On an alternative method of estimating effective dose equivalent.
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Biomedical subjects
Publications and source records attributed to T Smith.
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The lower portion of the basilar artery is a site of significant disease, both aneurysmal and stenotic, but has been considered inaccessible via traditional surgical approaches. A baboon model was used to evaluate the feasibility of a direct surgical reconstruction via a transoral-transclival approach, utilizing temporary occlusion of the basilar artery. An arteriotomy was performed and either repaired primarily or a venous patch graft was sutured in place. All animals survived the surgery; one suffered fatal postoperative upper airway obstruction, but the other four were neurologically intact at the time of death. Patency at the site of repair was confirmed both angiographically and histologically. We conclude that temporary clamping in conjunction with direct reconstruction of the basilar artery is feasible in this primate model. Future studies will focus on further applications of this technique.
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The antiepileptic effect of intravenous immunoglobulin (Sandoglobulin, Sandoz) was investigated in Lennox-Gastaut syndrome by an add-on, placebo-controlled, single-blind trial. Ten patients, aged 4-14 years, with insufficient response to conventional anticonvulsive therapy received placebo and Sandoglobulin 400 mg/kg two times each with an interval of two weeks. The washout period was four weeks and the total observation period 14 weeks, during which parents daily registered number and type of seizures. EEG, in vitro lymphocyte transformation tests and concentrations of immunoglobulins including IgG subclasses were evaluated before and after active treatment. Two children showed an immediate reduction in their high-frequency and invariable seizure activity from 42% to 100% and a less abnormal EEG. In addition, general well-being and intellectual performance was improved. The strongest response was observed in one child with a concomitant finding of a low level of IgG2, the only abnormal immunologic test in this study. The remaining 8 children, who had either a high or a low but variable seizure frequency showed no immediate change as EEG and their general condition was unaffected. We conclude that intravenous immunoglobulin had an immediate and pronounced effect on break-through seizure activity and a simultaneous neurophysiologic effect in 20% of our patients with Lennox-Gastaut syndrome. The effect was not confined to patients with immunologic abnormalities.
The product of the human GRO gene is a cytokine with inflammatory and growth-regulatory properties; GRO is also called MGSA for melanoma growth-stimulatory activity. We have identified two additional genes, GRO beta and GRO gamma, that share 90% and 86% identity at the deduced amino acid level with the original GRO alpha isolate. One amino acid substitution of proline in GRO alpha by leucine in GRO beta and GRO gamma leads to a large predicted change in protein conformation. Significant differences also exist in the 3' untranslated region, including different numbers of ATTTA repeats associated with mRNA instability. A 122-base-pair region in the 3' region is conserved among the three GRO genes, and a part of it is also conserved in the Chinese hamster genome, suggesting a role in regulation. DNA hybridization with oligonucleotide probes and partial sequence analysis of the genomic clones confirm that the three forms are derived from related but different genes. Only one chromosomal locus has been identified, at 4q21, by using a GRO alpha cDNA clone that hybridized to all three genes. Expression studies reveal tissue-specific regulation as well as regulation by specific inducing agents, including interleukin 1, tumor necrosis factor, phorbol 12-myristate 13-acetate, and lipopolysaccharide.
Thirty-two 160 kg dairy heifers were used to measure the effects of increasing dietary protein content on growth and heat production. A basal diet containing (g/kg) 550 sodium hydroxide-treated straw, 220 barley, 220 sugarbeet pulp and 10 urea was offered with 0, 76 and 152 g fishmeal/kg dry matter of the basal diet (F0, F1 and F2 levels respectively). The three diets were each given at two levels of feeding (low, L; high, H): 57.6 g/d per kg metabolic body-weight (W0.75) for the LFO diet and 74.7 g/d per kg W0.75 for the HFO diet. Apparent digestibility of the diets increased in response to the addition of fishmeal. Mean dry matter digestibility values were 0.67, 0.67, 0.69, 0.66, 0.68 and 0.69 and those for acid-detergent fibre digestibility were 0.60, 0.63, 0.66, 0.58, 0.60 and 0.65 for diets LF0, LF1, LF2, HF0, HF1 and HF2 respectively. Nitrogen retention increased in response to both fishmeal and feeding level. Live-weight gains were 170, 296, 434 g/d for the LF0, LF1 and LF2 diets and 468, 651 and 710 g/d for the HF0, HF1 and HF2 diets respectively. There were significant effects of increasing the plane of feeding and the level of fishmeal in the diet on live-weight gain. Dietary effects on live-weight gains were accompanied by increases in mean energy retention of 23, 45, 82, 94, 160 and 152 kJ/d per kg W0.75 for diets LF0, LF1, LF2, HF0, HF1 and HF2 respectively, but no definite evidence was obtained that dietary supplementation with fishmeal modified the efficiency of utilization of metabolizable energy for growth.
The purpose of the study was threefold: (1) to determine if protocol constraints affected scores on a box-lifting task; (2) to identify any differences in impact of protocol changes on male and female scores; and (3) to determine if these protocol changes affected correlations between maximal box-lifting scores and maximal scores obtained on isoinertial lifting tests. Two hundred and sixty nine participants (143 males and 126 females) completed maximal isoinertial lifting tests to 1.50 m and 1.80 m using a constrained protocol on an Incremental Lifting Machine (ILM). Participants were divided into three samples for completion of a maximal box-lifting task, with each sample using one of the following task protocols: (1) set style; (2) free style; and (3) ergonomically redesigned. Statistical analyses using general linear models procedures revealed that changes in protocol constraints significantly affected scores on lifting tasks. Removal of protocol constraints resulted in greater percentage increases in task scores for females than for males. Furthermore, disparate patterns between genders in task-test correlations were observed. It was concluded that the ILM was unable to predict female lifting capabilities accurately using any of the three protocols.
The clinical significance of myelopathy associated with HIV infection is poorly understood. Recently, a prospective electrophysiological follow-up study of spinal-evoked potentials in HIV-seropositive men without AIDS revealed a 32% prolongation of the latency from the gluteal crease to the 12th thoracic vertebra (T12) following tibial nerve stimulation at the ankle performed after an interval of 2 years. In AIDS patients this transmission delay did not increase further. Instead, the latency prolongation took place proximal to T12. We assume that myelopathy is an integral part of HIV infection that it is asymptomatic in the early disease phase, spreads from the lumbar part the spinal cord in a rostral direction and leads to the development of leg weakness and ataxia during the later stages of the disease.
Introduction of a radioactive gastrointestinal marker (51CrCl3) into a combined study (75SeHCAT + 58CoB12) of ileal function by whole body counting has been undertaken. The technique was assessed in 23 subjects (15 patients with inflammatory bowel disease, six on non-steroidal anti-inflammatory drugs for rheumatoid arthritis, and two normal subjects). Mean (SD) 51CrCl3 retention was only 4.1 (6.0)% on day 4, and was similar on day 7 in subjects given a second dose of 51CrCl3 on day 4. Only one subject had more than 20% of 51CrCl3 retention after four days. A 51CrCl3 correction method adequately corrected for colonic hold up of 58CoB12, when compared with final equilibrium values of 58CoB12 retention. Use of the non-absorbed 58CoB12 fraction as a gastrointestinal marker gave good agreement with the 51CrCl3 method in correcting 75SeHCAT values. In all subjects studied, corrections for colonic retention of 75SeHCAT on day 4, were small (less than 7% of dose) and did not affect the assessment of any subject. In conclusion, an additional gastrointestinal marker such as 51CrCl3 is unnecessary in our combined study since that role can be effected, when indicated by the non-absorbed 58CoB12 fraction.
Symptomatic polyneuropathy in human immunodeficiency virus (HIV) infection was studied in ten men with acquired immunodeficiency syndrome (AIDS) and in ten men without the immune deficiency. In both groups of patients electrophysiological signs of polyneuropathy of the axonal type were present in the sural, median and peroneal nerves. The AIDS patients had a greater reduction of the mean (SD) sural nerve action potential, 3.1 (2.7) microV, than in patients without AIDS, 10.2 (6.1) microV (p less than 0.01) and greater slowing of peroneal nerve conduction velocity, 42.6 (1.4) m/s in AIDS patients versus 52.6 (3.3) m/s in patients without AIDS (p less than 0.0001). These findings indicate that in most HIV infected patients the severity but not the type of neuropathy depends on whether an immune deficient state has developed. Seven patients with symptomatic polyneuropathy were treated with azidothymidine (AZT) for an average of 10 months and compared with a group of five untreated patients with similar symptoms. No effect of AZT treatment on sural or median nerve amplitude or conduction velocity or on the vibratory or temperature thresholds was observed.
Trabeculectomy was performed on 14 consecutive phakic eyes, and measurements of axial anterior chamber depth were taken preoperatively and on postoperative days 1, 2, 3, 6 and 14. The mean maximal change in anterior chamber depth occurred on the 1st postoperative day, while the anterior chamber reached its shallowest state on the 2nd postoperative day. No significant change in mean anterior chamber depth occurred on successive visits from postoperative day 1 through 14. The anterior chamber approached the preoperative level by postoperative day 14. Because reformation of anterior chamber after trabeculectomy takes about 2 weeks, close observation is essential when marked shallowing occurs early.
Although some cultured human melanoma cell lines are responsive to melanotropins (melanocyte-stimulating hormones [MSH]), the prevalence and tissue distribution of MSH receptors in melanoma are unknown. We report here the use of an in situ binding technique to demonstrate specific MSH receptors in surgical specimens of human melanoma. The distribution and binding properties of specific MSH binding sites were determined by autoradiography and image analysis after incubation of frozen tumor tissue sections with a biologically active, radiolabeled analogue of alpha-MSH, [125I]iodo-Nle4, D-Phe7-alpha-MSH ([125I]NDP-MSH). In melanoma specimens from 11 patients, 3 showed high levels of specific binding, 5 showed low levels, and in 3 patients specific binding of [125I]NDP-MSH was not detectable. Specific MSH binding sites were present in melanoma cells, but not in adjacent connective or inflammatory tissues. Melanotropins, including alpha-MSH, NDP-MSH, and ACTH, inhibited [125I]NDP-MSH binding in a concentration-dependent manner, whereas unrelated peptides (somatostatin and substance P) did not. The apparent affinity of alpha-MSH for this binding site was in the nanomolar range (EC50 = 2 X 10(-9) M for inhibition of [125I]NDP-MSH binding in situ), similar to that recently described for the murine melanoma receptor. In one patient, analysis of multiple intratumor samples and tumors excised on three separate occasions revealed high levels of specific MSH binding in all samples. These results suggest that endogenous melanotropins may modulate the activities of human melanoma cells in vivo.
An ELISA technique has been used to study the incidence of antibody against Chlamydiae: the results obtained with a panel of control sera were compared with those for the complement fixation (CF) and whole inclusion immunofluorescence (WIF) tests. The results indicate that the ELISA results correlate well with the WIF test but poorly with the CF test; and the correlation allows ELISA results to be directly related to WIF antibody titres. Using the ELISA test, the incidence of antibody to Chlamydiae by age was determined in sera collected in Great Britain and Iraq; and in sera collections made at three periods during the last 30 years in Great Britain: the results indicate the higher incidence of antibody in this country compared to Iraq, but do not suggest an increased incidence of antibody in Great Britain during the last 30 years. Studies on sera collected from patients with non-gonococcal urethritis and pelvic inflammatory disease indicate significantly higher titres and incidence of antibody compared to controls, which suggest a contiguous spread of infection for the primary genital lesion to involve more distant tissues and organs. A higher incidence of antibody was also seen in patients with cervical intraepithelial neoplasia (CIN) which may be interpreted as either indicating a causal relationship between Chlamydiae and CIN or indicating the importance of a venereal infection in this condition.
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