored treatment for each patient selected from the anonymous mass of cases of advanced prostate cancer would be the highest reward of our continued collaboration with all the study groups.

Aged↗

Prevalence of gastroesophageal reflux in elderly patients in a primary care setting.

Despite the aging of our population, there remains a paucity of information about gastroesophageal reflux (GER) in the elderly. To assess the prevalence and characteristics of GER within this patient population, questionnaires evaluating symptoms associated with GER were administered to 313 consecutive patients 62 yr old or older from a primary care setting. Fourteen percent of these patients reported having at least weekly heartburn. Ambulatory 24-h esophageal pH monitoring was accomplished in 54 of the 313 patients surveyed. Twenty percent (11/54) of this subgroup exhibited increased acid contact time (pH less than 4 for more than 6% of the monitoring period). Twenty-two percent (12/54) complained of heartburn, yet only six individuals (11%) exhibited both symptomatic and objective indications of acid reflux. Surprisingly, 31% (17/54) of the patients studied exhibited significant alkalinity within the distal esophagus (pH greater than 8 for greater than 1.5% of the monitoring period). Whereas 29% of these patients (5/17) reported heartburn, 40% of those reporting heartburn (2/5) had acid GER as well as excessive alkalinity. In contrast to patients with acid GER--none of whom reported pulmonary symptoms--24% (4/17) of these patients with esophageal alkalinity reported wheezing, nocturnal cough, or paroxysmal nocturnal dyspnea. Of the four patients with significant distal esophageal exposure to both acid and alkali, two reported heartburn and a third reported dysphagia. In addition to the somewhat higher prevalence of acid reflux than anticipated, a surprisingly high prevalence of esophageal alkalinity was observed.

Aged↗

Hazards of alpine sport.

Alpine sports in Australia include downhill skiing, cross country skiing, snowboarding, snowmobiling and tobogganing. Despite a popular impression that the sport is risky the injury rate is low and there has been a large decrease in injuries relative to increased participation in the past 20 years. Nevertheless, more young skiers are sustaining injuries, many of which could be avoided.

Adolescent↗

Nizatidine versus placebo in gastroesophageal reflux disease: a 12-week, multicenter, randomized, double-blind study.

Two doses of nizatidine (150 mg bid and 300 mg hs), an H2-receptor antagonist, were compared with placebo in a 12-wk, multicenter, randomized, double-blind, parallel study in 466 patients with endoscopically documented gastroesophageal reflux disease. Antacid tablets were given concomitantly as needed for pain. Compared with placebo, nizatidine 150 mg twice daily was highly effective in rapidly reducing the severity of heartburn, regardless of esophagitis severity at entry. Significantly greater complete mucosal healing of esophagitis occurred after 6 wk of therapy with nizatidine 150 mg bid (vs. nizatidine 300 mg hs or placebo) only in patients with erosive esophagitis [16/68 (24%) vs. 8/65 (12%)] and erosive and ulcerative esophagitis combined [21/99 (21%) vs. 10/94 (11%)]. At wk 12, healing with nizatidine 150 mg bid was also significantly greater than placebo in erosive [19/68 (28%) vs. 9/65 (14%)], ulcerative [10/31 (32%) vs. 3/29 (10%)], and erosive and ulcerative esophagitis combined [29/99 (29%) vs. 12/94 (13%)]. These results show that twice-daily therapy with nizatidine 150 mg is very effective at relieving heartburn, and can also heal erosive and ulcerative esophagitis. Nizatidine 300 mg hs was not effective in healing esophagitis, compared with placebo.

Analysis of Variance↗

Elevated intracranial pressure and computed tomography of the brain in fulminant hepatocellular failure.

Cerebral herniation is a leading cause of death in patients with fulminant hepatocellular failure. Classical signs of elevated intracranial pressure are often absent in these patients. A reliable noninvasive method by which the presence of cerebral edema could be determined is much needed. To assess the efficacy of computed tomography of the brain in this setting, we compared the radiographic findings to the intracranial pressure measured by an epidural monitor in patients with fulminant hepatic failure. Unfortunately, a considerable difference existed between the presence of cerebral edema diagnosed by computed tomography of the brain and elevation of the intracranial pressure. Our observations suggest that in patients with fulminant hepatic failure and advanced hepatic encephalopathy, computed tomography of the brain is of little value in detecting cerebral edema. Pressure monitoring is most important to establish the presence and guide the therapy of intracranial hypertension.

Brain↗

Orchidectomy versus Zoladex plus Eulexin in patients with metastatic prostate cancer (EORTC 30853).

A total of 327 patients with metastatic prostate cancer have been randomized to either orchidectomy or treatment with goserelin (Zoladez) 3.6 mg depot preparation combined with flutamide (Eulexin) 250 mg t.i.d. in a phase III study (EORTC 30853). A small but statistically significant difference in time to subjective and objective progression of disease was found in favour of the combination treatment. However, time from objective progression to death was longer in the group initially allocated to orchidectomy. Thus no difference was found in overall survival between the two treatment groups. The clinical significance of these differences requires further follow up and analysis.

Aged↗

Esophageal motility, heartburn, and gastroesophageal reflux: variations in clinical presentation of esophageal dysphagia.

Dysphagia is a potentially important symptom, often leading to the finding of an anatomical or motility disorder of the esophagus. Dysphagia and heartburn represent two of the most common symptoms associated with esophageal motility disorders. To explore the relationship of symptomatic esophageal dysphagia and heartburn and their association with primary esophageal motor disorders, we have performed a retrospective assessment of 1035 patient evaluations performed at our gastrointestinal laboratory. A clear statistical association of symptomatic dysphagia and heartburn was established; however, no pattern diagnostic of a specific motility disorder was discernible. A sizable fraction of our patient population with dysphagia demonstrated normal esophageal motility. A significant portion of dyspeptic patients exhibited both normal motility and acid exposure. The differences observed between the incidence of subjective symptoms and objective dysfunction may be explained in part by an altered or increased esophageal sensitivity of these patients.

Adult↗

A method for the quantitative analysis of molecular species of alkylacylglycerol and diacylglycerol.

We describe a method for the quantitative analysis of molecular species of diacylglycerol and alkylacylglycerol as their diradylglycerobenzoate derivatives. Synthetic internal standards were used to provide quantitative determinations of the low levels of diacylglycerol and alkylacylglycerol and their individual molecular species in cultured cells. Diradylglycerols were isolated by thin-layer chromatography (TLC), converted to their benzoate derivatives and separated into subclasses by TLC. The molecular species of each subclass were analyzed by reversed-phase high performance liquid chromatography. Thirty-six species of diglyceride-type molecules were identified in Madin-Darby canine kidney cells. These cells were shown to contain 7.88 nmoles of diacylglycerol and 3.97 nmoles of alkylacylglycerol per mumole of phospholipid. Both subclasses contain predominantly monoenoic and saturated species. This technique should be valuable for studies examining the origin and metabolism of these important intracellular mediators.

Animals↗

Treatment of extremity soft tissue sarcomas with surgery and radiotherapy.

The results of treatment with a combination of surgery and radiotherapy of 102 patients with nonmetastatic extremity soft tissue sarcoma are reported. Seventy-nine patients were previously untreated and 23 had locally recurrent disease. Sixty-six tumours were situated in the lower limb and 16 in the limb girdles. Fifty-nine were high grade lesions, and 64 were over 5 cm in length. Surgical clearance was "good" (wide or radical) in only 34 cases. Sixty-eight patients received post-operative irradiation, 23 pre-operative irradiation and 11 both pre- and post-operative radiotherapy. Seventeen patients subsequently developed local recurrence and 9 of these remain disease-free after further surgery. Actuarial 5 year local control and disease-free survival rates for new cases were 87 and 65.4%; and for previously recurrent cases these figures fell to 75 and 54.8%. Following a univariate analysis of patient, tumour, surgical and radiotherapeutic factors only previous local recurrence (p less than 0.1 greater than 0.05) was found to significantly increase the risk of further local relapse. Multivariate analysis found high tumour grade [relative risk (RR) 8.4], tumour size greater than 15 cm (RR 3.66), previous local recurrence (RR 6.47) and proximal site (RR 12.7) to be independent poor risk factors for survival.

Actuarial Analysis↗

Orchidectomy vs. Zoladex plus flutamide in patients with metastatic prostate cancer. The EORTC GU Group.

Treatment with bilateral orchidectomy was compared with Zoladex, 3.6 mg depot, plus flutamide, 250 mg t.i.d., in a randomized prospective study by the European Organization for Research and Treatment of Cancer (EORTC). Small but statistically significant differences in time to subjective and objective progression of disease were found in favor of Zoladex plus flutamide. However, time from objective progression to death was longer in the orchidectomy group. The clinical significance of these differences requires further follow-up and analysis. No difference was found in overall survival between the 2 treatment groups.

Aged↗

Subacute and subchronic toxicity of ethylene glycol administered in drinking water to Sprague-Dawley rats.

Subacute (10-day) and subchronic (90-day) toxicity studies of ethylene glycol (EG) were conducted in male and female Sprague-Dawley rats to provide the U.S. Environmental Protection Agency's (EPA) Office of Drinking Water with toxicity data for final preparation of a Health Advisory for the chemical. Ethylene glycol was administered in drinking water at concentrations of 0.5, 1.0, 2.0, and 4.0% for both sexes in the 10-day study. Based on a projected consumption rate of 100 ml/kg/day, the respective doses on a mg/kg/day basis would be 554, 1108, 2216, and 4432. These dose levels were also used in the 90-day study for females, but dose levels for the males in the 90-day study were 0.25, 0.5, 1.0, and 2.0% (227, 554, 1108, and 2216 mg/kg/day). At time of sacrifice necropsies were performed and tissues were prepared for histological evaluation. Blood samples were taken for hematology and clinical chemistry determinations. Body weights were measured weekly. Water and food consumption were determined three times weekly. No mortality occurred in the 10-day study. In the 90-day study 8/10 females and 2/10 males in the high dose group died prior to sacrifice. Body weights were suppressed in a dose response fashion for males and females. Hemoglobin, hematocrit, erythrocytes, and leukocytes were all significantly decreased in female rats receiving 4% EG for 10 days. The most significant histopathological findings, seen predominantly in males, were kidney lesions which included calcium oxalate crystals in tubules and pelvic epithelium; tubular dilation and degeneration; intratubular proteinaceous material; and inflammation in tubules and pelvic epithelium. At the same dose of ethylene glycol, males had more kidney lesions and much higher incidence and severity of lesions than the females.

Administration, Oral↗

Ninety-day oral toxicity study of dibromochloromethane in Sprague-Dawley rats.

Male and female Sprague-Dawley rats received dibromochloromethane daily by gavage to evaluate its subchronic toxicity. Dose levels were 0, 50, 100, and 200 mg.(kg-day)-1, with 10 animals/sex/group for 90 consecutive days. Corn oil was used as the vehicle. No changes were found in mortality, clinical signs, ophthalmoscopic examinations, or hematology that were considered to be related to treatment. Mean final body weight and body weight gain (weeks 0-13) were significantly decreased in male and female high dose animals relative to the vehicle control. Food consumption was decreased in males in a dose-related fashion, reaching statistical significance at the highest treatment level. Indications of hepatotoxicity in the clinical chemistry included elevated alanine amino-transferase (mid and high dose males) and alkaline phosphatase (high dose males and females). Increased serum creatinine (mid- and high dose males and high dose females) and decreased potassium (high dose males) were considered to be suggestive of nephrotoxicity. Absolute and relative weights of several organs in male and female animals were depressed and were related to the decreased body weights. The decreases in brain and thymic weights, and increases in liver and kidney weight (female only) were considered to be treatment related. Histopathological changes included findings of lipidosis of the liver and slight to moderate degenerative changes within the proximal tubular cells of the kidney. Based on the results of this study, the (LOAEL) lowest observed adverse effect level for DCBM when administered to Sprague-Dawley rats in corn oil gavage was 50 mg.(kg-day)-1.

Administration, Oral↗