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The risk of becoming infected or infecting others with human immunodeficiency virus (HIV) substantially increases if a person has a sexually transmitted disease (STD), such as chancroid, genital herpes, syphilis, trichomoniasis, gonorrhea, or chlamydial infection. Effective female-controlled topical microbicides can be used to enhance the ability of women to avoid sexually transmitted infections. The topical microbicides are preparations for the intravaginal or intrarectal uses that are microbicidal and have the ability to prevent sexually transmitted infections. Classes of microbicidal compounds include detergents, defensins and other antimicrobial peptides, antibodies, organometallic complexes, and reverse transcriptase inhibitors. The development of safe and effective topical microbicides involves a broad-based research agenda that spans the basic biomedical and behavioral research, product development, and clinical/behavioral evaluation. They are evaluated through vitro systems, ex vivo systems, and animal models. The chemical barriers that inactivate pathogens in vaginal/cervical secretions, as well as in the ejaculate, reduce female-to-male and male-to-female transmissions.

In animals and humans, intravenous administration of the antiviral nucleotide analogue cidofovir results in a dose-limiting nephrotoxicity characterized by damage to the proximal tubular epithelial cells. Probenecid, a competitive inhibitor of organic anion transport in the proximal tubular epithelial cells, was evaluated for its effect on the chronic toxicity and pharmacokinetics of cidofovir. Cynomolgus monkeys (5/sex/group) received cidofovir for 52 consecutive weeks as a once weekly intravenous bolus injection at 0 (saline), 0.1, 0.5, or 2.5 mg/kg/dose alone or at 2.5 mg/kg/dose in combination with probenecid (30 mg/kg/dose via oral gavage 1 h prior to cidofovir administration). Cidofovir-associated histopathological changes were seen only in the kidneys, testes, and epididymides. Nephrotoxicity (mild to moderate cortical tubular epithelial cell karyomegaly, tubular dilation, basement membrane thickening) was present only in monkeys receiving 2.5 mg/kg/dose cidofovir without probenecid. The incidence and severity of testicular (hypo- and aspermatogenesis) and epididymal (severe oligo- and aspermia) changes were increased in monkeys administered cidofovir at 2.5 mg/kg/dose, either alone or in combination with oral probenecid. Renal drug clearance was decreased between Weeks 1 and 52 in the 2.5 mg/kg/dose groups and resulted in an increased systemic exposure to cidofovir (as measured by AUC) that was significantly greater in monkeys administered cidofovir alone (312% increase in males, 98% in females) than in those coadministered probenecid (32% increase in males, 3% in females). These results demonstrate that oral probenecid coadministration protects against the morphological evidence of nephrotoxicity and the accompanying decrease in renal clearance in monkeys receiving chronic intravenous cidofovir treatment.

Transcatheter fenestration and balloon dilation of an atrial baffle created from native atrial tissue was attempted in a 15-year-old girl with failing Fontan physiology and protein-losing enteropathy. After transseptal puncture, initial dilations with a 10-mm and 12-mm diameter balloon resulted in an inadequate fenestration, with no significant decrease of right atrial pressure or systemic arterial saturation. Dilation of the fenestration with a 16-mm-diameter balloon produced a tear of the atrial septum and subsequent death. Balloon dilation of native atrial tissue may result in uncontrolled tears of the atrial septum.

Purpose: This study compares the radiation dose-volume of the cervical esophagus during head and neck radiotherapy using three different techniques. Methods: Treatment plans of 58 patients from 3/04 to 1/06 treated with bilateral head and neck radiotherapy were analyzed retrospectively. A comparison of the cervical esophagus dose with three-field 3D conformal RT (3DRT, n = 34), whole-field IMRT (WF-IMRT, n = 12), and half-beam IMRT (HB-IMRT, n = 12) was performed. The volumes of esophagus receiving P50 Gy (V50), P54 Gy (V54) and P60 Gy (V60) and lengths receiving circumferential dose P50 Gy (L50) and P54 Gy (L54) were evaluated. Results: Maximum dose, V54 and L54 were greater for the first 2 cm and entire cervical esophagus with WF-IMRT than HB-IMRT or 3DRT. In patients requiring a high match, WF-IMRT was associated with a greater maximum dose, V54 and L54 than HB-IMRT and 3DRT (p < 0.05). In the low match group, WF-IMRT was associated with a greater V54 and L54 (p < 0.05). Low neck disease, low primary site, and definitive radiotherapy were associated with increased irradiation of the esophagus. Conclusion: Treatment of the lower neck with IMRT is associated with increased irradiation to the cervical esophagus, and dose constraints should be included to reduce toxicity. c 2007 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 87 (2008) 274–280.

Bacterial meningitis is a major cause of childhood morbidity and mortality in South Africa. However, comprehensive regional or national epidemiological data, essential for rational public health interventions, are lacking. The purpose of this 1-year prospective study, from 1 August 1991 to 31 July 1992, was to define the magnitude of the problem of childhood bacterial meningitis in Cape Town. The study group consisted of all children, aged1 month to14 years, who presented with proven bacterial meningitis at all the hospitals in the Cape Town metropolitan area. During the year 201 cases were identified: 101 (50.2%) were due to Neisseria meningitidis, 74 (36.8%) were due to Haemophilus influenzae and 26 (12.9%) were due to Streptococcus pneumoniae. The overall incidence rate (95% confidence interval) for children less than 14 years, 5 years and 1 year was 34 (30-40), 76 (65-88) and 257 (213-309) per 100,000 children, respectively. The rate was highest in black infants, 416 (316-545)/100,000. This was 2 times greater than the rate in coloured infants and about 4.5 times greater than the rate in white infants. The median age of all the children was 10 months. The ages of children with haemophilus and pneumococcal meningitis were similar, 9 and 7.5 months respectively (P = 0.43), while children with meningococcal meningitis were significantly older (22 months) than the others (P0.01). The overall case fatality rate was 5%, and 12.9% of survivors had significant neurological sequelae (disability) on discharge.

Edited by Adam H Balen, Sarah M Creighton, Melanie C Davies, Jane MacDougall, Richard Stanhope. Cambridge: Cambridge University Press, 2004, pp 540, £150.00. ISBN 0 521 80961 4 The management of young and adolescent girls with disorders of the genital tract and associated illnesses has long fallen between many subspecialties. With few adolescent gynaecologists in this country, paediatric surgeons and physicians, adult gynaecologists, and endocrinologists work with (or not as the case may be) clinical geneticists and psychologists to diagnose, explain, and manage sometimes simple and sometimes extremely complex problems. Pre-adolescent and adolescent gynaecology has always been on the margins of most professionals’ knowledge and practice and there is a dearth of supporting reference texts. The range …

Significant Reduction of Radiation Related Morbidities in the Extremity Sarcoma Patients Treated With Image Guided Radiation Therapy to Reduced Target Volume: Results of RTOG 0630 D. Wang, Q. Zhang, B. Eisenberg, J. Kane, X. Li, D. Lucas, C.R. Freeman, A. Trotti, Y. Hitchcock, and D. Kirsch; Medical College of Wisconsin, Milwaukee, WI, RTOG Statistical Center, Philadelphia, PA, Dartmouth Hitchcock Medical Center, Lebanon, NH, Roswell Park Cancer Institute, Buffalo, NY, University of Michigan, Ann Arbor, NY, McGill University, Montreal, QC, Canada, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, University of Utah, Salt Lake City, UT, Duke University Medical Center, Durham, NC

After intravenous administration of [14C]cidofovir to African green monkeys (43 mg/kg, 29.5 microCi/kg), the drug distributed rapidly into extracellular fluid. Concentrations of radioactivity in plasma were described by a three-compartment model with alpha, beta, and gamma half-lives of 0.67, 3.02, and 36.0 hr, respectively (N = 3). These phases are believed to represent renal elimination, efflux of free cidofovir from cells, and efflux from cells of cidofovir produced from dephosphorylation of metabolites, respectively. Less than 5% of the dose was phosphorylated, based on the proportion of total AUC in the gamma-phase. The clearance of cidofovir (211 +/- 16.6 ml/hr/kg) was dependent on dose and exceeded the theoretical glomerular filtration rate. Concentrations of cidofovir in kidney declined with a half-life of 23 hr and were1,000-fold higher than plasma levels by 120 hr. Clearance of cidofovir after multiple intravenous doses of 4.9 mg/kg/day (18.5 microCi/kg/day) decreased significantly by day 10, consistent with the observed nephrotoxicity. Oral and subcutaneous bioavailabilities of cidofovir were 21.8 +/- 9.44 and 98.5 +/- 15.8%, respectively. After intravenous administration of [14C]cidofovir to cynomolgus monkeys (10 mg/kg, 100 microCi/kg) alone or 1 hr after oral probenecid (30 mg/kg), mean +/- SD (N = 3) urinary recoveries of total radioactive dose were 91.4 +/- 11.3% and 94.4 +/- 29.8%, respectively, at 7 days postdose. The mean +/- SD half-lives of the terminal elimination phases were 33.3 +/- 10.6 and 24.4 +/- 5.0 hr, respectively. Cidofovir accounted for 98% of the radioactivity recovered in urine; the remainder was attributed to cidofovir phosphocholine. The prolonged elimination phase observed in monkeys is consistent with the long intracellular half-life of phosphorylated cidofovir in vitro and supports infrequent dosing of the drug for antiviral therapy.

Although considerable global attention and effort have been devoted to preventing and controlling the spread of HIV/AIDS, comparatively little focus has been given to controlling other sexually transmitted diseases (STD). However, since HIV, like other STDs, may be transmitted through unprotected sexual intercourse, measures implemented to check the spread of HIV through sexual contact also help to limit the transmission of other STDs. Gonorrhea, chlamydia, trichomoniasis, genital herpes, syphilis, and human papillomavirus infections cause infertility, cervical cancer, and adverse outcomes of pregnancy such as spontaneous abortion, prematurity, and stillbirth. Many people, however, remain unconvinced that STD infection has important adverse effects upon the health of women and their infants. There are enormous morbidity, mortality, and health care costs associated with these STDs. The author discusses how women are at increased risk relative to men, as well as primary, secondary, and tertiary prevention.

This paper presents a brief overview of sexually transmitted diseases (STDs), including acquired immunodeficiency syndrome (AIDS), in adolescent populations. Using the framework of a mathematical model (which considers how, why, and whether an infection spreads within a population), the epidemic of STDs among adolescent populations is considered. The unique aspects of adolescent behavior, adolescent biology, and the social context of adolescents' lives are highlighted.

A series of 5’-derivatives and modified pyrimidine analogues of 2’,3’-didehydro-3’-deoxythymidine (d4T, stavudine, 1) were synthesized to determine their potential as oral prodrugs of d4T. Utilizing a screen developed for the rapid evaluation of a variety of prodrugs in mice, it was determined that 5’-acetate 2 provided comparable plasma levels of d4T after oral administration of the prodrug to that when d4T was administered alone. The relative oral bioavailabillty of methoxy acetate 3 and cyclohexyl carbonate 5 was 79 and 41%, respectively. Dihydropyridine ester 6 did not provide detectable levels of d4T up to 1 h after oral administration of 6. Thiopyrimidines 8 and 9, as well as aminopyrimidine 10 also failed to provide measurable levels of d4T after oral administration. 5’-Derivatives 3, 5, and 6 showed similar activity to that of d4T against HIV and MuLV, as did 5’-benzoyl-4-thio derivative 8. However, the corresponding 4-thio 5’- alcohol 9 was inactive.

Little is known about the epidemiology of Haemophilus influenzae infections in South Africa. This study was designed to determine the prevalence, serotype distribution, antimicrobial susceptibility pattern and effect of age and hospitalisation on the carriage of H. influenzae in 322 Cape Town children. The overall and type b specific carriage rates in normal children (N = 107) were 45.8% and 4.7% respectively. The yield following nasopharyngeal culture was twice that following throat culture (P0.001). Children hospitalised with tuberculosis (N = 62) had significantly greater carriage rates, 66.1% and 37.1% respectively (P = 0.02). Institutionalised mentally handicapped children (N = 77) and children with tuberculosis attending an outpatient clinic (N = 76) had lower carriage rates (P0.02). Antimicrobial resistance was a major problem only in children hospitalised with tuberculosis (rifampicin 100%, penicillin 43.9%, erythromycin 85.4%, co-trimoxazole 82.9%). This universal resistance to rifampicin has not been reported previously. There was no difference in the mean age of children with positive or negative cultures, with the exception of those hospitalised with tuberculosis. In this group children infected with type b were much younger (mean 19.7 months) than those with other and non-typeable infections (32.1 months) and the non-infected (50.1 months) (P = 0.04). Duration of hospitalisation or outpatient therapy in the patients with tuberculosis did not influence carriage rates.(ABSTRACT TRUNCATED AT 250 WORDS)

The full spectrum of invasive Haemophilus influenzae disease has not been documented previously in Africa. This 1-year prospective study was designed to determine the epidemiology of invasive Haemophilus influenzae disease in Cape Town children. During this period, 142 children with invasive disease were hospitalized; 85 (59.9%) presented with meningitis, 35 (24.6%) with pneumonia and 22 (15.5%) with other diseases. No cases of epiglottitis were seen. Sixty per cent of cases were male and 40% female. The median age of the children was 9 months, with a range of 1-144 months, and 65.5% were aged12 months. Neurological dysfunction was noted in 40% and 18% of children with meningitis on admission and discharge, respectively. The overall case fatality rate (95% confidence intervals) was 9.2% (4.9-15.7), and for meningitis, pneumonia and septicaemia it was 4.7% (1.2-16.4), 14.3% (4.6-31.8) and 40% (8-78.1), respectively. Serotype b accounted for 86.5% of all cases, 97.3% of cases of meningitis, 71.4% of cases of pneumonia, 50% of cases of septicaemia, all cases of arthritis and cellulitis and none of mastoiditis. The incidence rates (95% confidence intervals) for all invasive type b infections were 169 (122-198) and 47 (39-57) per 100,000 population for children1 and5 years, respectively. For meningitis the rates were 112 (84-148) and 34 (25-40) per 100,000, respectively. Rates for mixed race and white children were similar, but those for black children were more than double those rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Given that sexually transmitted diseases (STDs) are transmitted by individuals engaging in definable physical behaviors and that many STDs are not curable, it is clear that an effective STD prevention program must include a component that focuses on changing high-risk or maintaining low-risk behaviors. Furthermore, a behavior change program is also necessary to encourage people to determine whether or not they have been exposed to a particular STD, as well as to get them to seek and use available treatments. In this chapter, we illustrate how the theory of reasoned action (Ajzen & Fishbein, 1980; Fishbein, 1980, 1967; Fishbein & Ajzen, 1975), can be used to empirically identify the determinants of any given behavior (i.e., the factors underlying it). Perhaps more important, we also try to show how, once identified, information about these determinants can be used to develop interventions that can successfully influence behaviors involved in the control and spread of STDs, including AIDS.

Purpose: Two methods to generate ITV on 4DCT images are explored: direct contouring on MIP images and combining GTV contours on individual phase images. We compared these two methods on multiple 4D data sets from the same subjects. Methods: 42 simulation and image guidance 4DCT data sets, for 9 SBRT patients treated 3–5 fractions each, were retrospectively analyzed. Two sets of ITV contours were generated from the raw 4DCT cine data for each patient scan: MIP image set [ITV(MIP)‐ direct contouring on MIP] and 10 phase‐binned image sets [ITV(10phase)‐ Boolean OR of GTVs contoured on 10 phase image sets]. A single operator segmented all ITVs using a semi‐automated approach with the ITK‐SNAP 3D segmentation tool. Results: The mean volumetric ratio of ITV(MIP) to ITV(10phase) across all patients was 1.02 (Range 0.56 – 1.77; 1 = ideal). The distance between the Center Of Mass of the two sets of ITVs, across all patients, had a median of 1.3 mm (range 0.1 – 7.5 mm), thus indicating that both volume and location of the ITVs generated by these two methods agree well on average across all patients, but can differ non‐trivially for select cases. Interestingly, we observed large variations between the two contouring methods for repeated scans of the same patient. For example, one patient demonstrated excellent agreement for the first (simulation) scan (agreement ratio=1.02), but then poor agreement for three subsequent scans (agreement ratios = 0.85, 1.11, 1.15). Conclusion: ITVs generated by the two methods of MIP, and combination of 10 phases on 4DCT, agreed well on average, but differed non‐trivially for select cases. In particular, we observed the potential for large variation within the same patient, when multiple 4D scans of the same patient were evaluated. This is likely attributable to daily breathing pattern variations.

A 2-month-old infant presented with acute onset of heart failure, having previously undergone anatomical repair of transposition of the great arteries and ventricular septal defect (VSD). Echocardiography demonstrated aneurysmal dilation of the native pericardial patch used for VSD closure, resulting in right ventricular inflow obstruction. The pericardial patch was excised, and the VSD closed using a GoreTex patch.

By 8 wk gestation, the human fetal oesophagus is identifiable as a hollow epithelium-lined tube with primitive nerve and muscle precursors present. From 8-16 wk gestation, the muscle layers and innervation mature until fetal swallowing commences at 16 wk. This study examines quantitatively the development and maturation of nerve fibres and cell bodies within the oesophagus using histochemistry. Oesophageal samples (n = 35) from 8 wk gestation to 28 months of age and adults (n = 3) were immunostained using antisera for the general nerve marker, protein gene product (PGP 9.5), the glial tissue marker S100, and the synaptic vesicle protein synaptophysin (p38). Histochemical staining for NADH diaphorase enzyme activity was also used to identify neurons. Computer-assisted image analysis of the muscularis externa permitted detailed quantification of cell size, nerve density and myenteric (plexus) fraction. At 8 wk gestation, PGP and synaptophysin were present in immature neurons throughout the cytoplasm, but from 10 wk synaptophysin was localised solely at nerve synapses. S100 immunoreactivity was also detected from 8 wk gestation onwards and was confined to glial tissue. Nerve cell size increased with maturation from 6 microns at 8 wk gestation to 20 microns at term and 21 microns at 28 months. The numbers of cells, nerve density (% area occupied by nerves throughout section) and myenteric fraction (% area occupied by ganglion cells and nerve fibres within the myenteric plexus) all peaked at 16-20 wk gestation and, whereas the number and density then fell towards adult levels, the myenteric fraction fell during the late second trimester and became constant from 30 wk gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

(S)-1-[3-Hydroxy-2-(phosphonylmethoxy)propyl]cytosine (HPMPC) is an antiviral phosphonate nucleotide analogue that displays activity against a range of herpesviruses. Anion exchange high performance liquid chromatography analysis of the 60% methanol extract from [14C]HPMPC-treated cells reveals the formation of three major metabolites. Two of these were identified as phosphorylated forms of HPMPC, HPMPC phosphate, and HPMPC diphosphate, by liberation of HPMPC upon acid digestion and coelution with synthetic standards on high performance liquid chromatography. The third metabolite, which is resistant to alkaline phosphatase cleavage but sensitive to phosphodiesterase, is proposed to be an HPMPC phosphate adduct. In herpes simplex virus-1-infected cells the same three metabolites are detected, at concentrations comparable to those in uninfected cells. When HPMPC is removed from the medium, the concentrations of the metabolites in cells decrease slowly, with half-lives of approximately 6, 17, and 48 hr for HPMPC phosphate, HPMPC diphosphate, and the HPMPC phosphate adduct, respectively. HPMPC diphosphate inhibits herpes simplex virus-1 and -2 DNA polymerases with a lower Ki than that for DNA polymerase alpha, and enzyme inhibition is competitive in each case. The formation and the persistence of HPMPC phosphates in cells and the selective inhibition of viral DNA polymerases by HPMPC diphosphate can explain why cells pretreated with HPMPC remain refractory to viral infection even long after HPMPC is removed from the medium.

2',3'-Didehydro-2',3'-dideoxythymidine (D4T) is a potent inhibitor of human immunodeficiency virus (HIV), with low hematological toxicity. In the present study, the cellular pharmacology of D4T was investigated in human bone marrow cells (BMC), in an attempt to understand the mechanism of the observed low bone marrow toxicity. After exposure of human BMC to 10 microM [3H]D4T for 24 hr, D4T-5'-triphosphate (D4T-TP) was the predominant metabolite, reaching a concentration of 0.3 pmol/10(6) cells. The D4T-5'-monophosphate levels were slightly lower, whereas the D4T-5'-diphosphate levels were about 6-fold lower than those of D4T-TP at 24 hr. Nucleic acids of human BMC exposed to 10 microM [3H]D4T for 24 hr were purified and analyzed by cesium sulfate density gradient centrifugation. No radioactivity was detected in the RNA region, whereas a limited amount was associated with the DNA region. The amount of label incorporated into DNA correlated with the extracellular D4T concentration and the length of incubation time. Enzymatic hydrolysis of radiolabeled DNA and subsequent analysis by high performance liquid chromatography demonstrated incorporation of both D4T and thymidine (dThd) into DNA. Degradation of D4T to thymine and subsequent formation of labeled dThd was also detected in human BMC. Pulse (24 hr)-chase (48 hr) experiments with 10 microM [3H]D4T demonstrated that the amount of radiolabel from D4T in DNA decreased over time during the chase. Under similar conditions, [3H]3'-azido-3'-deoxythymidine (AZT) incorporated into DNA of human BMC did not decrease during the chase. Although D4T-TP standard was demonstrated to be unstable at 37 degrees and neutral pH, D4T was much more stable in solution when incorporated into newly synthesized DNA isolated from human BMC, suggesting that enzymatic excision may be the mechanism for D4T removal from DNA. In summary, although higher concentrations of D4T-TP, compared with AZT-5'-triphosphate, are observed in human BMC, after exposure of cells to similar extracellular concentrations of parent drug, steady state levels of D4T incorporated into DNA are 10-50-fold lower, compared with AZT. Competition with dTTP formed by D4T metabolism and excision of D4T from DNA may be responsible, in part, for these effects. This study further demonstrates that incorporation of 2',3'-dideoxynucleosides into nuclear DNA of human BMC may be related to the ability of these anti-HIV agents to induce hematological side effects.

Purpose: Commercially available IMRTtreatment planning systems (TPS) often include a smoothing function which allows the user to vary the irregularity/complexity of delivered beam fluence patterns. The cost of reducing the complexity of inverse‐planned optimal fluence patterns may be a reduction in plan quality. In this study we evaluated the behavior of 3 treatment planning systems when using varying smoothing parameters. Method and Materials: We evaluated three cases treated by IMRT in our clinic: a sinonasal carcinoma (SNL), a base of tongue carcinoma (BOT), and a glioblastoma multiforme (GBM). Varian Eclipse v6.5, BrainLab Brainscan v5.31, and Nomos Corvus v6.2 TPS were studied for the SNL and GBM plans. Only Eclipse and Corvus TPS were studied for BOT planning due to field size constraints of the MM3 collimator. For each TPS, plans were first optimized using the vendor recommended default “smoothing”. Treatment plans were then reoptimized with various smoothing levels being explored for each of the planning systems. Key metrics were recorded for each plan, including efficiency factors and conformity index. Results: Results varied widely by vendor with regard to smoothing's impact on both plan quality and delivery efficiency. The Corvus TPS allowed, as might be reasonably expected, increased OAR sparing for the majority of structures as smoothing was incrementally decreased. Both Eclipse and BrainScan also experienced an expected trend for decreased efficiency as smoothing was decreased. However, this increase in expected complexity did not result in appreciably improved OAR sparing for either TPS. Conclusions: Depending on the treatment planning system, the potential benefits of optimizing fluence smoothing levels can be significant, allowing for increases in either delivery efficiency or plan quality. Because of the variability in behavior of smoothing functions by TPS vendor, it is important that users familiarize themselves with the effects of varying smoothing/efficiency parameters for their respective TPS.

Strains of Neisseria gonorrhoeae were used to evaluate bactericidal and opsonic properties of McAb 10 directed against the Neisserial outer membrane antigen, H.8. Gonococci were either serum resistant in the absence but serum sensitive in the presence, of McAb 10, or serum sensitive or serum resistant regardless of the presence of McAb 10. Strain JS3, which fell in the former category, was used in subsequent studies. C1 zymogen formed by reassociation of isolated C1 subunits was not directly activated by JS3 in the presence or absence of C1-inhibitor. JS3 thus was unable to directly activate the classical pathway independently of antibody. When purified classical pathway components were used to deposit C3 on JS3 in the absence of serum regulatory proteins or antibodies, added C1-inhibitor reduced C3 binding to background levels. When McAb 10 was present, C3 binding was unaffected by C1-inhibitor. Covalently bound, large molecular weight C3 alpha-chain-gonococcal complexes were disbanded by methylamine release of ester linkages. Released 125I-C3 migrated as C3b without degradation by gonococcal proteases. Purified classical components alone or McAb 10 alone facilitated JS3 killing by neutrophils; when combined, the two provided maximal killing. Levels of McAb 10 that only slightly increase C3 deposition on JS3 are bactericidal in serum and maximally opsonic in combination with purified classical pathway components.