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Biomedical subjects

G E Thomas

Publications and source records attributed to G E Thomas.

At least 19 recordsLinked to original sources

gamma-Interferon administration after 90yttrium radiolabeled antibody therapy: survival and hematopoietic toxicity studies.

PURPOSE: Hematopoietic toxicity is the dose-limiting factor for radioimmunotherapeutic regimens. Cytokines have been shown to decrease hematopoietic toxicity in animals exposed to whole-body irradiation. The purpose of this study was to investigate the effects of murine gamma-interferon (gamma-IFN) on survival and hematopoietic toxicity in mice treated with high dose 90yttrium labeled anticarcinoembryonic antigen (CEA) monoclonal antibody. METHODS AND MATERIALS: Balb/c nu/nu mice were injected intravenously with 250 Ci 90Y-T84.66 (a murine anti-CEA monoclonal antibody). Thirty thousand units of gamma-IFN was administered i.v. 24 h later. Control mice received either 250 Ci 90Y-T84.66 alone or 30,000 units gamma-IFN alone. Survival, antibody biodistribution, and bone marrow histologic studies were then performed. RESULTS: Only 7% of the animals treated with 90Y-T84.66 survived up to 40 days posttreatment, when the study was terminated. In contrast, 52% of the mice treated with both 90Y-T84.66 and gamma-IFN survived 40 days posttherapy. No toxic deaths were seen in the control group administered gamma-interferon alone. Histologic examination of the bone marrow of animals receiving 90Y-T84.66 and gamma-IFN showed cellular depletion of 40-70% of the hematopoietic cells by 48 h. Cell depletion was 50-70% and 20% by 72 h and 8 days posttherapy, respectively. The marrow of the 90Y-T84.66-treated control group was depleted to a level of 50-80% at 48 h, and remained depleted at 90% at 72 h and 8 days posttherapy. No marrow cell reduction was seen in the gamma-IFN-only treated group. Biodistribution studies showed no alterations in antibody biodistribution or kinetics that could account for the changes in bone marrow toxicity after gamma-IFN. CONCLUSION: These results demonstrate that gamma-IFN can reduce the hematologic toxicity resulting from high dose radioimmunotherapy. Histologic studies of bone marrow suggest that gamma-IFN acts primarily to accelerate myelorestoration of the bone marrow. Further studies exploring the use of gamma-IFN as an adjunct to radioimmunotherapy are therefore warranted.

Animals

Body mass index centile charts to assess fatness of British children.

Body mass index (BMI) relates weight to height and reflects the shape of a child, but because of age dependency it has not been used conventionally for the estimation of fatness in children. From measurements of Tayside children (n = 34,533) centile charts were constructed for BMI (wt/ht2) from the raw data of height and weight, using Cole's LMS method for normalised growth standards. These data were compared with the only available European BMI charts published from data of French children obtained over a period of 24 years from 1956-79. British children appear to be 'fatter'. Within a subgroup (n = 445) the BMI values were correlated with estimations of body fat, for boys and girls, from skinfold thickness (r = 0.8 and 0.81) and bioelectrical impedance (r = 0.65 and 0.7). The limits of acceptable BMI have yet to be defined.

Adipose Tissue

Surgical treatment of complications 45 years after extraperiosteal pneumonolysis and plombage using acrylic resin balls for cavitary pulmonary tuberculosis.

An infected axillary sinus tract discharged balls made of an acrylic resin consisting essentially of polymerized methyl methacrylate (Lucite) 45 years following performance of an extraperiosteal pneumonolysis and Lucite ball plombage for collapse therapy of right upper lobe cavitary tuberculosis. Surgical extraction of the balls was performed, followed by a partial decortication of the lung and intrathoracic transposition of a pectoralis major muscle flap to fill the residual pleural space. Primary healing was attained, and the patient is well 1 1/2 years after surgery.

Axilla

In vitro and in vivo expression of opioid and sigma receptors in rat C6 glioma and mouse N18TG2 neuroblastoma cells.

Mouse N18TG2 neuroblastoma and rat C6 glioma cell lines were injected into male nude mice, and the tumors were passaged serially. At each generation, tumors were analyzed for delta opioid binding using [3H][D-Ala2,D-Leu5]enkephalin and for sigma 1 and sigma 2 binding with 1,3-[3H]di-o-tolylguanidine in the presence and absence of 1 microM pentazocine. Receptor density (Bmax) and affinity (KD) were estimated by homologous competition binding assays. Opioid and sigma Bmax values in the solid tumors were significantly lower than their original levels in vitro. KD values for opioid/sigma ligands were similar in vitro and in vivo. With successive passages in the murine host, delta opioid and sigma 1 binding of the neuroblastoma-derived solid tumors became undetectable. In contrast, sigma 2 receptor Bmax values were unchanged with successive passages of the neuroblastoma-derived tumors and doubled in the nude mouse-borne gliomas. When neuroblastoma-derived solid tumors that were devoid of delta opioid binding were returned to culture, opioid receptors appeared to be up-regulated as compared with their original in vitro levels. Serial passaging of these recultured cells in vivo again resulted in a rapid decline in opioid receptor content. The opioid data are consistent with our prior findings on opioid binding diminution in human brain tumors. The pattern of change for sigma binding was more complex, with the sigma 2 response in late passages of the glioma being reminiscent of the formerly observed increase in number of sigma sites in transformed human meninges, kidney, and colon tissue.

Animals

Overexpression of sigma receptors in nonneural human tumors.

Previous data indicated that opioid receptors occur in both neural and nonneural human tumors. However, it has recently been shown that some of the putative opioid binding may be attributable to sigma sites. In this study the occurrence of sigma and opioid receptors in nonneural human tumors was assessed. The neoplasms included renal and colon carcinomas and a sarcoma. [3H]1,3-di-o-tolylguanidine was used to assay sigma receptors by homologous competition binding assays, which when analyzed provided dissociation constant and receptor density values. Opioid binding was measured with [3H]-(-)-ethylketocyclazocine, a ligand which interacts with mu, delta, and kappa subtypes. Fresh surgical specimens were obtained from 9 human neoplasms, selected for their large size, and compared with nonmalignant tissues. All 9 tumors contained sigma sites, and dissociation constant values were within the range of 27-83 nM. Occasionally, two-site fit the data better than one-site binding, suggesting the presence of multiple sigma sites. Opioid binding was not detected. Intratumoral variability was evaluated by sampling several locations on the periphery of the mass and one in the center. Each of the samples was bisected, with a portion reserved for histological examination to correlate morphological features with receptor data. Changes in sigma binding were not associated with the extent of fibrosis, viability, or necrosis. Receptor density values displayed moderate intra- and intertumoral variation (coefficients of variation, 8-39 and 27-49%, respectively). More important, sigma binding in tumors was found to be greater than or equal to 2-fold higher than that of control nonmalignant tissue.

Binding, Competitive

Sigma and opioid receptors in human brain tumors.

Human brain tumors (obtained as surgical specimens) and nude mouse-borne human neuroblastomas and gliomas were analyzed for sigma and opioid receptor content. Sigma binding was assessed using [3H]1,3-di-o-tolylguanidine (DTG), whereas opoid receptor subtypes were measured with tritiated forms of the following: mu, [D-ala2,mePhe4,gly-ol5]enkephalin (DAMGE); kappa, ethylketocyclazocine (EKC) or U69,593; delta, [D-pen2,D-pen5]enkephalin (DPDPE) or [D-ala2,D-leu5]enkephalin (DADLE) with mu suppressor present. Binding parameters were estimated by homologous displacement assays followed by analysis using the LIGAND program. Sigma binding was detected in 15 of 16 tumors examined with very high levels (pmol/mg protein) found in a brain metastasis from an adenocarcinoma of lung and a human neuroblastoma (SK-N-MC) passaged in nude mice. kappa opioid receptor binding was detected in 4 of 4 glioblastoma multiforme specimens and 2 of 2 human astrocytoma cell lines tested but not in the other brain tumors analyzed.

Adenocarcinoma

Nine-gunshot suicide.

In this article, we describe an unusual case of suicide involving nine gunshot wounds to the anterior chest. This illustrates that individuals may function for a short time with fatal wounds and stresses the importance of a complete investigation.

Female

An approach to modelling radiation damage by fast ionizing particles.

This paper presents a statistical approach to modelling the damaging effects of radiation by fast heavy ionizing particles in small biological structures such as enzymes, viruses, and some cells. Irreparable damage is assumed to be caused by the occurrence of ionizations within sensitive regions of a structure. For structures containing double-stranded DNA, one or more ionizations occurring within each strand of the DNA will cause inactivation; for simpler structures without double-stranded DNA a single ionization within the structure will be sufficient for inactivation. Damaging ionizations occur along tracks of primary irradiating particles or along tracks of secondary particles released at primary ionizations. An inactivation probability is derived for each damage mechanism, and is expressed in integral form in terms of the radius of the biological structure (assumed spherical), the rate of ionization along primary tracks, and the maximum energy for secondary particles. The performance of each model is assessed by comparing results from the model with results derived from data from various experimental studies extracted from the literature. For the simpler structures, where a single ionization is sufficient for inactivation, the model gives qualitatively promising results. However, for larger more complex structures containing double-stranded DNA, the model requires some further refinements.

DNA

Death and injury caused by methyl bromide, an insecticide fumigant.

Methyl bromide (MeBr) is used as an insecticide fumigant. Four deaths and three recent hospitalizations have resulted from exposures to MeBr in Dade County, FL. Six cases occurred during burglaries of tented houses over a nine-month period. In four lethal exposures, the symptoms of nausea, vomiting, and malaise preceded fulminant respiratory failure. Two of these also had seizures, delirium, and agitation. Serum or plasma bromide ion levels ranged from 40 to 583 mg/L. Pulmonary edema, hyaline membranes, and hemorrhagic alveolitis were present at autopsy along with varying degrees of cerebral edema. The nonlethal exposures resulted in symptoms of conjunctival irritation, headache, or nausea. Plasma bromide concentrations varied between 17.5 and 321 mg/L. Methyl bromide characteristics, use, morbidity, and mortality in Florida during the past 25 years are reviewed. Remedies for illegal entry are proposed.

Adolescent

The acetaminophen experience in south Florida.

Toxicology records of the Dade County Medical Examiner Department were reviewed for the years 1972 to 1981. Any case in which acetaminophen was detected, regardless of the cause of death, was included in the study. Of 95 cases where acetaminophen was detected, no trends were observable in age, sex, or race. Acetaminophen deaths have increased in recent years, probably because of increased marketing of products containing this substance. Some two thirds of the cases involved suicides or accidental deaths, with 40 cases being directly attributable to overdose with a variety of drugs. It is suggested that acetaminophen may be a useful indicator of polydrug overdoses.

Acetaminophen

Peritoneoscopy in a developing country.

Peritoneoscopy in medical cases remains largely unpopular in the USA and the UK. In many developing countries there is often a heavy demand on medical facilities and the rapid diagnosis of intra-abdominal problems is of major importance. We present a series of 193 patients in whom peritoneoscopy was carried out during a 2 1/2-year period. Eighty-six per cent (166) of examinations yielded information of positive diagnostic value. The most common diagnoses were hepatocellular carcinoma, liver cirrhosis, bilharzial fibrosis and peritoneal tuberculosis. The peritoneoscopic appearances in the various lesions are illustrated and discussed. Peritoneoscopy is a safe procedure and its value in a developing country is great, both in terms of economy of man-hours employed and, more particularly, of diagnostic yield.

Adolescent

Survey of management in acute upper gastrointestinal haemorrhage.

The answers to a questionnaire concerning attitudes of members of the British Society of Gastroenterology to the management of acute upper gastrointestinal bleeding are analysed. In the majority of cases patients were admitted to general wards under the care of physicians. Use of intensive therapy units and venous pressure monitoring varied widely. Emergency endoscopy appeared readily available and was usually the first diagnostic procedure. Double contrast radiology and emergency angiography were available in relatively few centres. Specific nonoperative treatments (angiographic and endoscopic) were scarcely employed. Most respondents agreed that elderly patients fared badly, but there was little agreement concerning other factors which influence re-bleeding or outcome. There was a wide divergence of opinion concerning the need for surgical intervention in certain hypothetical clinical situations. Despite the difficulties involved, we believe that controlled trials are necessary to improve the management of bleeding patients.

Acute Disease

Cirrhosis of the liver in Rhodesian Blacks.

Thirty-five Black patients with cirrhosis of the liver were admitted to the professorial unit over a 1-year period and were included in a carefully planned prospective study. Men predominated over women in a ratio of 3:1. Alcohol consumption in the form of African beer was significantly higher in cirrhotic patients than in a control population. The clinical picture was neither predominantly that of alcoholic nor of cryptogenic cirrhosis. Hepatomegaly, porphyria cutanea tarda, ascites, splenomegaly and oesophageal varices were common. There was a complete absence of gynaecomastia, spider naevi and liver palms. Histologically, the majority of patients had macronodular cirrhosis, and only 1 patient had micronodular cirrhosis and minimal fatty change. Hepatitis B surface antigen (HbsAg) was not detected in any patient, despite a positive HbAg rate of 4% in Black African blood donors, determined by means of the same laboratory technique.

Adult

Advantages of the plasma uptake method for measuring vitamin B12 absorption.

The plasma uptake method for determining vitamin B12 absorption is reassessed. The results of this study demonstrate the ease with which normal controls can be separated from patients with intestinal malabsorption of vitamin B12 and from those with pernicious anaemia. This method is also shown to be a sensitive index of improved vitamin B12 absorption after treatment of small-intestinal disease and with the addition of intrinsic factor in pernicious anaemia. The advantages, particularly for developing countries, over the more commonly used Schilling test are discussed. It is emphasized that, because of the lack of a universally accepted normal value, healthy controls should be studied to define the normal range for the community under investigation.

Anemia, Pernicious

Small bowel ischaemia and infarction in young women taking oral contraceptives and progestational agents.

Case histories of three young women who suffered small bowel infarction associated with oral contraceptives and progestational agents are presented. Two infarctions were due to superior mesenteric artery thrombosis and one to superior mesenteric vein thrombosis. All of these patients were of blood group A and smokers, factors which are known to predispose to vascular thrombosis. A study was made of 18 additional cases reported in the literature. It was found that many of these cases presented with a history of symptoms of 2 weeks of more and at operation some of the cases appeared to be reversible. One case was reported where apparent reversion of the process of vascular thrombosis occurred after cessation of the oral contraceptive.

Adult

Hepatocellular carcinoma in the Rhodesian African.

We have carried out a prospective survey of 28 primary liver carcinomas over one year. Hepatocellular carcinoma is the commonest malignancy seen in Rhodesian blacks, which results in a high index of suspicion and accounts for the 96.4% positive diagnosis before death in this study. The age distribution was evenly spread through adult life with no definite peak incidence. Some were young and without evidence of chronic liver disease, but many had the stigmata of established hepatic disease. This contrasts with the common assertion that in areas of high incidence for primary liver cancer those affected are mainly young and lack signs of chronic liver disease. The commonest presenting symptoms were abdominal pain and swelling and weight loss. Hepatomegaly, often tender and nodular, was present in all but one. The incidence of alpha-feto protein, 46.5%, is low compared with other countries where primary liver cancer is common. Hepatitis B antigen was absent in all 28, suggesting that there is no association between the persistence of the antigen and hepatocellular carcinoma in Rhodesia. Liver function tests, although abnormal, were never diagnostic of primary liver cancer. We have confirmed the association of high alcohol consumption and cirrhosis with hepatocellular carcinoma.

Adult