Central nervous system manifestations in human immunodeficiency virus infection without AIDS.

To characterize neurological and neuropsychological findings associated with human immunodeficiency virus type-I (HIV) infection, 77 seropositive homosexual or bisexual males with no or minor symptoms of HIV were compared prospectively to 44 HIV seronegative men by observers blinded to serological status of the subjects. Neurological symptoms and examination findings were not significantly different between seropositives and seronegatives except for cranial nerve findings, predominantly mild hearing impairment. Mean performance scores for a 15-test neuropsychological battery were within an unimpaired range for both groups, although for five tests, mean scores were significantly poorer in seropositives. After adjustment for vocabulary score, and demographic and psychosocial variables, the mean score of seropositives was significantly worse only for the Benton Visual Retention Test. Magnetic resonance (MR) images of brain were abnormal in 14 (27%) of 52 seropositives and one of 10 seronegatives (value was not significant). HIV was isolated from cerebrospinal fluid (CSF) in 31 (61%) of 51 seropositives. The only clinical or laboratory difference between CSF culture positives and negatives was a higher CSF immunoglobulin synthesis rate in the former subjects (medians of 10.3 versus 0.1 mg/day; p = 0.03). An additional 13 seropositive subjects had immunologic evidence of central nervous system HIV infection, defined by a serum-to-CSF HIV antibody ratio of less than 5.5. Intracranial abnormalities on MR imaging were associated with CSF immunologic responses to HIV. Nervous system involvement occurred in the vast majority of men with early HIV infection, but clinically significant impairment was uncommon.

Comparative study of ceftriaxone and spectinomycin in the treatment of uncomplicated gonorrhea in women.

Single-dose ceftriaxone, 125 mg given intramuscularly, was compared with spectinomycin 2.0 g given intramuscularly in the treatment of women with uncomplicated gonorrhea. Cervical or anorectal gonococcal infection was eradicated in 54 (98 percent) of 55 women treated with ceftriaxone and 22 (96 percent) of 23 treated with spectinomycin. Cure rates for pharyngeal gonococcal infections were nine of 10 for ceftriaxone and four of eight for spectinomycin (p = 0.18). Neither agent eradicated concurrent Chlamydia trachomatis infection. The geometric mean minimal inhibitory concentration for ceftriaxone was 0.0038 microgram/ml for 65 pretreatment cervical isolates of beta-lactamase-negative Neisseria gonorrhoeae and all isolates were inhibited by 0.063 microgram/ml. Neither drug caused perceptible toxicity, but patient acceptance was better for ceftriaxone than for spectinomycin. A single 125 mg dose of ceftriaxone is an excellent regimen in the treatment of uncomplicated gonorrhea in women.

Cytomegalovirus infection in homosexual men. Relationship to sexual practices, antibody to human immunodeficiency virus, and cell-mediated immunity.

To investigate the relationships among cytomegalovirus infection, sexual behavior, human immunodeficiency virus (HIV) seropositivity, and indexes of cellular immunity, 180 homosexual men and 26 heterosexual men were studied. Among the homosexual men, cytomegalovirus seropositivity was associated with increased T8 lymphocyte counts (p less than 0.001) and reduced T4/T8 ratios (p = 0.006); these results were independent of HIV infection. Cytomegalovirus seropositivity was also associated with increasing age, numbers of sexual partners, and the practice of anal-receptive intercourse. At the first visit, cytomegalovirus was isolated from none of 13 cytomegalovirus-seropositive heterosexual subjects, compared with 62 (36 percent) of 171 seropositive homosexual men (p less than 0.005). Viral isolation was most common from semen. Among 32 cytomegalovirus-seropositive homosexual subjects from whom culture specimens were obtained more than four times over 10 to 30 months, 72 percent of the specimens were culture-positive. The mean duration of cytomegalovirus excretion in semen was 22 months, and in urine, the duration was nine months. Cytomegalovirus excretion was associated with younger age and reduced lymphocyte proliferation in response to cytomegalovirus, but not with antibody to HIV. Cytomegalovirus infection is sexually transmitted among homosexual men, perhaps by rectal intercourse, and is associated with alterations in T lymphocyte subsets. Most seropositive homosexual men excrete cytomegalovirus intermittently, primarily in the semen.

Agonist-inverse agonist characterization at CB1 and CB2 cannabinoid receptors of L759633, L759656, and AM630.

We have tested our prediction that AM630 is a CB2 cannabinoid receptor ligand and also investigated whether L759633 and L759656, are CB2 receptor agonists. Binding assays with membranes from CHO cells stably transfected with human CB1 or CB2 receptors using [3H]-CP55940, confirmed the CB2-selectivity of L759633 and L759656 (CB2/CB1 affinity ratios = 163 and 414 respectively) and showed AM630 to have a Ki at CB2 receptors of 31.2 nM and a CB2/CB1 affinity ratio of 165. In CB2-transfected cells, L759633 and L759656 were potent inhibitors of forskolin-stimulated cyclic AMP production, with EC50 values of 8.1 and 3.1 nM respectively and CB1/CB2 EC50 ratios of > 1000 and > 3000 respectively. AM630 inhibited [35S]-GTPgammaS binding to CB2 receptor membranes (EC50 = 76.6 nM), enhanced forskolin-stimulated cyclic AMP production in CB2-transfected cells (5.2 fold by 1 microM), and antagonized the inhibition of forskolin-stimulated cyclic AMP production in this cell line induced by CP55940. In CB1-transfected cells, forskolin-stimulated cyclic AMP production was significantly inhibited by AM630 (22.6% at 1 microM and 45.9% at 10 microM) and by L759633 at 10 microM (48%) but not 1 microM. L759656 (10 microM) was not inhibitory. AM630 also produced a slight decrease in the mean inhibitory effect of CP55940 on cyclic AMP production which was not statistically significant. We conclude that AM630 is a CB2-selective ligand that behaves as an inverse agonist at CB2 receptors and as a weak partial agonist at CB1 receptors. L759633 and L759656 are both potent CB2-selective agonists.

Treatment of uncomplicated gonorrhea in women with single-dose cefonicid.

The efficacy of cefonicid (1.0 g given in a single intramuscular dose) was assessed in 50 women with uncomplicated infections due to beta-lactamase-negative strains of Neisseria gonorrhoeae. Forty-three (96%) of 45 cervical infections but only 23 (82%) of 28 anorectal infections were eradicated; overall, 44 (90%) of 49 women were cured of anogenital gonorrhea. Cefonicid failed to eradicate six (55%) of 11 pharyngeal gonococcal infections and 17 (85%) of 20 endocervical infections with Chlamydia trachomatis. Cefonicid had good activity against N. gonorrhoeae in vitro; 41 (98%) of 42 isolates were inhibited by less than or equal to 1.0 micrograms/ml. However, because of its poor efficacy against anorectal and pharyngeal gonococcal infections, single-dose cefonicid is not suitable for the treatment of gonorrhea in women or homosexually active men.

Comparative study of ceftriaxone and spectinomycin for treatment of uncomplicated gonorrhoea in men.

Single-dose ceftriaxone, 125 mg or 250 mg intramuscularly (IM), was compared with spectinomycin, 2 g IM, for treatment of men with uncomplicated urethral or anorectal infections due to penicillinase-negative Neisseria gonorrhoeae. Cure rates were 100% for 31 and 28 men treated with 125 mg and 250 mg ceftriaxone, respectively, and 97% for 58 men given spectinomycin. Among patients followed up for greater than or equal to 14 days, post-gonococcal urethritis occurred in 25% of 44 men treated with ceftriaxone and 19% of 47 given spectinomycin (p = NS). The geometric mean minimum inhibitory concentration of ceftriaxone for 79 pre-treatment isolates of N gonorrhoeae was 0.0058 microgram/ml, and all strains were inhibited by less than or equal to 0.063 micrograms/ml. Neither drug caused perceptible toxicity, but patient acceptance was greater for ceftriaxone than for spectinomycin. Ceftriaxone in a single dose of 125 mg is effective against uncomplicated urethral or anorectal gonorrhoea in men and may become a regimen of choice for this infection.

Dose-ranging study of ceftriaxone for uncomplicated gonorrhea in men.

Uncomplicated gonorrhea in men was successfully treated with ceftriaxone in single intramuscular doses of 125 mg (15 patients), 250 mg (16 patients), or 500 mg (15 patients). All 45 pretreatment gonococcal isolates tested were inhibited by

Antibody to human immunodeficiency virus (HIV) and suboptimal response to hepatitis B vaccination.

STUDY OBJECTIVE: To analyze the relation between human immunodeficiency virus (HIV) infection and the antibody response to plasma-derived hepatitis B vaccine. DESIGN: Open-label longitudinal cohort study; blinded laboratory studies. SETTING: University-affiliated municipal hospital. PATIENTS: Homosexually active men with negative assays for hepatitis B surface antigen (HBsAg), hepatitis B core antigen, and antibody to HBsAg; recruited in a sexually transmitted disease clinic or referred from community practitioners. INTERVENTIONS: Immunization with 20 micrograms of plasma-derived hepatitis B virus vaccine intramuscularly, repeated after 1 and 6 months; standardized evaluation at entry and at 1, 2, 6, and 7 months. MEASUREMENTS AND MAIN RESULTS: Low antibody response or nonresponse to vaccination occurred in 7 of 16 HIV-seropositive patients, compared with 6 of 68 HIV-seronegative patients (P = 0.002). Median levels of antibody to HBsAg 7 months after the first vaccine dose were 205.3 sample ratio units for HIV-seronegative patients and 15.5 sample ratio units for HIV-seropositive patients. By multivariate analysis, vaccine response was associated with HIV antibody status and not with cytomegalovirus infection, lymphocyte subset results, or impaired cutaneous delayed hypersensitivity. CONCLUSIONS: Infection with HIV is associated with suboptimal antibody response to plasma-derived hepatitis B virus vaccine. Determination of antibody levels after vaccination in HIV-seropositive patients may be warranted.

Relationship between antibody to LAV/HTLV-III and the natural course of subclinical cellular immune dysfunction in homosexual men.

To assess the epidemiology and natural history of persistent generalized lymphadenopathy (PGL) and subclinical immunodeficiency in relation to serologic evidence of lymphadenopathy-associated virus/human T-lymphotropic virus type III (LAV/HTLV-III) infection, 109 homosexual men with PGL, 47 homosexual men without lymphadenopathy who attended a sexually transmitted disease (STD) clinic, 25 homosexual male university students, and 26 heterosexual men who attended the STD clinic were studied. In 1982-1983 antibody to LAV/HTLV-III was present in 97%, 35%, 21%, and 4% of the four groups, respectively (P less than .001). Subclinical immunodeficiency was more closely associated with LAV/HTLV-III seropositivity than with lymphadenopathy. Cohorts of 78 homosexual subjects with PGL, 35 homosexual subjects from STD clinic, and 15 homosexual university students were followed for median periods of 13.5, 20, and 14.5 months, respectively. The seroconversion rate was 23% per year among seronegative subjects, and 4% of seropositive subjects developed overt acquired immunodeficiency syndrome (AIDS). Among seronegative subjects, there was significant improvement in T4:T8 ratios (P = .001), whereas most seropositive subjects continued to have subnormal total counts of T4 lymphocytes and low T4:T8 ratios. Some cases of subclinical cellular immunodeficiency apparently are unrelated to LAV/HTLV-III infection, and the presence of antibody to this virus is associated with an unfavorable immunologic prognosis.

Cytomegalovirus infection in women attending a sexually transmitted disease clinic.

To evaluate prospectively the relationship between current and past sexual practices and seroprevalence of cytomegalovirus (CMV) in adult women, 1481 women (1101 white, 301 black, 79 other) attending a sexually transmitted disease clinic underwent a standardized interview and genital examination. CMV seroprevalence was higher in black (78%) than in white (59%) women. In logistic regression models that adjusted for age and years of education, CMV seropositivity in white women was associated with younger sexual debut (P = .001), more lifetime sex partners (P = .025), recent new partner(s) (P = .003), and parity (P = .002), and was inversely associated with use of barrier contraception (P = .006). In black women, after adjustment for demographic characteristics, CMV antibody was associated with greater numbers of recent sex partners (P = .007), new sex partners (P = .04), and with cervical infection with Chlamydia trachomatis (P = .05). This study confirms that sexual activity is an important determinant of CMV infection in both white and black women; however, the relative contributions of sexual and nonsexual transmission of CMV apparently vary and require further investigation.

Fertility parameters in men infected with human immunodeficiency virus.

The effect of human immunodeficiency virus type 1 (HIV) infection on semen parameters that assess fertility was investigated in 50 semen specimens from 21 asymptomatic or minimally symptomatic HIV-seropositive men and 3 specimens from 3 men with AIDS. HIV was isolated from 15 (30%) of 50 specimens from asymptomatic or minimally symptomatic persons and from 1 of 3 specimens from patients with AIDS. The men with AIDS all had pyosemia and grossly abnormal sperm. In contrast, semen specimens from other seropositive men did not differ significantly from semen specimens from healthy seronegative semen donors. No abnormality in sperm count, morphology, numbers or types of leukocytes in semen, or other seminal parameters was associated with HIV shedding in semen. Zidovudine therapy did not affect sperm morphology or seminal characteristics. Thus, although patients with AIDS had abnormal semen, the laboratory parameters that assess fertility were not affected by shedding of HIV in semen or concomitant therapy with zidovudine.

Recovery of human immunodeficiency virus type 1 from semen: minimal impact of stage of infection and current antiviral chemotherapy.

Because exposure to semen is important for the sexual transmission of human immunodeficiency virus type 1 (HIV), the relationship of stage of infection and antiviral chemotherapy to isolation of HIV from semen was investigated. Whereas HIV was isolated from peripheral blood mononuclear cells of all seropositive persons tested, it was isolated from semen in only 11 (32%) of 34 men, including 3 of 6 who were studied sequentially over time. HIV was isolated from 6 (32%) of 19 semen specimens from 14 asymptomatic persons (Centers for Disease Control [CDC] class II or III) and from 10 (28%) of 36 semen specimens from 20 symptomatic patients (CDC class IV). Isolation of HIV from semen did not correlate with CD4+ or CD8+ T lymphocytes counts or zidovudine therapy. Seropositive men may shed HIV in semen early in the course of infection, and zidovudine therapy seems to have no effect on the recovery of HIV and, thus, on the potential for sexual transmission of HIV.

Neurologic Manifestationsof HIV Infection Without AIDS:Follow-UP of a Cohortof Homosexual and Bisexual Men.

To identify neurological abnormalities in HIV infection, 159 HIV-seropositive men without AIDS and 76 seronegative controls underwent standardized general and neurological examinations, lumbar puncture (LP), neuropsychological (NP) assessment, and brain magnetic resonance (MR) imaging. History, physical, and laboratory evaluations were repeated every six months. NP tests (all subjects) and MR imaging (seropositives only) was repeated every 6-12 months; LP (seropositives only) was repeated yearly. Mean follow-up was 24.6 months. Neurological abnormalities, most related to hearing, were seen in 60 (38.2%) of 157 seropositives and 23 (30.3%) of 76 controls at baseline (p = NS). During follow-up, 43 (31.6%) of 136 seropositives had persistent hearing abnormalities compared to 9 (14.1%) of 64 seronegatives (p = 0.008). Seven HIV-seropositives developed peripheral neuropathy; this was more common among those with hearing abnormalities (p = 0.03). HIV-seropositives performed less well on NP tests than controls, but overall performance did not decline. Worsening brain atrophy by MR imaging or cerebrospinal fluid abnormalities are more common in HIV-seropositives than seronegatives and may share a common mechanism with peripheral neuropathy. Further study is needed to determine whether these abnormalities portend more serious neurological disease.