Herpes simplex virus type 2 seroprevalence and incidence in acute and chronic HIV-1 infection.

Herpes simplex virus type 2 (HSV-2) HIV co-infection is common and associated with increased risk of HIV transmission. HSV-2 seroprevalence was assessed on stored samples from baseline and one year follow-up from 81 patients identified with acute HIV infection and 81 age-matched chronically infected men. HSV-2 seroprevalence at baseline was lower for those with acute rather than chronic HIV-infection, 51.9 versus 71.6% (P = 0.01); relative risk 0.72 (95% confidence interval [CI] 0.57-0.92). Since HSV-2 seroprevalence is lower in those newly HIV-infected, the diagnosis of early HIV infection may allow for counselling to reduce subsequent HSV-2 acquisition.

Steady-state pharmacokinetics of oral testosterone undecanoate with concomitant inhibition of 5α-reductase by finasteride.

Oral testosterone undecanoate (TU) is used to treat testosterone deficiency; however, oral TU treatment elevates dihydrotestosterone (DHT), which may be associated with an increased risk of acne, male pattern baldness and prostate hyperplasia. Co-administration of 5α-reductase inhibitors with other formulations of oral testosterone suppresses DHT production and increases serum testosterone. We hypothesized that finasteride would increase serum testosterone and lower DHT during treatment with oral TU. Therefore, we studied the steady-state pharmacokinetics of oral TU, 200 mg equivalents of testosterone twice daily for 7 days, alone and with finasteride 0.5 and 1.0 mg po twice daily in an open-label, three-way crossover study in 11 young men with experimentally induced hypogonadism. On the seventh day of each dosing period, serum testosterone, DHT and oestradiol were measured at baseline and 1, 2, 4, 8, 12, 13, 14, 16, 20 and 24 h after the morning dose. Serum testosterone and DHT were significantly increased into and above their normal ranges similarly by all three treatments. Co-administration of finasteride at 0.5 and 1.0 mg po twice daily had no significant effect on either serum testosterone or DHT. Oral TU differs from other formulations of oral testosterone in its response to concomitant inhibition of 5α-reductase, perhaps because of its unique lymphatic route of absorption.

Fill-tube-induced mass perturbations on x-ray-driven, ignition-scale, inertial-confinement-fusion capsule shells and the implications for ignition experiments.

On the first inertial-confinement-fusion ignition facility, the target capsule will be DT filled through a long, narrow tube inserted into the shell. microg-scale shell perturbations Delta m' arising from multiple, 10-50 microm-diameter, hollow SiO2 tubes on x-ray-driven, ignition-scale, 1-mg capsules have been measured on a subignition device. Simulations compare well with observation, whence it is corroborated that Delta m' arises from early x-ray shadowing by the tube rather than tube mass coupling to the shell, and inferred that 10-20 microm tubes will negligibly affect fusion yield on a full-ignition facility.

Evidence of efficacy of the Lederle/Takeda acellular pertussis component diphtheria and tetanus toxoids and pertussis vaccine but not the Lederle whole-cell component diphtheria and tetanus toxoids and pertussis vaccine against Bordetella parapertussis infection.

A subanalysis of a recent cohort efficacy trial of a pertussis vaccine was performed to determine its efficacy against cough illnesses due to Bordetella parapertussis infections. Infants received four doses of either the Lederle/Takeda acellular pertussis component diphtheria and tetanus toxoids and pertussis (DTaP) vaccine or the Lederle whole-cell component diphtheria and tetanus toxoids and pertussis (DTP) vaccine at 3, 4.5, 6, and 15-18 months of age; controls received three doses of diphtheria and tetanus toxoids (DT) vaccine only. All subjects were prospectively followed for cough illnesses of > or = 7 days' duration; cases of B. parapertussis infection were confirmed by positive culture, household contact, or serology. Seventy-six cough illnesses due to B. parapertussis were identified; 24 occurred in 929 DTaP recipients, 37 in 937 DTP recipients, and 15 in 321 DT recipients, resulting in an efficacy of 50% for DTaP vaccine (95% CI [confidence interval], 5% to 74%) and 21% for DTP vaccine (95% CI, -45% to 56%). The data in the present analysis suggest that the Lederle/Takeda DTaP vaccine but not the Lederle whole-cell component DTP vaccine has efficacy against B. parapertussis infection.

The effect of investigator compliance (observer bias) on calculated efficacy in a pertussis vaccine trial.

BACKGROUND: In the course of a large pertussis vaccine efficacy trial we realized that investigator compliance could have a major impact on calculated vaccine efficacy. DESIGN: In our pertussis vaccine efficacy trial, the study investigators were to monitor illness in study families by telephone every 2 weeks. If a cough illness of >/=7 days duration was noted, the study child was to be evaluated. If the cough illness persisted for >/=14 days, the child was to be referred to a central investigator. For this report we analyzed study physician evaluation rates and rates of referral to the central investigators. Physician practices were separated into three compliance categories: high, intermediate, and low. We analyzed vaccine efficacy of an acellular pertussis component DTP vaccine (DTaP) and a whole cell pertussis component DTP vaccine (DTP) by compliance category. Bordetella pertussis infection was documented by culture of the organism in the study child or in a household contact or by a significant antibody response to pertussis toxin determined by enzyme-linked immunosorbent assay. RESULTS: Using a clinical case definition that included both mild and typical pertussis (cough illness >/=7 days duration) efficacy of DTaP vaccine was 40% (95% confidence interval [CI] = -3-65) in the high compliance category and 78% (95% CI = 65-86) and 75% (95% CI = 53-87) in the intermediate and low compliance groups, respectively. Similar, but less marked, differences in efficacy were noted with DTP vaccine recipients. Using a clinical case definition that required >/=21 days of cough with paroxysms, whoop, or vomiting (typical pertussis) the efficacy of DTaP vaccine was 69% (95% CI = 41-83) in the high compliance category and 86% (95% CI = 76-92) and 84% (95% CI = 64-93) in the intermediate and low compliance groups, respectively. In contrast, the efficacy of DTP vaccine did not vary by compliance category using this case definition. The attack rate in children vaccinated with diphtheria and tetanus toxoids vaccine (DT) was twofold less in low compliance physician practices when compared with the rates in high and intermediate groups. The DT/DTaP and DT/DTP fold-change differences were less in the high compliance group compared with the intermediate and low compliance groups. CONCLUSIONS: Our data suggest that observer compliance (observer bias), can significantly inflate calculated vaccine efficacy. It is likely that all recently completed efficacy trials have been effected by this type of observer bias and all vaccines have considerably less efficacy against mild disease than published data suggest.

A comparative efficacy trial in Germany in infants who received either the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine, the Lederle whole-cell component DTP vaccine, or DT vaccine.

BACKGROUND: The goal of the trial was to determine the efficacy of a multicomponent acellular pertussis vaccine against Bordetella illnesses in comparison with a whole-cell product and DT. DESIGN: In a randomized, double-blind fashion, 2- to 4-month-old infants received 4 doses of either DTP or DTaP vaccine at 3, 4.5, 6, and 15 to 18 months of age. The controls received 3 doses (3, 4.5, 15 to 18 months of age) of DT vaccine. The DTP vaccine was Lederle adsorbed vaccine (licensed in the United States) and DTaP was Lederle/Takeda adsorbed vaccine. Follow-up for vaccine efficacy started 2 weeks after the third dose (DTP/DTaP) and at the same age (6.5 months) in DT recipients. Reactogenicity of all doses of all three vaccines was documented by standardized parent diary cards. In addition, all subjects were monitored for respiratory illnesses and serious adverse events by biweekly phone calls. RESULTS: From May 1991 to January 1993, a total of 10 271 infants were enrolled: 8532 received either DTP or DTaP and 1739 received DT. Specific efficacy against B pertussis infections with cough >/=7 days duration was 83% (95% confidence interval [CI]: 76-88) and 72% (95% CI: 62-79) for DTP and DTaP, respectively; results for DTP and DTaP based on >/=21 days of cough with either paroxysms, whoop or posttussive vomiting (PWV) were 93% (95% CI: 89-96) and 83% (95% CI: 76-88), respectively. For DTaP vaccine, efficacy was higher after the fourth dose as compared with its efficacy after the third dose (78% vs 62% for cough >/=7 days and 85% vs 76% for cough >/=21 days with PWV). For DTP vaccine, efficacy was less varied after the third and fourth dose (78% vs 85% for cough >/=7 days and 93% vs 93% for cough >/=21 days with PWV). In contrast with DTP, the DTaP vaccine had some efficacy against B parapertussis infection (point estimate for cough >/=7 days: 31% [95% CI: -10-56]). All vaccines were generally well-tolerated. However, side reactions were significantly less after DTaP compared with DTP. CONCLUSIONS: Like other multicomponent acellular pertussis vaccines, the Lederle/Takeda DTaP vaccine demonstrated good efficacy against mild and typical pertussis due to B pertussis infections. Interestingly, it also may have some efficacy against B parapertussis. Based on the results of this trial, the vaccine was licensed in the United States in December 1996 for all 5 doses of the currently recommended immunization schedule in this country.

Transitional cell carcinoma of the kidney with tumor thrombus into the vena cava.

Transitional cell carcinoma of the upper urinary tract with inferior vena cava tumor thrombus is an unusual entity. We report the 16th such case and review the previous cases in the world literature. Preoperative diagnosis was correct in only 5 of the cases. This type of condition can be easily presumed to be renal cell carcinoma. Fifteen of the cases were managed with radical nephrectomy; 8 patients were managed with partial or complete resection of the vena cava due to adherence of the tumor thrombus to the vessel wall. Overall outcome was poor, with short postoperative survival. Correct preoperative diagnosis, although difficult, could allow more complete preoperative planning or appropriate nonoperative management.

Risk factors of infantile spasms compared with other seizures in children under 2 years of age.

To analyze the magnitude of the risk factors for infantile spasms, we evaluated the records of 80 children with infantile spasms, 474 children with other types of epilepsy, 2,196 children with febrile seizures, and 262 children with CNS infections. There was a family history of seizures in 13.8% of children with infaNtile spasms, 28.5% of children with other forms of epilepsy, 25.5% of children with febrile seizures, and 5.3% of children with CNS infections. Children with a family history of seizures were 2.82 times more likely to have infantile spasms, 7.05 time more likely to have other epilepsy, and 6.08 time more likely to have febrile seizures than controls (children with CNS infections). However, a family history of seizures increased the risk for infantile spasms only in the cryptogenic group. Children with infantile spasms were significantly more likely to have cerebral palsy, microcephaly, hydrocephaly, CNS malformations, neonatal hypoxia, or neonatal seizures than children with other types of epilepsy, febrile seizures, or CNS infections. There was a modest genetic predisposition to seizures in children with infantile spasms. However, our data suggest a much stronger association with underlying neurologic abnormalities, mainly neonatal seizures, neonatal hypoxia, and CNS malformations.

Household contact study of Bordetella pertussis infections.

Household contacts of primary pertussis cases were evaluated. Infection was determined by culture, direct fluorescent antibody assay, and serological criteria. Agglutinin titers and values of ELISA IgG and IgA antibodies to lymphocytosis-promoting factor, filamentous hemagglutinin, and pertactin were determined. In 39 households 255 subjects were exposed; 114 remained well (group 1), 53 had mild illness (group 2), and 88 had pertussis (group 3). The infection rates were 46% (group 1), 43% (group 2), and 80% (group 3). In a subgroup of subjects seen within 14-28 days of exposure, it was found that none with clinical pertussis had a value of IgG antibody to pertactin in acute-phase sera of > or = 50 ELISA units (EU) per mL or an agglutinin titer of > 256. Of the primary cases, 53% were > or = 13 years of age. These data point out the importance of Bordetella pertussis infections in adolescents and adults as a source of infection in young children. Our subgroup data suggest that high values of antibody to pertactin and high agglutinin titers may be predictive of protection against clinical pertussis.

Frequency of unrecognized Bordetella pertussis infections in adults.

To investigate the frequency of unrecognized Bordetella pertussis infections in adults, we performed IgA and IgG ELISA antibody studies with four B. pertussis antigens--i.e., lymphocytosis-promoting factor, filamentous hemagglutinin, pertactin, and fimbriae-2--in 51 health care workers from whom six consecutive yearly serum samples (from 1984 to 1989) were available. Overall, 90% of the subjects had a significant increase in antibody (IgA or IgG) to one or more antigens between 2 consecutive years during the 5-year study period; 55% of subjects had evidence of two infections, 17% had three infections, and 4% had four infections. Infections occurred in all study years, with the following rates: 1984-1985, 32%; 1985-1986, 24%; 1986-1987, 40%; 1987-1988, 29%; and 1988-1989, 43% (P = .12). Some antibody rises may have been due to responses to cross-reacting antigens (Bordetella parapertussis, nontypable Haemophilus influenzae), but overall these data suggest that B. pertussis infections in adults are common, endemic, and usually unrecognized.

Comparison of values of antibody to Bordetella pertussis antigens in young German and American men.

Pertussis is well controlled in the United States by routine childhood immunization. In contrast, this disease is endemic and epidemic in Germany because routine immunization has not been implemented. To gain information relating to the epidemiology of Bordetella pertussis infections, we examined the prevalence and magnitude of B. pertussis agglutinins and of IgG and IgA antibodies (detected by enzyme-linked immunosorbent assay) to four B. pertussis antigens--lymphocytosis-promoting factor, filamentous hemagglutinin, pertactin, and fimbriae-2--in the sera of 119 American university students and 119 German military recruits of similar age. Geometric mean titers of agglutinins and geometric mean values for IgG antibodies to the four antigens were two- to threefold higher in sera from the American students than in sera from German recruits. In contrast, the geometric mean IgA values and the percentage of subjects with detectable IgA antibodies to the four antigens were similar in the two populations. Since IgA antibody results mainly from infection and not from immunization, our data suggest that B. pertussis infections are common among both American and German young adults despite the marked difference in rates of clinical pertussis in the two countries.

Protection provided by Haemophilus influenzae type b conjugate vaccines in Los Angeles County: a case-control study.

The objective was to assess the degree of disease control and to evaluate the protective efficacy of licensed Haemophilus influenzae type b (Hib) conjugate vaccines (HbOC, PRP-OMP, PRP-D) used routinely in children 2 to 35 months of age. We conducted a case-control study in Los Angeles County between January 1, 1991, and December 31, 1992, and a cohort analysis of Hib cases between 1983 and 1992. For the case-control study 105 cases of invasive Hib disease were identified and 767 geographically and age-matched controls were selected by random digit telephone dialing. Sixteen HbOC vaccine failures occurred > 14 days after a single dose of vaccine, 6 vaccine failures after 2 doses and 3 failures after 3 doses; 2 cases occurred 6 and 12 days, respectively, after an initial dose of HbOC. The protective efficacy of a single HbOC vaccine dose was 71.1% (95% confidence interval (CI), 37.5 to 87.2%). After 2 doses the efficacy was 88.8% (95% CI, 59.5 to 96.9%) and after 3 doses it was 94.4% (95% CI, 68.0% to 99.0%). Similar 95% CIs were seen for 1 and 2 doses of PRP-OMP vaccine. Adjustment of efficacy estimates for potential confounding variables did not significantly alter the results. Despite relatively low rates of immunization (20 to 60%) the rates of Hib disease decreased strikingly between 1990 and 1992 (from 24.2 to 4.4/100,000 children < 5 years of age). The HbOC conjugate vaccine, used predominantly but incompletely during this period, provided substantial protection against invasive Hib disease in children immunized between 2 and 35 months of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical characteristics of illness caused by Bordetella parapertussis compared with illness caused by Bordetella pertussis.

In conjunction with a pertussis vaccine efficacy trial in Germany, nasopharyngeal specimens were collected from May, 1992, to March, 1993, from patients with cough illnesses. Clinical data were obtained by initial and follow-up questionnaires. Bordetella parapertussis was isolated from 38 patients (mean age, 3.5 years; 68% girls). Clinical characteristics in these cases were compared with those of 76 patients (matched by age and sex) with illness caused by Bordetella pertussis during the same period. Findings were: (B. pertussis/B. parapertussis): cough > 4 weeks 57%/37% (P = 0.06); whoop 80%/59% (P = 0.07); whoop > 2 weeks 26%/18% (P = 0.05); paroxysms 90%/83% (P = 0.5); body temperature > or = 38 degrees C 9%/0% (P = 0.17); vomiting 47%/42% (P = 0.69); and mean leukocyte and lymphocyte counts 12,500/mm3 and 7600/mm3 (P < 0.0001) and 7800/mm3 and 3500/mm3 (P < 0.0001), respectively. Illness caused by B. parapertussis was typical of pertussis but less severe than that caused by B. pertussis. In contrast with B. pertussis infection, lymphocytosis is not a characteristic of B. parapertussis infection. This is most likely a result of the lack of production of lymphocytosis-promoting factor toxin by B. parapertussis.

Comparative study of Lederle/Takeda acellular and Lederle whole-cell pertussis-component diphtheria-tetanus-pertussis vaccines in infants in Germany.

In preparation for a large efficacy trial in Germany, a pilot study was initiated in December 1990. In this study 149 infants were enrolled; with double-blind randomization 75 received Lederle/Takeda acellular pertussis component diphtheria-tetanus-pertussis vaccine (APDT) and 74 received Lederle whole-cell pertussis component diphtheria-tetanus-pertussis vaccine (DTP). The mean age at first dose was 3.5 months, and the second and third doses followed at 6-week intervals. Reactions were relatively mild with both vaccines; in general they were less frequent following APDT. The IgG antibody responses to lymphocytosis promoting factor (LPF) and fimbriae-2 were similar in both groups whereas the responses to pertactin and filamentous haemagglutinin (FHA) were greater in APDT recipients. DTP recipients had greater responses to tetanus and diphtheria toxoids. When age of first dose was examined (8-12 weeks versus 16-20 weeks), it was found that young age had a suppressive effect on antibody responses in DTP but not APDT recipients to LPF toxoid, pertactin, fimbriae-2, and tetanus and diphtheria toxoids. High values of transplacentally acquired antibody lessened the response to LPF toxoid and tetanus toxoid in DTP recipients and to tetanus toxoid in APDT vaccinees. The IgG immune response to LPF toxoid, FHA and fimbriae-2 was found to be more uniform in APDT recipients than in DTP vaccinees. An IgA antibody response to fimbriae-2 was noted in 13% of DTP recipients but in no APDT vaccinees. The broad immunogenicity and mild reactogenicity of this APDT vaccine justifies its use in the German efficacy trial.

Growth of the human optic disk and nerve during gestation, childhood, and early adulthood.

We measured vertical and horizontal diameters of the optic disk and retrobulbar optic nerve in eyes from 95 patients on whom autopsies were performed at the UCLA Medical Center over a 20-year period. Ages at death ranged from 4.8 months' gestation to 21.9 years. Optic disk surface area and nerve cross-sectional area were calculated for each subject by using the formula for an ellipse. Approximately 50% of the growth of the optic disk and nerve occurs by 20 weeks' gestation, and 75% by birth; 95% of the growth occurs before the age of 1 year. All optic disk and nerve measurements correlate strongly (correlations > .67; P < .0001) with subject height and globe anteroposterior diameter. We applied our results to the current understanding of optic disk and nerve development, and compared them to previous clinical and pathologic studies of optic nerve dimensions in adults and older children.