Sialylated human apolipoprotein E (apoEs) is preferentially associated with neuron-enriched cultures from APOE transgenic mice

Mice transgenic for human APOE2, E3, and E4 alleles express native 34-kDa human apoE and two sialylated apoE isoproteins with approximate molecular weights of 37 kDa (apoEs) and 39 kDa (apoEs2) in brain. These multiple apoE/apoEs/apoEs2 band patterns on Western blot are also observed in human brain, but are not seen in wild-type mouse brain. Both the 37-kDa apoEs and 39-kDa apoEs2 are coprecipitated with native 34-kDa apoE by antibody to human apoE. Neuraminidase digestion eliminates the 37- and 39-kDa forms and results in a downward shift in the bands to the position of the 34-kDa native form. These sialylated apoE isoproteins are found preferentially associated with neurons and contribute significantly (50-60%) to the total neuronal apoE in neuronal cultures from transgenic mice, while only 5-10% of total apoE is sialylated in cultures enriched in glial cells. In situ hybridization and immunocytochemistry demonstrate apoE mRNA and apoE immunoreactivity are predominantly located in cell soma of neurons, not in neuronal processes.     

Adequacy of prenatal care among women with psychiatric diagnoses giving birth in California in 1994 and 1995

OBJECTIVE: Although poor prenatal care is detrimental to maternal and infant health, few studies have assessed the adequacy of prenatal care among women with psychiatric diagnoses. This investigation examined the association between chart-recorded psychiatric and substance use diagnoses at the time of delivery and adequacy of prenatal care among all women delivering babies in California hospitals during 1994 and 1995. METHODS: The authors undertook an archival analysis of data from the California Health Information for Policy Project (CHIPP), which consists of linked hospital discharge and birth certificate data for 1,094,178 deliveries in 1994 and 1995. The associations between International Classification of Diseases, 9th Revision, Clinical Modification psychiatric and substance abuse diagnoses and level of prenatal care were examined. Logistic regression analyses were conducted to assess the association between maternal diagnostic category and inadequate prenatal care while controlling for payment source, age, education, race, marital status, and parity (previous births). RESULTS: Women who received psychiatric and substance use diagnoses demonstrated significantly increased risk of inadequate prenatal care compared with women without those diagnoses. CONCLUSIONS: Psychiatric diagnoses were associated with an increased risk of inadequate prenatal care; the association between psychiatric and substance use diagnoses and poor prenatal care persisted even after the analysis controlled for known risk factors. Future investigations will need to elucidate the processes of prenatal care for women with psychiatric disorders so that preventive interventions can be developed.     

The tubulointerstitium in progressive diabetic kidney disease: more than an aftermath of glomerular injury?

Although the glomerulus, particularly the mesangium, has been the focus of intense investigation in diabetes, tubulointerstitial injury is also a major feature of diabetic nephropathy and an important predictor of renal dysfunction. The renal tubule in diabetes is subject to both direct and indirect pathogenetic influences as a consequence of its position in the nephron and its resorptive function. On exposure to glucose, proximal tubular cells elaborate vasoactive hormones, including angiotensin II and injurious cytokines such as transforming growth factor-beta (TGF-beta), as well as extracellular matrix proteins. In turn, angiotensin II may further increase TGF-beta expression in both proximal tubular and interstitial cells, thus amplifying the stimulus to fibrogenesis in the renal tubulointerstitium. In addition to these mostly direct influences, the renal tubule, particularly its proximal segment, is exposed to glomerular effluent. In the diabetic state, this includes large quantities of advanced glycation end products and glucose and, at later stages in the evolution of diabetic nephropathy, protein, all of which are factors that may induce TGF-beta expression and fibrosis. Diabetic nephropathy should therefore be viewed as a disease affecting the entire nephron. Continued exploration into tubulointerstitial disease in addition to glomerular injury in diabetes may help provide further insights into the pathogenesis of diabetic nephropathy and additional targets for therapeutic intervention.     

Evolving trends in liver transplantation: an outcome and charge analysis

BACKGROUND: Due to the limited supply and increased demand for donor livers, waiting times are progressively lengthening, which may lead to transplantation at more advanced and less cost-effective stages of disease. The purpose of this study was to evaluate the outcomes and hospital charges of liver transplantation during two recent eras to identify areas for providing more cost-effective care. METHODS: A total of 144 primary liver allografts were performed from 1991 to 1996. Patient characteristics, outcome measures, and hospital charges were compared for patients receiving allografts between 1991 and 1993 (group A) versus those receiving grafts between 1994 and 1996 (group B) using unpaired Student t tests for continuous data and chi-squared tests for categorical data. RESULTS: In comparing groups A and B, no significant differences in patient demographics, relative contraindications, or indication for transplantation existed; median waiting time from date of listing until transplant increased from 88 days to 159 days; and a shift in UNOS priority status at time of transplantation occurred, as the percentage of patients requiring inpatient care increased from 58% to 75% (P=0.034). Despite this, patient hospital and 1-year survival significantly improved from 75.0% to 90.3% (P=0.016), and from 68.1% to 88.9% (P=0.002), respectively. Total hospital charges, without correction for inflation, were $174,908+/-16,388 in A and $193,525+/-14,444 in B (P=0.288). The increased charges were associated with longer inpatient length of stay (LOS) before transplant, resulting in increased pretransplant charges from $24,088+/-4134 (A) to $39,490+/-6,196 (B) (P=0.011). Room and service (54%) was the largest pretransplant contributor to charges, while blood products (23%), room and service (21%), organ acquisition (13%), and operating room charges (11%) contributed the most after transplant. CONCLUSIONS: Longer waiting times resulting in transplantation at later stages of disease have occurred, leading to longer pretransplant LOS and its associated charges. Despite more advanced disease, patient survival rates have significantly improved with fewer infection-related deaths. LOS pretransplant, blood products, and operating room services represent potential areas for providing more cost-effective care.     

Percutaneous Testis Biopsy: An Alternative to Open Testicular Biopsy in the Evaluation of the Subfertile Man

Purpose

We evaluated the safety and efficacy of percutaneous testis biopsy by comparing the ultrasound appearance and histological status of testicular parenchyma obtained to those noted after open testis biopsy.

Materials and Methods

A total of 51 consecutive infertile men with azoospermia or severely impaired semen quality, in whom ductal obstruction was suspected, underwent percutaneous (31) or open (20) testis biopsy, with 58 and 34 procedures performed, respectively. Scrotal ultrasound was performed preoperatively, and at 2 weeks and 1, 3 and 6 months after biopsy. In addition, immunoglobulins G and A antisperm antibody assays were obtained preoperatively and postoperatively. Two biopsy specimens were obtained from each testis for formal histological evaluation. A touch preparation was also performed and examined immediately for mature spermatozoa using phase contrast microscopy.

Results

All biopsies yielded adequate tissue for diagnosis and morphometric analysis. Of 58 percutaneous biopsies 4 (7 percent) demonstrated sonographic evidence of intratesticular bleeding, characterized by a hypoechoic region within the testicular parenchyma, which resolved by 6 months postoperatively. In contrast, 10 of 34 open biopsies (29 percent) showed evidence of intratesticular bleeding or a new area of increased echogenicity at 1 month after the procedure (intraparenchymatous scar). All intraparenchymatous scars persisted to 6 months postoperatively. No patient undergoing percutaneous or open testis biopsy had antisperm antibodies in the seminal fluid or serum (azoospermia cases) or on sperm postoperatively. Of the 32 and 20 patients undergoing percutaneous and open testis biopsy 3 (9 percent) and 14 (70 percent), respectively, required narcotic analgesia. All patients returned to routine activities within 24 hours after percutaneous testis biopsy. No postoperative infections or extratesticular hematomas were noted. Pathological study was diagnostic in all specimens.

Conclusions

Percutaneous testis biopsy is well tolerated by the patient, with fewer apparent complications than and diagnostic value equal to open testis biopsy. Percutaneous testis biopsy should be considered an alternative to open biopsy.     

Genetic effects of chlorinated anilines and azobenzenes onSalmonella typhimurium

The mutagenicity of 19 herbicide-derived chlorinated azobenzenes and structurally related chlorinated anilines and nitrobenzenes was assayed towards several strains ofS. typhimurium, using the plate incorporation method and the fluctuation test, in the presence or in the absence of liver post-mitochondrial fractions, in aerobic and anaerobic conditions.Positive results were obtained with 4,4-dichloroazobenzene, 4,4-dichloroazoxybenzene, 3,4-dichloronitrobenzene and, to a much lesser extent, with 3,4,3,4-tetrachloroazobenzene. No mutagenic effect was observed with 2,3,7,8-tetrachlorodibenzo-p-dioxin in any condition.     

Cross-resistance of drug-resistant murine P388 leukemias to toxol in vivo

Summary The antimicrotubule agent taxol (NSC 125973) has shown clinical antitumor activity against several classically refractory tumors. We developed a drug-resistance profile for taxol using ten drug-resistant P388 leukemias to identify potentially useful guides for patient selection for further clinical trials of taxol and possible non-cross-resistant drug combinations with taxol. Multidrug-resistant P388 leukemias exhibited either clear (leukemia resistant to amsacrine) or marginal cross-resistance (leukemias resistant to doxorubicin, actinomycin D, and mitoxantrone) to taxol. Leukemias resistant to vincristine (non-multidrug-resistant leukemia), camptothecin, melphalan, cisplatin, 1--d-arabinofuranosylcytosine, and methotrexate were not cross-resistant to taxol. The data suggest that (1) it may be important to exclude or to monitor with extra care patients who have previously been treated with amsacrine, doxorubicin, actinomycin D, or mitoxantrone and (2) a combination of one of the non-cross-resistant drugs and taxol might exhibit therapeutic synergism.This work was supported by contract NO1-CM-07315 with the Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute     

Black males who always use condoms: their attitudes, knowledge about AIDS, and sexual behavior.

One hundred six black males completed a questionnaire concerning attitudes and knowledge about the use of condoms and acquired immunodeficiency syndrome (AIDS). Of the 106 males in the study, 27 (26%) reported that they "always" used condoms, 31 (29%) did not use condoms and had low intentions of using them, and 48 (45%) reported high intentions to use condoms. Results indicated that knowledge about AIDS was exceptionally high for black males in all three groups. Black males with low intentions to use condoms reported significantly more negative attitudes about the use of condoms (eg, using condoms is disgusting) and reacted with more intense anger when their partners asked about previous sexual contacts, when a partner refused sex without a condom, or when they perceived condoms as interfering with foreplay and sexual pleasure. A significantly larger percentage of low intenders were treated for gonorrhea, syphilis, herpes, and genital warts than males in the other groups. Drug use did not differentiate the three groups, although marijuana was used more often by males in the low-intender group. Finally, a larger percentage of black males in the low-intender group reported experiences with anal intercourse and sex with a prostitute, but considered themselves at lower risk for AIDS than did their high-intender or steady-user counterparts.     

A performance analysis of an extracorporeal shock wave lithotripter: spatial pressure distribution and the effects of lithotripter voltage, electrode life, and tissue attenuation

The Dornier MPL-9000 lithotripter was analyzed as a function of lithotripter voltage, electrode efficiency, and bovine muscle attenuation. The maximum pressure at 20 kV measured 65 +/- 4 MPa (mean +/- SD). The region containing 50% of the maximum pressure was a cylindrical volume with a diameter of 2.5 cm and a height of 7 cm. Pressure varied in a linear fashion with lithotripter voltage (r = 0.996). The average pressure produced by an electrode throughout the course of 2,200 shock waves was 78% of its maximum pressure. Shock wave pressure was reduced from 65 +/- 4 MPa to 49 +/- MPa, 44 +/- 3 MPa, and 44 +/- 1 MPa with 1-, 2-, and 3-cm thickness of intervening bovine muscle, respectively. There was a statistically significant decrease in pressure when muscle was interposed, but there was no significant difference in reduction of pressure between 1, 2, and 3 cm of muscle (ANOVA, Newman-Keuls, alpha = 0.01). Frequency spectral analysis revealed the major contribution to the shock wave comes from 0-200 kHz with a peak near 50 kHz. Major frequency intensities were reduced with a decrease in lithotripter voltage, attenuating tissue, and distance away from the center of the focal zone.