Mitochondrial tRNA(Thr) mutations and lethal infantile mitochondrial myopathy.
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Biomedical subjects
Publications and source records attributed to M D Brown.
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Complications in chemonucleolysis are inevitable. However, the incidence of these may be minimized with attention to detail. Proper patient selection, based on a knowledge of the natural history of lumbar disk herniation and elimination of patients with contraindications to diskolysis, will result in a higher success rate with lower incidence of complications in diskolysis. Once the proper patient has been selected, attention must be turned to technique with respect to the use of local anesthesia, appropriate patient positioning, good fluoroscopic control, and two-needle technique for appropriate needle positioning. Immunologic complications can be nearly eliminated with the use of a preoperative enzyme immunoassay test. Carefully considering all of these factors will allow chemonucleolysis to present a safe alternative to disk surgery.
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Floppy eyelid syndrome is a clinical entity associated with a chronic papillary conjunctivitis which is resistant to topical therapeutic agents. The disorder is usually found in older, obese males with upper eyelids which are loose, rubbery, and easily everted. This paper is a review of the clinical characteristics and treatment of the syndrome and includes a case of a 16-year-old male with floppy eyelid syndrome, one of the youngest reported.
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BACKGROUND: Severe plaque-type psoriasis has been successfully treated with orally administered cyclosporine, but there has been no comparative, controlled evaluation of various dosages and their efficacy and side effects. METHODS: In a 16-week, double-blind trial, we randomly assigned 85 patients with severe psoriasis to receive 3, 5, or 7.5 mg of cyclosporine per kilogram of body weight per day or a placebo consisting of the vehicle for the drug. After eight weeks the dose could be adjusted to improve safety or efficacy while maintaining blinding. RESULTS: The psoriasis improved in a dose-dependent fashion. After eight weeks of fixed-dose therapy, 36, 65, and 80 percent of the patients receiving 3, 5, and 7.5 mg of cyclosporine per kilogram per day, respectively, were rated as being clear or almost clear of psoriasis; each group had significant improvement (P less than 0.0001) as compared with the group receiving vehicle, in which none of the patients were rated as clear or almost clear. The patients who received 5 mg per kilogram were the least likely to require dosage adjustments because of side effects or a lack of efficacy. The glomerular filtration rate, measured in a subgroup of 34 patients receiving cyclosporine, decreased by a median of 16 percent. Higher doses of cyclosporine had greater adverse effects on systolic blood pressure, glomerular filtration rate, and serum levels of creatinine, uric acid, bilirubin, and cholesterol. Delayed-type hypersensitivity reactions to skin-test antigens were reduced by cyclosporine administration. Cyclosporine appears to become concentrated in skin. CONCLUSIONS: Cyclosporine therapy leads to a rapid and thorough clearing of psoriasis; an initial dose of 5 mg per kilogram per day seems to be appropriate. However, the safety of cyclosporine for the long-term treatment of psoriasis remains to be determined.
Swelling of the intervertebral disc nucleus pulposus may be a contributing factor in lower back pain syndromes. We have designed and tested a new osmometer for in vitro determination of nucleus pulposus swelling pressure. The functional principle of the osmometer involves compressing a sample of nucleus pulposus with nitrogen gas until saline pressure gradients across a 0.45-micron Millipore filter are eliminated. Swelling pressures of both pooled dog and pooled pig lumbar disc nucleus pulposus were measured on the new osmometer and were compared with swelling pressure determined using the equilibrium dialysis technique. The osmometer measured swelling pressures comparable to those obtained by the dialysis technique. This osmometer provides a rapid, direct, and accurate measurement of swelling pressure of the nucleus pulposus.
Discriminant analysis is applied to 250 quantified low back patient pain drawings to study the ability of a computerized statistical method for classifying novel cases into one of five clinically-significant lumbar spine disorders. Tests on independent data were 46.2 percent (%) correct overall. Benign disorder (55.6%), herniated disc (51.7%), and psychogenic (56.3%) pain drawings were more accurately discriminated than the spinal stenosis (32.2%) and underlying disorder cases (35.2%). It is concluded that computerized patient pain drawings provide valid "initial impressions" of lumbar spine disorders. Further research is suggested to better distinguish between herniated disc and spinal stenosis pain descriptions, and for better recognition of serious underlying disorder pain drawings.
The effects of three human premixes (Mixtard, Actraphane, Humulin M3), syringe mixed 30% regular and 70% NPH insulin, regular insulin alone and NPH insulin alone, on intermediary metabolism, plasma free insulin levels and action profiles were compared using the euglycemic clamp technique. Seven normal volunteers received 20 IU of each insulin subcutaneously in a randomized fashion on separate days. The first and last 60 min of the 6 h clamp were chosen as summary measures of clinical importance. Significantly elevated plasma free insulin levels were found with all treatments compared to NPH insulin alone during the first hour, although by the final hour only Mixtard produced significantly higher levels compared to NPH (19.4 +/- 1.2, 10.5 +/- 0.3 mU/l P less than 0.01, respectively). Analysis of area under the incremental insulin absorption curve demonstrated that Mixtard produced significantly increased levels compared to syringe-mixed regular: NPH (7.6 +/- 0.8), Actraphane (9.6 +/- 1.0) and Humulin M3 (9.0 +/- 0.8 mU/l all P less than 0.05). Mixtard also resulted in significantly higher glucose infusion rates compared to the other premixes. No difference in action was found between regular and pre- or syringe-mixed human insulins during the first hour of the studies. The effects on intermediary carbohydrate and lipid metabolism were similar for syringe and premixed insulins. We conclude that: (1) fixed human insulin mixtures with NPH cause no blunting of the action of the soluble component. (2) Actraphane and Humulin M3 are similar but Mixtard may have a greater effect on some aspects of insulin action. (3) In clinical practice, fixed human insulin mixtures will be as efficacious as syringe-mixed preparations but may be easier and more convenient to use.
Multiple modalities exist for the treatment of keratoacanthoma. Excisional surgery is currently the treatment of choice for the majority of keratoacanthomas. This can result in functional and cosmetic defects when large or strategically located lesions are treated. An effective nonsurgical treatment would be desirable in such cases. Intralesional therapy, particularly with 5-fluorouracil, has been shown to be effective in the treatment of keratoacanthomas. Systemic methotrexate has been tried, with variable success. We report an open, noncontrolled study of nine consecutive patients with unusually large or strategically located solitary keratoacanthomas treated successfully with intralesional methotrexate. All lesions responded promptly, with complete resolution after a mean of 3.0 weeks and a mean of 1.7 injections. No side effects occurred, and scarring was minimal. We concluded that intralesional methotrexate is a simple and effective modality for the treatment of select keratoacanthomas and may offer greater efficacy, a more rapid response, decreased pain, and lower cost compared with intralesional 5-fluorouracil.
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STUDY OBJECTIVE: Growth of capillaries in the adult heart can occur after long term vasodilator treatment. This study investigated the effects of increased stroke volume and/or force of contraction in addition to coronary blood flow on myocardial capillary growth. DESIGN: Coronary blood flow, cardiac function, and capillary supply were evaluated after chronic treatment with the inotrope dobutamine, at a dose shown to increase contraction force (dP/dt) acutely by 20% (p less than 0.05) and coronary blood flow by 60% (NS). EXPERIMENTAL MATERIAL: New Zealand Red rabbits received dobutamine (20 micrograms.kg-1.min-1 by intravenous infusion) for 2 weeks prior to measurements, under pentobarbitone anaesthesia, of coronary blood flow by radiolabelled microspheres, left ventricular dP/dtmax and maximum noradrenaline induced cardiac work, computed from cardiac output (thermodilution) and blood pressure. Capillary density.mm-2 was estimated in frozen 12 microns sections of left ventricular myocardium stained for alkaline phosphatase. MEASUREMENTS AND MAIN RESULTS: Capillary density was 29% greater after 2 weeks dobutamine infusion than in saline infused controls, which exceeds increases observed after longer infusions of vasodilators alone. Cardiac function was improved; maximum stroke work was significantly higher, stroke volume capacity larger, and dP/dt increased more during noradrenaline challenge. Coronary blood flow was unchanged in dobutamine treated hearts, hence efficiency of utilisation of coronary flow in terms of work was enhanced. Heart to body weight ratio was also greater after dobutamine, at 0.238(SEM 0.008) v 0.206(0.120), p less than 0.05. CONCLUSIONS: Greater capillary growth can be elicited in the heart by increased stretch and/or force of contraction of myocytes in addition to moderate changes in blood flow than by increased blood flow alone. Chronic dobutamine treatment induced adaptive enhancement of maximal cardiac work capacity.
Six of seven species of Mesocyclops copepods, collected from northeastern Australia, showed potential as biological control agents of Aedes mosquitoes. Methods of laboratory evaluation included predation trials at different larval mosquito densities, population growth rates at different temperatures, and laboratory cage simulations. The predation efficacy of Mesocyclops aspericornis, M. australiensis, and M. mb1 from southern Queensland, and M. darwini, M. mb2, M. notius and M. mb3 from northern Queensland were compared with M. aspericornis (used successfully in French Polynesia) against laboratory populations of Aedes aegypti (L.), Culex quinquefasciatus Say, and Anopheles farauti Laveran (No. 1). M. aspericornis (L. Kurwongbah) proved to be the most effective Queensland predator and exhibited an elevated reproductive rate at 20-25 degrees C. M. darwini was less efficient as a predator but was more fecund at 25-35 degrees C. Based on these evaluations, M. aspericornis (L. Kurwongbah) has been selected for small-scale field trials in Queensland.
Twelve dogs were divided into two equal groups and given lumbar intradiscal injections of 10, 50, or 100 U/ml of chondroitinase ABC reconstituted in sodium acetate buffer. Radiographs of the lumbar spine were made before and after surgery in both groups. Additional films were made at 5 days after surgery in Group I and at 7, 14, and 21 days after surgery in Group II. All spaces injected with 50 or 100 U/ml chondroitinase ABC demonstrated significant radiographic narrowing in both groups compared with uninjected control and buffer injected discs (P less than 0.001). Discs injected with 10 U/ml of chondroitinase ABC showed increased narrowing over time from 7 to 21 days (P less than 0.05). A zone of safranin O depletion was present in the ventral anulus fibrosus adjacent to the nucleus pulposus in all treated discs, indicating proteoglycan loss. All histologic effects of chondroitinase ABC were confined to intervertebral disc tissues. Chondroitinase ABC appears to be effective for chemonucleolysis in dogs.
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The parents of sixty-three patients who were less than twenty-one years old and who had operatively confirmed herniation of a lumbar disc were interviewed regarding a history of sever back pain, sciatica, and herniated disc, to determine whether aggregation of herniation of a lumbar disc occurs in families of patients in this young age-group. The parents of sixty-three additional patients who had a non-spinal orthopaedic diagnosis (control group) were matched for age and sex with the study group and were given the same interview. Of the patients who had herniation of a lumbar disc and were less than twenty-one years old, 32 per cent had a positive family history for that lesion compared with 7 per cent of the control group. The relative risk of development of herniation of a lumbar disc before the age of twenty-one years is estimated to be approximately five times greater in patients who have a positive family history. The results indicate a familial basis for herniation of a lumbar disc in patients who are less than twenty-one years old.
Computerized methods are used to recognize the characteristics of patient pain drawings. Artificial neural network (ANN) models are compared with expert predictions and traditional statistical classification methods when placing the pain drawings of low back pain patients into one of five clinically significant categories. A discussion is undertaken outlining the differences in these classifiers and the potential benefits of the ANN model as an artificial intelligence technique.
As the incidence of melanoma continues to increase, so does the role of the dermatologist as both medical and surgical oncologist for these patients, especially those with stage I disease. The dermatologist holds a key role in all phases of care, including prevention, diagnosis, treatment, and follow-up. The dermatologist is best trained to complete a full and thorough skin examination and is best able to recognize a melanoma at its earliest stages of radial growth. In large part because of advances in dermatology, the dysplastic nevus syndrome has been identified as an important marker and precursor lesion for melanoma; the dermatologist has the best knowledge base for the recognition and management of both sporadic and familial dysplastic nevi. Dermatologists also have the unique opportunity (by virtue of their patient population concerned with skin problems) to prevent melanoma through patient education concerning sun protection, self-examinations, and the ABCDs of melanoma recognition. The dermatologist is well trained to obtain an appropriate, full-thickness skin biopsy specimen and is also knowledgeable to interpret the pathologist's report, understanding the significance of the various histologic prognostic indices. Because of the changing trends in excisional margin size and fewer recommendations for ELND, the dermatologist is becoming more active in the surgical management of melanoma patients. In the MDMC, the dermatologist was clearly recognized as a capable surgeon to perform the wide local excisions for stage I patients. Almost one half of the patients seen (49%) were surgically treated in the department of dermatology. Of group I patients, 78% were treated by dermatologists. The dermatologist as surgeon should be capable of performing a wide local excision to the level of deep subcutaneous tissue or muscle fascia with an appropriate primary layered closure, local flap, or graft. Our experience confirms that the majority of patients present with local disease and a thin Breslow depth and thus can be skillfully treated in an outpatient setting under local anesthesia by a dermatologic surgeon. In follow-up, the dermatologist should provide continuity of care and should be knowledgeable in appropriate interval examinations and tests. The dermatologist is thoroughly skilled at the cutaneous examination and has the knowledge base to perform a careful and competent lymph node examination. As primary medical oncologist to these patients, the dermatologist needs to recognize stage II and stage III disease and be able to comprehensively discuss with the patient the options for treatment and how they affect their prognosis.(ABSTRACT TRUNCATED AT 400 WORDS)