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Biomedical subjects

S Mitchell

Publications and source records attributed to S Mitchell.

At least 19 recordsLinked to original sources

Foscarnet and Ganciclovir in the treatment of CMV retinitis in AIDS patients: a randomised comparison.

Ganciclovir and Foscarnet were compared in an open randomised trial as treatment and secondary prophylaxis of cytomegalovirus (CMV) retinitis in patients with AIDS. Patients responded more rapidly to Ganciclovir than to Foscarnet although eventual response rates were similar with both drugs. During maintenance therapy there were trends towards more delayed reactivation of CMV and fewer adverse events requiring changes in therapy, in the Ganciclovir group. However, these patients had more line infections and a higher blood transfusion requirement.

Acquired Immunodeficiency Syndrome

Relevance of antibody content and test format in HIV testing of pooled sera.

OBJECTIVE: To determine the effects of HIV-1 antibody level and test-format characteristics on testing pooled sera. DESIGN: This study was designed with a laboratory exercise followed by test observations on serosurveillance samples. METHODS: Sera with low, medium and high (n = 22, 12 and 20, respectively) antibody titers were pooled with HIV-1-negative sera and tested with two enzyme-linked immunosorbent assays (ELISA) and a particle agglutination test. The same kits were used to test single and pooled (batches of five, 10 and 20) samples collected from 3000 blood donors and sex workers. These samples were then seeded with 50 varying antibody-containing sera and similarly tested. Initial reactivities, sensitivities, and specificities for all test kits were calculated and compared. RESULTS: In the laboratory exercise, all reactive pools of five were detected. False-negative pools in batches of 10 and 20 with low antibody titers were noted with one or both ELISA, but not with the particle agglutination method. Testing 3000 samples revealed three confirmed reactive samples and 100% sensitivity/specificity for all kits, for both single and pooled sera testing. Increased initial reactivity (IR) was noted for the two ELISA. Examinations of pools of the seeded 3000 samples with the two ELISA showed false-negative reactivity with pools of 10 and 20 when pools contained low antibody sera (sensitivities and specificities of 92-97.9% and 98.1-100%, respectively). Again, increased IR was seen with the ELISA. False-negative pool and increased IR was not seen with the agglutination test (sensitivity/specificity 100%). CONCLUSIONS: We recommend the use of the particle agglutination assay for testing pooled sera of batches of 20 or less. Components of reactive pools should then be tested and reactive samples should undergo supplementary testing. Pooled samples tested by ELISA should not exceed five per batch. Retesting of reactive pools, testing of its components, and supplemental test(s) of reactive sera should then follow. The optimum pool size for most laboratories is five, with the best technical and economic performance seen with the particle agglutination assay.

Enzyme-Linked Immunosorbent Assay

Effect of dietary fiber on total carbohydrate losses in ileostomy effluent.

Studies were performed in three ileostomate subjects to determine the effect of intake of various carbohydrate-containing foods on the ileostomy losses of macronutrients. The percent recovery of available carbohydrate in ileostomy effluent varied between 1.09% and 22.63% for the various foods. Available carbohydrate recovery (%) was positively correlated with fiber (r = 0.91) and protein (r = 0.46) intake, but negatively with available carbohydrate intake (r = -0.66). Stepwise regression indicated that dietary fiber intake was the principal factor determining the amount of available carbohydrate in ileostomy effluent. Fiber intake was negatively correlated with water concentration of the effluent (r = -0.61). This study demonstrates that although fiber has been considered the chief substrate available for colonic fermentation, as the fiber intake increases, so the total fermentable load entering the colon is likely to increase due to losses of available carbohydrates in addition to fiber. Simple assessment of dietary fiber is likely to grossly underestimate the fermentable load on high-fiber, high-carbohydrate diets.

Adult

A complicated case of exertional heat stroke in a military setting with persistent elevation of creatine phosphokinase.

A case is presented of exertional heat stroke in a military setting with numerous complications that have been previously described. In addition, the complication of late rhabdomyolysis with profound elevation of creatine phosphokinase (CPK) is here described for the first time. This rare condition responded to systemic steroids on this occasion. Late elevation of CPK is a rare complication of exertional heat stroke that appears to respond to systemic steroids.

Adult

Isolation and characterization of human melanoma cell variants expressing high and low levels of CD44.

Variants of the human melanoma cell line LT5.1 were selected for high and low expression of the Mr 90,000 CD44 glycoprotein by using the Hermes-3 monoclonal antibody combined with fluorescence-activated cell sorting. Cells were single cell cloned and clones of CD44 high-expressing and CD44 low-expressing phenotype were isolated. The variants, which exhibited up to a 7-fold difference between high and low expression, have maintained a stable phenotype over a period of 3 months in tissue culture. Northern blot analysis of mRNA from the different clones showed correlation of levels of transcripts with fluorescence-activated cell sorting analysis data. Wound migration assays, utilizing the different clones, showed that the low-expressing clones manifested less motility than did cells showing high levels of CD44. Homotypic aggregation of cells was increased in those cells expressing high levels of CD44, and these variants were also better able to adhere to hyaluronate substrates. All of these activities were inhibited by the presence of anti-CD44 antibody. When injected i.v. into nu/nu BALB/c mice, the low-expressing clones gave significantly fewer lung nodules than the high-expressing clones, although the two variant types did not differ in their capacity to form s.c. tumors in similar mice. These results suggest that the CD44 molecule, possibly as a function of its activities as a hyaluronate receptor, may play a vital role in determining the fate of hematogenously disseminating melanoma cells.

Animals

Angiographic localization of spinal cord blood supply and its relationship to postoperative paraplegia.

Forty-seven patients underwent selective catheterization of middle and lower thoracic intercostal and upper lumbar arteries to define the origin of the artery of Adamkiewicz. One patient had significant atheroembolism, and a second had transient lower extremity paresthesias. No other complications occurred. The origin was found in 26 (55%), and 21 patients underwent thoracoabdominal aneurysm repair with this knowledge. When the critical lumbar or intercostal artery could be included as part of a long proximal or distal anastomosis, all 12 patients could be included as part of a long proximal or distal anastomosis, all 12 patients survived, and one was paralyzed. However, if the aneurysm repair mandated a midgraft anastomosis to intercostal arteries critical to spinal cord perfusion, seven of nine patients either died or were paralyzed (p less than 0.05). In the group of 19 patients operated on in whom spinal cord blood supply was not identified three patients had a technically unsuccessful operation; two died, and one was paralyzed. Twelve of 16 patients who had an adequate, but unsuccessful attempt at localization were treated by intercostal "neglect" and survived. Late paresis developed in two patients, but they are walking now. One of the patients who died had multiple systems failure and awakened paraplegic. She had a patent, enlarged, thoracic radicular artery at T-5 which probably supplied to spinal cord and which was missed angiographically. Paralysis was associated with aneurysm extent (group 2 and III B, dissections vs group 1 & 3, p less than 0.05). Selective intercostal angiography requires further refinement, but it is safe and offers the promise of understanding the mechanisms and risks of spinal cord complications after repair of extensive thoracoabdominal aneurysms.

Adult

Factors affecting light scatter in contact lens wearers.

We measured forward light scatter at 3.5, 10, and 28 degrees using a portable stray light meter. Subjects included 66 normal subjects (age range 19 to 79 years), 17 established hydrophilic contact lens wearers, and 15 rigid gas permeable (RGP) contact lens wearers. Contact lens deposits were measured using a modified Rudko procedure and a Leitz/Wild Makroscope M240. Corneal health was assessed using slitlamp biomicroscopy. Results showed a significant increase in light scatter with age, particularly after the age of 40 years. Stray light scores were significantly lower in pigmented non-Caucasian subjects, particularly at larger angles. The stray light scores were significantly greater in contact lens wearers than in age-matched normals, but were not found to correlate with the amount of lens deposits. Scores from hydrophilic lens wearers after removal of their lenses were significantly higher than results from RGP wearers after removal of their lenses and from age-matched normals. This suggests the presence of subclinical corneal edema in some of these subjects.

Adult

Evidence for interconnections between the two segments of the globus pallidus in primates: a PHA-L anterograde tracing study.

Small injections of the lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) in the external segment of the pallidum (GPe) in the squirrel monkey (Saimiri sciureus) and in the rhesus monkey (Macaca mulatta) led to anterograde labeling of fibers in the internal segment of the pallidum (GPi). These fibers formed numerous large varicosities reminiscent of terminal boutons, which closely surrounded GPi cell bodies and primary dendrites. Conversely, PHA-L injections in the GPi of squirrel monkeys produced anterograde fiber labeling in the GPe. However, in contrast to fibers in GPi, those in GPe did not make prominent pericellular contacts. Instead, they displayed a rather linear course, had long intervaricose segments, and appeared to contact several GPe neurons along their course by close appositions on cell bodies and primary dendrites. These results suggest the existence of a reciprocal connection between the two pallidal segments, which may play a crucial role in the functional organization of the basal ganglia in primates.

Animals

5HT2 receptor changes in rat cortex and platelets following chronic ritanserin and clorgyline administration.

Chronic administration of clorgyline or ritanserin to adult rats for 28 days followed by a 3 day drug-free period results in a significant decrease in 5HT2 receptor number (Bmax) in rat frontal cortex from 315.23 +/- 10.72 fmol/mg protein to 249.63 +/- 13.99 fmol/mg protein and 222.55 +/- 17.17 fmol/mg protein, respectively. On rat blood platelets, ritanserin significantly increases recept number from 26.18 +/- 3.83 fmol/mg protein to 50.94 +/- 7.96 fmol bound/mg protein, whereas clorgyline has no significant effect (21.32 +/- 4.78 fmol/mg protein). Following both drug regimens, the affinity (Kd) of the respective ligands for the receptor is not significantly different from controls: the mean Kd value of the three groups for [3H]ketanserin is 1.57 +/- 0.05 nM in cortex and 0.83 +/- 0.25 nM for [125I]iodolysergic acid diethylamide (LSD) on platelets. Clorgyline increases serotonin (5HT) and noradrenaline (NA) levels in cerebellum, and decreases 5-hydroxyindole acetic acid (5HIAA) and homovanillic acid (HVA): ritanserin does not change the levels of the amines or their metabolites. The data shows that platelet and brain changes are not comparable after ritanserin administration. The receptor binding data demonstrates that curve fitting to two data points provides information which is comparable to and as statistically robust as that obtained from eight point saturation curves. Thus, if pilot studies show that the data follows a rectangular hyperbola, two point assays (optimal at 0.1 Kd and 3 Kd) can be used to obtain estimates of Bmax and Kd.

Animals

A cumulative review of studies on travellers, their experience of illness and the implications of these findings.

A cumulative review of illness experienced by 13,816 travellers returning to Scotland since 1977, shows an overall attack rate of 36%. Alimentary complaints predominated; 18% of travellers had these alone and a further 10% had other symptoms as well as their gastro-intestinal disorder. Higher attack rates were noted in those taking package holidays. Inexperience of travel, smoking, more southerly travel and younger age (particularly those between 20- and 29-years-old) were other contributing factors. A similar pattern emerged from a I year study of hospital in-patients with travel related admissions. Serological studies of 470 travellers showed that 20% had incomplete immunity to poliomyelitis; 25% of those tested (312 travellers) had serological evidence of typhoid immunisation, I.9% (of 760 travellers) had antibodies to Legionella pneumophila, 64% (5II travellers tested) had antibodies to hepatitis A, 87% (288 tested) had adequate levels of tetanus antitoxin but only 40% of the 225 travellers tested had adequate levels of diphtheria antitoxin. Amongst a subgroup of 645 travellers the travel agent was the most frequently consulted source of pre-travel health advice. This carries particular significance for the dissemination of relevant advice in view of the inadequacies found from study of the health information in travel brochures. These findings, viewed against the perspective of the continuing growth in international travel, means that travellers, the medical profession, the travel trade, health educators, global health agencies and health authorities in those countries accepting and encouraging tourists, will be required to recognise the health implications of further tourism development if this problem of illness associated with travel is to be brought under control.

Adolescent

Long-term survival after chemotherapy with cisplatinum, adriamycin and cyclophosphamide for carcinoma of the ovary.

Forty six patients with FIGO Stage II, III, and IV ovarian cancer received treatment with cisplatinum, adriamycin and cyclophosphamide. After a minimum follow-up time of 60 months 13 patients remain free of recurrence. The overall 5-year survival is 39% and the median survival is 39 months. The 5-year survival for Stages II, III, and IV is 64%, 40% and 0% respectively. The 5-year actuarial survival for those who had less than 2 cm residual disease (including those with complete debulking) is 72%, while for those who had greater than 2 cm residual disease (including those who had biopsy only) is 15%. None of the patients have developed any second neoplasm.

Antineoplastic Combined Chemotherapy Protocols

Cosmetic results of early breast carcinoma treated with wide local excision, external beam radiotherapy and iridium-192 boost.

Cosmetic results of 80 patients with axillary lymph node negative or unknown T1 and T2 carcinoma of the breast who were treated with wide local excision, external beam radiotherapy and iridium-192 boost, were evaluated by the patient and the radiotherapist at 18-36 months. Their overall cosmetic results were assessed as good, very good or excellent by 80% of the patients. The radiotherapist's assessment was similar but in general the patients score was more favourable. After a follow-up of 24-72 months recurrence was found in only one patient at 40 months. This approach offers good cosmesis with low local recurrence rates in early breast carcinoma patients with negative axillary lymph nodes.

Adult

Computerized electrocardiographic interpretation: an analysis of clinical utility in 5110 electrocardiograms.

This study describes the initial experience with a computerized electrocardiographic interpretation system in a teaching hospital. The sensitivity and specificity of the 13,375 diagnostic statements that were used to describe the first 5110 electrocardiograms were analysed to determine the predictive accuracy of computerized electrocardiographic interpretation. Reviewing cardiologists inserted 1320 statements, deleted 1792 statements and modified 484 computerized statements. The over-all sensitivity and specificity (and standard error [SE]) of computerized diagnosis was 90.1% +/- 0.3% and 89.6% +/- 0.2%, respectively, with an over-all positive predictive accuracy (+/- SE) of 87.1% +/- 0.3% and a negative predictive accuracy (+/- SE) of 92.2% +/- 0.2%. Sensitivity and specificity were lowest for the category of ST-T wave changes (83.1% +/- 0.8% and 84.1% +/- 0.7%, respectively) and were highest for the category of sinus rhythm (96.6% +/- 0.3% and 97.0% +/- 0.6%, respectively). The positive predictive accuracy of computerized diagnosis was lowest for the category of hypertrophies (74.2% +/- 1.0%) and was highest for the category of sinus rhythm (99.5% +/- 0.1%), while for the category of myocardial infarctions it was 87.6% +/- 0.8%. The negative predictive accuracy ranged from 96.7% +/- 0.3% for the category of hypertrophies to 81.8% +/- 1.3% for the category of sinus rhythm. We conclude that the computerized analysis of electrocardiograms has a satisfactory predictive accuracy when used in an environment with a high prevalence of abnormalities. Electrocardiograms that are classified as normal by computerized analysis may not require checking; however, all electrocardiograms with abnormalities should be interpreted by a competent electrocardiographer.

Cardiology

Ibotenate-induced total septal lesions reduce resistance to extinction but spare the partial reinforcement extinction effect in the rat.

Rats were given sham operations, vehicle injections, or injections of the axon-sparing excitotoxin ibotenic acid into the septum. In Experiment 1, behavioural testing commenced 16 days after the operation; in Experiment 2 behavioural testing commenced following testing on another task, 31 days after the operation. The rats were trained to run in an alley for food reward given on every trial (Continuous Reinforcement, CR) or on a random fifty percent of trials (Partial Reinforcement, PR) and then the running response was extinguished. All the experimental groups showed the normal partial reinforcement extinction effect (PREE) in that PR-trained animals were significantly more resistant to extinction than CR-trained animals. However the rats with ibotenic acid lesions also showed a significant decrease in resistance to extinction regardless of training condition. The same pattern of results was seen at each of the two post-operative testing times. The results were thus readily replicable, and entirely unlike previous reports of the behavioural effects on this task of conventional septal lesions of equivalent size. In Experiment 3, neurochemical analysis of the hippocampus in rats with ibotenic acid-induced lesions demonstrated that choline acetyl-transferase levels were reduced to the same extent as in rats with comparable conventional lesions.

Animals

Interventional uroradiology.

Major interventional uroradiologic techniques including percutaneous nephrostomy, vascular augmentation and reduction procedures, percutaneous cyst aspiration, chronic peritoneal dialysis catheter manipulation and urethroplasty are reviewed. A brief history of the development and techniques for performing these procedures are included. The results of clinical series are assessed and their role in patient management is addressed. The development of these procedures has had a significant impact on patient care by providing effective nonoperative therapy.

Angioplasty, Balloon