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Biomedical subjects

D Brown

Publications and source records attributed to D Brown.

At least 505 records · Page 28Linked to original sources

Hepatitis C virus-polymerase chain reaction of routinely processed liver biopsies.

The aim of the study was to evaluate the specificity and sensitivity of detection of hepatitis C virus (HCV)-RNA in formalin-fixed paraffin-embedded (FFPE) liver biopsies by polymerase chain reaction (PCR). Routinely processed FFPE diagnostic needle liver biopsies as well as stored serum samples from 43 patients with liver disease were tested for HCV-RNA by reverse transcription-nested PCR using the same sets of primers and following strict anticontamination measures. Twenty-nine cases were positive and 14 were negative for serum HCV-RNA. Tissue HCV-RNA was detected in 17 out of the 29 serum HCV-RNA-positive cases but not in any of the 14 serum HCV-RNA-negative cases. Compared to serum-PCR, tissue-PCR was 100% specific, 58.6% sensitive, and 72% efficient. HCV-RNA was detected more frequently in biopsies stored for less than 1 year, than in those stored for more than 1 year (P = 0.046). In biopsies stored for up to 1 year detection of HCV-RNA by PCR was 81.8% sensitive and 90.9% efficient. Short (< 0.5 cm) liver biopsies were as sufficient for nucleic acid extraction and amplification as long (> 0.5 cm) ones. It is concluded that following strict anticontamination measures, HCV-RNA detection by PCR in routinely fixed, processed, and stored diagnostic liver biopsies provides a valuable adjunct to diagnosis of HCV infection. In this study, this option was free from contamination problems, even though routine batch histological processing schedules were used.

Base Sequence↗

If you can replicate the handedness-immune disorder effect, the more power to you.

Bryden, McManus, and Bulman-Fleming's (1994) meta-analysis of studies examining the Geschwind-Behan-Galaburda hypothesis indicates that the original data set supports the hypothesis significantly more than the body of replication attempts. We present data on 2256 subjects that clearly fail to support the hypothesis and describe practical and statistical reasons suggesting why the original data cannot be easily replicated. A power analysis suggests that to find the effect in a general sample, one should plan to have 17,000 to 40,000 subjects.

Child↗

Hard choices: the gynecologic cancer patient's end-of-life preferences.

Few reports in gynecologic literature have addressed patient preferences about terminal care. In light of the current discussions about end-of-life decision-making, a study was designed to assess the desires of patients with gynecologic cancer. A questionnaire was completed by 108 patients under treatment for gynecologic cancer at the University of Michigan Medical Center and by 39 patients from the routine gynecology clinic at the same institution. Participants were asked about their reactions to a poor prognosis, their desires for the location of terminal care, and their preferences for withdrawing or withholding life-sustaining technologies. Five percent of these cancer patients anticipated giving up the fight against their disease. Seventy-eight percent specifically expressed resolve to continue the fight against their disease. Feedback from these patients about their end-of-life preferences served to define the concept "fight." A majority preferred to receive care at home. Ninety percent of these cancer patients could envision their conditions deteriorating to the point that they would not want ventilator support. Thirty-four percent could envision refusing surgery for another life-threatening condition; 37%, a time when artificial nutrition would be refused; 22%, a time when antibiotics would be rejected. This study suggests that limiting the use of artificial respiratory support while continuing the use of artificial nutrition and hydration support would be consistent with the preferences of gynecologic cancer with end-stage disease.

Adult↗

Water transport in renal tubules is mediated by aquaporins.

Water reabsorption in mammalian renal tubules is mediated by channel-forming membrane glycoproteins termed aquaporins (AQP). So far three different kinds of AQP have been described in renal tubules. AQP CHIP is localized to the luminal and contraluminal membranes of the proximal tubule and descending thin limb cells, i.e., in tubule segments that exhibit a constitutive high permeability to water that is insensitive to vasopressin. AQP-CD is present in subapical vesicles and the luminal membrane of collecting duct principal cells. Its intracellular distribution depends on vasopressin or hydration status of the animal and, thus, may represent the vasopressin-sensitive water channel. The basolateral integral protein (BLIP) may represent the vasopressin-insensitive water channel in basolateral membrane of collecting duct principal cells. The exact localization of a recently cloned homologue, WCH3, which may be either related to BLIP or represent yet another kind of AQP, is not known. Heterogeneity of aquaporins in the renal tubule may provide a molecular basis for the treatment of certain diseases with disturbances in water homeostasis.

Animals↗

Modelling the luteinizing hormone-releasing hormone pulse generator.

Pituitary hormones are released in pulses as a result of episodic patterns of electrical activity in neuroendocrine neurons. The mechanisms underlying such pulsatility have, however, been difficult to elucidate. For example, the luteinizing hormone-releasing hormone neurons regulating reproductive functioning have a sparse and scattered distribution within the hypothalamus which has made definitive electrophysiological investigation impracticable. Little is known not only of their electrical characteristics, but also of the critical neural components with which they interact to form the so-called "luteinizing hormone-releasing hormone pulse generator". We have used here a neural modelling approach, based on the FitzHugh-Nagumo model of a single neuron, to provide a simple dynamical network model of this neuroendocrine pulse generator. We have found that the minimal components required to generate pulsatile luteinizing hormone secretion arise from combining luteinizing hormone-releasing hormone neurons with reciprocally connected inhibitory interneurons and an external stimulatory input. Local GABA neurons and ascending noradrenergic and/or adrenergic inputs have been used as the biological basis for these respective components. The network displays a wide repertoire of behaviours comparable with experimental observations, including some thought previously to be paradoxical. The capacity of this model network to display complex behavioural features interpretable against experimental evidence suggests that this type of modelling may become a necessary adjunct to empirical studies of pulsatile neuroendocrine systems.

Action Potentials↗

Growth after recombinant human growth hormone treatment in children with chronic renal failure: report of a multicenter randomized double-blind placebo-controlled study. Genentech Cooperative Study Group.

OBJECTIVE: To determine whether treatment with recombinant human growth hormone (rhGH) enhances growth rate in growth-retarded children with chronic renal failure. DESIGN: One hundred twenty-five prepubertal growth-retarded children with chronic renal failure were randomly assigned to receive either rhGH (n = 82) or placebo (n = 43) for 2 years. SETTING: The study was undertaken at 17 pediatric nephrology centers in the United States. MEASUREMENTS: Growth rate, standardized height, bone age, fasting and 2-hour postprandial glucose and insulin levels, biochemical values, and insulin-like growth factor I and anti-growth hormone antibody levels were evaluated serially during the 2-year study period. RESULTS: Standardized height increased from -2.94 to -1.55 in the rhGH group after 24 months of treatment, and decreased from -2.82 to -2.91 in the placebo group (p < 0.00005). Patients in the rhGH group who completed 24 months of study (n = 55) had a greater growth rate during the first year (10.7 +/- 3.1 cm/yr) than during the second year (7.8 +/- 2.1 cm/yr) of treatment. These growth rates were significantly greater than those in the placebo group (n = 27) in the first (6.5 +/- 2.6 cm/yr) and second (5.5 +/- 1.9 cm/yr) years (p < 0.00005 for both years). The mean delta height age minus the delta bone age was positive in the rhGH group, suggesting improved final height potential. There was no significant difference in the change in calculated creatinine clearance over baseline values in the rhGH group from that in the placebo group after 24 months of study (p = 0.63). Mean fasting and postprandial insulin values were elevated at 12 months but not at 24 months in the rhGH-treated patients. Mean fasting and 2-hour postprandial glucose values at 24 months were not significantly elevated over baseline values in either group. CONCLUSIONS: Growth rate and standardized height were significantly increased in growth-retarded prepubertal children with chronic renal failure when rhGH was used. The acceleration in growth was not associated with undue advancement of bone age. No clinically significant side effects were associated with rhGH treatment. The use of rhGH in growth-retarded children with chronic renal failure may facilitate the achievement of the inherent growth potential of such children.

Antibodies↗

Internal jugular vein blowout complicating head and neck surgery.

Internal jugular venous rupture after head and neck surgery is a rare but important condition to recognize. The Toronto General Hospital experience of this condition, together with its identification and management is reported. Jugular vein rupture should be considered in patients undergoing primary tumour excision with modified or functional neck dissection complicated by a pharyngo-cutaneous fistula. Typically, bleeding is venous and occurs repeatedly. However, haemorrhage may be substantial and life-threatening. Treatment requires exploration and ligation of the venous system. The carotid artery should be assessed and protected at surgery, since there is a likelihood of a carotid blowout as the conditions have a common aetiology. It is important to distinguish jugular vein haemorrhage from carotid arterial rupture, since the former has a far better outcome if treated properly.

Adult↗

Outbreak of measles in a teenage school population: the need to immunize susceptible adolescents.

An outbreak of measles occurred in a community school and the surrounding area in Crowborough, East Sussex, UK, from December 1992 to February 1993. There were 96 suspected cases reported: 66 cases among 1673 students at one school and 30 community cases. The majority of suspected cases were in those aged 11-17 (78%), 2 cases occurred in infants < 1 year old and 8 cases in adults aged 18 years or over. Data collected on 60 (91%) of the 66 suspect school cases showed 56 (93%) had an illness which met a case definition of measles. Eighteen had confirmatory IgM measles antibody. Two cases were hospitalized. The local percentage uptake for measles immunization for the school age years affected varied between 64% and 84%. A survey of parents showed that approximately 74% of the students attending the school had a history of measles immunization. The immunization rates reported by parents for children who developed measles was 21%, (29% based on GP records) compared with 77% for those who remained well. Vaccine efficacy was estimated to be 92%. This outbreak, along with others recently reported in older unimmunized children in the UK, reinforces the need for catch-up immunization programmes to reach this susceptible group of adolescents.

Adolescent↗

Integrating child injury and abuse-neglect research: common histories, etiologies, and solutions.

Research on injuries, the leading health threat to children in the United States, has been infrequent and badly fragmented. Research on unintentional injuries and research on abuse-neglect have similar histories, including recent rapprochement with behavioral interventions, and reveal similar etiologies for child injury. Further, recent studies document difficulties in discriminating between unintentional and abuse-neglect-related injuries. The areas also face similar methodological and conceptual challenges. Finally, the same interventions may prevent negative outcomes in both areas. A working model to summarize a more integrated approach to injury prevention is offered. Increasing societal awareness of the threat posed by injuries and strengthening mutually applicable strategies of injury prevention would be sought-after results of unifying efforts in these historically isolated arenas.

Caregivers↗

Umbilical venous catheterizations: audit by the Study Group for Complications of Perinatal Care.

The Study Group for Complications of Perinatal Care, through 13 of its participating neonatal intensive care units, conducted a prospective audit to describe contemporary use of umbilical venous catheters (UVCs) over 3 months in 1951 admissions. Frequency of UVC attempts was 15.5% for all patients and greatest (50%) in patients of 1000 g or less birthweight (BW), with a wide range of frequency by institution and by BW grouping. Institutions with more 1500 g or less BW infants tended to use UVCs more frequently. The most common reason for placement was general intravascular access. A variety of fluids were infused, and in most cases heparin was employed. Mean duration of use was 4.4 days for all patients and longest (5.5 days) in infants in the 1001 to 1500 g BW group. The most common reason for UVC removal was lack of further need. UVCs appear to be used more commonly and for a longer duration than is currently recommended. There is a need for a prospective, randomized trial to assess the risks properly and maximize the benefits of UVC usage.

Canada↗

Evaluation of a device to exercise hip extensor muscles in children with cerebral palsy: a clinical and field study.

This research includes the effectiveness of a tricycle (hip extensor tricycle) designed to isolate and exercise the hip extensor muscles in children with cerebral palsy. Five children diagnosed with cerebral palsy were given hip extensor tricycles for home use during an 8-week test period. The hip extensor strength and gait pattern of the subjects were recorded at 2-week intervals. Additional recorded information included the time and duration of subject use and a parent evaluation that noted subjective physical and psychological improvements. A panel of experts judged that the gait patterns of four subjects improved during the course of the study. There was an assignable cause for the lack of improvement in the fifth subject. The results of the strength testing were found to be inconclusive. The subjects used the device on a regular basis and enjoyed doing so. Parent evaluations indicated that the use of the hip extensor tricycle improved the subjects' physical condition, coordination, sense of accomplishment, and self esteem. It is recommended that future research implement a longer test period along with improved hip extensor strength measurement methods and focus on improvements in evaluation of gait and physical condition.

Cerebral Palsy↗

Reactive eosinophilic pulmonary vascular infiltration in patients with spontaneous pneumothorax.

Prominent nonnecrotizing eosinophilic inflammation of muscular pulmonary arteries was seen in resected lung tissue from two patients with spontaneous pneumothorax. Other histologic features included reactive eosinophilic pleuritis (REP) and fibrobullous disease. Eosinophilic vascular infiltration was not contiguous to REP. In neither patient was there a specific and recognized cause of eosinophilic vasculitis. Both patients are without pulmonary symptoms 1 and 4 years after pneumothorax. Eosinophilic vascular infiltration initially suggested the diagnosis of allergic angiitis or pulmonary eosinophilic granuloma. These diagnoses were excluded by clinical and morphologic data. We subsequently reviewed 30 cases of lung tissue resected from patients with pneumothorax and found REP in 18 patients (60%) and mild pulmonary vascular and perivascular eosinophilia in five patients (17%). REP was present in all cases with eosinophilic vascular infiltration. We conclude that this eosinophilic vascular lesion is an unusual reaction in patients with REP and pneumothorax. Occasionally this lesion mimics allergic angiitis or eosinophilic granuloma. The pathogenesis is probably related to vascular transport of eosinophils to the injured pleural surface.

Adult↗

Antibody response and viral excretion after live polio vaccine or a combined schedule of live and inactivated polio vaccines.

A randomized controlled trial was performed in infants undergoing routine immunization in North Hertfordshire. Ninety-six children received a single dose of inactivated polio vaccine, followed by two doses of live attenuated oral polio vaccine and 97 children received three doses of live attenuated oral polio vaccine at 2, 3 and 4 months of age. Blood samples were taken by study nurses 6 weeks after vaccination and stool samples were collected by parents weekly for 4 weeks after each dose of vaccine. Follow-up was completed for 92 of 96 (96%) children in the combined schedule group and 92 of 97 (95%) in the control group. After vaccination the proportions of children with detectable antibody to poliovirus serotypes 1, 2 and 3 were high and similar between groups and geometric mean titers (95% confidence interval) to poliovirus types 1, 2 and 3 were 264 (200 to 347), 375 (311 to 450) and 189 (144 to 250) in the combined schedule group and 369 (290 to 469), 401 (321 to 498) and 206 (145 to 293) in the live vaccine group, respectively. The only significant difference between groups in rates of viral excretion was observed after the second dose of live attenuated oral polio vaccine, when excretion of type 3 poliovirus was reduced in those children who had received prior inactivated polio vaccine (P = 0.05). This study suggests that, compared with the current schedule, a combined schedule of inactivated and live poliovaccines is likely to produce equivalent individual protection against poliomyelitis and is unlikely to substantially alter circulation of poliovirus in the community.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗

Reinnervated lateral antebrachial cutaneous neurosome flaps in oral reconstruction: are we making sense?

Eight patients who underwent a partial glossectomy and associated floor of the mouth resection for squamous cell carcinoma were reconstructed with a sensate radial forearm flap in which the lateral antebrachial cutaneous nerve was anastomosed to the (divided) lingual nerve. The patients were compared prospectively with matched controls who received noninnervated forearm flaps for the same defect. A "blinded" therapist performed detailed sensory testing at least 6 months following surgery. In all modalities examined, the sensate proved superior to the nonsensate flap and not statistically different from the opposite side of the tongue. Two-point discrimination and pressure sensitivity were much greater in the innervated forearm flaps than in the forearms from which they came. The results are discussed with reference to the density of sensory receptors, the degree of cortical representation, and the subcortical anatomy of the neurosensory tracts. It appears that the density of sensory receptors is not directly related to the sensory potential in a given tissue transfer and that this potential is more related to the cortical fidelity of the recipient nerve. A historical matched cohort of 10 patients receiving pectoralis flaps for similar defects also was examined. Although the follow-up was longer, reinnervation was of a very low order--even worse than with noninnervated forearm flaps. This work supports the concept that sensory reinnervation should be attempted whenever possible following ablative oral surgery. This would include suture or grafting of major sensory nerves as well as the reinnervation of flaps.

Aged↗

Glucocorticosteroids up-regulate human elastin gene promoter activity in transgenic mice.

Recent characterization of the human elastin gene identified three putative glucocorticoid responsive elements (GRE) within the 5'-flanking DNA. To test the functionality of these cis-elements, transgenic mice that express a human elastin promoter-reporter gene (CAT) construct in a tissue-specific manner were injected with triamcinolone acetonide (TMC) or dexamethasone (DEX), two glucocorticosteroids in clinical use. Subcutaneous injection of these glucocorticoids resulted in a marked, up to 28-fold, enhancement of the CAT activity in the skin at the site of injection. Similarly, intraperitoneal injection of DEX resulted in significant increases in the elastin promoter activity in various internal organs. Furthermore, incubation of skin fibroblast and aortic smooth muscle cell cultures established from the transgenic animals with TMC (10 ng/ml) resulted in marked increases in the elastin promoter activity. These studies demonstrate that glucocorticosteroids act as powerful up-regulators of human elastin promoter activity in transgenic mice.

Animals↗