Targeted disruption of the mouse prosaposin gene affects the development of the prostate gland and other male reproductive organs

The prosaposin gene encodes a 65-70 kilodalton (kd) protein, which is secreted or targeted to lysosomes. In lysosomes, prosaposin is the precursor of 4 activator proteins, designated saposins A, B, C, and D, which promote by acidic hydrolases, the degradation of glycosphingolipids with short oligosaccharide chains. Mutations of the prosaposin gene have been linked to several lysosomal storage disorders. An animal model was recently developed by creating a null allele in embryonic stem cells through gene targeting in order to investigate the phenotypic diversity of prosaposin mutations, the involvement of this protein in lysosomal storage diseases, and to develop potential therapeutic approaches. Mutant homozygous mice die at 35-40 days of age and neurological disorders contribute to their early death. Secreted prosaposin is present in milk and in cerebrospinal and seminal fluids. In the nervous system, prosaposin exhibits a trophic activity. Examination of reproduc-tive organs in homozygous mutant males shows several abnormalities such as a decrease in testis size with reduced spermiogenesis, and an involution of the prostate, seminal vesicle, and epididymis, although levels of testosterone in blood remain normal. In the prostate of homozygous mutants, only basal cells appear to be present, whereas secretory cells are absent. The epithelia in efferent ducts is formed by ciliated cells, whereas heterozygotes exhibit a majority of nonciliated cells. Our data indicate that prosaposin is involved in the development and maintenance of male reproductive organs. In prostatic epithelium, targeted disruption of the prosaposin gene appears to inactivate the mitogen-activated protein kinase pathway and to interfere with differentiation of secretory cells.     

Influence of obesity on the appearance of proteinuria and renal insufficiency after unilateral nephrectomy

BACKGROUND: Some patients develop proteinuria and progressive renal failure after unilateral nephrectomy, although the majority of patients maintain normal renal function. Reasons to explain this different evolution are not known. METHODS: A cross-sectional study was performed in 73 patients who had undergone unilateral nephrectomy 13.6 +/- 8.6 years before. Patients with morphologic abnormalities in the remaining kidney, systemic disorders, or abnormal renal function at the time of nephrectomy were excluded. All of the 73 included patients showed normal renal function and negative proteinuria at nephrectomy. The patient's medical records were reviewed, and clinical and analytical data throughout follow-up were obtained. RESULTS: Fifty-three out of the 73 patients (group I) showed a normal renal function and negative proteinuria at the cross-sectional study. The remaining 20 patients (group II) showed proteinuria (3.4 +/- 3.1 g/day). The time elapsed between nephrectomy and proteinuria appearance was 10.1 +/- 6.1 years. Thirteen patients of group II had developed renal insufficiency (serum creatinine at the cross-sectional study of 3.9 + 3.2 mg/dL) in addition to proteinuria. The time elapsed between proteinuria appearance and the onset of renal insufficiency was 4.1 +/- 4.3 years. Renal insufficiency showed a slowly progressive course in most of these patients. There were no significant differences between group I and group II patients in age, gender, renal function, or blood pressure at the time of nephrectomy. In contrast, group II patients showed a body mass index (BMI) that was significantly higher than group I at nephrectomy (31.6 +/- 5.6 vs. 24.3 +/- 3.7 kg/m(2), P < 0.001), at cross-sectional study (33.3 +/- 6.6 vs. 25.1 +/- 3.5 kg/m(2), P < 0.001), and throughout follow-up. Among the 14 obese (BMI > 30 kg/m(2)) patients at the time of nephrectomy, 13 (92%) developed proteinuria/renal insufficiency. In contrast, among the 59 patients with BMI < 30 kg/m(2), only 7 (12%) developed these complications (P < 0.001). Kaplan-Meier estimated probability of negative proteinuria and normal renal function 10 years after nephrectomy was 40 and 70%, respectively, in obese patients at nephrectomy. At 20 years after nephrectomy, these percentages were 8 and 35%, respectively. In contrast, in nonobese patients, the probability of negative proteinuria and normal renal function was 93 and 98%, respectively, at 10 years (P < 0.001) and 77 and 91%, respectively, at 20 years (P < 0.001). Multiple logistic regression analysis showed that the risk of developing renal disease was only statistically correlated with BMI at the time of unilateral nephrectomy (odds ratio 1.34, 1.03 to 1.76 CI). CONCLUSIONS: Obese patients are at risk for developing proteinuria and chronic renal failure after unilateral nephrectomy. Regular and long-term follow-up are recommended in these patients.     

Effect of Dexamethasone Therapy on the Neonatal Ductus Arteriosus

Patent ductus arteriosus (PDA) is believed to be a contributing factor in the etiopathogenesis of bronchopulmonary dysplasia (BPD). We studied the effects of early dexamethasone therapy on persistent ductal patency and the role of PDA in the etiopathogenesis of BPD during the course of a randomized double-blind trial of dexamethasone to prevent BPD. Infants, who weighed between 700 and 999 g, had severe RDS, and had been given surfactant, were randomized to receive a 12-day course of dexamethasone (n= 13) or placebo (n= 17) starting within the first 12 hours of postnatal life. The diagnosis of PDA was made clinically and was confirmed by cardiac ultrasound. The incidence of clinically significant ductus in infants who weighed less than 1000 g was 23% in the dexamethasone-treated group, as compared with 59% in infants who were given placebo. This difference was marginally significant, p= 0.05, odds ratio 0.21, 95% confidence interval 0.04–1.05. None of the infants in the dexamethasone group had recurrence of PDA after indomethacin therapy as compared with three infants in the placebo group. Dexamethasone significantly reduced the number of days infants required ventilator and supplemental oxygen as compared with infants who received placebo. Dexamethasone, as compared with placebo, also reduced the incidence of BPD, p= 0.025, odds ratio 0.08, 95% confidence interval 0.01–0.58. Dexamethasone may reduce the incidence of PDA in premature infants who weigh less than 1000 g at birth and thereby reduce the incidence of BPD.     

Severe incisional pain and long thoracic nerve injury after port-access minimally invasive mitral valve surgery

The authors describe the occurrence of severe postoperative pain and long thoracic nerve injury after Port-Access minimally invasive mitral valve surgery. The potential for these events and the impact on postoperative hospitalization and rehabilitation are emphasized.     

Satisfaction with provider communication among Spanish-speaking Medicaid enrollees.

OBJECTIVE: To determine if differences between English- and Spanish-speaking parents in ratings of their children's health care can be explained by need for interpretive services. METHODS: Using the Consumer Assessment of Health Plans Survey-Child-Survey (CAHPS), reports about provider communication were compared among 3 groups of parents enrolled in a Medicaid managed care health plan: 1) English speakers, 2) Spanish speakers with no self-reported need for interpretive services, and 3) Spanish speakers with self-reported need for interpretive services. Parents were asked to report how well their providers 1) listened carefully to what was being said, 2) explained things in a way that could be understood, 3) respected their comments and concerns, and 4) spent enough time during medical encounters. Multivariate logistic regression was used to compare the ratings of each of the 3 groups while controlling for child's gender, parent's gender, parent's educational attainment, child's health status, and survey year. RESULTS: Spanish-speaking parents in need of interpretive services were less likely to report that providers spent enough time with their children (odds ratio = 0.34, 95% confidence interval = 0.17-0.68) compared to English-speaking parents. There was no statistically significant difference found between Spanish-speaking parents with no need of interpretive services and English-speaking parents. CONCLUSIONS: Among Spanish- versus English-speaking parents, differences in ratings of whether providers spent enough time with children during medical encounters appear to be explained, in part, by need for interpretive services. No other differences in ratings of provider communication were found.     

Peripheral nervous system neurotoxicity secondary to chemotherapy treatment]

Peripheral neurotoxicity is a crucial side effect of chemotherapeutic agents. It is the only situation where there is no preventive treatment. Neuromuscular toxicity has become the major dose limiting side effect for many chemotherapeutic agents. The iatrogenic toxic neuropathy is a growing neurologic problem, as cancer patients are beign treated with increasing doses of chemotherapy drugs. Major advances in cancer treatment have resulted from the use of drug combinations; for some combinations this raises the possibility of sinergistic neurotoxicity. The following report reviews the SNP toxicities encountered with cisplatin, vincristine, taxanes and others, and methods to minimize the deleterious effect of chemotherapeutic agents.     

Radiologically placed temporary hepatic artery catheter for treatment of liver cancer

Hepatic artery infusion (HAI) chemotherapy is associated with higher response rates compared to systemic chemotherapy in those patients with unresectable liver malignancies. Operative hepatic artery catheter (HAC) insertion has significant morbidity and mortality, especially in patients with high‐volume disease, some of whom may not respond to HAI chemotherapy. We report our experience in 45 patients with high‐volume liver disease who were initially treated with HAI chemotherapy via a radiologically placed temporary HAC to try to select the responders who then went on to have an operative HAC. In these 45 patients who had 62 radiologically placed HAC, we found very few major complications, and certainly no complications such as cholecystitis, vascular or malperfusion problems.