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Biomedical subjects

L Brady

Publications and source records attributed to L Brady.

At least 37 records · Page 2Linked to original sources
PubMed1998

Radiotherapy for unilesional mycosis fungoides.

PURPOSE: To evaluate the treatment outcome and natural history of patients with the diagnosis of unilesional mycosis fungoides, treated according to a prospective radiotherapy protocol in our institution since July 1975. METHODS AND MATERIALS: A total of 325 patients with the diagnosis of mycosis fungoides have been referred to the Department of Radiation Oncology at Allegheny University of Health Sciences from July 1975 through September 1996. Of these, 18 patients (5%) were classified as having unilesional mycosis fungoides and were irradiated with a curative intent using local electron fields. One patient received 22 Gy; 1 patient received 40 Gy, and the rest of the patients 30.6 Gy. Daily fractions ranged from 1.8 to 2.0 Gy. Treatments prior to radiation consisted of topical steroids and/or antifungal creams in the majority of patients, with temporary partial responses. One patient had received 2 years of topical mechlorethamine (HN2) and another patient had received topical carmustine solution (BCNU) without response prior to irradiation. RESULTS: The responses were measured clinically; posttreatment skin biopsy was not performed routinely unless there was clinical evidence of disease persistence. Complete response rate was 100%; all treated lesions cleared completely within 4 to 8 weeks after the completion of radiation. With a median follow-up of 43 months (range 12 to 240 months), 2 relapses have occurred, 2 and 71 months after the completion of radiation. Both relapses were confined to the skin and were remote from the original site. Both relapses responded to topical application of HN2. There have been no recurrences in the irradiated field nor systemic dissemination. No long-term side effects were found related to treatment, and all the patients are currently alive and without evidence of disease. Actuarial relapse-free and overall survival at 10 years are, respectively, 86.2% and 100%. CONCLUSION: Unilesional mycosis fungoides has a long natural history, is possibly the earliest manifestation of a malignant process, and local treatments, including local radiotherapy, result in long-term disease-free intervals and, possibly, cure. Total skin electron beam radiotherapy is not indicated for this disease entity.

Adult↗
PubMed1998

Radical Sphincter preservation surgery with coloanal anastomosis following high-dose external irradiation for the very low lying rectal cancer.

High-dose preoperative radiation and specifically designed surgical techniques were used to extend the application of sphincter preservation surgery for cancer of the distal 3 cm of the true rectum. A total of 203 consecutive patients with rectal cancer were treated with external-beam irradiation (45-70 Gy) and radical curative surgery. The cancer was at the level of 0.5-3.0 cm in 65 patients. In these 65 patients treated by radical resection with coloanal anastomosis six suffered recurrence (9%), and the 5-year actuarial survival was 85%. There was a single death. There was no local recurrence among 44 patients in whom the postradiated cancer resided in the rectal wall with or without nodal involvement. With proper selection, high-dose preoperative radiation therapy thus permits extended use of sphincter preservation surgery with coloanal anastomosis for cancers of the distal 3 cm of the true rectum.

Adult↗
PubMed1998

Complications in 100 living-liver donors.

OBJECTIVE: A review of 100 living-liver donors was performed to evaluate the perisurgical complications of the procedure and thus to help quantify the risks to the donor. SUMMARY BACKGROUND DATA: Despite the advantages of living-donor liver transplantation (LDLT), the procedure has received criticism for the risk it imposes on healthy persons. A paucity of data exists regarding the complications and relative safety of the procedure. METHODS: One hundred LDLTs performed between November 1989 and November 1996 were reviewed. Donor data were obtained by chart review, anesthesia records, and the computerized hospital data base. Patient variables were compared by Fisher's exact test and the Student's t test. RESULTS: There were 57 women and 43 men with a median age of 29. Donors were divided into two groups: group A (first 50 donors), and group B (last 50 donors). There were 91 left lateral segments and 9 left lobes. There were no deaths. Fourteen major complications occurred in 13 patients; 9 occurred in group A and 5 in group B. Biliary complications consisted of five bile duct injuries (group A = 4, group B = 1) and two cut edge bile leaks. Complications were more common in left lobe resections (55%) than in left lateral segment grafts (10%). Minor complications occurred in 20% of patients. A significant reduction in overall complications (major and minor) was observed between the groups (group A, n = 24 [45%] vs. group B, n = 10 [20%]). In addition, surgical time and hospital stay were both significantly reduced. CONCLUSIONS: Although the procedure is safe, many LDLT donors have a perisurgical complication. Surgical experience and technical modifications have resulted in a significant reduction in these complications, however. To minimize the risks for these healthy donors, LDLT should be performed at institutions with extensive experience.

Adult↗
PubMed1997

HIV integrase: a target for AIDS therapeutics.

HIV integrase catalyses the incorporation of virally derived DNA into the human genome. This unique step in the virus life cycle provides a variety of points for intervention and hence is an attractive target for the development of new therapeutics for the treatment of AIDS. In this review we summarize current knowledge of the function of this enzyme and discuss some of the obstacles to the development of appropriate drugs.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Use of barbiturates in the treatment of cyclic vomiting during childhood.

BACKGROUND: Cyclic vomiting is an uncommon disorder that can be described as recurrent, self-limiting, fairly uniform episodes of intractable nausea and vomiting with no identifiable organic cause, separated by symptom-free intervals. There is no established therapeutic regimen for this disorder. METHODS: Fourteen children referred to the Pediatric Gastroenterology Clinic were diagnosed with cyclic vomiting from May 1984 to January 1995. Vomiting, the predominant symptom, was present in all children and was severe enough to require hospitalization in 11. Associated symptoms included abdominal ain, headache, nausea, aura, and fever. Diagnostic studies were done to rule out organic causes as indicated in individual patients. Daily phenobarbital was prescribed in all 14 patients. The dose ranged from 30 to 120 mg/hs, (mean 2 mg.kg-1.day-1), with a median dose of 60 mg/hs [corrected]. Prior therapy with propranolol (3 patients) and butalbital (2 patients) had been ineffective. RESULTS: Eleven patients had complete resolution of their symptoms, and 3 patients had marked improvement in their symptoms with infrequent attacks of reduced severity. The only side effects associated with long-term phenobarbital therapy were behavioral in nature, namely hyperactivity and disruptive behavior at school. CONCLUSIONS: The results of our series of 14 patients, all of whom received barbiturates, support the usefulness of this therapeutic approach. Hence we feel that daily low-dose phenobarbital therapy is a safe and effective therapy in preventing episodes of cyclic vomiting in children.

Adolescent↗
PubMed1996

Distribution of hippocampal mineralocorticoid and glucocorticoid receptor mRNA in a glucocorticoid resistant nonhuman primate.

Glucocorticoids regulate the activity of the hypothalamic-pituitary-adrenal axis through both mineralocorticoid (MR) and glucocorticoid (GR) receptors in the hippocampus. In addition, glucocorticoids down-regulate hippocampal expression of MR and GR mRNA and protein, presumably decreasing their own effect. Marmosets are a New World primate characterized by extraordinarily high levels of circulating ACTH and cortisol. The relative glucocorticoid insensitivity of these animals to their massive levels of glucocorticoids was attributed to a decreased affinity of their GR for glucocorticoids, as well as a compromised ability of this receptor to transactivate glucocorticoid-responsive genes. The lack of mineralocorticoid excess, on the other hand, was attributed to a renal MR which responded poorly to cortisol, but normally to aldosterone. The purpose of this study was to examine MR and GR mRNA expression in the marmoset (Callithrix jacchus jacchus) hippocampus. Overall, steady state levels of both MR and GR mRNA were elevated in all of the hippocampal subfields of the marmoset, and this was obvious in rough comparisons with those of a typical glucocorticoid-sensitive Old World primate, the rhesus monkey (Macaca mulata). Notable were the extremely high levels of GR mRNA in the dentate gyrus and field CA3 of the marmoset. The GR mRNA density distribution of the marmoset also appeared to differ from that in the rhesus and from those previously reported in rats and humans. These findings suggest that there is a compensatory elevation of MR and GR mRNAs in the marmoset hippocampus, which appears to be the result of target tissue resistance to glucocorticoids and inappropriate down-regulation by the elevated, but ineffective, circulating cortisol.

Animals↗
PubMed1996

The acute phase response to cardiopulmonary bypass in children.

The endocrine phase of the stress response to cardiopulmonary bypass in children is known to be subtly different from that seen in adults. The aim of this investigation was to determine whether there are similar differences in the acute phase response. Thirteen children were studied (mean age 2.65 years). Each child had congenital heart disease and underwent corrective cardiac surgery. Blood samples taken two days prior to operation and at 6, 9, 12, 24, 48 and 120 hours after were analysed for C-reactive protein, albumin, caeruloplasmin, zinc and copper concentrations. Metal:carrier protein molar ratios were also calculated. Results demonstrate changes which, although similar to those seen in adults, differed both quantitatively and qualitatively. This is explained by the concept of immaturity leading to a generally poor capacity for protein synthesis and a relative inability to respond to altered circumstances.

Acute-Phase Reaction↗
PubMed1993

Regression of retinoblastoma after plaque radiotherapy.

A review of 400 consecutive patients with retinoblastoma disclosed that 103 tumors in 103 eyes were treated with solitary plaque radiotherapy. The tumors were from 1 to 16 mm (mean, 7 mm) in basal diameter and from 1 to 8 mm (mean, 4 mm) in thickness. Thirty-one tumors were treated with plaque radiotherapy as initial treatment, whereas 72 tumors were treated with plaque radiotherapy as secondary treatment after failure of other methods. Of the 102 tumors on which adequate follow-up data were available, all responded initially to plaque radiotherapy with tumor regression. Over the mean follow-up of 38 months (range, six to 192 months), 89 tumors (87%) showed persistent regression and 13 (13%) showed tumor recurrence. The recurrence occurred at a mean interval of five months (range, one to 11 months) after plaque radiotherapy. A statistical analysis of tumor size, tumor location, tumor proximity to the optic disk and foveola, presence of vitreous seeds, radioactive plaque diameter, plaque shape, radioisotope, and primary or secondary treatment disclosed no important predictors of tumor recurrence. Carefully selected retinoblastoma, even juxtapapillary and macular tumors and those with localized vitreous seeds, can be successfully treated with plaque radiotherapy.

Brachytherapy↗
PubMed1992

Immunoquantitation of carnitine palmitoyl transferase in skeletal muscle of 31 patients.

We studied 31 patients suspected of having muscle carnitine palmitoyl transferase 2 (CPT2) deficiency. The catalytic activity of CPT2 was measured in muscle biopsies by the isotope exchange method and CPT2 immunoreactivity was quantitated by an enzyme-linked immunosorbent assay. Nine patients had normal enzyme activity and immunoreactivity. Eight patients had significant deficiencies in catalytic activity (> 3 S.D. below reference mean) of which six were also deficient in immunoreactivity. An additional nine patients were significantly deficient in immunoreactivity with normal catalytic activity and five patients had partial deficiencies in both. At least two categories of alterations in CPT may exist which lead to a deficiency based on the data presented: (1) a regulatory defect in CPT which only alters the enzyme active site; and (2) a structural defect due to altered synthesis, increased degradation, or changes in the immunoreactive site. It may prove to be of diagnostic importance to combine the analysis of enzyme activity and immunoreactivity in patients suspected of having a CPT deficiency and to further investigate the condition of partial CPT deficiency.

Adolescent↗
PubMed1991

Structure and molecular model refinement of Aspergillus oryzae (TAKA) alpha-amylase: an application of the simulated-annealing method.

Monoclinic crystals of a neutral alpha-amylase from Aspergillus oryzae, containing three molecules in the asymmetric unit, have been reported previously and studied at 3 A resolution [Matsuura, Kunusoki, Harada & Kakudo (1984). J. Biochem. 95, 697-702]. Here we report the solution of the structure of this enzyme in a different crystal form (space group P2(1)2(1)2(1), a = 50.9, b = 67.2, c = 132.7 A), with only one molecule in the asymmetric unit. The structure was solved by the molecular replacement method, using a model of acid alpha-amylase from a related fungus A. niger [Brady, Brzozowski, Derewenda, Dodson & Dodson (1991). Acta Cryst. B47, 527-535]. Conventional least-squares crystallographic refinement failed to converge in a satisfactory manner, and the technique of molecular dynamics in the form of the XPLOR package [Brunger (1988). XPLOR Manual. Yale Univ., USA] was used to overcome the problem. A large rigid-body type movement of the C-terminal domain was identified and accounted for. The final round of restrained least-squares refinement (at 2.1 A resolution) including 3675 protein atoms and 247 water molecules resulted in a conventional crystallographic R factor of 0.183 and an atomic model which conforms well to standard stereochemical parameters (standard deviation of bond lengths from their expected values is 0.028 A, while that for planar groups is 0.029 A).

Aspergillus oryzae↗