Human cervicovaginal mucus contains an activity that hinders HIV-1 movement.

Cervical and vaginal epithelia are primary barriers against HIV type I (HIV-1) entry during male-to-female transmission. Cervical mucus (CM) is produced by the endocervix and forms a layer locally as well as in the vaginal compartment in the form of cervicovaginal mucus (CVM). To study the potential barrier function of each mucus type during HIV-1 transmission, we quantified HIV-1 mobility in CM and CVM ex vivo using fluorescent microscopy. Virions and 200-nm PEGylated beads were digitally tracked and mean-squared displacement was calculated. The mobility of beads increased significantly in CVM compared with CM, consistent with the known decreased mucin concentration of CVM. Unexpectedly, HIV-1 diffusion was significantly hindered in the same CVM samples in which bead diffusion was unhindered. Inhibition of virus transport was envelope-independent. Our results reveal a previously unknown activity in CVM that is capable of impeding HIV-1 mobility to enhance mucosal barrier function.

Internal jugular vein thrombosis secondary to a permanent cardiac pacemaker: an unusual case of lateral neck swelling.

OBJECTIVE: To describe an unusual case of lateral neck swelling in a patient with a permanent cardiac pacemaker. CASE REPORT: We describe a patient who presented with a painful, lateral neck swelling due to an internal jugular vein thrombus. This thrombus originated from around pacemaker wires in the subclavian vein. This case is unusual, as the vast majority of thromboses in patients with cardiac pacemakers are found in the subclavian vein alone. We also review the literature on the relationship between cardiac pacemakers and internal jugular vein thrombosis, and on the management of the latter. CONCLUSION: Our patient illustrates a rare cause of a painful, lateral neck swelling: an internal jugular vein thrombus secondary to a cardiac pacemaker. Clinicians should be wary of such pathology in similar patients, in order to ensure early treatment and avoidance of complications.

Evaluation of ER, PgR, HER-2 and Ki-67 as predictors of response to neoadjuvant anthracycline chemotherapy for operable breast cancer.

Primary systemic therapy (PST) for operable breast cancer enables the identification of in vivo biological markers that predict response to treatment. A total of 118 patients with T2-4 N0-1 M0 primary breast cancer received six cycles of anthracycline-based PST. Clinical and radiological response was assessed before and after treatment using UICC criteria. A grading system to score pathological response was devised. Diagnostic biopsies and postchemotherapy surgical specimens were stained for oestrogen (ER) and progesterone (PgR) receptor, HER-2 and cell proliferation (Ki-67). Clinical, radiological and pathological response rates were 78, 72 and 38%, respectively. There was a strong correlation between ER and PgR staining (P < 0.0001). Higher Ki-67 proliferation indices were associated with PgR- tumours (median 28.3%, PgR+ 22.9%; P = 0.042). There was no relationship between HER-2 and other biological markers. No single pretreatment or postchemotherapy biological parameter predicted response by any modality of assessment. In all, 10 tumours changed hormone receptor classification after chemotherapy (three ER, seven PgR); HER-2 staining changed in nine cases. Median Ki-67 index was 24.9% before and 18.1% after treatment (P = 0.02); the median reduction in Ki-67 index after treatment was 21.2%. Tumours displaying >75% reduction in Ki-67 after chemotherapy were more likely to achieve a pathological response (77.8 vs 26.7%, P = 0.004).

Use of implantable cardioverter defibrillator and anti-arrhythmic agents in a parturient.

We describe a case of a 36-yr-old patient who presented at 14 weeks gestation with multifocal dysrrhythmic episodes. Despite treatment with anti-arrythmic agents and an implantable cardioverter defibrillator (ICD) in situ, she continued to experience persistent dysrrhythmic episodes. She was delivered by Caesarean section at 34 weeks under general anaesthesia. We discuss some of the anaesthetic challenges of parturients with ICD devices.

Virologic and immunologic determinants of heterosexual transmission of human immunodeficiency virus type 1 in Africa.

More than 80% of the world's HIV-infected adults live in sub-Saharan Africa, where heterosexual transmission is the predominant mode of spread. The virologic and immunologic correlates of female-to-male (FTM) and male-to-female (MTF) transmission are not well understood. A total of 1022 heterosexual couples with discordant HIV-1 serology results (one partner HIV infected, the other HIV uninfected) were enrolled in a prospective study in Lusaka, Zambia and monitored at 3-month intervals. A nested case-control design was used to compare 109 transmitters and 208 nontransmitting controls with respect to plasma HIV-1 RNA (viral load, VL), virus isolation, and CD4(+) cell levels. Median plasma VL was significantly higher in transmitters than nontransmitters (123,507 vs. 51,310 copies/ml, p < 0.001). In stratified multivariate Cox regression analyses, the risk ratio (RR) for FTM transmission was 7.6 (95% CI: 2.3, 25.5) for VL > or = 100,000 copies/ml and 4.1 (95% CI: 1.2, 14.1) for VL between 10,000 and 100,000 copies/ml compared with the reference group of <10,000 copies/ml. Corresponding RRs for MTF transmission were 2.1 and 1.2, respectively, with 95% CI both bounding 1. Only 3 of 41 (7%) female transmitters had VL < 10,000 copies/ml compared with 32 of 93 (34%) of female nontransmitters (p < 0.001). The transmission rate within couples was 7.7/100 person-years and did not differ from FTM (61/862 person-years) and MTF (81/978 person-years) transmission. We conclude that the association between increasing plasma viral load was strong for female to male transmission, but was only weakly predictive of male to female transmission in Zambian heterosexual couples. FTM and MTF transmission rates were similar. These data suggest gender-specific differences in the biology of heterosexual transmission.

Chest wall thickness measurements and the dosimetric implications for male workers in the uranium industry.

The Human Monitoring Laboratory has measured the chest wall thickness and adipose mass fraction of a group of workers at a Canadian uranium refinery, a conversion plant, and a fuel fabrication site using ultrasound. A site-specific biometric equation has been developed for these workers, who seem to be somewhat larger than other workers reported in the literature. Chest wall thickness is a very important modifier on lung counting efficiency and these data have been put into the perspective of the impending Canadian dose limits that will reduce the limit of occupationally exposed workers to 100 mSv in a 5-y period with a maximum of 50 mSv in any one year. The sensitivity of the germanium and phoswich based lung counting systems have been compared. Over a range of chest wall thickness of 1.6 cm to 6.0 cm and using a 30-min counting time, the achievable MDA's lie in the range of 6.7 mg to 19.1 mg or 6.7 mg to 30 mg with a two-phoswich-detector array or a germanium lung counting system, respectively. Depending on chest wall thickness, these achievable MDA's are close to, or exceed, the predicted amounts of natural uranium that will remain in the lung (absorption type M and S) after an intake equivalent to the Annual Limit on Intake that corresponds to 20 mSv. Neither system is sufficiently sensitive to detect an intake of Type S natural uranium in a worker with a chest wall thickness that corresponds to the average (3.73 cm) if it occurred more than 7 d prior to the lung count.

Pre-operative estimation of primary breast cancer size: a comparison of clinical assessment, mammography and ultrasound.

This prospective study aimed to determine which is the most precise modality for the pre-operative measurement of primary breast cancers: clinical palpation; mammography; or ultrasound. Analysis of the difference between the measurement of the maximum tumour diameter by these three modalities and by the histological measurement was performed in 210 cases. Clinical palpation tended to overestimate tumour size and gave the largest standard deviation of the difference. Ultrasound and mammography both gave a similar standard deviation of the difference, with ultrasound tending to underestimate tumour size. For all modalities, the standard deviation and the 95% confidence intervals of the difference increased with increasing tumour size. There is little difference between the precision of ultrasound and mammography in measuring tumour size. The wide 95% confidence intervals for any method of pre-operative tumour measurement should be considered when planning patient management.

Effect of chlorpromazine and clozapine on plasma concentrations of haloperidol in a patient with schizophrenia.

A 40-year-old patient being treated for schizophrenia developed elevated plasma levels of haloperidol (HAL) in combination with chlorpromazine (CPZ) and during overlap treatment with clozapine. Competitive inhibition of HAL by first CPZ and then clozapine is discussed as a possible mechanism.

Radiofrequency ablation of idiopathic left ventricular tachycardia at the site of earliest activation as determined by noncontact mapping.

INTRODUCTION: The most effective method for guiding radiofrequency (RF) ablation of idiopathic left ventricular tachycardia (ILVT) has yet to be determined. We investigated the use of noncontact mapping in five patients with this condition. METHODS AND RESULTS: The multielectrode array was positioned in the left ventricular apex via the retrograde approach. Isopotential color maps of ILVT were examined to determine the site of earliest endocardial activation. The ablation catheter was steered to the target site using the locator signal. Pace mapping was performed and contact electrograms examined for diastolic potentials. RF energy was applied to the target site. Sustained ventricular tachycardia was induced in 2 patients and nonsustained ventricular tachycardia in 3. The site of earliest activation was at the apical septum in 3, the inferior apex in 1, and the base of the inferior wall in 1. Mean timing was 21 +/- 10 msec before onset of the surface QRS. Diastolic activity was visualized with noncontact mapping at the base of the septum in 1 patient. A Purkinje potential was seen at the ablation site in only 1 patient. No diastolic activity was seen in the remaining 3 patients. Tachycardia was successfully terminated in all 5 patients with a median of four RF applications. No patient suffered a recurrence after 9.6 +/- 4.7 months of follow-up. CONCLUSION: By identifying the precise site of earliest activation during ILVT, noncontact mapping has been shown to be an effective and safe method for guiding RF ablation.

Electrophysiological mapping and ablation of intra-atrial reentry tachycardia after Fontan surgery with the use of a noncontact mapping system.

BACKGROUND: Atrial tachyarrhythmias are a complication of Fontan surgery. Conventional electrophysiological mapping and ablation techniques are limited by the complex anatomic and surgical substrate and a high arrhythmia recurrence rate. This study investigates the use of noncontact mapping to identify arrhythmia circuits and guide ablation in Fontan patients. METHODS AND RESULTS: Eleven arrhythmias were recorded in 6 patients. Noncontact mapping improved recognition of the anatomic and surgical substrate and identified exit sites from zones of slow conduction in all clinical arrhythmias. Radiofrequency linear lesions were targeted across these critical zones in 5 patients. One patient underwent surgical cryotherapy. Although immediate success was achieved in 3 of 5 patients with radiofrequency ablation, 2 patients had a recurrence after a mean of 6.4 months of follow-up. The patient who underwent cryoablation remains free of arrhythmias. CONCLUSIONS: Noncontact mapping can identify arrhythmia circuits in the Fontan atrium and guide placement of ablation lesions. Arrhythmia recurrence is high, possibly because of inadequate lesion creation rather than inaccurate mapping and lesion targeting.

Atypical infective endocarditis.

BACKGROUND: Although infective endocarditis has changed in the recent past as a result of microbiologic and risk factors, it continues to be clinically challenging. The disease is characterized by the formation of septic masses of platelets on the surfaces of heart valves. Several mechanisms can cause or contribute to the development of endocarditis. Although risk factors for infective endocarditis are well known, patients with atypical signs and symptoms continue to challenge us. METHODS: We describe a case report of a patient admitted to our inpatient service with back pain and presumed pyelonephritis. A MEDLINE literature search was conducted, using the key words "endocarditis," "back pain," and "bacterial," for the years 1986 to the present. RESULTS AND CONCLUSIONS: A 42-year-old woman with a history of intravenous drug abuse was admitted to the family practice service with back pain and pyelonephritis. She developed hypoxia and a new heart murmur and had continued fevers. Blood cultures drawn in the emergency department grew methicillin-resistant Staphylococcus aureus. A bone scan and magnetic resonance imaging led to the diagnosis of epidural abscess. What appeared to be a simple case of pyelonephritis with back pain became a case of infective endocarditis complicated by an epidural abscess.

Description and outcomes of a Medicare case management program by nurses.

During the current environment of cost-cutting and restructuring, case management is viewed as a means of providing comprehensive, coordinated care while reducing costs. Studies of community-based case management have been disappointing. This study evaluates a Medicare service, Management and Evaluation of the Care Plan (MAE), as a model of nurses providing case management in the home. Three groups were compared: MAE (N = 176), non-MAE (N = 187) and newly discharged (N = 93). Utilization data was collected over one year. Overall, subjects were unmarried older women with three functional limitations, four medical diagnoses and averaged 43 home care visits and one hospitalization. MAE patients were older, had more functional and environmental limitations, less ADL independence, and a worse prognosis, yet used significantly less health care than non-MAE recipients did. Regression analysis was performed using group membership and hospital and home care utilization as dependent variables. Although the project was conducted at one site, overall the sample was similar to the national Medicare population.

Comparison of the LLNL and JAERI torso phantoms using Ge detectors and phoswich detectors.

The Human Monitoring Laboratory has compared the LLNL and JAERI torso phantoms using its germanium detector lung counting system by measuring the counting efficiencies for radioactive materials in the phantoms at photon energies of 17.7 keV, 59.5 keV, 121.8 keV, and 344 keV to assess the similarity (or differences) in performance characteristics. The counting efficiencies obtained from the two phantoms were compared by converting the Chest Wall Thickness data and Adipose Mass Fractions of the phantoms to Muscle Equivalent Chest Wall Thicknesses. The counting efficiencies for the two phantoms were found to be within a factor of 1.44 of each other at 17.7 keV, 1.30 at 59.5 keV, 1.25 at 121.8 keV, and 1.17 at 344 keV when using a four detector array (JAERI efficiency divided by LLNL efficiency). However, individual detector responses show that the counting efficiencies from the two phantoms differ considerably in the region of the heart (up to a factor of 6 at 17 keV). Other areas above the lungs give counting efficiencies that are similar to each other. A routine intercomparison exercise with Cameco Corporation has shown that the counting efficiencies derived from the LLNL and JAERI phantoms were found to be within a factor of 1.18 (JAERI/LLNL) when a natural uranium lung set was used to calibrate a lung counter consisting of phoswich detectors. This work has also shown that over the energy range 63 keV-185 keV the LLNL phantom can be used to calibrate phoswich detector systems that are positioned on the back of the subject.

Rapid HIV testing and counseling for voluntary testing centers in Africa.

OBJECTIVE: Voluntary HIV testing and counseling (VTC) has been shown to reduce the incidence of HIV in cohabiting couples who now represent the majority of new infections in many African cities. Community and client perceptions of a 1-day voluntary testing and counseling program in Lusaka, Zambia, were assessed, and a rapid HIV-testing algorithm was evaluated for VTC centers. METHODS AND DESIGN: Between May 1995 and June 1996, outreach workers distributed written invitations door to door. The 1-day program was held 6 days/week including weekends. Transport, child care and lunch were provided. Community and client surveys followed in July 1996. RESULTS: Over 3500 couples married for a median of 4-5 years requested testing: 23% were HIV+/+, 57% were HIV-/- and 20% were discordant with one HIV+ and one HIV- partner. Sixty-eight per cent of couples surveyed had made the decision to be tested before attending the 1-day program and 80% had not previously known where to obtain HIV testing. Knowledge that couples could show discordant results rose from 29 before to 88% after pretest counseling. Clients reported high levels of satisfaction with the services and 90 out of 99 (92%) preferred to receive their results the same day. Clients at another center who waited 10 days for their results reported more fear, and 19 out of 31 (61%) would have preferred to get their results the same day. Over 99% of those who attended the program thought active promotion of voluntary HIV testing in the community was a positive thing, as did 90% of those who were invited but did not attend. Sensitivity and specificity of the rapid test algorithm were both 99.4% in this setting. CONCLUSIONS: Active promotion of voluntary HIV testing and counseling in couples is needed to reduce the spread of HIV in high-prevalence areas. The use of rapid, on-site HIV testing allows clients to receive result-specific counseling in a single visit. Ongoing quality control of a subset of samples at an outside laboratory is essential.

PIP: Voluntary, confidential HIV testing and counseling centers (VTCs) are becoming increasingly popular in African cities with high HIV prevalence. This strategy is especially effective among HIV-discordant couples. During a 12-month period during 1995-96, community outreach workers distributed written invitations to attend a VTC in Lusaka, Zambia, in which couples would receive testing and result-specific counseling in a single visit; transportation, child care, and lunch were offered. Over 3500 couples, one-third of those invited, responded to the invitation and underwent rapid HIV testing. The Dipstick HIV-1 + 2 rapid test was used for screening and the Capillus HIV-1/HIV-2 rapid test was employed for confirmation. Both partners were HIV-positive in 23% of cases and both were HIV-negative in 57%; in the remaining 20% of couples, 1 partner was HIV-positive and the other was uninfected. 68% of participating couples had decided to seek HIV testing before receiving notice of the VTC, but 80% of them did not know where to obtain such services. Couples who attended the VTC that offered same-day test results reported substantially less fear than those who had to wait 10 days for their results. 99% of those who participated in the program thought active community promotion of VTC was desirable, as did 90% of those who were invited but did not attend. The rapid test algorithm had both a sensitivity and specificity of 99.4%. Continued retesting of a subset of samples at an outside laboratory remains essential, however. This intervention is associated with an estimated cost of US $84 per HIV infection prevented.

Perforation rate using a single pair of orthopedic gloves vs. a double pair of gloves in obstetric cases.

Our purpose was to determine the perforation rate for a single pair of orthopedic gloves vs. a double pair of regular gloves in obstetric cases. Faculty, residents, medical students, and surgical technicians were assigned randomly to use either double gloves or single orthopedic gloves. After each procedure, the gloves were examined by filling with water, occluding the cuff, and observing for streams of water. The perforation rate for the double gloves (both inner and outer glove at the same location) was 7% (12/169), similar to the 7% (12/172) for single orthopedic gloves (P < 0.9). After adjusting for procedure type there was no association between the type of gloves and perforation rate. Fifty-four percent of all perforations were not recognized intraoperatively. Of those individuals with glove perforations, 4/24 (17%) observed blood on the hand at the end of the procedure. Double-gloved users complained more frequently than single-gloved users of loss of dexterity (77/169, 46%, 95% CI 38-53%) vs. (6/172, 3.5%, 95% CI 0.7-6%) (P < 0.001) and numbness (12/169, 7%, 95% CI 3.2-11%) vs (1/172 0.6%, 95% CI 0.55-1.7%) (P < 0.005). Although the use of a single pair of orthopedic gloves is more costly than a double pair of regular gloves ($78 vs. $15 per box), it is as safe and as effective as a double pair of gloves in maintaining a sterile barrier. The primary advantage of a single pair of orthopedic gloves is that surgical dexterity is minimally compromised when compared to double gloves.

Isolation and characterization of mouse Xrcc-1, a DNA repair gene affecting ligation.

Human DNA repair gene XRCC1 complements the strand-break rejoining defect in Chinese hamster mutant EM9 and encodes a protein that is apparently required for optimal activity of DNA ligase III. Toward the goal of producing transgenic mice that carry a mutation in the Xrcc-1 locus, the murine homolog of XRCC1 was cloned from both cosmid genomic and cDNA libraries. Upon transfection into EM9 cells, cosmids containing the functional mouse gene efficiently corrected (94-100%) the high sister-chromatid-exchange defect. Mouse Xrcc-1 is 26 kb in length, contains 17 exons, and maps by metaphase in situ hybridization to the 7A3-7B2 region of mouse chromosome 7. Isolated cDNA clones were highly truncated and were extended by anchored polymerase chain reactions. The 1893-bp open reading frame of mouse Xrcc-1 encodes 631 amino acids, compared with 633 for the human homolog. The predicted mouse Xrcc-1 protein of 69.1 kDa and pI of 5.95 is 86% identical and 93% similar to human XRCC1.

Medicare case management.

Medicare reimbursement allows home care nurses to provide management and evaluation (MAE) of the patient care. The service is a model of nurses providing case management for persons at risk for rehospitalization. This article describes the program, lists criteria for identifying MAE-eligible patients, and describes documentation issues when providing MAE-type care.