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Biomedical subjects

A Brown

Publications and source records attributed to A Brown.

At least 145 records · Page 8Linked to original sources
PubMed1999

Histology of familial thyroid tumours linked to a gene mapping to chromosome 19p13.2.

This paper describes the pathology of thyroid tumours showing an autosomal mode of inheritance linked to a gene that maps to chromosome 19p13.2. All the affected members from the family (seven males and two females; mean age 23 years) were clinically euthyroid and presented with nodular goitre; tumour recurrence after thyroidectomy was observed in four. In four of the five patients studied, the tumours were multifocal, bilateral well demarcated or encapsulated and composed of follicles, papillae, trabeculae/solid areas (often resembling hyalinizing trabecular adenoma of the thyroid) or an admixture, formed by cells with pale to intense cytoplasmic eosinophilia. A diagnosis of multiple adenomatous goitre was made in the thyroidectomy specimen from two patients, while the other two patients showed, in addition to multiple adenomas, a co-existent oxyphil papillary carcinoma. The fifth patient had an oxyphil cell carcinoma. All tumours were of follicular cell origin as shown by immunocytochemistry. Less than a third of the benign tumours and all three carcinomas showed a variable number of neoplastic cells diffusely immunostained for mitochondria. Histological findings of a 'multiple adenomatous goitre', non-endemic 'multinodular goitre' or multiple neoplasms of follicular cell origin with the morphology of those described here, particularly in young patients, should alert the pathologist and physician to the possibility of an inherited trait, with its implications for family screening. The tumours are usually benign and well demarcated but because of multicentricity and consequently increased risk of recurrence and/or progression to carcinoma, total thyroidectomy should be advocated.

Adenoma↗
PubMed1999

Diskus and diskhaler: efficacy and safety of fluticasone propionate via two dry powder inhalers in subjects with mild-to-moderate persistent asthma.

BACKGROUND: Fluticasone propionate is a topically active glucocorticoid with potent antiinflammatory activity in the treatment of asthma. OBJECTIVE: This study evaluated the safety and efficacy of fluticasone propionate administered via the Diskus and Diskhaler powder delivery devices in subjects with mild-to-moderate asthma. METHODS: Fluticasone propionate (500 microg twice daily) or placebo was administered via the Diskus and Diskhaler to 213 adolescent and adult asthma subjects in a randomized, double-blind, double-dummy, parallel-group study for 12 weeks. Subjects were stratified according to baseline therapy of inhaled corticosteroids or beta2-agonists alone. Subjects were dropped from the study if they met predefined criteria for lack of efficacy. RESULTS: Fluticasone propionate improved pulmonary function both in subjects previously treated with inhaled corticosteroids or beta2-agonists alone. At endpoint, fluticasone propionate significantly improved forced expiratory volume in 1 second (P < .001), morning and evening peak expiratory flow (P < .001), and asthma symptom scores (P < or = .016), and significantly reduced nighttime awakenings (P = .016; Diskhaler group only) and rescue albuterol use (P < .001). Overall, efficacy measurements for the Diskus and Diskhaler were similar. More placebo-treated subjects (34%) withdrew from the study due to lack of efficacy than subjects in the Diskus (5%) or Diskhaler (5%) groups. The incidence and severity of adverse events were similar across groups. Measurement of plasma fluticasone propionate and cortisol concentrations showed no apparent influence of device on systemic exposure. CONCLUSION: Fluticasone propionate powder, administered via the Diskus or Diskhaler inhalation devices, was well tolerated and effective in the treatment of mild-to-moderate persistent asthma.

Administration, Inhalation↗
PubMed1999

Thyroid pathologic findings in patients with Cowden disease.

We describe the histologic findings in thyroid glands from six female and five male patients with Cowden disease. The patients were aged 9 to 43 years (mean age, 26 years). The salient thyroid lesions in this syndrome were multicentric follicular adenomas and adenomatous (parenchymatous, hyperplastic) nodules showing a wide range of nonspecific cytoarchitectural patterns. Multiple tiny cellular foci, so-called microadenomas, were also a feature. Specific lesions composed of oxyphil or clear cells, a tumor with features of hyalinizing trabecular adenoma, and an adenolipoma also occurred. Two cases showed a follicular carcinoma in addition to multiple benign follicular cell proliferations. The follicular carcinomas occurred at an older age and were larger in size than the clinically significant benign nodular lesions, suggesting tumor progression. All tumors showed thyroglobulin immunoreactivity and were negative for calcitonin. The histologic findings of a multiple adenomatous goiter or multiple follicular adenomas, particularly in children and young adults, should alert the pathologist and physician to the possibility of an inherited trait, such as Cowden disease, with its implications for family screening. The tumors are usually benign and well demarcated, but, because of multicentricity and increased risk of recurrence or progression to carcinoma, total thyroidectomy should be advocated.

Adenocarcinoma, Follicular↗
PubMed1999

Carotene, tocopherol, and ascorbate contents in subspecies of Brassica oleracea.

Cruciferous vegetables contain high levels of vitamins that can act as antioxidants, compounds that may protect against several degenerative diseases. The edible portions of 50 broccoli and 13 cabbage, kale, cauliflower, and Brussels sprouts accessions were assayed to determine variation in alpha-carotene, beta-carotene, alpha-tocopherol, gamma-tocopherol, and ascorbate contents within and between subspecies of Brassica oleracea. Ascorbate content was estimated in fresh samples using HPLC. Tissues for carotene and tocopherol analysis were lyophilized prior to extraction. Carotene and tocopherol concentrations were simultaneously measured using a reverse phase HPLC system. Results indicate that there is substantial variation both within and between subspecies. Kale had the highest levels of vitamins, followed by broccoli and Brussels sprouts with intermediate levels and then by cabbage and cauliflower, with comparatively low concentrations. Variability in vitamin content among the broccoli accessions suggests that potential health benefits that accrue with consumption are genotype dependent.

Antioxidants↗
PubMed1999

A double-blind placebo controlled trial of simvastatin for the treatment of dyslipidaemia in renal allograft recipients.

BACKGROUND: With current techniques, renal failure patients are now able to regain near-normal health following renal transplantation. However, the development of premature cardiovascular disease is a major problem. Dyslipidaemia may be an important contributor to this. The use of lipid lowering agents in renal allograft recipients has been limited by potential interaction of these agents with the now widely used immunosuppressive agent, cyclosporine. AIM: This study was designed to investigate efficacy and safety of simvastatin in subjects taking either cyclosporine or azothioprine post renal transplantation. METHODS: Fifty-one subjects (32 females, 19 males -- mean age 51 +/- 12.5 yr) who were at least 1 yr post transplant, had creatinine < or = 2.5 mmol/L and a total cholesterol > or = 6 mmol/L were enrolled in a prospective, double-blind, placebo-controlled study. After an initial 10-wk dietary period, the last 4 wk on placebo, subjects were randomised to receive either 5 mg simvastatin/d for 6 wk followed by 10 mg simvastatin/d for 6 wk, or matching placebo. After this 12-wk double-blind phase, there was an open-label phase when all subjects were treated with 10 mg simvastatin/d for a period of 36 wk. RESULTS: Compared to placebo, 5 mg simvastatin/d significantly decreased total cholesterol by 20% (p < 0.01), low-density lipoprotein cholesterol (LDL cholesterol) by 29% (p < 0.01), and Apolipoprotein B (ApoB) by 26% (p < 0.01). Increasing simvastatin to 10 mg/d did not lead to further significant changes. But high-density lipoprotein cholesterol (HDL cholesterol) increased by 9% (p < 0.01) and Apolipoprotein A1 (ApoA1) by 7% (p < 0.01) only on 10 mg simvastatin/d. During the open-label phase, subjects previously randomised to placebo achieved similar significant changes to their lipoprotein profile. The benefits achieved from simvastatin were maintained to the end of the study. There were three withdrawals from the study, all from the simvastatin/ cyclosporine group. Two subjects had musculoskeletal pain and 1 had abdominal pain. Minor adverse events were similar in both the simvastatin- and placebo-treated groups. CONCLUSION: Low-dose simvastatin is an effective and well-tolerated agent in the treatment of dyslipidaemia in renal allograft recipients.

Adolescent↗
PubMed1999

A hookworm allergen which strongly resembles calreticulin.

Immmoglobulin E-rich plasma from patients from Papua New Guinea infected with Necator americanus has been used to probe an adult N. americanus cDNA library for the presence of hookworm allergens. Using this approach, one hookworm allergen has been identified as calreticulin, which was subsequently expressed in Escherichia coli. Little serological cross reactivity was seen between the recombinant calreticulins of this hookworm and its host. Prospective roles for hookworm calreticulin in the host-parasite relationship are discussed in depth.

Allergens↗
PubMed1999

Cu/Zn superoxide dismutase in excretory-secretory products of the human hookworm Necator americanus. An electron paramagnetic spectrometry study.

EPR spectrometry was used to investigate the effect of excretory/secretory product from Necator americanus on superoxide radical anions generated by xanthine/xanthine oxidase as a measure of excretory/secretory product superoxide dismutase activity. Using 1,1',5,5'-dimethylpyrollidine-N-oxide (DMPO) as a superoxide spin-trapping agent a 12-line EPR spectrum characteristic of the DMPO-OOH adduct was observed to decrease in the presence of excretory/secretory product. Superoxide dismutase activity was proportional to excretory/secretory protein concentration, was inhibited with cyanide treatment and was progressively destroyed with increasing time of heat denaturation of excretory/secretory product. Using a purpose-built chamber the superoxide dismutase activity of excretory/secretory product from live worms in culture was shown to accumulate with time to a maximum at 4 h. The electron paramagnetic resonance spectrum obtained for the frozen excretory/secretory product of N. americanus recorded at 77 K is typical of Cu(II) in a protein matrix. The results are consistent with the presence of an active Cu/Zn superoxide dismutase in excretory/secretory product from N. americanus and demonstrate a method for the unequivocal determination of the fate of superoxide anions in the presence of live worms.

Animals↗
PubMed1999

Decreasing lengths of stay: the cost to the community.

BACKGROUND: Patients who are discharged earlier from hospital frequently require support from professional and unpaid carers at home after discharge. Hospitals save money per patient by discharging earlier, but it is not known whether the costs to community services and unpaid caters outweigh the savings to the hospital. METHODS: We prospectively studied the total costs, patient satisfaction, time off work and pain scores of 224 patients who underwent elective herniorrhaphy or laparoscopic cholecystectomy and who lived locally before and after re-engineering the elective surgical service. The components of the re-engineered surgical service were a peri-operative unit, pre-admission anaesthetic assessment based on self-reported questionnaires, day of surgery admissions, enhanced patient education, clinical pathways, and post-acute care. RESULTS: The patients treated through the re-engineered surgical service had a significantly shorter length of stay (LOS) (mean LOS: 2.2 vs 3.2 days; P < 0.001) but neither they nor their carers required more time off work. Significant determinants of time off work were smoking, heavy lifting at work and a higher pain score at day 7. Patients treated through the re-engineered surgical service recorded significantly higher satisfaction with their treatment. The cost saving to the hospital outweighed the cost of increased services provided in the community, so that the overall cost of providing treatment was over $200 less per patient through the re-engineered service. CONCLUSIONS: This study demonstrates that changes in care provision that result in shorter LOS and greater cost effectiveness may better meet patients' needs than existing systems.

Adult↗
PubMed1999

Pathogenesis of secondary hyperparathyroidism.

Secondary hyperparathyroidism is a universal complication in patients with chronic renal failure. Hyperplasia of the parathyroid glands is typically seen in these patients. In early renal failure, alteration in vitamin metabolism, decreased levels of calcitriol and moderate decreases in ionized calcium may allow greater synthesis and secretion of PTH. As the disease progresses, there is a decrease in the number of vitamin D receptors (VDR) and calcium receptors (CaR). The decreased number of VDR and CaR makes the parathyroid glands more resistant to calcitriol and calcium. Phosphorus induces hyperplasia of the parathyroid glands independent of calcium and calcitriol, and by a post-transcriptional mechanism increases PTH synthesis and secretion. Experimental work in uremic rats demonstrated that if the animals are fed a high-phosphorus diet, they not only developed secondary hyperparathyroidism but parathyroid cell hyperplasia. If the diet is then reduced in phosphorus, the levels of PTH return to normal. However, the parathyroid cell hyperplasia persists and no apoptosis is seen. Thus, the control of the three most important factors, calcium, calcitriol and phosphorus, is critical to prevent the development of secondary hyperparathyroidism and hyperplasia of the parathyroid glands.

Animals↗
PubMed1999

New analogs of vitamin D3.

Calcitriol, the most active metabolite of vitamin D, controls parathyroid gland growth and suppresses the synthesis and secretion of parathyroid hormone (PTH). However, because of its potent effects on intestinal calcium absorption and bone mobilization, calcitriol treatment can induce hypercalcemia, often precluding its use at therapeutic doses. Hyperphosphatemia is also a persistent problem among patients undergoing chronic hemodialysis and can be aggravated by therapeutic doses of calcitriol. Several pharmaceutical companies were able to modify the side-chain of the 1,25(OH)2D3, allowing some of these new analogs to retain the action on the parathyroid glands while decreasing their hypercalcemic and hyperphosphatemic effects. The structure-activity relationship for ligand-mediated transcriptional regulation has been studied in detail. In some analogs the serum binding protein (DBP) plays a key role in determining the pharmacokinetics of the vitamin D compound. The affinity to DBP for 22-oxacalcitriol (OCT), an analog of calcitriol for the treatment of secondary hyperparathryoidism, is approximately 300-400 times lower than that of calcitriol and the analog is rapidly cleared from the circulation. The mechanisms for the selectivity of 19-nor-1,25(OH)2D2 (paricalcitol) (Zemplar) another analog of calcitriol, is clearly different from OCT. Although the mechanisms of action is not completely known, it does appear that paricalcitol down-regulates the VDR in the intestine. It is likely that the unique biological profiles of vitamin D analogs in vivo are due to multiple mechanisms. Understanding the molecular basis of the analog selectivity will not only provide an explanation for their unique actions but allow intelligent design of more effective analogs in the future.

Animals↗
PubMed1999

Upper extremity infections in patients with diabetes mellitus.

Forty-five consecutive diabetic patients with 46 upper extremity infections who underwent surgical debridement were retrospectively reviewed. The infections involved the skin or subcutaneous tissue in 19 patients and the fascia, tendon, muscle, or bone in 27. Twenty-three infections (50%) required a single operation and 23 required more than 1. Eighteen infections (39%) required an amputation and there were 3 deaths directly related to an infection. Six of 7 infections in which anaerobic organisms were cultured culminated in amputation. Four patients were diagnosed with necrotizing fasciitis. Twenty-one cultures (46%) were polymicrobial. An increased rate of amputation was associated with deep infections below the subcutaneous tissue, renal failure, and infections with gram-negative, anaerobic, or polymicrobial cultures. An increased rate of repeat surgery and a prolonged hospitalization were associated with deep infection and polymicrobial infections.

Amputation, Surgical↗
PubMed1999

Sequential pharmacotherapy with magnesium chloride and basic fibroblast growth factor after fluid percussion brain injury results in less neuromotor efficacy than that achieved with magnesium alone.

Combinational pharmacotherapy with individually efficacious agents is a potential strategy for the treatment of traumatic central nervous system (CNS) injury. Basic fibroblast growth factor (bFGF) has been shown to be neuroprotective against excitotoxic, ischemic, and traumatic injury to the CNS, while acute posttraumatic treatment with magnesium (Mg2+) has been shown to decrease the motor and cognitive deficits following experimental brain injury. In this study, bFGF and Mg2+ were evaluated separately and in combination to assess their potential additive effects on posttraumatic neurological recovery and histological cell loss (lesion volume). Twenty minutes after fluid percussion (FP) brain injury of moderate severity (2.2-2.4 atm), anesthetized rats received a 15-min intravenous infusion of either 125 mumol of MgCl2 or vehicle, followed 5 min later by a 24-h constant intravenous infusion of either bFGF (16 micrograms/h) or vehicle. Injured animals had a significant motor deficit when compared to sham (uninjured) animals at both 48 h and 7 days postinjury. At 48 h postinjury, there were no significant differences among injured animals when compared by treatment. By 7 days postinjury, injured animals treated with MgCl2 alone displayed significantly improved motor function when compared to brain-injured, vehicle-treated animals (p < 0.05). Animals treated with either bFGF alone or a combination of MgCl2 and bFGF displayed no significant neurological improvement relative to vehicle-treated injured animals at 7 days. No effect of any drug treatment of combination was observed on the extent of the postinjury lesion volume in the injured cortex. These results suggest that caution must be exercised when combining "cocktails" of potentially neuroprotective compounds in the setting of traumatic brain injury.

Analysis of Variance↗
PubMed1999

EYA4, a novel vertebrate gene related to Drosophila eyes absent.

We have isolated a family of four vertebrate genes homologous to eyes absent (eya), a key regulator of ocular development in Drosophila. Here we present the detailed characterization of the EYA4 gene in human and mouse. EYA4 encodes a 640 amino acid protein containing a highly conserved C-terminal domain of 271 amino acids which in Drosophila eya is known to mediate developmentally important protein-protein interactions. Human EYA4 maps to 6q23 and mouse Eya4 maps to the predicted homology region near the centromere of chromosome 10. In the developing mouse embryo, Eya4 is expressed primarily in the craniofacial mesenchyme, the dermamyotome and the limb. On the basis of map position and expression pattern, EYA4 is a candidate for oculo-dento-digital (ODD) syndrome, but no EYA4 mutations were found in a panel of ODD patients.

Alternative Splicing↗
PubMed1999

Critical review of GABA-ergic drugs in the treatment of schizophrenia.

GABA-ergic medications may have a potential role in the treatment of schizophrenia. Laboratory evidence has generally supported the ability of gamma-aminobutyric acid (GABA) to reduce dopaminergic activity and has suggested that GABA may be effective in combating hypofrontality by acting on mesoprefrontocortical tracts in patients resistant to treatment with antipsychotic drugs. Although the results of clinical trials of several GABA-ergic compounds have been inconclusive because of methodologic limitations and drug toxicity, benzodiazepines and valproate seem to be associated with favorable treatment outcomes, especially when combined with typical antipsychotic agents. This study concludes that further investigation of the use of GABA in schizophrenia is likely to improve the understanding of the psychopathology of this illness and to expand our treatment alternatives. Also provided are suggestions to enhance the design of future studies, improve the potential for favorable treatment outcomes, and assist in predicting patients' responses to GABA-ergic medications.

Anti-Anxiety Agents↗