Effect of local mupirocin application on exit-site infection and peritonitis in an Indian peritoneal dialysis population.

BACKGROUND: Staphylococcus aureus-associated peritonitis and catheter exit-site infections (ESIs) are important causes of hospitalization and catheter loss in patients undergoing chronic peritoneal dialysis. Intranasal and topical use of mupirocin has been found to be an effective strategy in decreasing S. aureus-related infectious complications in persons who are carriers of S. aureus; however, there is no consensus regarding the prophylactic use of mupirocin irrespective of carrier status. We aimed to determine the potential effectiveness of application of mupirocin cream at the catheter exit site in preventing ESI and peritonitis irrespective of carrier status in a tropical country such as India. METHODS: This prospective historically controlled study was done in a total of 40 patients. From August 2003, all patients, incident and prevalent, were instructed to apply 2% mupirocin cream daily to the exit site instead of the older practice of povidone-iodine and gauze dressing. Patients were not screened to determine whether they were S. aureus carriers. The infection-related data for 1 year, until July 2004, were compared with the historical control, which was infection-related data for the year preceding the year of mupirocin application. RESULTS: Mean age of the study population was 62 years, with 61.8% being male and 64.3% being diabetic. Local application of mupirocin led to a significant reduction in the incidence density per patient-month of both ESI and peritonitis compared to controls (0.15 vs 0.37 and 0.37 vs 0.67, p = 0.01 for both). This amounted to a relative reduction of 60.5% and 55% respectively. ESI and peritonitis due to S. aureus were also significantly lower in the study group compared to controls (incidence density per patient-month 0.05 vs 0.13 and zero vs 0.17 respectively, p < 0.01 for both). There occurred no catheter removal due to infection-related complications during the study period compared to two during the control period. None of the patients reported a mupirocin-related adverse effect. CONCLUSIONS: Daily application of mupirocin at the exit site is a well-tolerated and effective strategy in reducing the incidence of ESI and peritonitis in a tropical country such as India. It can thus significantly reduce morbidity, catheter loss, and transfer to hemodialysis in peritoneal dialysis patients.     

Evaluation and assessment of high sensitivity thyrotropin methods as an index for thyroid function

We report the evaluation of four new commercially available sensitive assay kits for determination of thyrotropin (TSH) and their clinical utility in normal subjects and patients with thyroidal and non-thyroidal illnesses. The sensitivity for the reliable detection of serum TSH by these methods ranged from 0.1-0.4 mU/L and their decreasing order was : NML greater than Serono greater than Abbott EIA greater than Hybritech. The coefficient of variation ranged from 2.0-5.8% for intra-assay and 2.3-8.6% for interassay at different concentration levels. Patients studied (n = 130) were assigned into four groups on the basis of the serum thyroxine value and their clinical findings. In total, there were 17 discrepancies (five with Hybritech, three with NML, five with Abbott EIA, and four with Serono) in making the correct diagnosis using these sensitive TSH methods as a single diagnostic test. These discrepancies were mainly in the same patients who were clinically euthyroid but had subnormal TSH values. There were no discrepancies in making the correct diagnosis for patients with hyperthyroidism or hypothyroidism using these sensitive TSH methods. Our observations indicate that the sensitive TSH methods are reliable in measuring subnormal levels and may be used to detect hyperthyroidism without affecting in any way their value in detecting hypothyroidism.     

Factors affecting the use of peritoneal dialysis among the ESRD population in India: a single-center study.

OBJECTIVES: Factors such as limited health-care budget allotment and poor accessibility of the majority of the population to hemodialysis (HD) facilities should favor the use of peritoneal dialysis (PD) in India. However, only 6% of end-stage renal disease patients undergoing dialysis in India are on PD. We undertook this prospective study to evaluate various factors that could contribute to this low rate of use of PD at a tertiary-care state-run hospital in Northern India. METHODS: All the patients who entered our HD or PD program from August 2001 to December 2003 were interviewed using a preset questionnaire. The questionnaire recorded their basic disease and comorbidity, social and demographic characteristics, awareness of the various modalities of renal replacement therapy (RRT), and the reasons for choosing their present modality of therapy. Treating nephrologists were also interviewed with respect to the factors that, in their opinion, were responsible for the limited use of PD at our institute. RESULTS: In total, 342 patients on HD, 66 patients on PD, and 24 nephrologists were interviewed. The rate of PD use was 16.2%. Mean age of patients on HD and PD was 34.6 +/- 11.8 years and 62.9 +/- 10.3 years respectively (p < 0.0001). The incidence of diabetes mellitus and coronary artery disease in the HD and PD populations was 2.5% and 62.5%, and 9.1% and 46.7% respectively (p < 0.0001 for both). Only 30.4% of patients on HD were aware of PD as a modality of RRT and 83.6% of them found PD to be expensive, 65.4% had low enthusiasm toward a domiciliary therapy such as PD, and 61.5% were not recommended PD by their nephrologist. Only 5 (7.6%) patients were initiated on PD directly, the remaining 61 patients were shifted from HD after a mean duration on HD of 185.3 +/- 15.4 days: 67.1% were shifted due to poor tolerance of HD, 29.4% were advised to shift to PD because of comorbidity and vascular access problems, and only 3.3% took up PD because of the independent lifestyle it offered. None of the interviewed nephrologists routinely discussed PD in predialysis counseling. They found financial constraints (100%), lack of patient enthusiasm (100%), doubtful patient compliance (83.2%), and lack of an organized PD program (79.2%) to be the main factors limiting more widespread use of PD at our institute. CONCLUSIONS: Peritoneal dialysis is an underused modality of RRT at our institute. The patients who are taken up for PD at our institute are elderly and have a higher incidence of other comorbid conditions, such as diabetes mellitus and coronary artery disease. Also, most patients who switch to PD do so due to their unsuitability for HD rather than by their own choice. The factors contributing to this low rate of use of PD are ignorance of PD, increased cost of therapy, low enthusiasm toward domiciliary therapy, and lack of adequate infrastructure for PD at our institute. Effective predialysis counseling, reduction in the cost of the therapy, and development of an adequate infrastructure can increase the rate of use of PD.     

Control of feeding and sexual behaviors by neuropeptide Y: physiological implications

Recent evidence suggests that a variety of hypothalamic neuropeptides may mediate interneuronal communication to coordinate diverse neuroendocrine and behavioral functions. In this work, we describe the effects of neuropeptide Y (NPY) on feeding and sexual behaviors. We observed that central administration of bolus NPY stimulated a robust, dose-related feeding response in satiated male and female rats. Continuous NPY receptor activation also evoked dose-related, intermittent feeding in a manner normally observed during nocturnal feeding. It appears that the paraventricular nucleus in the hypothalamus may be the primary site of NPY action because the anticipated reciprocal changes in NPY concentrations, in response to food deprivation followed by ad libitum food intake, occurred only in this site. Additional findings revealed that NPY-induced feeding may follow either substantial reduction or complete restraint of an inhibitory influence on feeding mediated by alpha 2-adrenoreceptor systems in satiated rats. Further, NPY was found to suppress male and female sexual behaviors. The suppressive effects on sexual behavior were apparent prior to or at the time of the onset of feeding after NPY administration. These observations may provide a neurochemical basis for clinical and animal studies on disorders of feeding associated with diminished reproductive functions.     

The effect of hypoxia on acquired drug resistance and response to epidermal growth factor in chinese hamster lung fibroblasts and human breast-cancer cells in vitro

Prolonged hypoxia induced transient drug resistance in Chinese hamster lung fibroblasts. Previously hypoxic cells were resistant to adriamycin and resistant to etoposide. Complete recovery of etoposide sensitivity was observed following re-aeration for 24 hr. A change in P-glycoprotein expression was unlikely to contribute to the resistance caused by hypoxia, since adriamycin resistance was not reversed by verapamil. However, alteration in the plasma membrane structure may be involved, since previously hypoxic cells were resistant to extracellular superoxide radical generated by the addition of xanthine/ xanthine oxidase. In contrast, adriamycin sensitivity was not altered by hypoxia in 3 human breast-cancer cell lines. MDA-468 and MCF-7/Adr differed in their response to EGF, independent of the presence of hypoxia. These results suggest that hypoxic-stress-induced drug resistance is not generalized.     

Neonatal exposure to estradiol prevents the expression of ovarian hormone-induced luteinizing hormone and prolactin surges in adulthood but not antecedent changes in neuropeptide Y or adrenergic transmitter activity: Implications for sexual differentiation of gonadotropin secretion

Sex differences in adult patterns of mating behavior and gonadotropin secretion in rats are determined in part by the presence or absence of gonadal steroids during a perinatal critical period. For example, male rats and female rats exposed neonatally to androgen do not exhibit LH surge patterns when treated appropriately with ovarian hormones in adulthood, and there is evidence that this may be due to a failure of ovarian hormones to activate the hypothalamic neuronal systems that stimulate LH secretion in such animals. Because considerable evidence suggests that estradiol formed centrally from testosterone is responsible for the permanent defeminization of mating behavior and gonadotropin secretion, the present studies compared normal females with normal males and with females treated neonatally with estradiol on the ability of ovarian hormones to induce several important neurochemical changes antecedent to the LH surge, including changes in neuropeptide Y (NPY) and LH-releasing hormone (LHRH) concentrations in the median eminence, as well as changes in turnover rates for catecholamine transmitters in the medial basal hypothalamus and medial preoptic area. Normal ovariectomized female rats responded to sequential treatment with estradiol followed by progesterone with afternoon LH and prolactin (PRL) surges, and with sequential accumulation followed by decline in concentrations of LHRH and NPY in the median eminence prior to the LH surge. In addition, administration of progesterone increased the turnover rates of norepinephrine (NE) and epinephrine (EPI) in the arcuate-median eminence region of normal females. Gonadectomized male rats receiving the same ovarian hormone treatment failed to exhibit LH or PRL surges and displayed none of the changes in neurotransmitter turnover or peptide concentrations characteristically seen in the normal female. Unexpectedly however, when females that were treated with estradiol benzoate on days 1–3 postpartum were ovariectomized and treated with ovarian hormones in adulthood, they showed the same accumulation/decline in median eminence NPY concentrations and the same activation of NE and EPI turnover in the arcuate-median eminence region as normal females, even though they showed no LH or PRL surges or changes in median eminence LHRH concentrations. These results suggest that estradiol may not mediate all of the defeminizing actions of androgen exerted during the early neonatal period, and particularly those actions that result in a lack of responsiveness in central noradrenergic, adrenergic and NPY systems in adulthood. However, an action of neonatal estradiol may result in uncoupling of the LHRH neurosecretory system from normal excitatory neurochemical influences.     

Indomethacin and cognitive function in healthy elderly volunteers.

1. The aim of this randomised, double-blind four way crossover study was to assess the interaction between the new calcium antagonist, lacidipine and atenolol, in patients with mild to moderate hypertension. 2. Sitting blood pressure at 4 h post-dosing with lacidipine (4 mg) and atenolol (100 mg) alone was significantly lower compared with placebo (137/89 +/- 3/3 mmHg; 142/89 +/- 5/3 mmHg; and 154/98 +/- 5/3 mmHg respectively; P < 0.001). Co-administration of both drugs produced a significant additive effect compared with atenolol and lacidipine alone (124/80 +/- 4/2 mmHg; P < 0.002). 3. Heart rate on treatment with lacidipine alone was significantly greater at 4 h compared with placebo (86 +/- 1 beats min-1 and 74 +/- 2 beats min-1 respectively; P < 0.001). When both drugs were used in combination, there was a significant decrease in pulse rate compared with lacidipine alone (58 +/- 1 beats min-1 and 86 +/- 1 beats min-1 respectively; P < 0.001). 4. Home blood pressure recordings confirmed the statistically significant reduction in blood pressure on co-dosing (120/82 +/- 10/2 mmHg) compared with lacidipine (140/92 +/- 5/3 mmHg) and atenolol (146/90 +/- 6/3 mmHg) given alone (P < 0.05). 5. Lacidipine alone produced a significant exercise tachycardia compared with atenolol alone and the atenolol/lacidipine combination (97 +/- 8 beats min-1; 65 +/- 4 beats min-1 and 75 +/- 7 beats min-1 respectively; P < 0.001). Exercise tolerance was not adversely affected by the co-administration of both lacidipine and atenolol.