Gut Microbiome Changes Occurring with Norovirus Infection and Recovery in Infants Enrolled in a Longitudinal Birth Cohort in Leon,Nicaragua

Noroviruses are associated with one fifth of diarrheal illnesses globally and are not yet preventable with vaccines. Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. In this study, we characterized infant gut microbiome changes occurring with norovirus-associated acute gastroenteritis (AGE) and the extent of recovery. Metagenomic sequencing was performed on the stools of five infants participating in a longitudinal birth cohort study conducted in León, Nicaragua. Taxonomic and functional diversities of gut microbiomes were profiled at time points before, during, and after norovirus infection. Initially, the gut microbiomes resembled those of breastfeeding infants, rich in probiotic species. When disturbed by AGE, Gammaproteobacteria dominated, particularly Pseudomonas species. Alpha diversity increased but the genes involved in carbohydrate metabolism and glycan biosynthesis decreased. After the symptoms subsided, the gut microbiomes rebounded with their taxonomic and functional communities resembling those of the pre-infection microbiomes. In this study, during disruptive norovirus-associated AGE, the gut microbiome was temporarily altered, returning to a pre-infection composition a median of 58 days later. Our study provides new insights for developing probiotic treatments and furthering our understanding of the role that episodes of AGE have in shaping the infant gut microbiome, their long-term outcomes, and implications for oral vaccine effectiveness.     

Immunoglobulin Analysis in Clinical Diagnosis

Serum protein electrophoresis, ultracentrifugation, immunoelectrophoresis and immunodiffusion are the four methods commonly used for quantitation of immunoglobulins. Deficiencies of one or more of the five known types of immunoglobulins are demonstrable in a diverse group of diseases making up the antibody deficiency syndromes, while increased amounts of immunoglobulin may be found in various other diseases.     

Procoagulant activity of reversibly acylated human factor Xa

The plasma clotting factors used to treat hemophiliacs who have developed inhibitory antibodies have a shared history of limited clinical safety and utility. To improve on existing bypass factors, we have developed a reversibly acylated form of human plasma factor Xa capable of providing a time-dependent release of procoagulant activity. Factor Xa was treated with p-amidinophenyl p'-anisate to generate anisoyl Xa. The chemical modification of the protein involves acylation of the active site serine residue of factor Xa. Anisoyl Xa deacylated in a time, pH, and temperature-dependent manner. Active factor Xa generated on deacylation of anisoyl Xa exhibited amidolytic and prothrombinase complex activities in in vitro assays, the level being comparable to those of untreated factor Xa. When Anisoyl Xa was infused into rabbits, active factor Xa was generated on deacylation of the acylated enzyme, which shortened the activated partial thromboplastin time (APTT) in a dose-dependent manner. The duration of effect on rabbit APTT could be directly correlated to the level of human plasma factor Xa. Because anisoyl Xa bypasses the "tenase" complex that is compromised in hemophilia A and B and is unaffected by inhibitory antibodies, it has the potential to be used as an effective bypass therapy.     

Patient survival after surgery for osseous metastases from renal cell carcinoma

BACKGROUND: Skeletal metastases from renal cell carcinoma are highly destructive vascular lesions. They pose unique surgical challenges due to the risk of life-threatening hemorrhage and resistance to other treatments. The goal of this retrospective study was to evaluate factors that may affect survival after surgical treatment of metastases of renal cell carcinoma. METHODS: We performed a retrospective review of a series of 295 consecutive patients who had been treated for metastatic renal cell carcinoma at one institution between 1974 and 2004. There were 226 men and sixty-nine women. A total of 368 metastases of renal cell tumors to the extremities and pelvis were treated. The surgical procedures included curettage with cementing and/or internal fixation (214 tumors), en bloc resection (117), closed nailing (twenty-seven), amputation (four), and other measures (six). Overall survival was calculated with Kaplan-Meier analysis. The log-rank test was used to evaluate the effect of different variables on overall survival. RESULTS: The overall patient survival rates at one and five years were 47% and 11%, respectively. The metastatic pattern had a significant effect on the survival rate (p < 0.0001): patients with a solitary bone metastasis had the most favorable overall survival rate. Patients with multiple bone-only metastases had a better survival rate than patients with pulmonary metastases (p = 0.009). A clear-cell histological subtype was also associated with better survival (p < 0.0001). The tumor grade did not predict survival (p = 0.17). Fifteen patients (5%) died within four weeks after surgery. The causes included acute pulmonary failure (seven patients), multiorgan failure (six), cerebrovascular accident (one), and hypercalcemia (one). There were no deaths attributable to intraoperative hemorrhage. Discussion: Survival beyond twelve months is possible for a substantial proportion of patients with metastatic renal cell carcinoma. Patients with a clear-cell histological subtype, bone-only metastases, and a solitary metastasis have superior survival rates. The presence of pulmonary metastases does not predict early death in a reliable manner, and some patients may survive for years with pulmonary and systemic disease. The data are important for surgeons to consider when choosing treatment for these patients. For example, local control of disease and implant stability are important issues for patients with a potential for a long duration of survival.     

The natural history of lower urinary tract dysfunction in men: the influence of detrusor underactivity on the outcome after transurethral resection of the prostate with a minimum 10-year urodynamic follow-up

OBJECTIVES: To assess the long-term outcome of the efficacy of transurethral resection of the prostate (TURP) in men with detrusor underactivity (DUA), a cause of lower urinary tract symptoms (LUTS) in a significant minority of men. PATIENTS AND METHODS: Neurologically intact men with LUTS, who were investigated in our department between 1972 and 1986, diagnosed with DUA and who underwent surgical intervention, were invited for a repeat symptomatic and urodynamic assessment. Identical methods were used, allowing direct comparison of the results. RESULTS: In all, 224 men were initially diagnosed with DUA; 87 (39%) of these died in the interim and 22 followed had a TURP, with a mean follow-up since surgery of 11.3 years. There were no significantly sustained reductions in any symptoms. There was a small but significant reduction of questionable clinical significance in the bladder outlet obstruction index, but this did not translate into an improved flow rate. Comparison with 58 age-matched patients with DUA who remained untreated showed no significant advantage of surgical intervention in the long-term; on the contrary, there was more chronic retention in those who had had surgery. CONCLUSIONS: There are no long-term symptomatic or urodynamic gains from TURP in men shown to have DUA. The results of TURP in men with DUA are important, as urologists who surgically treat patients based on the symptoms and uroflowmetry alone will do so in a significant minority of men with DUA. These results strengthen the argument for a routine preoperative urodynamic assessment.     

Left ventricular dysfunction in patients with angina pectoris, normal epicardial coronary arteries, and abnormal vasodilator reserve

Thirty-three patients with chest pain despite angiographically normal coronary arteries underwent both coronary flow studies during pacing and resting and exercise gated blood pool scintigraphy. During atrial pacing after administration of ergonovine, those patients developing their typical chest pain demonstrated significantly lower great cardiac vein flow (97 +/- 31 vs 150 +/- 33 ml/min, p less than .001), higher coronary resistance (1.27 +/- 0.43 vs 0.77 +/- 0.18 mm Hg/ml/min, p less than .005), and less lactate consumption (30.5 +/- 22.0 vs 69.7 +/- 41.1 mM . ml/min, p less than .005) and a higher left ventricular end-diastolic pressure after pacing (20 +/- 4 vs 12 +/- 1, p less than .001) compared with those without pain and in the absence of significant luminal narrowing of the epicardial coronary arteries. The 26 patients with abnormal vasodilator reserve demonstrated reduced left ventricular ejection fraction during exercise (58 +/- 8%) compared with the seven patients with appropriate vasodilator reserve (66 +/- 4%, p less than .05) and with a group of 52 control patients of similar age and sex distribution and free of known heart disease (66 +/- 10%, p less than .001). In addition, 12 of the 26 patients with abnormal vasodilator reserve demonstrated exercise-induced regional wall motion abnormalities. Many of these patients also manifested impaired left ventricular diastolic filling at rest compared with the control subjects (peak filling rate 2.6 +/- 0.7 vs 3.2 +/- 0.7 end-diastolic volume/sec, p less than .005). Thus, patients with chest pain resulting from abnormal vasodilator reserve demonstrate abnormalities of left ventricular systolic and diastolic function suggestive of myocardial ischemia.     

Effects of sublingual nifedipine on hemodynamics and systolic and diastolic function in patients with hypertrophic cardiomyopathy

The hemodynamic effects of sublingual nifedipine were examined in 36 patients with hypertrophic cardiomyopathy. Twenty-one patients were initially given 20 mg and 15 patients were given 10 mg of the drug; 30 min after this first dose 26 patients received 10 mg and one patient 20 mg as a second dose. Hemodynamic findings in patients who received different doses of the drug were similar. Peak effects included an increase in heart rate from 79 +/- 12 to 91 +/- 14 (mean +/- 1 SD) beats/min (p less than .01), and a decrease in mean blood pressure from 89 +/- 12 to 77 +/- 10 mm Hg (p less than .01). Cardiac index increased after nifedipine (2.8 +/- 0.6 to 3.3 +/- 0.8 liters/min/m2; p less than .01); stroke volume index, however, did not change (36 +/- 7 to 36 +/- 8 ml/beat/m2; NS). Peripheral vascular resistance index fell significantly from 822 +/- 261 to 610 +/- 197 dynes X sec X cm-5 (p less than .01). Overall, left ventricular outflow tract gradient (LVOTG) did not change in patients with significant (greater than or equal to 30 mm Hg) basal LVOTG (75 +/- 22 to 83 +/- 22 mm Hg; NS), but it increased significantly in those six patients in whom peripheral vascular resistance fell by 25% or more (73 +/- 28 to 99 +/- 22 mm Hg; p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)