Epidemiology of Staphylococcus aureus in patients with cystic fibrosis

Seven hundred and thirty-four isolates of Staphylococcus aureus, recovered from the sputum of 238 cystic fibrosis patients in six French hospitals, were characterized by esterase electrophoretic typing, capsular polysaccharide sero-typing and phage typing and tested against 14 antibiotics for sensitivity. Thirty-four esterase electrophoretic types were found with a genotypic diversity coefficient of 0·91. Five hundred and forty-eight (78·7%) isolates produced capsular polysaccharide and 350 (50·3%) were type 8. Four hundred and sixty isolates (66·6%) were phage typable and 202 (28·2%) were lysed by group III bacteriophages. No esterase electrophoretic type, capsular type or phage type was specific to cystic fibrosis. Isolates belonged to a wide range of types, similar to strains acquired outside hospitals. Eighty-five patients had three or more consecutive isolates over at least 6 months. The ability of S. aureus to persist for long periods of time has been demonstarated in 73% of them. Methicillin-resistance was enacountered among 73 strains (9·8%) which were also multiresistant. Two hundred and eighty-nine (39·9%) strains were sensitive to all antibiotics tested except to penicillin. Pristinamycin and co-trimoxazole were the most effective antibiotics. These results could contribute to the elaboration of a rational approach to the prophylaxis and therapy of respiratory staphylococcal infections in cystic fibrosis patients.     

Hemophilia B Leyden: substitution of thymine for guanine at position - 21 results in a disruption of a hepatocyte nuclear factor 4 binding site in the factor IX promoter

Hemophilia B Leyden is an X chromosome-linked bleeding disorder characterized by an altered developmental expression of blood coagulation factor IX. This form of hemophilia B has been found to be associated with a variety of single point mutations in the factor IX promoter region. We now describe a novel point mutation, T-->G at position -21, in two related patients with the hemophilia B Leyden phenotype. This mutation lies within the factor IX promoter region (-40 to -9) that contains overlapping binding sites for hepatocyte nuclear factor 4 (HNF-4) and androgen receptor. Transient transfection assays in HepG2 cells show that the -21 mutation causes a significant reduction in factor IX promoter activity. Gel mobility shift assays and transient cotransfection experiments revealed that the HNF-4-binding site but not the androgen-responsive element is disrupted by the -21 mutation. A comparison of the -21 mutation with the previously described -20 T-->A mutation (associated with the hemophilia B Leyden phenotype) and -26 G-->C mutation (associated with severe hemophilia B throughout life) was made. It shows that the -21 mutation reduced HNF-4 binding and transactivation to a similar level as the -20 mutation, whereas the -26 mutation completely abolished HNF-4 binding and transactivation. Mobility shift experiments indicate that there was no significant difference in binding affinity of recombinant androgen receptor protein for oligonucleotides containing wild-type and -21 or - 20 mutated DNA. The binding affinity for the oligonucleotide containing the -26 mutation was twofold lower. The results indicate that the disruption of the HNF-4-binding site by the -21 T-->G mutation is the cause of the bleeding disorder in these two patients. This study adds further support for the notion that the recovery from hemophilia at puberty may not only be related to an intact androgen-responsive element but also to the degree of disruption of the HNF-4-binding site.     

Effects of the platelet activating factor antagonists BN 52021 and BN 50730 on antigen-induced bronchial hyperresponsiveness and eosinophil infiltration in lung from sensitized guinea-pigs

The involvement of platelet activating factor (PAF) in antigen-induced bronchial hyperresponsiveness was investigated by the use of the PAF antagonists BN 52021 and BN 50730, in a guinea-pig model where sensitization and challenge were performed by aerosol. Male Hartley guinea-pigs were sensitized by two aerosol exposures at 48 hr intervals to a 0.9% NaCl solution (saline) containing 2 mg/ml ovalbumin for 30 min. Fifteen to 20 days later, guinea-pigs were challenged by exposure to five successive aerosols of increasing concentrations of ovalbumin (OA) or respectively, 10 microg/ml, 100 microg/ml, 1 mg/ml, 5 mg/ml and 10 mg/ml for 15 min each, or saline alone. Three to four hr and 18-24 hr after the aerosol challenge the guinea-pigs were prepared for recording of bronchopulmonary response and aerosol administrations were then generated with an ultrasonic nebulizer. The bronchopulmonary responses induced by successive 1-min aerosol bursts of acetylcholine (ACh) was assessed. As compared with saline-challenged guinea-pigs, an enhanced bronchopulmonary response to aerosol administration of cumulative doses of ACh was observed, 3-4 hr and 18-24 hr post-ovalbumin challenge. When the sensitized guinea-pigs were pretreated 1 hr before ovalbumin exposure with BN 52021 or BN 50730 (25 mg/kg, per os), a significant inhibition of the increase in the bronchopulmonary response to ACh was observed, both at 3-4 hr and 18-24 hr. Furthermore, when guinea-pigs were treated 3-4 hr after the ovalbumin exposure with BN 52021 or BN 50730, a significant inhibition of the hyperresponsiveness to ACh was recorded at 18-24 hr. A marked accumulation of eosinophils in the peribronchial regions was observed on histological preparations of lung specimens collected 4 hr or 24 hr after ovalbumin exposure. Pretreatment of the guinea-pigs by BN 50730 or BN 52021 did not modify the eosinophil accumulation in the peribronchial area. No significant difference in the number of eosinophils collected in the bronchoalveolar lavage fluid is observed, 24 hr post-ovalbumin challenge, under the pretreatment with BN 52021 or BN 50730. Pretreatment of guinea-pigs by BN 50730 or BN 52021 significantly reduced the PAF-induced (100 microg/ml) increase in eosinophil number in the peribronchial area. By contrast, they did not inhibit the eosinophilia induced by aerosol administration of LTB4 (5 microg/ml). These results suggest that the bronchial hyperresponsiveness observed in this study is associated with eosinophil accumulation in the lung. The potent inhibition of the bronchial hyperresponsiveness by the two unrelated antagonists of PAF suggests that the lipid mediator is involved in its triggering and duration, but not in the eosinophil infiltration.     

NEHUSHTAN: SIDE EFFECTS OF DRUGS

The role of the snake is ambivalent in the Bible. The primeval serpent was instrumental in the exile of Adam and Eve from Eden, but It did not really lie. The fruit of the tree did provide knowledge of good and evil and humankind has been blessed (cursed?) with that knowledge ever since (Gen 3:1–24).     

The development of SisterTalk: a cable TV-delivered weight control program for black women

Overweight and obesity have reached epidemic proportions in the United States, with black women disproportionately affected. SisterTalk is a weight control program designed specifically for delivery to black women via cable TV. The theoretical and conceptual frameworks and formative research that guided the development and cultural tailoring of SisterTalk are described. Social Action Theory was applied in the development of SisterTalk along with a detailed behavioral analysis of the way that black women view weight and weight loss within the context of their cultural and social realities. The entire intervention development process was framed using this information, rather than by changing only superficial aspects of program delivery. Community networking and both qualitative and quantitative interview techniques from the fields of social marketing and cultural anthropology were used to involve black women from Boston in the design and implementation of a program that would be practical, appealing, and culturally sensitive. Also discussed are strategies for evaluating the program, and lessons learned that might have broader applicability are highlighted. The development of the SisterTalk program could provide a useful starting point for development of successful weight control programs for black women in other parts of the United States as well as for other ethnic and racial groups.     

The influence of breakfast and a snack on psychological functioning.

Although there are reports that breakfast influences both mood and memory, there has been no attempt to consider whether a subsequent snack is beneficial. One hundred and fifty young female adults either fasted or consumed breakfasts of either 10 or 50 g of carbohydrate (corn flakes). Half received a further 25 g of carbohydrate in the form of corn flakes after 1 1/2 h (snack). Predictably, those who ate breakfast, and/or a snack, reported feeling less hungry. The larger the caloric intake, the less subjects reported hunger. Those who consumed a snack reported a better mood. Eating a larger breakfast was associated with poorer mood later in the morning, an effect reversed by eating a snack. Memory for the word lists was not influenced by eating breakfast, however, 20 but not 60 min after a midmorning snack, more words were recalled. Those who had eaten breakfast, as opposed to fasting, did, however, spend longer trying to recall the words. This finding was interpreted as evidence that eating breakfast was associated with better motivation. On a number of occasions, better memory was associated with lower blood glucose levels. These findings support previous observations that better glucose tolerance was associated with better memory.     

Respiratory syncytial virus pneumonia ventilated with high-frequency oscillatory ventilation

Abstract Four infants below 6 months of age with proven respiratory syncytial virus infection in need of assisted mechanical ventilation were successfully treated by high-frequency oscillatory ventilation. One of the four infants fulfilled the criteria for extracorporeal membrane oxygenation before the start of oscillation, and one on the second day on high-frequency oscillatory ventilation. However, extracorporeal membrane oxygenation was not needed in any of the infants. All survived, and three appeared to be without any pulmonary sequelae.     

Comparison of the effects of cyclosporin a on the metabolism of perfused rat brain slices during normoxia and hypoxia.

The authors evaluated and compared the metabolic effects of cyclosporin A in the rat brain during normoxia and hypoxia/reperfusion. Ex vivo 31P magnetic resonance spectroscopy experiments based on perfused rat brain slices showed that under normoxic conditions, 500 microg/L cyclosporin A significantly reduced mitochondrial energy metabolism (nucleotide triphosphate, 83 +/- 9% of controls; phosphocreatine, 69 +/- 9%) by inhibition of the Krebs cycle (glutamate, 77 +/- 5%) and oxidative phosphorylation (NAD+, 65 +/- 14%) associated with an increased generation of reactive oxygen species (285 +/- 78% of control). However, the same cyclosporin A concentration (500 microg/L) was found to be the most efficient concentration to inhibit the hypoxia-induced mitochondrial release of Ca2+ in primary rat hippocampal cells with cytosolic Ca2+ concentrations not significantly different from normoxic controls. Addition of 500 microg/L cyclosporin A to the perfusion medium protected high-energy phosphate metabolism (nucleotide triphosphate, 11 +/- 15% of control vs. 35 +/- 9% with 500 microg/L cyclosporin A) and the intracellular pH (6.2 +/- 0.1 control vs. 6.6 +/- 0.1 with cyclosporin A) in rat brain slices during 30 minutes of hypoxia. Results indicate that cyclosporin A simultaneously decreases and protects cell glucose and energy metabolism. Whether the overall effect was a reduction or protection of cell energy metabolism depended on the concentrations of both oxygen and cyclosporin A in the buffer solution.     

Effect of Waveform Tilt on Defibrillation Thresholds in Humans

Effect of Tilt on Defibrillation Threshold. Introduction : Despite the common use of the implantable cardioverter defibrillator to treat patients with life-threatening ventricular arrhythmias, the mechanism of defibrillation and the optimal waveform for implanted devices are poorly understood. All of the currently available pulse generators deliver exponentially declining pulses that are either automatically or manually truncated to achieve tilts of about 50% to 65%. Although this value was chosen based on experimental animal data, several theoretical models have been developed to describe defibrillation, which raise into question this choice of waveform shape. Accordingly, the present study was designed to test the effect of waveform tilt on defibrillation efficacy in humans.
Methods and Results : Twenty-three patients undergoing cardioverter defibrillator implantation were studied. Monophasic defibrillation thresholds (DFTs) were measured using a single reversal protocol at 35%, 50%, 65%, and 80% tilts by altering the pulse width of the shock. Mean defibrillation impedance was 41 ± 6 Ω. The DFT, measured by either leading-edge voltage or stored energy, was insensitive to altering the waveform tilt from 50% to 80%, only increasing when the tilt was reduced to 35%. A tilt of 65% yielded the lowest DFT voltage in only 8 of 23 patients. Significantly lower DFTs (≥ 40 V) were obtained using other tilts in seven patients. When the relationship between average current and pulse width was fit with a Weiss-Lapicque model, the data yielded a mean chronaxie of 4.6 ± 3.0 msec and a rheobase of 4.2 ± 1.7 A, but considerable patient variability was observed.
Conclusion : On average, DFTs in humans are insensitive to altering monophasic waveform tilts between 50% and 80%. There is, however, considerable patient variability, raising into question the premise that a single defibrillator waveform tilt is best for all patients.     

Analysis of solid renal dysplasia by flow cytometry: malignant potential?

Renal nodular blastema/nephroblastomatosis is a recognized precursor of Wilms tumor. It also has been shown that nodular renal blastemata are seen in association with dysplastic renal parenchyma secondary to obstructive uropathy (i.e., ureteroceles or ectopic ureters). In an attempt to improve our understanding of the critical relationship between renal dysplasia and neoplasia, we performed flow cytometric evaluation on 16 paraffinembedded specimens of dysplastic kidneys removed during the period 1984–1989. All nephrectomy specimens were associated with obstruction, either duplex collecting systems (10), ectopic ureters (2) or posterior urethral valves (2), or vesicoureteral reflux (2). One specimen was found to contain nodular renal blastema. No evidence of malignancy was found in any specimen. A specimen of normal kidney and two of Wilms tumor (favorable histology) were studied for comparison. Nuclear deoxyribonucleic acid (DNA) ploidy studies were performed on single dissociated nuclei after deparaffinization and staining with propidium iodide. All dysplastic specimens, including the specimen with nodular renal blastema, demonstrated a diploid pattern of DNA as did the specimens of normal renal tissue. The Wilms tumor specimens demonstrated a diploid and a tetraploid pattern. In view of the fact that Wilms tumor may demonstrate diploid DNA patterns on flow cytometry, the findings of diploid patterns on all specimens of solid dysplasia militate against but do not eliminate the possibility of malignant degeneration.