Issues to consider in operationalizing reproductive health.

The International Conference on Population and Development (ICPD) served as the international launchpoint for a broadened reproductive health agenda, bringing global attention to a variety of underlying issues that impact on women's health and well-being, and highlighting the need to redress imbalances in gender equity that have had negative health and social consequences in particular for women and girls. To meet the challenges of the ICPD, programs must assess, prioritize and implement an expanded set of reproductive health interventions within an environment of diminishing resources. This paper argues that hidden social and health costs that particularly affect women must be included in the assessment and prioritization of reproductive health interventions. In addition, it argues that issues of gender and sexuality cannot be separated from the delivery of appropriate family planning and reproductive health care if we are to have a significant impact on improving the reproductive health of current and future generations.

Low incidence of serum neutralizing factors in patients receiving recombinant alfa-2b interferon (Intron A).

The development of serum neutralizing factors against recombinant alfa-2b interferon (Intron A) was reviewed in a large clinical experience. In 537 patients receiving systemic therapy, neutralizing factors developed in only 13 (2.4 percent). In 1,326 patients who received intranasal administration and 154 with intralesional administration, the incidence was less than 1 percent. Patients in whom antibody developed had no predisposing characteristics that could be identified, no particular types of patients with cancer had a high rate of neutralizing factors, and two of 10 patients with cancer in whom neutralizing factor developed were still able to show clinical responses. In patients in whom neutralizing factor was present, there was no discernible difference in the incidence or severity of interferon side effects as compared with patients who had no demonstrable neutralizing factor levels. This form of recombinant alpha-2 interferon appears to have a very low antigenic potential.

Radioimmunoassay and opsonic antibody responses to pneumococcal capsular polysaccharide vaccine in serum and ascitic fluid of cirrhotic patients.

Pneumococcal capsular polysaccharide vaccine was administered to 19 cirrhotic patients and to 25 control subjects. Radioimmunoassay antibody concentration and opsonic titers (OT) were measured in sera and ascites collected before and 3 to 4 weeks after inoculation. The geometric mean antibody concentrations in prevaccination sera from the cirrhotic patients were significantly increased to types 3, 4, 7F, 8, 9N, and 12F antigens, and in postinoculation sera their geometric mean antibody concentration was increased to types 3, 9N, and 12F antigens. OT to Streptococcus pneumoniae type 3 correlated with the radioimmunoassay antibody concentration in postinoculation sera. Of 14 cirrhotic subjects, 3 had OT of greater than or equal to 4 in prevaccination sera, and the highest OT and radioimmunoassay antibody concentration were observed in postinoculation specimens from this group. Antibody and OT against S. pneumoniae type 3 were also observed in ascitic specimens. These data suggest that cirrhotic subjects respond to pneumococcal capsular polysaccharide with antibodies in both serum and ascitic fluid. However, the protective efficacy of this antibody response must be assessed by larger prospective studies.

Pharmacokinetics of ceftriaxone in pediatric patients with meningitis.

Pharmacokinetics of ceftriaxone after a single dose of 50 or 75 mg/kg were determined in 30 pediatric patients with bacterial meningitis. Data for doses of 50 and 75 mg/kg, respectively, were as follows (mean +/- standard deviation): maximum plasma concentrations, 230 +/- 64 and 295 +/- 76 mug/ml; elimination rate constant, 0.14 +/- 0.06 and 0.14 +/- 0.04 h(-1); harmonic elimination half-life, 5.8 +/- 2.8 and 5.4 +/- 2.1 h; plasma clearance, 51 +/- 24 and 55 +/- 18 ml/h per kg; volume of distribution, 382 +/- 129 and 387 +/- 56 ml/kg; mean concentration in cerebrospinal fluid 1 to 6 h after infusion, 5.4 and 6.4 mug/ml. A dosage schedule of 50 mg/kg every 12 h for bacterial meningitis caused by susceptible organisms is suggested for pediatric patients over 7 days of age.

Pharmacokinetic characteristics of intravenous ceftriaxone in normal adults.

The multiple-dose pharmacokinetics and tolerance of intravenous ceftriaxone were investigated in 44 adults with normal renal function. Doses of 0.5, 1.0, and 2.0 g every 12 h and 2 g every 24 h were administered intravenously at a constant rate over 30 min. Plasma and urine samples were collected after the first (day 1) and last (day 4) dose and assayed for ceftriaxone by high-pressure liquid chromatography. Considering all four doses, mean peak plasma concentrations ranged from 79 to 255 micrograms/ml on day 1 and from 101 to 280 micrograms/ml on day 4. Trough concentrations at 12 h on day 1 were 15 to 45 micrograms/ml and 20 to 59 micrograms/ml on day 4. After a dose regimen of 2 g every 24 h, trough levels were still in the clinically therapeutic range (13 to 15 microgram/ml). The mean beta-phase t1/2 was markedly long (6.3 to 6.9 h) and was independent of dose. The fraction of dose excreted unchanged in the urine (0.33 to 0.44) indicated a substantial nonrenal mechanism of elimination. The plasma clearance ranged between 1,002 and 1,449 ml/h, and renal clearance ranged from 353 to 529 ml/h. The apparent volume of distribution varied from 9.2 to 13.5 liters. The dose-related increases in calculated Vd and Clp could be attributed to concentration-dependent plasma protein binding because of a larger free fraction of drug at higher concentrations. The drug was well tolerated, and no significant clinical or laboratory abnormalities were noted.

Efficacy of ceftriaxone and gentamicin in an abscess model.

The therapeutic efficacy of ceftriaxone and gentamicin was investigated in a foreign body induced abscess model in the rat by implanting a dialysis tube contaminated with Klebsiella pneumoniae into the subcutaneous tissue. Animals were treated for four days with ceftriaxone, gentamicin, and their combination starting immediately following or 48 h after the implantation. Peak free ceftriaxone and gentamicin abscess fluid levels were 4.3 and 2.6 mcg/ml, which were 7.3% and 37.5% of peak blood levels respectively. Both agents persisted longer in abscess fluid than in blood. Ceftriaxone inhibited the development of abscess formation when administered shortly after the implantation of the contaminated foreign body whereas gentamicin alone was without beneficial effect. When administered after 48 h ceftriaxone was less effective than immediately after implantation and gentamicin was again without any therapeutic effect. The effect of the combination of ceftriaxone and gentamicin was slightly better than ceftriaxone alone. Low oxygen tension may be an explanation for the lack of bactericidal effect of gentamicin. Ceftriaxone may be more suitable for the therapy of closed space infections caused by susceptible microorganisms than gentamicin.

Intravenous pharmacokinetics and in vitro bactericidal activity of trimethoprim-sulfamethoxazole.

Trimethoprim-sulfamethoxazole (240 mg of trimethoprim plus 1,200 mg of sulfamethoxazole) was administered intravenously in a volume of 200 ml to 7 volunteers every 12 hr for 4 days. The mean peak levels of TMP and SMZ in plasma were 3.22 and 100 micrograms/ml, respectively, on day 1 and 5.91 and 178 micrograms/ml, respectively, on day 4, when a steady state was achieved. Tests of in vitro susceptibility indicated that these concentrations are bactericidal for a large proportion of enteric gram-negative bacilli.

Pneumococcal capsular polysaccharide vaccination in adult chronic hemodialysis patients.

PCP vaccine was administered to 21 adult hemodialysis patients and 25 control patients with no renal nor hepatic dysfunction. Antibody concentrations measured by the RIA technique were lower in the hemodialysis than in the control patients in both prevaccination sera and specimens obtained 3 to 4 weeks following vaccination. However, 6 months after vaccination, RIA GMACs in hemodialysis and control subjects were more nearly alike. OTs against Streptococcus pneumoniae, types 1 and 3, were measured in paired sera from vaccine recipients. Opsonic activity against S. pneumoniae, type I, was detected as frequently in the 3 to 4 week postvaccine sera of the dialysis as in those of control patients. However, there was a poor correlation between OTs and RIA-ACs against this organism. There was good correlation between OT and RIA-AC against type 3 pneumococci in 3 to 4 week postvaccine sera, and significantly more control patients had opsonic activity detectable in these specimens. No clinical S. pneumoniae infections have been observed in vaccine recipients. However, continued follow-up will be necessary to document the degree to which hemodialysis patients are protected by pneumococcal vaccines and the relationship between protection and antibody concentration or OTs.