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Biomedical subjects

C Rose

Publications and source records attributed to C Rose.

At least 127 records · Page 7Linked to original sources

Use of record linkage between a statewide genetics service and a Birth Defects/Congenital Malformations Register to determine use of genetic counselling services.

The Birth Defects/Congenital Malformations Register of the Victorian Department of Human Services contains detailed, confidential information on over 2,000 babies born with a birth defect each year in Victoria, Australia, representing approximately 3% of the annual number of births. For 1991 and 1993, the type of anomaly was categorised as warranting a high, moderate, or low need of referral for genetic counselling, depending on risk of recurrence and possible genetic cause. The Victorian Clinical Genetics Service at the Murdoch Institute, Melbourne, offers free, centralised genetic counselling services for the entire state. A comparison of case records between the two agencies has shown little difference in overall use of genetic counselling between 1991 (17%) and 1993 (16%). Rate of uptake in the "high need" category improved only slightly during that period, from 40% in 1991 to 43% in 1993. Utilization of genetic counselling services did not vary disproportionately with mother's country of birth, but was higher for older mothers. As was expected, rates were highest when a baby was born at the only hospital that provides on-site genetic counselling services. Even where a statewide genetic counselling service is in place, it is disappointing that over half of those judged at high need for genetic counselling are not making use of this service. This study will provide baseline information to which future studies can be compared. Using the same study methodology, it will be possible to examine whether the uptake rate increases in accordance with increased genetic services.

Congenital Abnormalities↗

Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial.

BACKGROUND: Irradiation after mastectomy can reduce locoregional recurrences in women with breast cancer, but whether it prolongs survival remains controversial. We conducted a randomized trial of radiotherapy after mastectomy in high-risk premenopausal women, all of whom also received adjuvant systemic chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF). METHODS: A total of 1708 women who had undergone mastectomy for pathological stage II or III breast cancer were randomly assigned to receive eight cycles of CMF plus irradiation of the chest wall and regional lymph nodes (852 women) or nine cycles of CMF alone (856 women). The median length of follow-up was 114 months. The end points were locoregional recurrence, distant metastases, disease-free survival, and overall survival. RESULTS: The frequency of locoregional recurrence alone or with distant metastases was 9 percent among the women who received radiotherapy plus CMF and 32 percent among those who received CMF alone (P<0.001). The probability of survival free of disease after 10 years was 48 percent among the women assigned to radiotherapy plus CMF and 34 percent among those treated only with CMF (P<0.001). Overall survival at 10 years was 54 percent among those given radiotherapy and CMF and 45 percent among those who received CMF alone (P<0.001). Multivariate analysis demonstrated that irradiation after mastectomy significantly improved disease-free survival and overall survival, irrespective of tumor size, the number of positive nodes, or the histopathological grade. CONCLUSIONS: The addition of postoperative irradiation to mastectomy and adjuvant chemotherapy reduces locoregional recurrences and prolongs survival in high-risk premenopausal women with breast cancer.

Adult↗

Decreased glutamate transporter (GLT-1) expression in frontal cortex of rats with acute liver failure.

It has been suggested that reduced astrocytic uptake of neuronally released glutamate contributes to the pathogenesis of hepatic encephalopathy in acute liver failure. In order to further address this issue, the recently cloned and sequenced astrocytic glutamate transporter GLT-1 was studied in brain preparations from rats with ischemic liver failure induced by portacaval anastomosis followed 24 h later by hepatic artery ligation and from appropriate sham-operated controls. GLT-1 expression was studied using reverse transcriptase-polymerase chain reaction (RT-PCR). Expression of GLT-1 transcript was significantly decreased in frontal cortex at coma stages of acute liver failure. Western blotting using a polyclonal antibody to GLT-1 revealed a concomitant decrease in expression of transporter protein in the brains of rats with acute liver failure. Reduced capacity of astrocytes to reuptake neuronally released glutamate, resulting from a GLT-1 transporter deficit and the consequently compromised neuron-astrocytic trafficking of glutamate could contribute to the pathogenesis of hepatic encephalopathy and brain edema, two major complications of acute liver failure.

ATP-Binding Cassette Transporters↗

[Tuberculosis, mycobacterium infection and hairy cell leukemia].

OBJECTIVES: Diagnosis of tuberculosis and/or mycobacteria infection is particularly difficult in immunocompromised patients. PATIENTS AND METHODS: We examined the clinical presentation, means of diagnosis, treatment and outcome of tuberculosis in a retrospective study of 6 patients among 75 with hairy cell leukemia diagnosed from 1982 to 1995. RESULTS: Hearlding symptoms of tuberculosis diagnosis were: fever (6/6), weight loss (4/6), pleural effusion (1/6), superficial adenopathy (1/6), persistence of cytopenia or splenomegaly during the treatment of hairy cell leukemia. Pulmonary symptoms were present in only two cases. Diagnosis was obtained by positive culture of mycobacteria in 2 cases (Mycobacterium tuberculosis in pleural effusion, Mycobacterium kansaii in adenopathy). Microbiological diagnosis was never obtained from sputum (6/6). Diagnosis was obtained by histopathology in all cases: from bone marrow (2 cases), lymph nodes (2 cases), liver (1 case), spleen (1 case), umbilical fat (1 case). Tuberculosis was disseminated in all cases. By clinical, biological, microbiological histopathological means and response to treatment, tuberculosis was considered as: hematopoietic in all cases, hepatic (in 4/6), pleural (1/6), pulmonary (1/6). A favorable outcome of tuberculosis was observed in all cases. No death was observed. CONCLUSIONS: Tuberculosis was found in 8% of hair cell leukemia patients. In hairy cell leukemia, tuberculosis is characterized by few pulmonary symptoms and scarse microbiological documentation. In contrast, histopathology is very interesting to confirm diagnosis. Tuberculosis is in most cases disseminated and in particular hematopoietic diffusions is always present. In spite of existensive localization, the prognosis remains excellent and all patients can be cured. In our opinion, this good prognosis may be linked to the improvement of hairy cell leukemia treatment observed since the advent of interferon pentostatin and 2cdA.

Adult↗

Perspectives of coronary excimer laser angioplasty: multiplexing, saline flushing, and acoustic ablation control.

BACKGROUND AND OBJECTIVE: Bubble formation, pressure wave generation, and cavitations constitute major factors influencing the outcome of clinical Excimer laser angioplasty. Thus, the rationale of this study was to determine the extent of pressure waves occurring during excimer laser ablation and to discuss possibilities that allow a less traumatic plaque removal in the coronary circulation. STUDY DESIGN/MATERIALS AND METHODS: Conventional and experimental Xenon-Chlorid-Excimer lasers emitting light at a wave-length of 308 nm and a pulse duration of 115 ns were used for testing of signals. Whereas the conventional excimer laser light source transmits light through all fibers of a 1.7 mm laser catheter simultaneously, the prototype excimer laser divides the laser beam into several areas of uniform energy fluence by scanning the beam from one section to the other using the intermission between two laser discharges. Hydrophones consisting of piezoelectric films detected the acoustic signals, which were obtained on normal arterial wall and atherosclerotic plaque. RESULTS: Multiplexing decreases maximum pressures for both normal arterial wall and calcified plaque significantly, whereas pressure rise time remains comparable. During ablation of pure blood, a linear increase of peak pressures of 1 MPa at 10 mJ/mm2 to 7.5 MPa at 50 mJ/mm2 is found. Contrast media intensifies the extent of pressure wave formation. At 20 mJ/mm2, 60% contrast media added to blood results in an increase of maximum pressures from 1.5 MPa up to 5 MPa. Dilution with saline solution is effective; however, high concentrations of > 90% are required to achieve a significant pressure wave reduction. CONCLUSION: Peak pressures of several thousand kPa occur during excimer laser ablation of contrast media, blood, calcified plaque, and normal arterial wall in a decreasing order. Multiplexing and saline flushing are capable of reducing the intensity of the generated acoustic signals during tissue ablation. It has to be taken into consideration, however, that high concentrations of saline solution are necessary to achieve a significant reduction of peak pressures.

Acoustics↗

Protective effect of L-carnitine in ammonia-precipitated encephalopathy in the portacaval shunted rat.

L-carnitine administration prevents the neurological symptoms of acute ammonia toxicity. To further evaluate its efficacy in the prevention of hepatic encephalopathy in hyperammonemic conditions, L-carnitine (16 mmol/kg, intraperitoneally [i.p.] was administered 1 hour before ammonium acetate (NH4OAc) (8.5 mmol/kg, subcutaneously) to portacaval shunted (PCS) rats. Cerebrospinal fluid (CSF) ammonia, lactate, and amino acid levels were measured in relation to deteriorating neurological status in these animals. None of 35 L-carnitine-treated animals showed neurological deterioration after NH4OAC administration compared with saline-treated controls; the latter manifested severe encephalopathy progressing through loss of righting reflex to coma. Survival rate was 100% in the L-carnitine-treated group compared with 5% in saline-treated controls. Following NH4OAC administration to PCS rats, CSF ammonia increased to 0.93 +/- 0.15 mmol/L and 1.24 +/- 0.15 mmol/L at precoma and coma stages of encephalopathy (P < .01) respectively. Treatment with L-carnitine reduced CSF ammonia at both precoma and coma stages; the time-course of this protective effect paralleled blood and CSF L-carnitine accumulation. CSF alanine and lactate increases following NH4OAC administration to PCS rats were significantly attenuated following L-carnitine treatment. However, L-carnitine treatment did not lead to significant reductions in plasma ammonia nor CSF or brain glutamine in these animals. These findings show the therapeutic efficacy of L-carnitine in ammonia-precipitated coma in PCS rats and suggest that this protective effect is centrally mediated involving improved mitochondrial respiration. L-carnitine could be of therapeutic benefit in the prevention of hepatic encephalopathy precipitated by ammoniagenic conditions in humans with chronic liver disease.

Amino Acids↗

[POEMS syndrome].

POEMS syndrome is an acronym defined by Bardwick (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal component and Skin changes). Other various clinical and biological features are reported: edema, cachexia, microangiopathic glomerulopathy, most rarely pulmonary hypertension, cutaneous necrosis. Thrombocytosis or polycythemia may be a prominent feature. POEMS syndrome is sometimes associated with lymphoproliferative disorder. Castelman-like disease is frequently observed as pathologic findings on lymph nodes. Distinction between POEMS syndrome and osteosclerotic myeloma is delicate. The rate of the monoclonal protein is modest-always less than 30 g/L-and is almost of the lambda light chain class. In contrast to multiple myeloma this syndrome is rarely associated with hypercalcemia, skeletal fracture, renal involvement and increasing of M component during evolution. Bone marrow plasmocytosis is usually less than 15% and the kinetic phenotype and genetic characteristics of the plasma cell remain those found in monoclonal gammopathy of undetermined significance. The pathophysiology of this syndrome remains largely unknown but overproduction of pro-inflammatory cytokines are reported, especially TNF alpha, IL-6 and IL-1 beta. Some clinical manifestations seem to be cytokine related. Polyneuropathy and cachexia are the main cause of death. A part corticosteroid and cure of solitary bone lesion, treatment is disappointing and survival is 60% at five years.

Humans↗

Estimates of the sources of variation (variance components) of bioelectric impedance and anthropometric measurements in an epidemiological case-control study of breast cancer.

OBJECTIVE: This study investigated the variability of anthropometric measurements and body fat estimated by bioelectric impedance analysis. Subsequently the methods were applied in a case-control study to investigate the association with breast cancer. DESIGN, SUBJECTS: The study group included 50 consecutive cases and 75 age-matched controls from the same area. The variation was investigated in 50 healthy women from the control group, who were repeatably measured using standardised measurement procedures, and the variation between-subjects, within-subjects, between-observers, and within-observers were estimated. RESULTS, CONCLUSIONS: The study showed that the variance components between-subjects were 64-99% of the total variance. The variables of skinfold thicknesses were characterised by having the highest relative observer variation and having many unavailable values that were out of the range of the Harpenden callipers. The mean body fat by bioelectric impedance analysis was 31.2%, and the total coefficient of variation 23%, while the variance components related to subject time, observer and measurement were 98.4%, 1.1%, 0.2%, and 0.4%, respectively. The body fat was significantly correlated with the variables of skinfold thicknesses. We decided to exclude the variables of skinfold thicknesses from the case-control study, and for the other variables to measure each subject only at one time by one observer. The case-control part of the study indicated a non-significant increase in body weight in the postmenopausal breast cancer patients (mean difference 3.6 kg; confidence interval from -0.9 kg to 8.0 kg). Similarly the body fat tended to be higher in the breast cancer patients (mean difference 1.2%; confidence interval from -1.6% to 4.0%).

Adult↗

POEMS syndrome: report on six patients with unusual clinical signs, elevated levels of cytokines, macrophage involvement and chromosomal aberrations of bone marrow plasma cells.

POEMS syndrome is a multisystemic disorder characterized by the association of polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes and various other systemic clinical signs. The pathophysiology of this syndrome remains largely unknown. In order to gain insight into its pathophysiology, we studied the clinical characteristics and performed serum analysis (auto-antibodies, cytokine levels) and phenotypic and cytogenetic studies of bone marrow plasma cells (BMPC) in six patients with unequivocal POEMS syndrome. Two unusual clinical signs were present in these patients: pulmonary hypertension (two patients) and diffuse cutaneous necrosis (one patient). No auto-antibodies against peripheral nerve (PN) antigens (SGPG and SGLPG glycolipids, GM1, GD1a, GD1b and GT1b gangliosides) were found. Sequential evaluations of serum cytokines (IL-1-beta, IL-6 and TNF-alpha) showed a moderate to marked elevations of IL-6 and TNF-alpha in all patients (up to six-fold for TNF-alpha and 16-fold for IL-6). Using in situ hybridization of these cytokines mRNAs on lymph node specimens of two patients who had an angiofollicular lymph node hyperplasia, a strong positivity was found with the IL-1-beta antisense probe in lymph node macrophages. On skin biopsy a high number of cells expressing TNF-alpha mRNA was observed in the dermis. The biological features of BMPC: phenotype (expression of CD19 and CD56 antigens), kinetics (Ki-67 index), karyotype, DNA content and chromosomal in situ hybridization remained those of BMPC found in monoclonal gammopathy of undetermined significance. We conclude that POEMS syndrome is a hypercytokinemic syndrome in which BMPC are not of malignant type. Macrophages are involved in this syndrome and their role has to be further investigated as well as treatments which act through an anti-cytokine mechanism.

Adult↗

The portacaval-shunted rat: a new model for the study of the mechanisms controlling voluntary ethanol consumption and ethanol preference?

Portacaval anastomosis (PCA) is a surgical procedure whereby blood from the portal vein is shunted into the inferior vena cava. PCA in the rat results in a significant increase (from 0.77 +/- 0.26 to 3.51 +/- 0.37 g of ethanol/kg/day) in voluntary ethanol consumption in a free-choice paradigm between water and 5% ethanol solution. After PCA surgery, increased voluntary ethanol consumption starts abruptly at 6 to 7 days and is maintained for > 28 weeks. Voluntary ethanol consumption in rats after PCA results in blood ethanol levels up to 158 mg%. After PCA, the ethanol preference ratio (defined as the percentage of total fluid intake constituted by ethanol) increased from 19 +/- 2% to 78 +/- 2% (P < 0.001). Administration of the nonselective opioid receptor antagonist naloxone (5 mg/kg, sc) resulted in a significant 6-fold attenuation of voluntary ethanol consumption by rats with PCA, an effect that was not mediated by an effect on locomotor activity. These findings, together with previous reports of widespread alterations of the mu- and delta-opioid receptors in the brain after PCA, suggest that increased voluntary ethanol consumption and ethanol preference in PCA rats may result from activation of the endogenous opioid system. Preliminary studies suggest that rats with PCA manifest behavioral signs consistent with the development of dependence. The portacaval-shunted rat may provide a useful preparation for the study of mechanisms, in particular those involving the liver, implicated in the development of increased voluntary ethanol consumption and ethanol preference.

Alcohol Drinking↗

Suramin in non-small cell lung cancer and advanced breast cancer. Two parallel phase II studies.

Suramin inhibits the growth of non-small cell lung cancer (NSCLC) and breast cancer in vitro by blocking the action of most known growth factors. The clinical efficacy of suramin was evaluated in patients with unresectable or relapsed NSCLC (n = 16) and advanced breast cancer (ABC) resistant to conventional therapies (n = 12). A plasma level > or = 200 micrograms/ml was maintained by three times weekly administrations using adaptive control with feedback. Treatment was continued until documented progression of disease or unacceptable toxicity. No clinical responses were observed in any patient. Median overall survival was 4.5 months in NSCLC and 9 months in ABC patients. Mean treatment duration was 6.6 weeks in NSCLC patients and 15.9 weeks in ABC patients. Treatment was discontinued due to disease progression in 14 patients, unacceptable adverse effects in 11 patients, while three patients refused to continue therapy. We cannot recommend this drug for further clinical trials in NSCLC and ABC.

Adult↗

Cognitive and behavioural effects of a school breakfast.

The cognitive and behavioural effects of a school breakfast were explored in a study of 55 children in Grade II and Standard 1 at a farm school outside Johannesburg. A previous study had confirmed widespread undernutrition and micronutrient deficiencies among the children. For comparative purposes, 55 children at an inner-city school, among whom no signs of undernutrition were found, were assessed in the same way. Three different types of measures of attention, distractibility, short-term memory and activity level were used: psychometric testing of the children; teacher ratings of children's classroom behaviour, and coded video-recorded classroom behaviour. A pre- and post-test design was employed to assess the effects of a school breakfast, continually in place in the experimental school for a period of 6 weeks. The results indicated significant change from pre- to post-test assessment among the experimental children in respect of the psychometric measures, teacher-rated hyperactivity and video-recorded classroom behaviour. With regard to the latter measure, the children showed a decline in both the occurrence and duration of off-task and out-of-seat behaviour, and an increase in active participation in class and positive peer interaction. While the children in the comparison group also showed some changes from pre- to post-test, probably attributable to the effects of observation, familiarity with the test materials and developmental change, the changes were not generalised or consistent. The findings support the conclusion that a school breakfast programme had a beneficial effect on the cognitive and behavioural performance of socially disadvantaged, undernourished children in their first 2 years of school.

Adolescent↗

[Merkel cell carcinoma. A rare differential keratoacanthoma diagnosis].

A 90 year old woman presented with a rapidly growing nodular tumor at the tip of the nose. Clinically, keratoakanthoma was tentatively diagnosed. Histological examination, however, revealed Merkel cell carcinoma. This case supports the necessity of a surgical excision with a subsequent histological examination even when the clinical aspect is suggestive for keratoacanthoma.

Aged↗

[Severe diffuse facial cellulitis].

Twenty cases of severe cervicofacial infections among 184 cases of cellulites treated in 1991 and 1992 at the Lille University Hospital were investigated. Outcome was compared with results reported in the literature. Outcomes were similar and emphasized the critical nature of this type of infection which caused 7 deaths in our series and severe anatomic and functional sequelae. All patients (n = 20) were given anti-inflammatory drugs prior to surgery. The correlation between disease severity and use of anti-inflammatory drugs would appear to be an established fact. Criteria predicting severity were identified in order to obtain a score for high or low risk and to better adapt the medical and surgical management strategy.

Adolescent↗