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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

Reasons for discontinuation of IVF treatment: a questionnaire study.

BACKGROUND: IVF and embryo transfer has become an established and increasingly successful form of treatment for infertility, yet significant numbers of couples discontinue treatment without achieving a live birth. This study aims to identify major factors that influence the decision to discontinue IVF treatment. METHODS: Questionnaires were sent to 1510 couples who had undergone IVF treatment at Ninewells Hospital and Medical School, Dundee, Scotland, between January 1995 and December 2001. The main outcome measure was the number of couples who discontinue treatment and the reasons for discontinuation including live birth, lack of success, lack of funding, psychological stress, medical advice, physical discomfort, personal and other reasons. RESULTS: The response rate was 55% (732/1327) with 183 questionnaires returned as address unknown. A total of 515 couples had discontinued treatment at time of response, with 266 (52%) having achieved a live birth. Achieving a live birth was the reason for discontinuation where a single reason was given. Those who did not conceive gave a combination of reasons. Lack of personal and/or National Health Service funding was cited by 23% of couples as a reason. Lack of success and psychological stress were reported as factors by 23 and 36% of couples respectively. These two factors are very strongly associated (P < 0.001), both being reported by 18% of couples with a reciprocal increase in those quoting lack of success and psychological stress as reasons for discontinuation with increasing number of attempts (P < 0.0005). Changes in personal circumstances were reported by 30% and <10% gave general discomfort or advice from medical staff as reasons. CONCLUSIONS: Though funding is an important issue, factors including lack of success and psychological stress play a greater role in influencing the decision to discontinue treatment. Better information and support are needed to improve the continuation rates.

Adult↗

Risk factors and costs associated with an asthma attack.

BACKGROUND: A study was undertaken to identify asthma patients at risk of an attack and to assess the economic impact of treatment strategies. METHODS: A retrospective cohort analysis of a representative data set of 12 203 patients with asthma in the UK over a one year period was performed. Logistic multiple regression was used to model the probability of an attack occurring using a set of categorised predictor factors. Health service costs were calculated by applying published average unit costs to the patient resource data. The main outcome measures were attack incidence, health service resource use, drug treatment, and cost estimates for most aspects of asthma related health care. RESULTS: Children under five years of age accounted for 597 patients (5%), 3362 (28%) were aged 5-15 years, 4315 (35%) 16-44, 3446 (28%) 45-74, and 483 (4%) were aged over 74 years. A total of 9016 patients (74%) were on some form of prophylactic asthma medication; 2653 (22%) experienced an attack in the year data collection occurred. Overall health care expenditure was estimated at pound2.04 million. The average cost per patient who had an attack was pound381 compared with pound108 for those who did not, an increase of more than 3.5 times. In those aged under five and those over 75 years of age there were no significant markers to identify risk, but both groups were small in size. The level of treatment step in the British Thoracic Society (BTS) asthma guidelines was a statistically significant factor for all other age groups. Night time symptoms were significant in the 5-15, 16-44 and 45-74 age groups, exercise induced symptoms were only significant for the 5-15 age group, and poor inhaler technique in the 16-44 age group. CONCLUSIONS: Patients at any treatment step of the BTS asthma guidelines are at risk of an asthma attack, the risk increasing as the treatment step increases. Poorly controlled asthma may have a considerable impact on health care costs. Appropriate targeting of preventive measures could therefore reduce overall health care costs and the growing pressures on hospital services associated with asthma management.

Adolescent↗

Kappa-opioid receptor binding varies inversely with tumor grade in human gliomas.

BACKGROUND: Opioid agonists can inhibit cell proliferation in various neural tumor cell lines, including rat gliomas. Because opioid antimitogenic effects are mediated by opioid receptors, it was of interest to the authors to determine opioid receptor levels in human brain tumors. METHODS: Specimens obtained at craniotomy from 30 patients with glioma and nonneoplastic brain disorders were evaluated for their kappa-opioid receptor binding. Kd and Bmax values were estimated from homologous competition binding curves with the kappa1-selective radioligand [3H]U69,593. RESULTS: Receptor binding density was greatest in nonneoplastic brain tissue, less in Grade 2 and 3 astrocytoma, and least in glioblastoma multiforme. CONCLUSIONS: These results suggest that opioid receptor-based stratification of grade may have clinical utility in distinguishing glioblastoma multiforme from lower grade astrocytomas, and thereby may facilitate diagnosis and treatment.

Astrocytoma↗

Effect of asthma and its treatment on growth: four year follow up of cohort of children from general practices in Tayside, Scotland.

OBJECTIVE: To investigate whether asthma or its treatment impairs children's growth, after allowing for socioeconomic group. DESIGN: 4 year follow up of a cohort of children aged 1-15. SETTING: 12 general practices in the Tayside region of Scotland. SUBJECTS: 3347 children with asthma or features suggestive of asthma registered with the general practices. MAIN OUTCOME MEASURES: Height and weight standard deviation scores. RESULTS: Children who lived in areas of social deprivation (assessed by postcode) had lower height and weight than their contemporaries (mean standard deviation score -0.26 (SD 1.02) and -0.18 (1.15) respectively, P < 0.001 for both). Children who were receiving > or = 400 micrograms daily of inhaled steroids and who were attending both hospital and general practice for asthma care had lower height and weight than average, independent of the effect of deprivation (mean standard deviation score -0.62 (1.01), P = 0.002, for height and -0.58 (0.94), P = 0.005, for weight). Children receiving high doses of inhaled corticosteroids also showed lower growth rates (mean change in standard deviation score -0.19 (0.51), P = 0.003). However, no other children with asthma showed growth impairment. CONCLUSION: Most children with asthma were of normal height and weight and had normal growth rates. However, children receiving high doses of inhaled steroids and requiring both general practice and hospital services had a significant reduction in their stature. This effect was independent from but smaller than the effect of socioeconomic group on stature.

Adolescent↗

Clinical evaluation of indium-111-labeled chimeric anti-CEA monoclonal antibody.

UNLABELLED: Chimeric T84.66 (cT84.66) is a high-affinity (1.16 x 10[11] M[-1]) IgG1 monoclonal antibody (MAb) against carcinoembryonic antigen (CEA). This pilot trial evaluated the tumor-targeting properties, biodistribution, pharmacokinetics and immunogenicity of 111In-labeled cT84.66. METHODS: Patients with CEA-producing metastatic malignancies were administered a single intravenous dose of 5 mCi 111In-diethylenetriaminepentaacetic acid-cT84.66. Serial blood samples, 24-hr urine collections and nuclear images were collected up to 7 days postinfusion. Human antichimeric antibody response was assessed up to 6 mo postinfusion. RESULTS: Imaging of at least one known tumor site was observed in 14 of 15 (93%) patients. Seventy-four lesions were analyzed with an imaging sensitivity rate of 45.1% and a positive predictive value of 94.1%. In one patient, two additional bone metastases developed within 6 mo of antibody administration at sites initially felt to be falsely positive on scan. One patient developed a human antichimeric antibody response predominantly to the murine portion of the antibody. The antibody cleared serum with a median T(1/2alpha) of 6.53 hr and a T(1/2beta) of 90.87 hr. Interpatient variations in serum clearance rates were observed and were secondary to differences in clearance and metabolic rates of antibody-antigen complexes by the liver. One patient demonstrated very rapid clearance of antibody by the liver, which compromised antibody localization to the primary tumor. Antibody uptake in primary and metastatic tumors ranged from 0.5% to 10.5% injected dose/kg, resulting in estimated radiation doses ranging from 0.97 to 21.3 cGy/mCi 90Y. Antibody uptake in regional lymph nodes ranged from 1.3% to 377% injected dose/kg, resulting in estimated radiation doses ranging from 2.0 to 617 cGy/mCi 90Y. CONCLUSION: Chimeric T84.66 demonstrated tumor targeting that was comparable to that of other radiolabeled intact anti-CEA Mabs. Its immunogenicity after single administration was lower than murine Mabs. These properties make cT84.66 or a lower molecular weight derivative attractive for further evaluation as an imaging agent. These same properties also make it appropriate for future evaluation in Phase I therapy trials. Finally, a wide variation in the rate of antibody clearance was observed, with one patient demonstrating very slow clearance, resulting in the highest estimated marrow dose of the group, and one patient demonstrating unusually rapid clearance, resulting in poor antibody localization to tumor. Data from this study suggest that serum CEA levels, antibody-antigen complex clearance and, therefore, antibody clearance are influenced by both the production and clearance rates of CEA. This underscores the need to further identify, characterize and understand those factors that influence the biodistribution and clearance of radiolabeled anti-CEA antibodies to allow for better selection of patients for therapy and rational planning of radioimmunotherapy.

Adult↗

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↗