Prevalence and incidence of hepatitis C virus infection in the US military: a seroepidemiologic survey of 21,000 troops.

Because of a high prevalence of hepatitis C virus (HCV) infection (10-20%) among veterans seeking care in Department of Veterans Affairs (VA) hospitals, current US military forces were evaluated for HCV infection. Banked serum samples were randomly selected from military personnel serving in 1997 and were tested for antibody to HCV (anti-HCV). Overall prevalence of anti-HCV among 10,000 active-duty personnel was 0.48% (5/1,000 troops); prevalence increased with age from 0.1% among military recruits and active-duty personnel aged <30 years to 3.0% among troops aged >/=40 years. Prevalence among 2,000 Reservists and active-duty troops was similar. Based on sequential serum samples from 7,368 active-duty personnel (34,020 person-years of observation), annual incidence of infection was 2/10,000. Of 81 HCV RNA-positive troops for whom genotype was determined, genotypes 1a (63%) and 1b (22%) predominated, as in the civilian population. These data indicate that HCV infection risk among current military forces is lower than in VA studies and the general civilian population aged <40 years. The low level of HCV infection may be attributed to infrequent injection drug use in the military due to mandatory testing for illicit drugs prior to induction and throughout military service.

Multicenter patient self-reporting questionnaire on impotence, incontinence and stricture after radical prostatectomy.

PURPOSE: We determined the incidence of patient self-reported post-prostatectomy incontinence, impotence, bladder neck contracture and/or urethral stricture, sexual function satisfaction, quality of life and willingness to undergo treatment again in a large multicenter group of men who underwent radical prostatectomy. We also determined whether the morbidities of sexual function satisfaction, quality of life and bladder neck contracture and/or urethral stricture are predictable from demographic and postoperative prostate cancer factors. MATERIALS AND METHODS: A self-reporting questionnaire was completed and returned by 1,069 of 1,396 eligible patients (77%) who underwent radical prostatectomy between 1962 and 1997. Of the respondents 868 (85.7%) underwent surgery after 1990 and in all prostatectomy had been done a minimum of 6 months previously. Questionnaire results were independently analyzed by a third party for morbidity tabulation and the association of patient reported satisfaction. RESULTS: The patient self-reported incidence of any degree of post-prostatectomy incontinence, impotence and bladder neck contracture or urethral stricture was 65.6%, 88.4% and 20.5%, respectively. The incidence of incontinence requiring protection was 33% and only 2.8% of respondents had persistent bladder neck contracture or urethral stricture. Although incontinence and impotence significantly affected self-reported sexual function satisfaction, quality of life and willingness to undergo treatment again (p = 0.001), 77.5% of patients would elect surgery again. This finding remained true even after adjusting for demographic variables, and the time between surgery and the survey by multiple logistic regression. CONCLUSIONS: Although radical prostatectomy morbidity is common and affects self-reported overall quality of life, most patients would elect the same treatment again. Impotence and post-prostatectomy incontinence were significantly associated with sexual function satisfaction, quality of life and willingness to undergo treatment again. Bladder neck contracture and/or urethral stricture was associated with willingness to undergo treatment again after adjusting for demographic variables and time from surgery to the survey.

Effect of IL-1alpha on the release of norepinephrine in rat hypothalamus.

The increased release of norepinephrine (NE) in the brain as part of the 'acute phase response' has been postulated to result from a direct action of IL-1 on the hypothalamus. To test whether the effects of IL-1alpha were direct, we carried out in vivo experiments using microdialysis and measured NE release in the hypothalamus using high pressure liquid chromatography (HPLC). Two groups of male Sprague Dawley rats were either injected intraperitoneally with 1 ml of IL-1alpha (2 microg/ml) or had IL-1alpha 2 microl (100 ng/ml) infused directly into the medial hypothalamus. A significant increase in extracellular hypothalamic NE was observed in the animal group treated with IL-1alpha intraperitoneally and not in the controls or the group treated with IL-1alpha intracerebrally. One-way ANOVA showed a significant effect of drug and route of administration with the ip IL-1alpha treated group, differing from all other groups (vehicle ip, IL-1alpha ic, and vehicle ic). Therefore these findings suggest that some aspects of IL-1alpha actions on the HPA may be indirect requiring other intermediate steps or mediators outside the central nervous system.

Prognostic significance of DNA replication errors in young patients with colorectal cancer.

OBJECTIVE: To determine the DNA replication error (RER) status in young patients with colorectal cancer (CRC), and to compare the clinical and pathologic characteristics of RER-positive and RER-negative cases. SUMMARY BACKGROUND DATA: Recent studies suggest that patients with RER-positive CRC have an improved prognosis. Further data are required to confirm this observation in young CRC patients. METHODS: All patients 40 years of age and younger with CRC admitted to the National Naval Medical Center between 1970 and 1992 were considered for inclusion in the study. After review, 36 patients for whom the original archived pathology specimen could be retrieved served as the study population. The RER status was determined using a previously described polymerase chain reaction-based assay. The clinical and pathologic features and survival data were compared to RER status. RESULTS: RER-positive tumors were found in 17 cases (47%). There was no significant difference in Dukes' stage or histologic grade at the time of diagnosis between patients with RER-positive tumors compared to RER-negative tumors. Patients with RER-positive tumors were found to have an improved prognosis: the 5-year survival probability for patients with RER-positive tumors was 68%, as compared to 32% for patients with RER-negative tumors (p < 0.05). CONCLUSIONS: RER-positive tumors are common in young patients with CRC, and patients with RER-positive tumors have a significantly improved prognosis. Because of their young age, survival data and prognosis play an important role in the overall treatment plan of young patients with CRC. Therefore, knowledge of RER status could affect initial therapy, postoperative chemotherapy, and follow-up.

Preoperative and operative factors to predict incontinence, impotence and stricture after radical prostatectomy.

The purpose of this study was to determine the incidence of patient-self reported post prostatectomy incontinence, impotence, bladder neck contracture or stricture, better, same or worse quality of life and willingness for same treatment again in a large group of radical prostatectomy (RP) patients and to determine if these morbidities are predictable with demographic, surgical or prostate cancer (PC) factors. Methods: A patient self-reporting questionnaire was completed and returned by 374 out of 458 eligible (81.7%) RP patients from one center, 267 (72.2%) have been operated since 1990 and all of whom were a minimum six month postoperative (75%>1 y). Questionnaire results were independently analyzed by a third party and correlated to demographic, operative, and tumor factors in an ongoing comprehensive PC database. Results: The patient self-reported incidence of post prostatectomy incontinence (any degree), impotence, and bladder neck contracture or stricture was 72.2, 87.4, and 25.9%, respectively. The reported rate of incontinence requiring protection was 39.0% and only 2.4% had persistent bladder neck contracture/stricture. Pathologic stage (continuous variable) was the only factor to significantly predict incontinence and no factor could predict impotence or bladder neck contracture/stricture in univariate analysis. No factor was predictive of morbidity by multivariate analysis. Despite incontinence and impotence significantly affecting QOL self-reporting (P=0.001, 0.001, respectively) and willingness to undergo RP again (P=0.001, 0.067, respectively), the majority of patients would choose surgery again. Conclusions: Although radical prostatectomy morbidity is common and affects patient-reported overall QOL, most patients would choose the same treatment again. Demographic, preoperative, operative, and tumor factors did not reliably predict patient-reported morbidity in this series.

Patient satisfaction with collaborative practice.

OBJECTIVE: To gather information on women's perceptions of the services delivered in collaborative obstetrics and gynecology practices and to determine whether patients perceive a difference in the delivery of services in a variety of practice settings. METHODS: A cross-sectional patient satisfaction survey was developed by the Collaborative Practice Advisory Group of ACOG. Ten collaborative practices were selected to participate: five in private offices, two in clinics, two in health maintenance organizations, and one in the military. Between April 15 and May 15, 1994, 3257 completed surveys were obtained for analysis. RESULTS: Between 71% and 92% of women, depending upon the practice setting, agreed with statements regarding the possible benefits from being cared for in a collaborative practice. The majority (75-92%) expected services provided in a collaborative practice to differ from those provided in a noncollaborative practice. Women making their first visit to a collaborative practice expected quicker appointments, more time with the provider, more health information, and more specific diet information than did women who had previously been seen in such a practice. There were minimal differences in comfort levels when discussing issues of sexuality and physical and sexual abuse in either public or private settings with physicians or non-physicians. CONCLUSIONS: Patients in this survey were accepting of the concept of collaborative practice and felt that it offered quicker appointments, more time with the provider, more health information, and more specific diet information than did physician-only practices.

Antepartum screening in the office-based practice: findings from the collaborative Ambulatory Research Network.

OBJECTIVE: To examine utilization patterns of four antepartum screening tests by office-based obstetricians. METHODS: The population surveyed was the Collaborative Ambulatory Research Network, a voluntary subset of 550 ACOG fellows from 130 practices participating in data collection regarding ambulatory practices. Responses from self-administered questionnaires concerning screening for hepatitis B, gestational diabetes, neural tube defects, and trisomy 21 were analyzed. RESULTS: Hepatitis screening was performed by all practices with 95% (2750 of 2886) of women tested; however, only 55% (six of 11) of at-risk newborns received treatment. For gestational diabetes screening, 94% (116 of 124) administer a 50-g glucose load to all parturients, regardless of risk factors, two-thirds initiate further testing for a 1-hour post-load glucose of 140 mg/dL or greater, and 34% do so at lower glucose levels (130-135 mg/dL). For neural tube defect screening, 92% (95 of 103) offer maternal serum alpha-fetoprotein (MSAFP) screening although when results are elevated, further recommendations are varied. For women under 35 years of age, 84% (87 of 103) offer serum screening for trisomy 21 risk, most (68%) with double or triple (MSAFP, hCG, and estriol) markers. For women over 35 years, a majority (87%) offer serum screening, although half do so only if amniocentesis is declined for age risk alone. The relatively high initial positive rate and poor specificity of serum screening were underappreciated by a large number of respondents. CONCLUSION: Increased initial and continuing education of antenatal care providers is warranted if these screening tools are to perform optimally within office practices.

Tuberculosis and HIV infection in new inmates in Federal Bureau of Prisons facilities.

A significant change in the manner in which medical data were managed in the Federal Bureau of Prisons (BOP) occurred in calendar year 1992 (CY 92). Prior to CY 92, all BOP medical data were stored only as hard copy medical records. Beginning with CY 92, medical records data for all inmates have been transcribed to magnetic tape using the BOP SENTRY system. This study was an initial attempt to determine if this innovation would permit the development of meaningful infectious diseases data on BOP inmates. Our objective was to define the prevalence of tuberculosis (TB) skin test positivity, active TB, and HIV infection in new BOP inmates in CY 92 and to compare the new inmate population with the total BOP 1992 prisoner population. This initial study is important for two reasons: (1) the BOP SENTRY system for demographic and medical data was found to be a feasible tool for disease surveillance purposes; and (2) the 1992 new inmate population had much greater prevalences of purified protein derivative positivity, active TB, and HIV infection compared to the total BOP population. These findings may signal an increase in serious infectious diseases in BOP prisoners.

Intussuscepted colonic lipomas: loss of fat attenuation on CT with pathologic correlation in 10 cases.

BACKGROUND: To determine if infarction and necrosis is the cause of the confusing soft tissue density on CT within intussuscepting lipomas of the colon. METHODS: The clinical records, radiologic examinations, and pathologic specimens of all 13 cases of colonic lipomas collected from 1988 to 1994 studied by CT and surgically resected were retrospectively reviewed. Ten of these cases were associated with intussusception; the CT attenuation of the lead point was graded according to its relative fat/soft tissue density. Pathologic specimens were graded independently by a GI pathologist and graded according to the degree of infarction/fat necrosis. RESULTS: The lipomas ranged from 4 to 7 cm in diameter (mean = 5 cm). Only one case with intussusception, and all three cases without, demonstrated pure fat attenuation on CT and demonstrated pure fat histologically. One case demonstrated soft tissue attenuation and corresponded with the most severely infarcted specimen histologically; two cases with similar but less severe infarction/fat necrosis corresponded with less than 25% fat attenuation. These latter three cases were originally misinterpreted as malignancies rather than lipomas. Six cases maintained greater than 50% fat density and intermediate amounts of infarction/fat necrosis. CONCLUSION: Lipomas may have an atypical appearance when intussuscepted due to varying degrees of infarction/fat necrosis.

Islet cell tumors of the pancreas: pathologic-imaging correlation among size, necrosis and cysts, calcification, malignant behavior, and functional status.

OBJECTIVE: The purpose of our study was to correlate the imaging and pathologic features of islet cell tumors with regard to tumor size, necrosis and cysts, calcification, malignant behavior, and functional status. MATERIALS AND METHODS: We retrospectively reviewed the clinical, pathologic, and imaging features of all 133 cases of pathologically proved islet cell tumors of the pancreas seen at the Armed Forces Institute of Pathology. Clinical data, including the patients' symptoms and serologic characteristics, were used to distinguish hyperfunctioning tumors (those causing symptoms related to elevated serum polypeptide levels) from nonhyperfunctioning tumors; hyperfunctioning tumors were divided further into insulin-producing and non-insulin-producing types. All patients had at least one cross-sectional imaging study, including CT (n = 118), sonography (n = 42), or MR imaging (n = 22). Clinical, pathologic, and imaging features were evaluated and correlated with tumor size, necrosis and cysts, calcification, local invasion, vascular invasion, metastases, and functional status. RESULTS: Islet cell tumors with areas of necrosis or cystic change found pathologically and on imaging studies (56/133) were larger (8.4 cm in mean transverse diameter) than homogeneous solid lesions (2.9 cm in mean transverse diameter) and were predominantly non-insulin producing (48/56) and nonhyperfunctioning (36/56). Of the 43 insulinomas, 35 were small (2.2 cm in mean transverse diameter), solid, and homogeneous. Larger size also was associated with calcification and malignant behavior, including local invasion, vascular invasion, and distant metastases. CONCLUSION: Our findings show that cystic and necrotic islet cell tumors are usually non-insulin-producing and nonhyperfunctioning neoplasms and larger than the typically solid and small insulinomas. Calcification, local invasion, vascular invasion, and metastatic disease are more commonly seen with larger neoplasms.

Biliary cystadenoma and cystadenocarcinoma: clinical-imaging-pathologic correlations with emphasis on the importance of ovarian stroma.

PURPOSE: To evaluate cross-sectional imaging in the distinction of biliary cystadenoma from cystadenocarcinoma and in the determination of the presence of ovarian stroma. MATERIALS AND METHODS: In 34 patients, radiologic studies and specimen photographs and descriptions were reviewed retrospectively without knowledge of the patient group. Histologic features were reviewed without knowledge of the radiologic findings and analyzed for epithelial and stromal components. Correlation was made between the radiologic findings, gross morphologic features, internal fluid characteristics, and histologic features. RESULTS: The 34 patients had 27 biliary cystadenomas, 22 with ovarian stroma, and seven cystadenocarcinomas, four with ovarian stroma. Gross morphologic and imaging features suggestive of biliary cystadenocarcinoma included internal septation and nodularity. Septation without nodularity was seen only in biliary cystadenoma. Nonbilious fluid was the only feature associated with the presence of ovarian stroma but was not distinguishable on images. CONCLUSION: Imaging studies accurately reflect the nodularity and septation seen grossly to distinguish biliary cystadenoma and cystadenocarcinoma but do not allow distinction of the presence or absence of ovarian stroma.

Intravenous immune globulin prophylaxis of late-onset sepsis in premature neonates.

To determine whether a single dose of intravenously administered immune globulin (IVIG) decreases late-onset sepsis in premature infants, we prospectively entered 753 neonates with birth weight 500 to 2000 gm, gestation < or = 34 weeks, and age < or = 12 hours into a multicenter, double-blind, controlled trial. Infants were randomly selected to receive a single intravenous infusion, 10 ml/kg, of either IVIG (500 mg/kg) or albumin (5 mg/kg) and were observed for 8 weeks for infection. Maternal and neonatal risk factors for infection did not differ between groups. Although serum IgG values before infusion were related to gestation (R = 0.62), the change in serum IgG or half-life of IgG after IVIG infusion was not (R < or = 0.09). The serum IgG concentration was increased (p < 0.05) in IVIG-treated patients for 8 weeks. There were 88 episodes of late-onset sepsis in 79 neonates (10.5%). Causative organisms included the following: Staphylococcus epidermidis (37 episodes), Enterococcus (9), Staphylococcus aureus (7), Candida (6), Escherichia coli (6), and multiple organisms (11). Sepsis, death, and death as a result of infection were unaffected by treatment. We conclude that a single infusion of IVIG, 500 mg/kg, shortly after birth was not effective prophylaxis for late-onset infection in premature neonates. Future studies of late-onset sepsis prophylaxis should consider IVIG with known pathogen-specific antibody concentrations against organisms causing these infections, in particular S. epidermidis.

Opsonic activity of commercially available standard intravenous immunoglobulin preparations.

Several standard intravenous immunoglobulin G (IVIG) products are available in the United States and have been used with the intent to treat or prevent infections in neonates. We evaluated more than 100 lots of IVIG, from 6 products, to determine the amount of opsonic antibody against neonatal pathogens. Neutrophil-mediated opsonophagocytosis was used to determine opsonic activity in these preparations for Staphylococcus epidermidis; Haemophilus influenzae type b; Streptococcus pneumoniae serotypes 3, 14 and 19; Group B Streptococcus serotypes Ia, Ib, Ia/c, II and III; and Escherichia coli (K1). Pathogen-specific opsonic activity of the lots tested ranged from undetectable to 1:80 and was detectable in < 10% to > 90% of lots tested depending on the organism and manufacturer. Within an IVIG lot there was variable opsonic activity against different strains or serotypes of the same organism. Opsonic activity was significantly (P < or = 0.05) affected by the manufacturer's donor pool and less so by the manufacturing method. We conclude that the pathogen-specific opsonic antibody activity of an IVIG lot is: (1) highly variable for several common neonatal pathogens; (2) predominantly dependent on the donor pool and not the manufacturing method. Clinicians may more appropriately select therapy if the pathogen-specific antibody content of IVIG products by lot are known. In the future neonatal IVIG research should focus on using preparations with known pathogen-specific antibody activity.

Both lisinopril and verapamil reduced platelet-derived growth factor-A chain mRNA levels in human saphenous vein endothelial cells stimulated by thrombin.

BACKGROUND: Both angiotensin-converting enzyme inhibitors and calcium channel blockers decrease postinjury intimal thickening in vivo, but their mechanisms of inhibitory action are unclear. Expression of the gene for platelet-derived growth factor (PDGF), a smooth-muscle mitogen, in endothelial cells (ECs) after vessel injury has been postulated to cause intimal thickening. In this study, we tested whether lisinopril, an angiotensin-converting enzyme inhibitor, or verapamil, a calcium channel blocker, would suppress the PDGF gene expression in stimulated human saphenous vein ECs. METHODS: Drugs were added to replicate EC cultures 30 minutes before adding 10 units/ml alpha-thrombin. Changes in PDGF-A chain mRNA levels were measured by Northern blot analysis or reverse transcription-polymerase chain reaction method. PDGF-AA homodimer in conditioned media was measured by ELISA: RESULTS: Lisinopril attenuated the induction by thrombin of PDGF-A chain mRNA levels significantly in human ECs at doses of 10(-6) mol/L and 10(-5) mol/L (p < 0.05) and appeared to decrease PDGF-AA homodimer released in conditioned medium. Verapamil also reduced thrombin induction of PDGF-A chain mRNA levels significantly at a dose of 10(-5) mol/L (p < 0.05) and appeared to reduce PDGF-AA homodimer secretion. CONCLUSIONS: These data suggest that one means by which lisinopril and verapamil both suppress intimal thickening might be inhibition of PDGF-A chain gene expression in ECs regrowing over vessel injury areas that are sites of thrombin generation.

Primary and preventive care services provided by obstetrician-gynecologists.

OBJECTIVE: To determine the level and types of primary and preventive care services delivered by obstetrician-gynecologists. METHODS: A self-administered questionnaire was mailed to a random sample of 1250 obstetrician-gynecologists practicing in the United States. The response rate was 71%. RESULTS: Fifty-three percent of the respondents indicated that they provide primary and preventive care during more than half of their practice time. Although obstetrician-gynecologists provide a wide range of preventive services, the proportion of doctors providing any specific service varies. Whereas virtually all (92% or more) obstetrician-gynecologists provide or order blood pressure screening, breast examinations, mammography, and Papanicolaou tests, only six of ten report regular cholesterol screening for most of their patients. A higher percentage of female obstetrician-gynecologists, who are on average younger than their male counterparts, report that they provide primary preventive services to most of their patients. CONCLUSION: The majority of obstetrician-gynecologists provide a wide range of primary and preventive care services to their patients, although there is variability in the proportion of doctors providing any specific service to most (60% or more) of their patients.

Standard versus hyperimmune intravenous immunoglobulin in preventing or treating neonatal bacterial infections.

Although current studies suggest that IVIg is safe, larger controlled trials will soon be published and will be important to confirm this observation. In addition, the current studies do not establish the efficacy of IVIg for either treating or preventing neonatal bacterial infections. Some studies with small numbers of infants suggest benefit of IVIg therapy and prophylaxis; however, the studies reviewed do not, individually or combined, prove efficacy. Clinicians and investigators must not confuse studies that prevent infection with those that treat infection because different therapeutic regimens may be necessary. Many questions remain concerning IVIg therapy, such as is IVIg efficacious in preventing or treating neonatal sepsis, what is the appropriate immunoglobulin dosage, and how variable is the pathogen-specific antibody activity of standard IVIg products. To determine the appropriate use of IVIg in neonates effectively, well-designed and carefully controlled trials are needed to address these issues using sufficiently large numbers of infants to arrive at valid scientific conclusions. Although many questions will be answered with the trials currently in progress, we must continue to base further recommendations for immunoglobulin therapy on solid scientific data.

Early-onset group B streptococcal sepsis: a current assessment.

Group B streptococcus (GBS) is a common cause of early-onset sepsis in neonates. The most recent reviews describing incidence, diagnosis, treatment, and outcome evaluated data on patients from the early 1980s. To obtain current information about this disease, we retrospectively evaluated data on neonates with GBS early-onset sepsis from nine hospitals in the United States between Jan. 1, 1987, and Dec. 31, 1989. There were 245 infants with GBS bacteremia identified among 61,809 live births, resulting in an incidence of 0.32%. Ninety-six infants (39%) were preterm (less than 38 weeks of gestational age). Maternal risk factors for infected preterm and term infants were similar. Antibiotics were administered during parturition in 10% of infants with bacteremia. Mothers of preterm infants received antibiotics up to 48 hours before delivery; mothers of term infants received antibiotics less than 4 hours before delivery. All preterm infants with bacteremia had symptoms; 22% of term infants with bacteremia had no symptoms. Group B streptococcal meningitis was confirmed in 6.3% of infants. Although 86% survived, GBS sepsis increased the birth weight-specific mortality rate up to eightfold in preterm infants and more than 40-fold in term infants. Although the incidence of GBS early-onset sepsis is not changing, we speculate that the improved birth weight-specific survival rate and the changing clinical presentation are due to improved intrapartum and neonatal management.

Intravenous immune globulin therapy for early-onset sepsis in premature neonates.

Newborn infants may have IgG deficiencies that increase their susceptibility to bacterial infection. To determine whether intravenous immune globulin (IVIG) therapy improves survival rates in early-onset sepsis, we prospectively entered 753 neonates (birth weight 500 to 2000 gm, gestation less than or equal to 34 weeks, age less than or equal to 12 hours) into a multicenter, double-blind, controlled trial. Blood culture specimens were obtained and infants randomly assigned to receive 10 ml (per kilogram) intravenously of a selected IVIG (500 mg/kg) or albumin (5 mg/kg) preparation. Maternal and neonatal risk factors were not different between groups. Thirty-one babies (4.2%) had early-onset sepsis; the causative organisms were group B streptococcus (12 babies), Escherichia coli (6), and others (13). Of these 31 neonates, 7 (23%) died. Total serum IgG was higher for 7 days after IVIG therapy than after albumin treatment (p less than 0.05). During these 7 days, 5 (30%) of 17 albumin-treated and none of 14 IVIG-treated patients died (p less than 0.05). The survival rate at 56 days of age, however, was not significantly improved. Group B streptococcus type-specific IgG antibody was significantly increased after IVIG treatment and appeared to be related to the amount of IVIG specific antibody. Infusion-related adverse reactions were less frequent in patients receiving IVIG therapy (0.5%) than in those receiving albumin. The IVIG therapy in neonates with early-onset sepsis, while reducing the early mortality rate, did not significantly affect the overall survival rate. Further studies are necessary to confirm these findings and to determine more effective therapeutic regimens.