Standardization of HbA1c measurement--the issues.
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Blood Chemical Analysis↗
Biomedical subjects
A Thomas
Publications and source records attributed to A Thomas.
[Outcome factors in severe skull-brain trauma. A retrospective analysis of 228 (161) patients].
OBJECTIVE: To study outcome from severe head injury (SHI: GCS < or = 8) and to investigate impact of prehospital factors and clinical intensive care parameters on outcome. To compare with former study results (1980-88) of our clinical setting. METHODS: Retrospectively, the history of 228 patients with SHI treated between 1988 and 1995 was looked into. The outcome was measured with the Glasgow Outcome Scale (GOS) post intensive care (median 9, min-max 2-77 days) and 6 months after trauma by a questionnaire. The GOS was related to age, Glasgow Coma Scale (GCS on the scene), prehospital hypotension and hypoxia (HH), intracranial pressure (ICP), cerebral perfusion pressure (CPP), intensive therapy including Tromethamine and/or Thiopentone. The rate of infections was determined. RESULTS: Increasing age influences outcome negatively. Prehospital GCS and HH were significantly correlated with outcome. GOS of 30 patients with HH: GOS 1: 53%, GOS 2 + 3: 27%, GOS 4 + 5: 20%. GOS of 40 patients without HH: GOS 1: 25%, GOS 2 + 3: 10%, GOS 4 + 5: 65%. During intensive care the level of CPP (not ICP) as well as tromethamine and/or thiopentone treatment for control of elevated ICP were significantly correlated with outcome. Mortality rate in 32 patients with CPP < 50 mmHq was 69%, in 29 patients with CPP > 50 mmHg only 20%. Patients treated additionally with Tromethamine and Thiopentone because of uncontrollable intracranial hypertension showed a significantly worse outcome: GOS 1: 66%, GOS 2 + 3: 6%, GOS 4 + 5: 28%, compared to those who needed neither Tromethamine nor Thiopentone: GOS 1: 27%, GOS 2 + 3: 18%, GOS 4 + 5: 55%. Thiopentone treatment was not associated with an increased rate of pulmonary and other infections. In comparison to our former outcome study, covering the years 1980-88, we have not seen any improvements in outcome, despite modifications in intensive care protocols. CONCLUSIONS: Prehospital hypotension and hypoxia have a significant negative impact on outcome by causing secondary brain damage. Despite various modifications in intensive care therapy an unchanged portion of secondary brain damage will not prove treatable. Therefore, prevention or early aggressive treatment of hypotension and hypoxia is the most promising way of improving outcome after severe head injury at the moment.
Adolescent↗
Developmental changes in cyclin B1 and cyclin-dependent kinase 1 (CDK1) levels in the different populations of spermatogenic cells of the post-natal rat testis.
Spermatogenesis is a highly ordered process which requires mitotic and meiotic divisions. In this work, we studied the relative changes in the levels of the two components of the M-phase promoting factor (MPF): the regulatory subunit cyclin B1 (CycB1) and its catalytic subunit cdk1, in spermatogenic cells of rats between 16 and 90 days of life. A multivariate flow cytometry analysis of forward scatter (FSC), side scatter (SSC) and DNA content was used to identify six populations of rat germ cells: spermatogonia with preleptotene spermatocytes, young pachytene spermatocytes, middle to late pachytene spermatocytes, secondary spermatocytes with doublets of round spermatids, round spermatids, and elongated spermatids. For any population studied no significant difference in the relative cellular content of CycB1 or cdk1 proteins between animals of different ages was observed. By contrast, CycB1 and cdk1 levels were different between the different populations of germ cells. CycB1 and cdk1 were rather high in young pachytene spermatocytes and culminated in late spermatocytes, i.e. just before the first meiotic division. The relative levels of the two proteins remained high in secondary spermatocytes then decreased in round spermatids at the exit of meiosis. Similar results were obtained by Western-blot analysis of total proteins obtained from lysates of elutriated fractions of spermatocytes and spermatids. MPF activity was assessed in lysates of germ cells from 32-day-old rats or adult animals using p13suc1 agarose and histone H1 as an exogenous substrate. H1 kinase activity was higher in pachytene spermatocytes than in round spermatid fractions from both adult and young rats. These results indicate that the meiotic G2/M transition is associated to high levels of CycB1 and cdk1 leading to high MPF activity irrespective of the age of the animals.
Animals↗
The predictive value of BRCA1 and BRCA2 mutation testing.
Genetic testing for mutations in BRCA1 and BRCA2, two genes predisposing to breast and ovarian cancers, is available to women with a relevant family history. The aim of this study was to estimate the positive and negative predictive value of clinical sequence analysis of these genes. A reference graph showing positive and negative predictive values over a range of pre-test risk was derived, taking into account the sensitivity and specificity of a full-sequence analysis test. High positive and negative predictive values were found for women with pre-test risk between 4% and 40%, a range of risk commonly seen in clinical testing. The predictive value of full sequence and single-site analysis of BRCA1 and BRCA2, therefore, compares favorably with other diagnostic medical tests. Our results provide a numerical estimate of the predictive value of BRCA testing, and as such, provide a valuable tool to healthcare providers and families as they interpret BRCA1 and BRCA2 test results.
BRCA1 Protein↗
Expression of a complete and functional complement system by human neuronal cells in vitro.
We demonstrate in vitro expression of complement components, i.e. C3, factor H (FH), factor B (FB), C4, C1-inhibitor (C1-inh), C1q, C5, C6, C7 and C9, by four human neuroblastoma cell lines IMR32, SKNSH, SH-SY5Y and KELLY. Activating proteins C4, C9 and C1q, and regulatory proteins FH and C1-inh were produced constitutively by the four cell lines. C3, C6 and FB were mainly produced by SKNSH and SH-SY5Y. Western blot experiments showed that secreted proteins were structurally similar to their serum counterparts. An additional polypeptide of 43 kDa with FH immunoreactivity was detected, which could correspond to the N-terminal truncated form found in plasma. Regulation of complement expression by inflammatory cytokines, lipopolysaccharide and dexamethasone was tested in vitro. These factors had no significant effects on activating synthesis of components C3, FB and C4, but expression of regulating components C1-inh and FH was strongly increased particularly by IFN-gamma and tumor necrosis factor-alpha. The rate of synthesis of complement components was dependent on the differentiation of neuroblastoma cells. This effect of differentiation was also observed on normal rat neurons. Rat cerebellar granule cells constitutively expressed mRNA for C4 and C1q, but expression of C3 mRNA was induced by differentiation. This study shows that neurons could be another local source of complement in the brain, besides astrocytes and microglia. Human neuroblastoma cell lines can constitute an interesting model to analyze complement biosynthesis by human neurons. Local complement expression by neurons in vivo may be implicated in some physio-pathological processes.
Animals↗
Standards for the management of cervical and vulval carcinoma.
OBJECTIVE: To examine the feasibility of achieving designated target standards for the management of women with cervical and vulval cancer. DESIGN: Retrospective casenote review. SETTING: The Gynaecological Oncology Centre at Hammersmith Hospital, London. POPULATION: Sixty-one women with cervical and vulval cancer presenting to the gynaecological oncology clinic at the Hammersmith Hospital during 1996 and 1997. Various aspects of the management of those women were compared with standards suggested by a multidisciplinary panel of local experts. Targets included the referral and treatment process, the accuracy of staging, and measures of surgical performance. RESULT: The target interval of seven days between receipt of the referral and the first visit at the cancer centre was achieved in 93% of women. Surgical treatment was administered to 92% of the women within the target of 20 working days from the first clinic appointment. Tumour close to or involving the margins of the specimen was noted in 13% of cervical and 9% of vulval cancers. The node count fell below the target standards in 13% of pelvic and 10% of groin dissections. Appropriate imaging investigations for staging were not undertaken in 15 of 39 cases (38%) of cervical cancer and in 5 out of 22 (23%) of vulval cancers. CONCLUSION: The suggested targets of process and surgical performance are reasonable and achievable. These standards would be appropriate for national use. The area most clearly identified where these targets were not achieved was the requesting of complementary staging investigations. This could be addressed by the use of a simple investigation protocol to be included in each patient's notes and available at specialist clinics and gynaecology wards.
Benchmarking↗
The association between white matter lesions on magnetic resonance imaging and noncognitive symptoms.
A number of studies have suggested that cerebral changes, particularly deep white matter lesions (WML) visualized on magnetic resonance imaging (MRI), may be involved in the genesis of late life depression. This has been confirmed in a prospective study which also found a relationship between the presence of WML and poor 3-year outcome in elderly depressed subjects. Most studies find these lesions to predominate in frontal lobe and basal ganglia, supporting the hypothesis of "fronto-striatal" dysfunction in depression. To investigate whether WML are associated with mood disturbance in dementia, proton density and T2-weighted images were obtained in 80 subjects with dementia (dementia with Lewy bodies, n = 27; Alzheimer's disease, n = 28; vascular dementia, n = 25) and 26 age-matched normal controls. Periventricular lesions (PVL), white matter lesions (WML), and basal ganglia hyperintensities (BG) were visually rated blind to diagnosis using a semiquantitative scale. Frontal WML were associated with higher depression scores in patients with dementia, implying a common pathophysiology of depression irrespective of diagnosis. Further study of the neurobiological basis of WML is needed. This can best be achieved by serial clinical assessment combined with in vivo and in vitro MRI and neuropathological examination.
Aged↗
Randomised placebo controlled trial of nebulised corticosteroids in acute respiratory syncytial viral bronchiolitis.
OBJECTIVE: To evaluate short and long term effects of giving nebulised budesonide early in respiratory syncytial viral (RSV) bronchiolitis. DESIGN: A multicentre randomised double blind placebo controlled trial. SUBJECTS: Infants admitted to hospital with their first episode of RSV positive bronchiolitis. INTERVENTION: Randomisation to receive either 1 mg of nebulised budesonide (Bud) or placebo (Pla) twice daily from admission until 2 weeks after discharge. Follow up was for 12 months. MAIN OUTCOME MEASURES: Duration of hospital admission, time taken to become symptom free, re-admission rates, general practitioner consultation rates, and use of anti-wheeze medication during follow up. RESULTS: 161 infants were studied. Both arms were similar with respect to initial clinical severity, age, sex, socioeconomic class, and tobacco exposure. Median time from first nebulisation to discharge: Bud and Pla, 2 days. Median number of days for 50% of infants to be symptom free for 48 hours: Bud, 10 days; Pla, 12 days. Respiratory re-admission rates in the 12 month follow up: Bud, 16%; Pla, 18%; median difference (95% confidence interval (CI)), -2 (-14 to 10). Median respiratory related general practitioner attendances: Bud, 4.0; Pla, 4.5; median difference (95% CI), -1 (-2 to 0). Percentage of infants receiving at least one prescription for anti-wheeze medication during follow up, corticosteroids: Bud, 50%; Pla, 60%; difference (95% CI), -10 (-26 to 6); bronchodilators: Bud, 60%; Pla, 67%; difference (95% CI), -7 (-22 to 8). CONCLUSIONS: There are no short or long term clinical benefits from the administration of nebulised corticosteroids in the acute phase of RSV bronchiolitis.
Acute Disease↗
Sphincter of Oddi dysfunction produces acute pancreatitis in the possum.
BACKGROUND: Sphincter of Oddi dysfunction has been implicated as a cause of various forms of acute pancreatitis. However, there is no direct evidence to show that sphincter of Oddi dysfunction can cause obstruction of trans-sphincteric flow resulting in acute pancreatitis. AIMS: To determine if induced sphincter of Oddi spasm can produce trans-sphincteric obstruction and, in combination with stimulated pancreatic secretion, induce acute pancreatitis. METHODS: In anaesthetised possums, the pancreatic duct was ligated and pancreatic exocrine secretion stimulated by cholecystokinin octapeptide/secretin to induce acute pancreatitis. In separate animals, carbachol was applied topically to the sphincter of Oddi to cause transient sphincter obstruction. Sphincter of Oddi motility, trans-sphincteric flow, pancreatic duct pressure, pancreatic exocrine secretion, plasma amylase levels, and pancreatic tissue damage (histology score) were studied and compared with variables in ligation models. RESULTS: Acute pancreatitis developed following stimulation of pancreatic exocrine secretion with peptides after pancreatic duct ligation (p<0.05). Neither pancreatic duct ligation nor stimulation of pancreatic exocrine secretion with cholecystokinin octapeptide/secretin alone resulted in acute pancreatitis. Topical carbachol stimulated sphincter of Oddi motility abolished trans-sphincteric flow, and increased pancreatic exocrine secretion (p<0.05) and pancreatic duct pressure to levels comparable with pancreatic duct ligation (p<0.001). Carbachol application (with or without combined peptide stimulation) elevated plasma amylase levels (p<0.01) and produced pancreatic tissue damage (p<0.05). Decompression of pancreatic duct ameliorated these effects (p<0.05). CONCLUSION: Induced sphincter of Oddi dysfunction when coupled with stimulated pancreatic secretion causes acute pancreatitis. This may be an important pathophysiological mechanism causing various forms of acute pancreatitis.
Acute Disease↗
Stability of Tringo's hierarchy of preference toward disability groups: 30 years later.
The hierarchy of preference toward disability groups was measured for 171 subjects on 16 disabilities. Results indicated that the hierarchy of preference reported by Tringo (1970) exists today despite many efforts by society to remove such stereotypes. Further, the rank-order of the hierarchy appears to be quite stable in that only individuals with cancer show an appreciable change in relative position.
Adult↗
Efficacy of the Ghajar Guide revisited: a prospective study.
OBJECT: The goal of this study was to compare the freehand technique of catheter placement using external landmarks with the technique of using the Ghajar Guide for this procedure. The placement of a ventricular catheter can be a lifesaving procedure, and it is commonly performed by all neurosurgeons. Various methods have been described to cannulate the ventricular system, including the modified Friedman tunnel technique in which a soft polymeric tube is inserted through a burr hole. Paramore, et al., have noted that two thirds of noninfectious complications have been related to incorrect positioning of the catheter. METHODS: Forty-nine consecutive patients were randomized between either freehand or Ghajar Guide-assisted catheter placement. The target was the foramen of Monro, and the course was through the anterior horn of the lateral ventricle approximately 10 cm above the nasion, 3 cm from the midline, to a depth of 5.5 cm from the inner table of the skull. In all cases, the number of passes was recorded for successful cannulation, and pre- and postplacement computerized tomography scans were obtained. Calculations were performed to determine the bicaudate index and the distance from the catheter tip to the target point. CONCLUSIONS: Successful cannulation was achieved using either technique; however, the catheters placed using the Ghajar Guide were closer to the target.
Adolescent↗
Images and diagnoses. Phaeochromocytoma from paraganglia of the urinary bladder wall.
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Adolescent↗
Utilization review in Maryland hospitals. A synopsis of the Maryland Insurance Administration's study.
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Costs and Cost Analysis↗
Changes in activity and regulation of the cardiac Ca2+ channel (L-type) by protein kinase C in chronic alcohol-exposed rats.
BACKGROUND: It has been reported recently that long-term alcohol exposure in rats increases the number of dihydropyridine binding sites in cardiac membrane preparations. We fed Sprague Dawley rats a liquid diet that contained ethanol as 36% of total calories for 4 to 6 months and studied how alcohol exposure affected the activity and regulation of the cardiac Ca2+ channel. METHODS: Dihydropyridine-sensitive cardiac Ca2+ channel activity was measured as the rate of Mn2+ quench of the cytosolic fura-2 signal in electrically stimulated myocytes. RESULTS: In control rat myocytes, pretreatment with phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), reduced the rate of Mn2+ quench to 68% of the untreated cell response. Pretreatment with GF109203X, a protein kinase C inhibitor, enhanced the rate of influx by 56%, whereas Gö6976, an inhibitor of PKC alpha, beta, and gamma, did not affect the rate of influx. By contrast, PMA did not affect the rate of Mn2+ quench in alcoholic myocytes; however, the PKC inhibitor GF109203X still enhanced the rate of Mn2+ quench by 33%. Similar to control myocytes, no effect was observed after pretreatment with Gö6976 in the alcoholic cells. In both Western blot and immunoprecipitation experiments, PKC epsilon expression in alcohol-exposed myocytes was reduced to 68% of the control. However, the ratio of membrane/ cytosolic distribution of PKC epsilon in alcoholic myocytes was increased from 1.6 to 2.6. No change was detected in the expression of PKC alpha and PKC delta. PKC activity, measured in the presence of Gö6976, which inhibits PKC alpha, beta, and gamma, was reduced in alcoholic myocytes to 57% of the control, but the proportion of PKC activity in the particulate fraction was increased from 26% in the control myocytes to 36% in the alcoholic myocytes. CONCLUSIONS: Altered expression and activity of PKC may be associated with changes in the regulation of the cardiac Ca2+ channel found in the hearts of rats chronically exposed to alcohol. Specifically, we found that the novel class of PKC isozymes is responsible for regulating the cardiac Ca2+ channel in control cardiomyocytes, and that the loss of PMA modulation found in the alcoholic cells may be due, in part, to reduced expression and altered distribution of PKC epsilon.
Alcoholism↗
[Informed consent of the surgery candidate].
Surgery is a special medical act requiring the patient's prior informed consent. Informed consent necessitates correct comprehensible information which must be documented in case of court claims. Consent must be given freely by the patient who has been properly informed. Consent from patients with impaired cognition raises particular problems as does consent from incarcerated patients. The French Code of deontology does not state how the information must be delivered and how the patient's consent must be recorded nor which party is charged with proof of information. The information delivered must be loyal (true with nothing hidden) and appropriate (adapted) for the health status of the patient and his/her personality and capacity to understand as well as for the proposed care. Information depends on the patient's and the physician's general culture. In addition to the information itself, documentary proof of its delivery is required in case of court claims. Carefully written documents are mandatory. They should meet certain requirements, remaining general enough (example: appendectomy and its risks), updated, and simple and comply with the rules of deontology.
France↗
Rapid detection of resistance to rifampicin in Mycobacterium leprae.
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Drug Resistance, Microbial↗
Recovering for burnout.
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Burnout, Professional↗
Effect of prenatal vitamin D (calcitriol) exposure on the growth and development of the prostate.
BACKGROUND: We previously found that in the absence of testosterone (T), calcitriol promotes proliferation of normal prostatic stroma, while in the presence of T, it has a differentiating effect on prostatic epithelium. The present study was conducted to determine the effect of calcitriol exposure in utero on the postnatal development of the normal prostate. METHODS: Pregnant rats were injected subcutaneously with either 1.25 microg of calcitriol or vehicle alone on alternate days till delivery. Calcitriol-exposed and control pups were sacrificed at age 25 days (prepuberty), 63 days (postpuberty), or 102 days (adults), and their prostates and seminal vesicles were harvested and weighed. RESULTS: Pups prenatally exposed to calcitriol and sacrificed before puberty (25 days) had a 35% greater mean prostatic weight than controls (0.0314 vs. 0.0422 g, P < 0.007), and calcitriol-exposed adult rats (102 days) had a 68% greater mean prostatic weight than controls (0.1365 vs. 0.2304 g, P < 0.005). No differences were observed in seminal vesicle weights, and in serum calcium and testosterone levels. A disproportionately high mortality rate from sudden death (71%) was observed at puberty in uncastrated male rats prenatally exposed to calcitriol. CONCLUSIONS: These findings suggest that high-dose calcitriol exposure in utero may uniquely influence subsequent prostatic growth. Nonandrogenic steroids such as calcitriol may also be involved in genetic imprinting of the prostate.
Animals↗