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Biomedical subjects

R M Walker

Publications and source records attributed to R M Walker.

At least 73 records · Page 4Linked to original sources
PubMed1968

Automated procedure for measuring antigenicity of extracted and intact influenza virus.

An automated serum-blocking (S-B) technique was developed in an attempt to find an in vitro test for the determination of the antigenicity of extracted influenza vaccines. The S-B test depends on the ability of an antigen to combine with (or block) specific (in this case, hemagglutination-inhibiting) antibodies. After mixing the test virus with a constant amount of specific antiserum and hemagglutinating virus in an Auto Analyzer, chicken erythrocytes were pumped into the system and the mixture was incubated by passing through coils. The hemagglutinated cells were removed and the residual cells were lysed. The optical density was read and recorded automatically. The S-B test was much more reproducible than the chicken cell agglutination (CCA) test. There was good correlation between the S-B and CCA titers of intact influenza virus, but not of ether-extracted influenza virus. The CCA titer of influenza strains of type A was reduced significantly during ether-extraction. The S-B titers indicated that there was no significant loss in specific antigenicity when influenza strains of types A and B were extracted with ether and Tween-80 according to the described procedure. The S-B test seemed to be a true measurement of the total antigens present in influenza vaccines.

Animals↗
PubMedDate not supplied

Acetaminophen-induced hepatotoxic congestion in mice.

Acetaminophen-induced (750 mg per kg p.o.) hepatotoxicity in mice is characterized by hepatomegaly and massive centrilobular congestion which precede the appearance of necrosis. The vascular changes are correlated with the morphologic features using liver hemoglobin content to quantitate erythrocyte sequestration, and hematocrit measurements and 125I-albumin injections to determine plasma and blood volume. The initial increase in liver size was a result of plasma accumulation due to endocytic vacuolation of hepatocytes and Disse space enlargement in centrilobular regions. Further increases in liver size after 3 hr were a consequence of erythrocyte and additional plasma sequestration within the damaged liver. These events occurred without any increase in intrahepatic or portal venous pressure. Hepatic hemoglobin and plasma levels increased 10- and 5-fold, respectively, by 4.5 to 6 hr after administration of acetaminophen. There are two major consequences of acetaminophen-induced hepatotoxic congestion. First, blood and plasma volumes fell significantly, and we suggest that hypovolemic shock contributes to early mortality after acetaminophen. Second, impaired circulation within the congested liver, as manifested by reduced 125I-albumin entry into the liver when 125I-albumin was injected after congestion had developed, probably aggravates the initial injury. Early lesions were always evenly distributed around central veins. However, the pattern of damage at 24 hr could be variable. Occasional large confluent areas of necrosis were always congested, which is consistent with the concept that secondary ischemic damage can develop. Congestion and hypovolemia are reversible and can be largely prevented by administration of the protective compound N-acetylcysteine (1,200 mg per kg p.o.) 3 hr after acetaminophen.

Acetaminophen↗
PubMedDate not supplied

Physicians' and nurses' perceptions of ethics problems on general medical services.

OBJECTIVE: To understand the kinds of clinical situations physicians and nurses regard as "ethics problems." DESIGN: The authors prospectively studied physicians' and nurses' perceptions of ethics problems using paired interviews. Individual interviews were conducted with physicians and nurses as they cared for the same patients during a six-week period. Each was asked whether any ethics problems had arisen in the care of his or her patients and, if so, to give a brief description of each problem. SETTING: Three general medical services in a 497-bed community teaching hospital. PARTICIPANTS: 13 physicians (mostly family medicine residents) and 42 nurses caring for 142 patients. MAIN RESULTS: The physicians and nurses thought ethics problems were present in 75 of the 142 patients cases. Physicians and nurses identified ethics problems with similar frequencies; however, they often identified ethics problems in different patient cases or identified different ethics problems in the same case. Physicians and nurses described a variety of problem types. Physicians identified more problems related to quality of life, inappropriate hospital admissions, and cost of care; nurses identified more problems related to patient preferences, family wishes, pain management, implementing treatments, and discharge planning. A fourth of the ethics problems identified by physicians and nurses involved interstaff conflicts. CONCLUSIONS: The physicians and nurses studied considered a broad range of clinical situations to be "ethics problems," and they perceived them to occur frequently. Systematic differences were found between physicians' and nurses' perceptions of ethics problems, and many ethics problems generated interstaff conflicts. Incorporating this kind of information into clinical ethics education programs, and into hospital policies, may represent a useful approach toward improving physician-nurse interaction.

Adult↗
PubMedDate not supplied

Histologic findings in persistent hyperinsulinemic hypoglycemia of infancy: Australian experience.

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is characterized by hyperinsulinism and profound hypoglycemia, with most children requiring pancreatic resection. The histological classification of PHHI is controversial. Most authors acknowledge the existence of focal areas of islet cell proliferation (adenomatosis) in 30%-50% of cases and a diffuse disorganisation of islet architecture, termed "nesidiodysplasia," in others. De Lonlay et al. reported that cases with adenomatosis are focal with normal remainder of pancreas and that focal and diffuse disease can be differentiated intraoperatively, on the basis of increased beta-cell nuclear size found only in the diffusely abnormal pancreas. We have examined pancreatic histology in a blinded controlled study of PHHI patients. Pancreatic tissue was obtained at autopsy from 60 normal subjects (age 17 weeks gestation to 76 years) and from surgical specimens of 31 PHHI patients. Sections from PHHI subjects (n = 294 blocks) and control sections were stained with hematoxylin and eosin, insulin, glucagon, somatostatin, NSE, cytokeratin 19, and vimentin. Three sections from each PHHI patient were randomly chosen for further analysis. Age-matched control (n = 34) and PHHI sections (n = 66) were examined, with the identity of subjects concealed. A diagnosis of normal histology, adenomatosis, or diffuse nesidiodysplasia was recorded for each section. The presence of large beta-cell nuclei (>19 microm), ductuloinsular complexes, and centroacinar cell proliferation was noted. Of a total of 65 subjects examined (34 control and 31 PHHI), 37 subjects were identified as normal on both sections examined. All the control cases were correctly identified as normal and none had large beta-cell nuclei or centroacinar cell proliferation. Of 31 PHHI patients, 28 were identified as abnormal, either on the basis of abnormal architecture and/or abnormally large beta-cell nuclei. Three patients were identified as normal in both sections. Fifteen of 31 patients had diffuse nesidiodysplasia only. Of 13 patients with areas of adenomatosis, 2 had resection of a nodule with adenomatosis present in most of the tissue removed at surgery. Nine patients had a diagnosis of adenomatosis in one section and a diagnosis of diffuse nesidiodysplasia in the other sections from nonadjacent pancreas. Only 2 of 31 PHHI cases had adenomatosis on one section examined and normal pancreas on the other section examined. Large beta-cell nuclei were variably found in PHHI sections. Only 5 of 15 patients with diffuse nesidiodysplasia had large nuclei in both sections examined. Centroacinar cell proliferation was identified in 12 PHHI subjects, 6 with adenomatosis and diffuse nesidiodysplasia and 6 with diffuse changes only. It was patchy in distribution within sections and present in only one section in 7 of the 12 subjects. In summary, we have shown that a blinded observer could differentiate control and PHHI pancreatic tissue. Only 2 of 31 patients (6%) had focal adenomatosis with normal nonadjacent pancreas, the majority (24 of 31) had diffuse nesidiodysplasia affecting the remainder of their pancreas, with 38% (9 of 24) also having areas of adenomatosis. Large beta-cell nuclei did not reliably identify those with diffuse disease in this study. There was evidence of significant ductal and centroacinar proliferation in 39% of PHHI cases, which was not observed in any of the controls. We have shown that PHHI subjects have a spectrum of pancreatic histological abnormalities, from no abnormality to diffuse subtle changes to florid adenomatosis. Patients could not be segregated into subtypes for different operative intervention despite the availability of full immunohistochemical staining.

Adolescent↗
PubMedDate not supplied

Hepatotumorigenicity and peroxisome proliferation induced by the hypolipidemic CI-924 in a two-year study in male and female B6C3F1 mice.

The hepatic tumorigenicity of CI-924 (5,5'-(1,1'-biphenyl)-2,5-diylbis(oxy)(2,2-dimethylpentanoic acid)), a hypolipidemic agent, was evaluated in 50 B6C3F1 mice/sex/dose given drug in the diet at 0, 5, 25, and 75 mg/kg/day for 2 yr. Peroxisomal and drugmetabolizing enzyme determinations, as well as ultrastructural evaluations, were conducted in subsets of these same groups, because drugs of this class cause peroxisome proliferation and hepatic tumors in rodents. CI-924 elicited dose-dependent increases in the incidence of hepatocellular adenomas and carcinomas in both sexes that were statistically significant at 75 mg/kg. Stereologic evaluation revealed significant increases in hepatocellular peroxisome volume ratio, due to increased numbers of peroxisomes, in females at all doses and males at 75 mg/kg. Peroxisomal enzyme activity measurements revealed no change in catalase, but dose-dependent increases in carnitine acetyltransferase and cyanide-insensitive beta-oxidation in both sexes. Peroxisome proliferation, determined biochemically or ultrastructurally, was twice as great in females compared to males. Total cytochrome P-450 was increased in both sexes given 75 mg/kg. There were dose-dependent decreases in glutathione S-transferase in males and increased glutathione peroxidase in both sexes at 25 and 75 mg/kg. In conclusion, this study demonstrated that while CI-924 induced hepatic tumors in male and female B6C3F1 mice the associated peroxisome proliferation, while moderate in females, was only weak in the males after 2 yr of exposure.

Adenoma↗