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Biomedical subjects

C Muller

Publications and source records attributed to C Muller.

At least 73 records · Page 4Linked to original sources

Postnatal development of vascular resistance of the rabbit isolated perfused kidney: modulation by nitric oxide and angiotensin II.

Studies were performed on isolated perfused kidneys (IPK) from postnatal developing rabbits to ask 1) whether the high renal vascular resistance (RVR) at birth involves intrinsic renal mechanisms, 2) whether nitric oxide (NO) release is involved in the modulation of renal vascular tone, and 3) whether NO modulates exogenous angiotensin II (AII)-induced vasoconstrictions. Kidneys isolated from 1-wk-old (during nephrogenesis), 3-wk-old (after nephrogenesis), and 6-wk-old rabbits were perfused in the presence of 10(-5) M indomethacin. RVR decreased with age from 12.7 +/- 0.6 at 1 wk to 10.1 +/- 0.5 mm Hg min g mL-1 at 6 wk. N omega-Nitro-L-arginine methyl ester (L-NAME, 10(-4) M) comparably increased RVR by about 30% at 1, 3, and 6 wk. The vasoconstrictions induced by 10(-8) M AII increased basal pressure from 28% at 1 wk to 78% at 6 wk and were potentiated by L-NAME by about 100%. In contrast, the vasoconstrictions induced by 10(-10) M AII decreased from 8% at 1 wk to 0% at 6 wk and were potentiated by L-NAME by about 250% at 1 and 3 wk. We conclude that during postnatal development: 1) RVR in IPK decreases in absence of AII and extrarenal influences, suggesting that high RVR at birth involves intrinsic mechanisms, 2) L-Arg/NO modulates basal tonus in developing IPK, and, 3) renal vasoconstrictor responses to exogenous AII are buffered by NO at early postnatal stages and follow an AII concentration-dependent developmental pattern. A specific neonatal high affinity AII/NO interaction disappearing after nephrogenesis completion precedes a low affinity AII/NO interaction, which progressively increases toward adult ages. These findings are in favor of a specific involvement of AII-NO interactions in the control of developing renal hemodynamics.

Age Factors↗

[Analysis of the results of 137 subclinical breast lesions excisions. Value of ultrasonography in the early diagnosis of breast cancer].

OBJECTIVE: Ultrasonography is invaluable for evaluation of palpable masses and masses detected by mammography. Ultrasound has no proved role in breast screening. Between 1991 and 1994, we included ultrasonography routinely in our screening mammography prescription, not only for evaluation of mass detected by mammography but also in radiographically dense, non-radiolucent breast. One hundred and thirty-seven suspicious but non palpable breast lesions were detected. We analyzed the results of the surgical excision biopsies of these lesions and evaluated the contribution of ultrasonography combined with mammography to detect occult breast cancers. MATERIAL AND METHODS: From 1991 to 1994, our institution performed 8,489 individual screening mammographies. All women underwent physical examination before mammography. Women with abnormal clinical breast examination are not included in the study. Ultrasonography was routinely performed for characterization of a mass detected by mammography and also in normal breast with dense, non-radiolucent tissue. One hundred and thirty-seven suspected breast lesions were removed after immediate preoperative stereotaxic or US-guided needle localization. Screened women were aged 29-72 years (mean 51 years). 48% of all screened women were aged 50 years and older. RESULTS: The histopathologic findings were as follow: invasive ductal carcinoma (IDC) 40 cases (59%), invasive lobular carcinoma (ILC) 7 cases (10%), ductal carcinoma in situ 21 cases (31%). Infracllnic cancer was identified by mammography alone in 45% of cases, by mammography and sonography in 43.2% of cases, by sonography alone in 11.8% of cases. About 31% of infraclinic cancer occur prior to the age of 50 (age range: 29-72, mean: 54). Cancer less than 10 mm in diameter were found in 57.5% of lesions. Axillary dissection was performed in 46 cases of invasive cancer, with a incidence of axillary node metastases of 15%. CONCLUSION: The combination of mammography and ultrasonography is effective to detect a greater number of occult breast cancers and we recommend ultrasonography not only for evaluation of a mass detected by mammography but also in radiographically dense non-radiolucent breast lesions.

Adult↗

[Interleukin-8 is an important inflammatory mediator in hemorrhagic rectocolitis and Crohn disease].

OBJECTIVES: The aim of the study was to assess in vitro the production of interleukin 8 in Crohn's disease and ulcerative colitis. PATIENTS AND METHODS: Interleukin 8 concentrations (measured by ELISA) were evaluated in the culture supernatants of: a) peripheral blood mononuclear cells from 13 patients with Crohn's disease, 7 patients with ulcerative colitis and 7 controls, b) organ cultures of inflamed (22 Crohn's disease, 15 ulcerative colitis) and uninflamed (21 Crohn's disease, 9 ulcerative colitis, 15 controls) intestinal mucosal biopsies. RESULTS: In patients with Crohn's disease and ulcerative colitis, the production of interleukin 8 by peripheral blood mononuclear cells and inflamed mucosa was higher than in controls (P < 0.01) without statistical difference between Crohn's disease and ulcerative colitis. Interleukin 8 production by normal mucosa was not different between the 3 groups. Interleukin 8 concentrations in the supernatants of organ culture were positively correlated to an endoscopical and a histological inflammatory index as well as to tumor necrosis factor, interleukin 1 and 6 concentrations. CONCLUSION: These results support the notion that interleukin 8 plays an important role in the pathogenesis of inflammatory bowel disease.

Adult↗

An unusual manifestation of Meckel's diverticulum: bleeding and perforation--a case report.

Meckel's diverticulum is the most common congenital abnormality of the gastrointestinal tract. Bleeding of the diverticulum from a peptic ulcer due to ectopic gastric mucosa makes up 25% of all complications in the disease. We report a case of a 20 year old male with chronic anemia, severe hematochezia and perforation due to Meckel's diverticulum. Segmental small bowel resection was performed. Difficulty of preoperative diagnosis is discussed, indication for incidental diverticulectomy is established and the literature reviewed.

Adult↗

[A rare breast tumor: mammary fibromatosis. Two case reports and a review of the literature].

Aggressive fibromatosis of the breast is an uncommon benign disease. The clinical and X-Ray findings can simulate breast cancer. The diagnosis relies on histology. The typical feature of this disease is a locally aggressive but non metastasizing lesion with high recurrence rate. Treatment consists in wide excision. The role of radiation and drug therapy including antiestrogens has not been clearly established. Colonoscopy is indicated to research for an association with Gardner syndrome.

Adult↗

Mistletoe lectins I, II and III induce the production of cytokines by cultured human monocytes.

The three mistletoe (Viscum album L.) lectins. ML I, ML II and ML III, were tested on their ability to enhance the secretion of the cytokines tumor necrosis factor (TNF)alpha, interleukin (IL)-1 alpha, IL-1 beta and IL-6 by human monocytes obtained from healthy donors. At lectin concentrations from 0.02 to 20/pg ml (100-10,000-fold lower than those showing toxic effects), stimulations of cytokine production several-fold over control values were observed. The immunoactivating concentrations by the three lectins were found different for each donor. At toxic concentrations, the amounts of IL-1 alpha, IL-1 beta and to a less extent of TNF alpha in monocytes supernatants were particularly high. The data are discussed in relationship with the cytotoxic and immunoactivating effects of mistletoe lectins and their interest in cancer treatment.

Cells, Cultured↗

Isolation of bone marrow plasma cells by negative selection with immunomagnetic beads.

In order to isolate bone marrow plasma cells from patients presenting with multiple myeloma or monoclonal gammopathy of undetermined significance, we developed a method for purifying these cells by negative selection using monoclonal antibodies and immunomagnetic beads. The results presented here were obtained from 75 procedures. Purity was extremely variable (2-100%) and was dependent on the percentage of plasma cells in the original bone marrow sample with a 10% cut-off, beyond which purity was over 96% in all cases. The mean yield was about 20%. The cells collected were viable and suitable for immunophenotyping, semi-quantitative studies of oncoproteins, and PCR.

Antibodies, Monoclonal↗

Epstein-Barr virus (EBV)-associated lymphoproliferations in severe combined immunodeficient mice transplanted with Hodgkin's disease lymph nodes: implications of EBV-positive bystander B lymphocytes rather than EBV-infected Reed-Sternberg cells.

To establish an in vivo model for the study of Hodgkin's disease and Reed-Sternberg (RS) cells, 25 lymph node tissue samples involved by Hodgkin's disease were grafted into severe combined immunodeficiency (SCID) mice. Ten Epstein-Barr virus (EBV)-associated tumors were obtained in SCID mice. EBV-positive tumors growing in SCID mice were correlated with the presence of EBV-positive nonneoplastic B cells in patient tumors (90% v 26.6%; P<.01) and was independent of the EBV status of RS cells. Our results suggested that EBV-positive tumors growing in SCID mice originated from normal EBV-positive small lymphocytes (bystander B lymphocytes). We also compared the characteristics of these tumors with those obtained after transplantation of 15 non-Hodgkin's lymphoma and four reactive lymph nodes. The latent period to observe a growing tumor in SCID mice was similar between the two groups (12.86 +/- 5.59 weeks for Hodgkin's disease v 13.6 +/- 5.36 weeks for non-Hodgkin's lymphoma and reactive lymph nodes). The relatively high number of EBV-positive small lymphocytes detected in Hodgkin's disease and T-cell lymphoma compared with B-cell lymphoma may account for the greater percentage of EBV-positive tumors obtained in SCID mice. Our results show that SCID mice do not provide the growth conditions that are required for in vivo growth of RS cells. We noted in some SCID tumors, the presence of binucleated and/or multinucleated giant cells resembling RS cells. However, the presence of such cells was not restricted to mice grafted with lymph nodes involved by Hodgkin's disease. We postulate that in previous reports, cells resembling RS cells were just binucleated EBV-positive lymphoma blastoid cells rather than actual RS cells.

Adult↗

Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study.

Increased bone turnover has been suggested as a potential risk factor for osteoporotic fractures. We investigated this hypothesis in a prospective cohort study performed on 7598 healthy women more than 75 years of age. One hundred and twenty-six women (mean years 82.5) who sustained a hip fracture during a mean 22-month follow-up were age-matched with three controls who did not fracture. Baseline samples were collected prior to fracture for the measurement of two markers of bone formation and three urinary markers of bone resorption: type I collagen cross-linked N- (NTX) or C-telopeptide (CTX) and free deoxypyridinoline (free D-Pyr). Elderly women had increased bone formation and resorption compared with healthy premenopausal women. Urinary excretion of CTX and free D-Pyr, but not other markers, was higher in patients with hip fracture than in age-matched controls (p = 0.02 and 0.005, respectively). CTX and free D-Pyr excretion above the upper limit of the premenopausal range was associated with an increased hip fracture risk with an odds ratio (95% confidence interval) of 2.2 (1.3-3.6) and 1.9 (1.1-3.2), respectively, while markers of formation were not. Increased bone resorption predicted hip fracture independently of bone mass, i.e., after adjustment for femoral neck bone mineral density (BMD) and independently of mobility status assessed by the gait speed. Women with both a femoral BMD value of 2.5 SD or more below the mean of young adults and either high CTX or high free D-Pyr levels were at greater risk of hip fracture, with an odds ratio of 4.8 and 4.1, respectively, than those with only low BMD or high bone resorption. Elderly women are characterized by increased bone turnover, and some markers of bone resorption predict the subsequent risk of hip fracture independently of hip BMD. Combining the measurement of BMD and bone resorption may be useful to improve the assessment of the risk of hip fracture in elderly women.

Absorptiometry, Photon↗

Caffeine consumption in hospitalized psychiatric patients.

A total of 98 consecutively admitted psychiatric inpatients were asked for their daily consumption of coffee, tea and other products containing caffeine. Calculation of the corresponding daily caffeine intake was performed using data from the literature and from caffeine measurements carried out in different coffee and tea preparations in the hospital. Of the patients 13% presented a high (> or = 750 mg daily) caffeine consumption before hospitalization. The average caffeine consumption per day decreased from 405 mg before to 332 mg during hospitalization (P < 0.04), but the before and during hospitalization caffeine consumptions were highly correlated (rho = 0.651; P < 0.00001). The decrease in caffeine consumption seems to be influenced by a lower availability of caffeine at hospital. Among the diagnostic groups (DSM-III-R criteria), the caffeine intake was highest in schizophrenia and lowest in anxiety and major depression patients. Patients under a neuroleptic treatment before admission presented a higher caffeine intake. At hospital the high caffeine users showed the highest score on the factor depression (Hopkins Symptom Checklist; HSCL-58). However, the influence of other factors, such as weight and cigarette consumption, which correlated also with the caffeine intake (rho = 0.359; P < 0.001; and rho = 0.83; P < 0.00001, respectively), have also to be considered. Our data suggest that inquiry into caffeine consumption should be included routinely for psychiatric patients, e.g. at admission, because patients with a psychotic disorder undergo a higher risk for an excessive caffeine consumption.

Adult↗

The choice of medical providers in rural Bénin: a comparison of discrete choice models.

In this paper we estimate three different discrete choice models of provider choice using data from the rural District of Ouidah in Bénin. These three model are: Multinomial Logit (ML); (2) Independent Multinomial Probit (IMP); (3) Multinomial Probit (MP). A comparison of IMP and MP allows us to reject the independence assumption between providers. Furthermore, the cross-price elasticities computed from the restrictive specifications (ML and IMP) are dramatically different from those computed from the more general one (MP). These results cast some doubt on the validity of the previous findings and policy recommendations that are typically based on the ML specification.

Benin↗

Alterations of breathing in chronic heart failure: clinical relevance of arterial oxygen saturation instability.

1. In patients with chronic heart failure (CHF) alterations of breathing such as Cheyne-Stokes respiration (CSR) or periodic breathing, (PB) have been frequently described during both day- and night-time. These respiratory rhythm disorders are associated with marked oscillations of arterial oxygen saturation (SaO2) which may expose the patients to prolonged hypoxia. 2. In 40 stable CHF patients and 8 controls during awake day-time, we studied the relationship between alterations of breathing and SaO2, to verify the effect of voluntary control of respiration or oxygen therapy on the instability of SaO2 (analyzed as standard deviation (SD) of the mean value). Simultaneous recordings of ECG, lung volumes and SaO2 were made during 10 min. resting and 4 min. controlled breathing In a subgroup of 5 CHF the effect of oxygen therapy was compared to that of controlled breathing. 3. It was found that 62% of CHF had CSR or PB. Mean SaO2 and SD of SaO2 were significantly different in CHF as compared to controls (respectively 92.4 +/- 2.5 vs 95.4 +/- 0.5%, p < 0.002 and (1.27 +/- 0.9 vs 0.28 +/- 0.13%, p < 0.01), but among CHF pts those with CSR and PB had a lower SaO2 and a more pronounced instability of SaO2. Controlled breathing eliminated apneas and reduced or abolished the variation of tidal volume. In both control and CHF it resulted in an increase of mean SaO2 while a significant reduction of SaO2 instability was observed only in CHF, particularly if CSR or PB were present. Voluntary control of respiration was similar to oxygen therapy in increasing SaO2, but more effective on SaO2 SD. 4. It is concluded that in stable CHF, resting SaO2 is reduced and showed a marked instability particularly when periodic alterations of breathing were present. Continuous beat-to-beat recording of SaO2 may detect patients who have PB or CSR. Training to produce more regular breathing, regardless of the amount of ventilation, may represent a useful intervention.

Adult↗

Emergence of antibiotic-resistant bacteria in cases of peritonitis after intraabdominal surgery affects the efficacy of empirical antimicrobial therapy.

In cases of community-acquired peritonitis, the adequacy of emprical antibiotic treatment has been shown to attenuate mortality and morbidity. The impact of empirical antibiotics on the outcome of postoperative peritonitis has never been evaluated. This study included 100 consecutively studied patients with postoperative peritonitis. The adequacy of emprical treatment was determined by means of culture and susceptibility data obtained at the time of reoperation, and the effect of such treatment on outcome was evaluated. One hundred resistant pathogens were isolated from 70 patients, of whom 45% died; by comparison, mortality among those from whom susceptible organisms were isolated was 16% (P < .05). Inadequate empirical treatment was administered to 54 patients and was associated with poorer outcome (P < or = .05). The outcome of postoperative peritonitis is affected by the choice and adequacy of the initial empirical antibiotic therapy. Late changes in antibiotic therapy based on culture results did not affect outcome when the initial regimen was inadequate.

APACHE↗

Pediatric AIDS at Mount Sinai Medical Center 1988-89: a study of costs and social severity.

Pediatric AIDS is a continuing problem because of maternal transmission. Medical management is often complicated by the loss of one or both parents and adverse home environments. This study explores the cost of inpatient and clinic care of children admitted with AIDS in 1988 or 1989 at Mount Sinai Medical Center in New York City, and also examines the social severity of the cases. Blue Shield allowances were used to price clinic visits and tests, and prices in a drug trade publication were used to determine medication costs. Inpatient costs calculated per person-month at risk amounted to $48,000 per year. Costs per person-month of the clinic care averaged $461 (38% of which was for drugs), annualized to around $5,500. These costs are higher than those shown by previous studies. A few cases requiring intensive inpatient services accounted for a large percentage of costs. The social severity analysis, based on the family environment at first admission and later, revealed that households were often stressed by chronic illnesses, drug abuse, marital problems and poor residential quality. Given the circumstances in which pediatric AIDS develops, the activities of social workers to strengthen families are essential to facilitating compliance, maintaining health and minimizing use of the hospital.

Acquired Immunodeficiency Syndrome↗

Vincristine degradation by serum from leukemic patients: role of myeloperoxidase.

Myeloperoxidase (MPO) has been shown to catalyze the in vitro degradation of vincristine (VCR). Given that MPO is a lysosomal enzyme that can be released into the circulation by both normal activated and leukemic myeloid cells, we investigated the possibility that sera from patients with acute myeloblastic leukemia (AML) might exhibit an increased capacity to degrade VCR. 31 serum samples (23 from patients with acute myeloblastic leukemia and 8 from patients with other conditions) were analyzed after incubation with ((3)H)VCR by using HPLC. Sera from patients with AML demonstrated an increased ability to breakdown VCR when compared to either normal sera or to sera from patients with lymphoid leukemias. VCR degradation was significantly increased by adding hydrogen peroxide, an electron donor for MPO, to the sera and was almost completely inhibited by adding 1 mM acetaminophen, an inhibitor of MPO. VCR peroxidation in the presence of hydrogen peroxide correlated both with the number of leukemic blasts in the circulation at the time the sera were obtained and with serum MPO concentrations determined by an immunoassay. These data suggest that the inactivity of VCR in AML may be due in part to its rapid peroxidation to inactive species by the MPO of leukemic myeloblasts.

Acetaminophen↗

Ku protein complex is involved in nucleotide excision repair of DNA.

The repair of UV-C (254 nm) DNA lesions by nucleotide excision repair (NER) has been studied in the rodent cell line xrs6 belonging to complementation group 5 of ionising radiation sensitive (IRs) mutants. xrs6 cell line shows a defect in the DNA-end binding protein complex Ku which is involved in the repair of double-strand breaks (DSB) due to IR. In agreement with IR sensitivity, a bleomycin sensitive phenotype of xrs6 cell line was found as compared to the parental CHO-K1 line (factor > 8 fold). xrs6 exhibited also a slight (factor 2) but reproducible sensitivity to UV-C-light, while a revertant cell line for Ku DNA-end binding activity, xrs6rev, showed a restoration of both IR and UV-C sensitivities to the parental level. The NER activity of these cell lines was measured in vitro in nuclear protein extracts in the presence of plasmid DNA repair substrate damaged with UV-C lesions repaired by NER: xrs6 cell extracts exhibited only 55% of NER activity as compared to the control CHO-K1 and xrs6rev cell extracts. These results indicate that the Ku DSB repair protein is involved also in the NER process.

Animals↗

Inhibition of lysosomal acid sphingomyelinase by agents which reverse multidrug resistance.

An increasing body of evidence appears to implicate the lipid bilayer of multidrug resistant (MDR) cells with P-glycoprotein activity. Several cationic amphiphilic drugs (CADs) have been extensively described as modulators of MDR. These same agents are also known to (1) inhibit lysosomal acid sphingomyelinase (ASmase), a phospholipid degrading enzyme, and/or (2) induce phospholipidosis in animal tissues or cultured cell lines. In this report, we randomly selected 17 CADs and evaluated their potency in modulating MDR in the murine MDR P388/ADR leukemia cell line. We compared these results with their ability to inhibit ASmase and observed a significant dose-dependent linear relationship (95% central confidence interval), between ASmase inhibition and MDR reversal. This approach permitted us to identify three new modestly potent chemosensitizers: trimipramine, desipramine, and mianserine. Modulation of MDR was not cell line specific, since CADs at 10 microM increased doxorubicin (DOX) and vinblastine (VBL) (but not methotrexate, MTX) cytotoxicity in both P388/ADR and the human MDR cell lines MES-SA/Dx5 and K562/R7, but not in the parental drug-sensitive cells. Although all chemosensitizing CADs at 10 microM significantly increased Rhodamine-123 (Rho-123) accumulation in the human leukemia MDR cell line K562/R7 and most presented significant displacement of the photoaffinity labelling probe iodoarylazidoprazosin, no correlation between these observations and the ability of CADs to sensitize MDR cells to DOX and VBL was found. In conclusion, our study strongly suggests that the chemosensitizing potency of agents such as CADs may be due to a dual mechanism of action: direct antagonism of P-gp activity and indirect modulation of P-gp activity through the disruption of cellular lipid metabolism.

Affinity Labels↗