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Biomedical subjects

P Becker

Publications and source records attributed to P Becker.

At least 37 records · Page 2Linked to original sources

HIV infection in general surgical patients at the Ga-Rankuwa/MEDUNSA complex South Africa.

OBJECTIVE: To assess the possible impact of HIV infection on the management of general surgical patients at the Ga-Rankuwa Hospital. DESIGN: A prospective study. SETTING: Ga-Rankuwa Hospital/Medical University of Southern Africa (MEDUNSA) Academic Complex, Pretoria, South Africa. SUBJECTS: Nine hundred and forty one patients admitted to general surgical wards. MAIN OUTCOME MEASURES: HIV infection and CD4 counts. RESULTS: Nine hundred and forty one patients admitted to general surgical wards from January 1966 to December 1997 were tested for HIV infection. Twelve per cent tested positive. HIV positive patients were significantly younger [33 +/- 10 versus 41 +/- 7 (men +/- SD) years, Chi-square = 51, p < 0.0001]. There was no correlation of HIV positivity to the patient's sex (p = 0.7). In forty three HIV positive patients treated surgically, mortality was attributed to HIV/AIDS in only one patient with a CD4 count of 47/ul who died following laparotomy for peritonitis. CD4 counts done during follow up in thirty one HIV positive patients revealed a count of < 500/ul in eleven patients. CONCLUSION: It is predicted that an increasing number of patients with HIV/AIDS will be admitted to general surgery wards of the Ga-Rankuwa Hospital. Surgeons are advised to take universal precautions to prevent HIV infection.

Adolescent↗

[Treatment of advanced heart failure by heart transplantation].

BACKGROUND: Heart transplantation currently provides the most effective treatment for advanced heart failure. However, medical therapy for this condition has also improved, heart donors are scarce and the cost of the procedure is high. Therefore the indications and management of these patients need reevaluation. AIM: To analyze the results of 24 patients submitted to heart transplantation for end-stage heart failure needing repeated hospitalizations and i.v. inotropes for compensation. PATIENTS AND METHODS: The group was comprised by 21 men and 3 women with a mean age of 36.8 years, mean left ventricular ejection fraction 19 +/- 4.5%, mean systolic pulmonary artery pressure 48 +/- 13 mmHg (24-70) and mean pulmonary vascular resistance 2.6 Wood Units (1-5). Fourteen patients (58%) had a previous median sternotomy. Immunosuppression did not include induction therapy and steroids were discontinued early. RESULTS: Operative mortality was 4% at 30 days. Actuarial survival at one year was 90% and at 5 years 72%. Freedom from rejection at one year was 76% and at 5 years 50%. Freedom from infection was 70% at one year and 56.5% at five years. All patients with more than 3 months of follow-up were in functional class I. CONCLUSIONS: These results justify the proposed modifications for transplantation protocols.

Actuarial Analysis↗

[Germline mutations of the ret proto-oncogene in Chilean patients with hereditary and sporadic medullary thyroid carcinoma].

BACKGROUND: Medullary thyroid carcinoma (MTC) may occur either as a sporadic or familial disease. Multiple endocrine neoplasia (MEN) type 2, inherited as an autosomal dominant disease, is characterized by MTC only (FMTC) or coexistence of MTC with other endocrine neoplasia (NEM 2A, 2B). Germline mutations of the RET proto-oncogene (cRet) are found in the inherited forms and in some apparently sporadic MTC cases. AIM: To study RET mutations in 8 families with MEN 2. MATERIAL AND METHODS: RET mutations were screened in peripheral blood DNA from 18 patients and 87 high risk carriers belonging to 8 MEN 2 families and 52 sporadic MTC. Exons 10, 11, 13, 14, 15 and 16 of the c-Ret were amplified by polymerase chain reaction (PCR) and examined by direct sequencing of PCR products and/or restriction enzyme analysis. RESULTS: Five MEN 2A and one FMTC families with a germline mutation at codon 634, one MEN 2A and one FMTC family carrying a mutation at codon 620 were identified. Mutations were found in 23 out of 87 high risk carriers. In addition, we detected a S891A (exon 15) germline mutation in a sporadic MTC patient and in one out of her three sons and V804M (exon 14) in another sporadic MTC case and in one out of his six relatives, indicating in both cases the presence of a sporadic misclassified familial disease. CONCLUSIONS: These results underscore the importance of routine application of c-Ret testing in all cases of MTC either familial or sporadic.

Adolescent↗

[Coronary reoperation: a 16 years retrospective analysis].

BACKGROUND: Coronary artery bypass grafting (CABG) reoperation is being performed with increasing frequency. AIM: To assess the early and long term results of coronary reoperations in our institution and to identify prognostic factors. PATIENTS AND METHODS: 214 patients subjected to coronary reoperations between 1983 and 1999 were retrospectively studied. RESULTS: Mean age was 64.2 years (range 42-79 years), 202 (94.4%) were male and 12 (5.6%) female. The mean interval between the operations was 125.7 months (range 6-252 months). 10 (4.6%) were emergency surgeries. Overall operative mortality was 5.6% (11 deaths) and in 5 patients (3.4%) a perioperative myocardial infarction was noted. Univariate analysis identified moderate or severe left ventricular failure (p = 0.048) as predictor of increased operative mortality, meanwhile age over 75 years (p = 0.02) and moderate or severe left ventricular failure (p = 0.01) were identified as predictors of increased in hospital mortality in the multivariate analysis. Follow up of in hospital survivors (mean interval 65 months, range 4 to 190 months) documented a 5 years survival rate of 82.9%, a 10 years survival rate of 73.1% and a 15 years survival rate of 53.4%. Moderate or severe left ventricular failure (p < 0.0001) and emergency surgeries (p = 0.007) were identified as factors influencing the late survival in the stepwise logistical regression analysis. Multivariate analysis identified left ventricular failure (p = 0.01) and peripheral vascular disease (p = 0.01) as predictors of decreased late survival. CONCLUSIONS: Coronary reoperation has a low mortality in patients with a normal ventricular function and also has an excellent overall and disease free survival in the first 10 years of follow up. Left ventricular function is an independent risk factor increasing in hospital and late mortality.

Adult↗

Modeling of olive oil degradation and oleic acid inhibition during chemostat and batch cultivation of Bacillus thermoleovorans IHI-91.

Olive oil degradation by the thermophilic lipolytic strain Bacillus thermoleovorans IHI-91 in chemostat and batch culture was modeled to obtain a general understanding of the underlying principles and limitations of the process and to quantify its stoichiometry. Chemostat experiments with olive oil as the sole carbon source were successfully described using the Monod chemostat model extended by terms for maintenance requirements and wall growth. Maintenance requirements and biomass yield coefficients were in the range reported for mesophiles. For a chemostat experiment at D = 0.3 h(-1) the model was validated up to an olive oil feed concentration of about 3.0 g L(-1) above which an inhibitory effect occurred. Further analysis showed that the liberated oleic acid is the main cause for this inhibition. Using steady-state oleic acid concentrations measured in chemostat experiments with olive oil as substrate it was possible to derive a kinetic expression for oleic acid utilization, showing that a concentration of 430 mg L(-1) leads to a complete growth inhibition. Oleic acid accumulation observed during batch fermentations can be predicted using a model involving growth-associated lipase production and olive oil hydrolysis. Simulations confirmed that this accumulation is the cause for the sudden growth cessation occurring in batch fermentations with higher olive oil start concentrations. Further, an oscillatory behavior, as observed in some chemostat experiments, can also be predicted using the latter model. This work clearly demonstrates that thermophilic lipid degradation by Bacillus thermoleovorans IHI-91 is limited by long-chain fatty acid beta-oxidation rather than oil hydrolysis.

Bacillus↗

gamma-Ray wavelength standard for atomic scales.

The wavelength of the 57Fe Mössbauer radiation is measured with a relative uncertainty of 0.19 ppm by using almost exact Bragg backscattering from a reference silicon crystal. Its value is determined as lambda(M) = 0.860 254 74(16)x10(-10) m. The corresponding Mössbauer photon energy is E(M) = 14 412.497(3) eV. The wavelength of the 57Fe Mössbauer radiation is easily reproducible with an accuracy of at least 10(-11)lambda(M) and could be used as a length standard of atomic dimensions.

Journal Article↗

Differential ligand-dependent protein-protein interactions between nuclear receptors and a neuronal-specific cofactor.

Nuclear receptors are transcription factors that require multiple protein-protein interactions to regulate target gene expression. We have cloned a 27-kDa protein, termed NIX1 (neuronal interacting factor X 1), that directly binds nuclear receptors in vitro and in vivo. Protein-protein interaction between NIX1 and ligand-activated or constitutive active nuclear receptors, including retinoid-related orphan receptor beta (RORbeta) (NR1F2), strictly depends on the conserved receptor C-terminal activation function 2 (AF2-D). NIX1 selectively binds retinoic acid receptor (RAR) (NR1A) and thyroid hormone receptor (TR) (NR1B) in a ligand-dependent manner, but does not interact with retinoid X receptor (RXR) (NR2B) or steroid hormone receptors. Interestingly, NIX1 down-regulates transcriptional activation by binding to ligand-bound nuclear receptors. A 39-aa domain within NIX1 was found to be necessary and sufficient for protein-protein interactions with nuclear receptors. Northern blot analysis demonstrates low-abundance RNA messages only in brain and neuronal cells. In situ hybridization and immunohistochemistry revealed that NIX1 expression is restricted to the central nervous system and could be confined to neurons in the dentate gyrus of the hippocampus, the amygdala, thalamic, and hypothalamic regions. In summary, protein-protein interactions between the neuronal protein NIX1 and ligand-activated nuclear receptors are both specific and selective. By suppressing receptor-mediated transcription, NIX1 implements coregulation of nuclear receptor functions in brain.

3T3 Cells↗

Isolation and characterization of lipid-degrading Bacillus thermoleovorans IHI-91 from an icelandic hot spring.

An efficient lipid-degrading thermophilic aerobic bacterium was isolated from an icelandic hot spring and classified as Bacillus thermoleovorans IHI-91. The aerobic bacterium grows optimally at 65 degrees C and pH 6.0 and secretes a high level of lipase (300 Ul(-1)). The newly isolated strain utilizes several lipids such as palmitic acid, stearic acid, lanolin, olive oil, sunflower seed oil, soya oil, and fish oil as sole carbon and energy source without an additional supply of growth factors. The degradation of about 93% of triolein, which is present in olive oil, was observed after only 7h of fermentation at a maximal growth rate of 1.0 h(-1). During growth at optimal conditions on yeast extract, the doubling time was only 15 min. Based on 16S rDNA studies, DNA-DNA hybridization and morphological and physiological properties, the isolate IHI-91 was identified as Bacillus thermoleovorans IHI-91 sp. nov. Because of its production of high concentrations of thermoactive lipases and esterases and the capability of degrading a wide range of lipids at high temperatures, the isolated strain is an ideal candidate for application in various biotechnological processes such as wastewater treatment.

Bacillus↗

[Myocardial revascularization of the anterior descending artery with the classical technic of mammary anastomosis].

INTRODUCTION AND OBJECTIVES: To establish the results obtained with the classical technique of mammary anastomosis of the anterior descending artery. MATERIALS AND METHODS: Between January 1982 and July 1997, 154 patients received an anastomosis of the left internal mammary artery to the left anterior descending coronary artery with use of the classical technique (sternotomy and extracorporeal circulation). RESULTS: There was no operative mortality in our group, nor paraoperational myocardial infarction, nor cephalic vascular accidents. One (0.6%) patient had sternal wound infection, and another (0.6%) required another reoperation for postoperational bleeding. All (100%) were followed-up from 3-183 months (average 64. 4 months). Actuarial global survival at 5, 10 and 15 years was 95.6%+/-2.1; 92.1%+/-4 and 85.5+/- 7.5 respectively, and the actuarial probability of being free from cardiac death was 99%+/-0.9; 99% and 99%. The actuarial probability of being free from myocardial infarction was 99%+/-0.9; 99%+/-0.9 and 99%; and from angina was 95%+/-2.2; 86.9%+/-4.9 and 74.5%+/-12.2 at 5, 10 and 15 years.Finally, the actuarial probability of being free from reoperation was 99%+/-0.9; 99%; 99% and from angioplasty 96.9%+/-1.7; 91.4%+/-4.1; 91.4%+/-4.1 at 5, 10 and 15 years, respectively. The average hospital charges in the last 10% of the patients was U$ 6.200. CONCLUSIONS: Revascularization of the left anterior descending with the left internal mammary artery and the classical technique (sternotomy and extracorporeal circulation) is a safe, minimal risk, effective, long lasting and cost efficient procedure with excellent results at 10 and 15 years.

Adult↗

Effects of infant and caregiving conditions on an infant's focused exploration of toys.

An infant's exploration of toys, in the context of the mother's regulating actions, is a setting for cognitive and social development. The aim of this study was to examine the contribution of infant and caregiving conditions to the quantity of focused exploration of toys for 8-month-old infants. Infant biological conditions were gender and birth weight, including a range of both prematurely and term-born infants. The infant behavioural condition was responsiveness to care. Caregiving conditions included mother's education, the supportive, stimulating and sustaining quality of the home environment, and the attention-directing and -supporting behaviour of the mother during play. The direct and indirect effects of these conditions on focused toy exploration were modelled using multiple regression. The sample of 79 mother-infant dyads included 43 full-term infants and 36 premature infants. The mother's attention-directing behaviour was a significant negative predictor of focused toy exploration. Infant birth weight did not have a significant direct effect on focused toy exploration. Birth weight did not interact significantly with responsiveness to care or with any of the caregiving environment conditions to affect focused toy exploration. Further study of infant responses to the mother's attention-regulating and emotion-regulating behaviour during play is recommended to better understand how the caregiving environment supports or thwarts focused toy exploration.

Adult↗

In vivo effects of interleukin-10 on human cytochrome P450 activity.

BACKGROUND: Injection of lipopolysaccharide into human volunteers leads to an increase in serum interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha and a significant decrease in cytochrome P450 (CYP)-mediated drug metabolism. The in vivo effects of the noninflammatory cytokine interleukin-10 (IL-10) on CYP-mediated drug metabolism was examined. METHODS: IL-10 (8 microg/kg) and placebo were administered for 6 days to 12 healthy volunteers in a double-blind crossover study. Tolbutamide (CYP2C9), caffeine (CYP1A2), dextromethorphan (CYP2D6 and CYP3A), and midazolam (CYP3A) were administered on days 4 and 5 to determine individual CYP activities. RESULTS: Few clinically apparent side effects were observed after administration of IL-10; however, blood chemistries reflected an acute-phase response. A significant drop in serum albumin (mean percentage change +/- SD between groups; 4.7% +/- 6.0%, P < or = .02), a significant increase in serum ferritin (736% +/- 717%, P < or = .001), and a significant reduction in platelet count (49% +/- 12%, P < or = .0001) was observed after administration of IL-10. IL-10 significantly (P < or = .02) decreased CYP3A activity 12% +/- 17%, as reflected by midazolam clearance. CYP2C9 activity was significantly (P < or = .005) increased by 38% +/- 35%, as reflected by the tolbutamide urinary metabolic ratio and oral clearance. However, administration of IL-10 resulted in a 40% increase in the fraction unbound of tolbutamide. Therefore no difference in the unbound clearance of tolbutamide was observed between placebo (23.3 +/- 9.7 L/h) or IL-10 (23.5 +/- 11.4 L/h) administration. No significant changes in either CYP1A2 or CYP2D6 activities were observed between placebo and treatment arms of the study. CONCLUSION: IL-10 administration resulted in an acute-phase response. Administration of IL-10 did not alter CYP1A2, CYP2C9, and CYP2D6 activities. CYP3A-mediated biotransformation was reduced by administration of IL-10.

Adult↗

Tapered conduits can buffer hydraulic conductance from path-length effects.

The model of West, Brown and Enquist showed that total hydraulic resistance in trees can be independent of path length, provided that vascular conduits taper sufficiently. This model assumes that the tree branch network is volume-filling, so that segment lengths increase exponentially from tree top to base. We show that partial buffering of hydraulic resistance from path-length effects can occur even for moderate tapering, and that this effect is stronger when segment lengths are fixed. Still needed are measurements of tracheary size and hydraulic resistance designed to test this model, which shows how hydraulic limitation of tree height growth may be mitigated.

Buffers↗

High-density lipoproteins inhibit fibrinogen binding on adenosine diphosphate-activated monocytes.

High levels of fibrinogen and low levels of high-density lipoprotein (HDL) cholesterol were reported to be risk factors for coronary heart disease. CD11b/CD18, a fibrinogen-binding protein, is expressed on the surface of monocytes, which play a crucial role in the formation of atherosclerotic lesions. In the present study, we investigate the effects of antibodies against CD11b and CD18, as well as HDL3 and low-density lipoprotein (LDL) cholesterol on fibrinogen binding on monocytes. We find that binding of fibrinogen on monocytes activated with adenosine diphosphate (ADP) was reduced to 66.0+/-8.3% (mean +/- SD) in the presence of anti-CD11b antibodies (12.5 microg/ml; P < or = 0.02) and to 54.5+/-4.9% in the presence of anti-CD18 antibodies (20 microg/ml; P < or = 0.01), respectively. Fibrinogen binding on Cytochalasin-B-activated monocytes was reduced to 79.8+/-6.0% in the presence of anti-CD18 (20 microg/ml; P < or = 0.05). Incubation of ADP-activated monocytes with HDL3 (0.5 g/l) led to a lowering of fibrinogen binding to 65.0+/-6.6% (P < or = 0.05). No effect of HDL3 on fibrinogen binding was seen on Cytochalasin-B-activated monocytes. A slight, non-significant stimulatory effect of LDL on fibrinogen binding on ADP-activated but not on Cytochalasin-B-activated monocytes was additionally observed. Neither incubation with HDL3 or with LDL had a significant influence on ADP-activated cellular binding of anti-CD11b or anti-CD18 antibodies. The inhibition of fibrinogen binding on monocytes in the presence of HDL3 is a major new finding of this study. Since inhibition of fibrinogen binding in the presence of HDL might impair both monocyte recruitment to the arterial wall and foam cells formation, our findings suggests a novel mechanism by which HDL may prevent development of arteriosclerosis.

Adenosine Diphosphate↗

Comparison of heat and cold stress to assess thermoregulatory dysfunction in hypothyroid rats.

How borderline impairment of thyroid function can affect thermoregulation is an important issue because of the antithyroidal properties of a many environmental toxicants. This study compared the efficacy of heat and cold stress to identify thermoregulatory deficits in rats subjected to borderline and overt hypothyroidism via subchronic exposure to propylthiouracil (PTU). After 3 wk of exposure to PTU in the drinking water (0, 2.5, 5, 10, and 25 mg/l), rats were subjected to a heat stress challenge (34 degrees C for 2.5 h). After one more week of PTU treatment, the same rats were subjected to a cold stress challenge (7 degrees C for 2.5 h). Core temperature (T(c)) was monitored by radiotelemetry. Baseline T(c) during the light phase was reduced by treatment with 25 mg/l PTU. The rate of rise and overall increase in T(c) during heat stress was attenuated by PTU doses of 10 and 25 mg/l. Cold stress resulted in a 1.0 degrees C increase in T(c) regardless of PTU treatment. The rate of rise in T(c) during the cold stress challenge was similar in all PTU treatment groups. There was a dose-related decrease in serum thyroxine (T(4)) at PTU doses >/=5 mg/l. Serum triiodothyronine (T(3)) was reduced at PTU doses of 5 and 25 mg/l. Serum thyroid-stimulating hormone (TSH) was marginally elevated by PTU treatment. Overall, heat stress was more effective than cold stress for detecting a thermoregulatory deficit in borderline (i.e., 10 mg/l PTU) and overtly hypothyroid rats (i.e., 25 mg/l PTU). A significant thermoregulatory deficit is manifested with a 78% decrease in serum T(4). A thermoregulatory deficit is more correlated with a reduction in serum T(4) compared with T(3). Serum levels of TSH are unrelated to thermoregulatory response to heat and cold stress.

Acclimatization↗

Case control study of environmental factors in the etiology of the first attack of acute pancreatitis: a pilot study.

The aim of this case control study was to assess environmental factors in the etiology of the first attack of acute pancreatitis (AP) in Soweto, South Africa, in the light of modern developments. The study group consisted of 30 patients presenting with a first attack of AP, and 30 healthy age- and gender-matched controls. Fruit intake was found to be a protective factor (odds ratio [OR] 5.3). Crude ORs, although of marginal importance, showed that daily alcohol intake and years of exposure to occupational chemicals may be of significance but would require a much larger study to test these factors. This would be necessary in order to explain the rapid increase in pancreatitis coincident with urbanization and industrialization in the community.

Acute Disease↗

[Multiple endocrine neoplasia: a clinical model for applying molecular genetic techniques].

Multiple endocrine neoplasias (MEN) are syndromes inherited as autosomal dominant. The application of the techniques of molecular biology has made possible the identification of the genes causing MEN 1 and 2. The gene responsible for MEN 1 belongs to the family of tumor suppressor genes and encodes for a protein named MENIN whose function remains to be elucidated. The identification of mutant MEN 1 gene carriers who are at risk of developing this syndrome requires frequent biochemical screening for the development of endocrine tumors. MEN 2 is a consequence of mutations in the Ret proto-oncogene (c-Ret). This gene encodes for a tyrosine kinase receptor thought to play a role in the development of neural crest-derived tissue. Members of kindred with either MEN 2A or MEN 2B should be screened by direct DNA testing early in life for mutations in c-Ret. Those with the mutation should be advised to have thyroidectomy at five years of age in children with MEN 2A and earlier in children with MEN 2B. Some cases of sporadic MTC are actually MEN 2A or Familial MTC after c-Ret testing is done, therefore routine application of this test is recommended in all cases of apparent sporadic MTC.

Adult↗

[Humoral rejection in heart transplantation. Report of 2 cases].

Heart transplantation is a therapeutic alternative for selected patients with refractory heart failure. Acute allograft rejection is one of the main causes of early death after transplantation. The cellular rejection is characterized by cellular infiltrates with or without myocyte necrosis. However, some patients develop left ventricular dysfunction due to rejection without evidence of cellular infiltration. In these patients, the rejection is mediated by antibodies and complement. Humoral rejection is a relative rare but potentially fatal form of acute allograft rejection. We report two patients with left ventricular dysfunction secondary to humoral rejection, shortly after cardiac transplantation. Both patients were treated with methylprednisolone, and azathioprine was substituted by cyclophosphamide. One patient underwent plasmapheresis. The clinical outcome was satisfactory and the left ventricular function returned to normal in both cases. The diagnostic and therapeutic strategies for the management of humoral rejection are reviewed.

Antibody Formation↗

Inverse association between endogenous glucocorticoid secretion and L-selectin (CD62L) expression in trauma patients.

Exogenously administered glucocorticoids downregulate inflammatory host response, i.e. by inhibition of adhesion molecule expression on leukocyte surfaces. Here, possible associations between the trauma-induced endogenous secretion of cortisol and the expression of neutrophil adhesion molecules (L-selectin/CD62L, CD 11b, CD54) were studied in humans. Standardized elective hip arthroplasty was investigated as an exemplary condition of acute inflammation. In 20 patients, blood for quantification of cortisol and adrenocorticotropic hormone was obtained at minutes 10, 20, 30, 60, hours 1, 2, 4 and 10 and days 1,3 and 7. Expression of L-selectin/CD62L, CD11b and CD54 on neutrophil surfaces was determined preoperatively, and postoperatively at hours 1, 2, 3, 4, and 10 and at days 1 and 3. Secretion of both, adrenocorticotropic hormone and cortisol was significantly increased between 1-10 hours after onset of tissue injury. Compared to baseline values, CD11b expression was increased at hour 1 and normalized after day 1, whereas L-selectin/CD62L expression, mirroring this pattern was decreased until day 1. Patients with high endogenous glucocorticoid secretion exhibited significantly decreased expression selectively of L-selectin/CD62L. However, we also observed that glucocorticoids do not directly induce L-selectin shedding from neutrophil surfaces in vitro, arguing for more indirect glucocorticoid action on adhesion molecule expression. Together, this study showed that increased endogenous cortisol secretion is associated with lower expression of L-selectin on neutrophil surfaces in humans that is consistent with a downmodulating role of this neuroendocrine stress response in inflammatory leukocyte recruitment.

Adrenocorticotropic Hormone↗