Risk of window period HIV infection in high infectious risk donors: systematic review and meta-analysis.

The OPTN defines high risk donors (HRDs), colloquially known as 'CDC high risk donors', as those thought to carry an increased risk of HIV window period (WP) infection prior to serologic detectability. However, the true risk of such infection remains unknown. To quantify the risk of WP infection in each HRD behavior category, we performed a systematic review and meta-analysis of studies of HIV prevalence and incidence. Of 3476 abstracts reviewed, 27 eligible studies of HIV infection in HRD populations were identified. Pooled HIV incidence estimates were calculated for each category of HRD behavior and used to calculate the risk of WP HIV infection. Risks ranged from 0.09-12.1 per 10 000 donors based on WP for ELISA and 0.04-4.9 based on nucleic acid testing (NAT), with NAT reducing WP risk by over 50% in each category. Injection drug users had the greatest risk of WP infection (4.9 per 10 000 donors by NAT WP), followed by men who have sex with men (4.2:10 000), commercial sex workers (2.7:10 000), incarcerated donors (0.9:10 000), donors exposed to HIV through blood (0.6:10 000), donors engaging in high-risk sex (0.3:10 000) and hemophiliacs (0.035:10 000). These estimates can help inform patient and provider decision making regarding HRDs.

Risk of window period hepatitis-C infection in high infectious risk donors: systematic review and meta-analysis.

The OPTN classifies high infectious risk donors (HRDs) based on criteria originally intended to identify people at risk for HIV infection. These donors are sometimes referred to as 'CDC high risk donors' in reference to the CDC-published guidelines adopted by the OPTN. However, these guidelines are also being used to identify deceased donors at increased risk of window period (WP) hepatitis C virus (HCV) infection, although not designed for this purpose. The actual risk of WP HCV infection in HRDs is unknown. We performed a systematic review of 3476 abstracts and identified 37 eligible estimates of HCV incidence in HRD populations in the United States/Canada. Pooled HCV incidence was derived and used to estimate the risk of WP infection for each HRD category. Risks ranged from 0.26 to 300.6 per 10,000 donors based on WP for ELISA and 0.027 to 32.4 based on nucleic acid testing (NAT). Injection drug users were at highest risk (32.4 per 10,000 donors by NAT WP), followed by commercial sex workers and donors exhibiting high risk sexual behavior (12.3 per 10,000), men who have sex with men (3.5 per 10,000), incarcerated donors (0.8 per 10,000), donors exposed to HIV infected blood (0.4 per 10,000) and hemophiliacs (0.027 per 10,000). NAT reduced WP risk by approximately 10-fold in each category.

Physiologic variations of serum testosterone within the normal range do not affect serum prostate-specific antigen.

OBJECTIVES: To determine the relationship between endogenous total serum testosterone levels and serum prostate-specific antigen (PSA) concentrations. If a correlation exists between these two parameters, then use of testosterone-specific reference ranges may enhance the utility of PSA as a marker for prostate cancer. METHODS: Data were obtained from 150 men without previous history of prostate cancer. PSA was measured by the Abbott IMX microparticle enzyme immunoassay and total testosterone determined by the Coat-A-Count radioimmunoassay. RESULTS: No correlation was found between testosterone and PSA, even when corrected for age and weight. CONCLUSIONS: The data suggest that determination of the total serum testosterone level does not improve the sensitivity or specificity of PSA as a tumor marker.

Color Doppler ultrasound analysis of ocular circulation after topical calcium channel blocker.

PURPOSE: To investigate the effect of topical administration of the calcium channel blocker verapamil on intraocular pressure and retrobulbar hemodynamics. METHODS: In this randomized, prospective, double-masked study, we examined the effects of single-dose topical administration of verapamil in ten normal human volunteers by using color Doppler ultrasound imaging to measure hemodynamic parameters. Limitations of this study include single-dose application of verapamil and relatively small sample size. RESULTS: No systemic effect on heart rate or blood pressure was detected after administration of topical verapamil. The intraocular pressure significantly decreased compared with baseline two hours after topical 0.125% and 0.25% verapamil (P = .015 and .040, respectively). Pourcelot's ratio, an index of vascular resistance, measured in the central retinal artery was significantly reduced after topical application of 0.125% verapamil (P = .008). The change in Pourcelot's ratio primarily resulted from an increased end diastolic velocity in the central retinal artery. No significant differences compared with baseline values were detected in the color Doppler ultrasound measurements of the posterior ciliary arteries and the central retinal vein two hours after topically administered verapamil. CONCLUSIONS: Topical administration of verapamil decreases intraocular pressure and alters ocular hemodynamics, reducing the vascular resistance index in the central retinal artery.

The influence of recombinant mediators on in vitro IgG subclass secretion by peripheral blood mononuclear cells from patients with hypogammaglobulinemia and from normal donors.

Patients with hypogammaglobulinemia have recurrent infections and fail to produce protective antibodies. In order for B cells to mature into antibody producing cells, several other cell types such as macrophages and helper T lymphocytes must be involved. They secrete several mediators such as interleukin-1 (IL-1), IL-4, IL-5, IL-6 and interferon-gamma (IFN-gamma). These factors, as recombinant mediators, were tested to assess their ability to correct the immunoglobulin production defect in vitro from pokeweed mitogen (PWM) stimulated cultures of peripheral blood mononuclear cells (PBMC) from 11 patients with hypogammaglobulinemia, and from 10 normals as controls. In general, PBMC from hypogammaglobulinemic patients secreted very little Ig in cultures, and no mediator induced a statistically significant increase in the secretion of any IgG subclass. When assessed on an individual basis, one patient demonstrated a variable pattern of increase in total IgG, IgG1, and IgG3, secretion induced by various mediators, to within one standard deviation of the average secretion of normal PBMC cultured in PWM. In the case of the normal cells, IL-4, IL-6 and IL-1 plus IL-4 were able to increase IgG2 secretion in culture with PWM. No increase in secretion of IgG1, IgG3 and IgG4 or total IgG was demonstrable however. Hence, although there is variability in responsiveness amongst the patients, there does not appear to be any one of these recombinant mediators which will correct the defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Exposure of tilapian fish to the pesticide lindane results in hypocellularity of the primary hematopoietic organ (pronephros) and the spleen without altering activity of phagocytic cells in these organs.

Tilapia were dosed by intraperitoneal injection for 5 consecutive days with either 20 or 40 mg/kg of the environmental contaminant hexachlorocyclohexane (lindane). The effects of this organochlorine pesticide on morphology and total cellularity of the spleen and pronephros were examined on the second day following termination of dosing. The functional capacity of phagocytic cells isolated from both spleen and pronephros was also evaluated as possible additional indicators of chemical-induced immunotoxicity. A dose-related reduction was found in spleen and pronephros total white blood cell counts in the fish exposed to lindane. In addition, hypocellularity of lymphoid regions in the spleen and pronephros was evident in chemical-exposed animals upon histopathological examination. However, phagocytosis of fluorescent microspheres by phagocytic cells isolated from the spleen and pronephros was not inhibited by the exposure to lindane. Similarly, no decrease in phorbolmyristate acetate (PMA)-stimulated hydrogen peroxide production was observed in phagocytic cells collected from lindane-exposed fish. These results suggest that cellular depletion in tilapia spleen and pronephros may represent a more sensitive indicator of lindane exposure than does the functional capacity of phagocytic cells isolated from these hematopoietic organs. Ultrastructural observations support this hypothesis and, further, suggest that lymphocytic cells may be targeted at the present exposure levels.

High-purity water supplies for biomedical research laboratories.

A quantitative bacteriological survey of high-purity water systems used in biomedical research laboratories at the National Institutes of Health revealed great variations among the systems. In general, distilled water had significantly lower contamination levels than deionized water. Interviews with investigators revealed their conceptions about the importance of bacterial contamination in high-purity water and some expectations about bacterial quality. Guidelines are suggested for the use of water from systems of varying quality.

Relationship of protein intake to urinary oxalate and glycolate excretion.

The relationship of protein intake to urinary oxalate and glycolate excretion was examined in a large cohort (N = 101) of normal individuals on self-selected diets and in 11 individuals on controlled protein diets. On self-selected diets no correlation was detected between protein intake and urinary oxalate or glycolate excretion. A moderate but significant correlation (r = 0.45; P < 0.001) of oxalate with urea excretion was observed in males but not females, suggesting that there may be a link between urea and oxalate synthesis in males. On controlled protein diets mean oxalate excretion in females on days 7 to 10 of a high protein diet (1.8 g/kg body wt) was 20% higher than on a low protein diet (0.6 g/kg body wt; P = 0.02), but there was no difference in males. Glycolate excretion was significantly higher (P < 0.001) on the high protein diet than on the low protein diet in both sexes. Only a weak precursor-product relationship was observed between glycolate and oxalate. A gender effect was apparent on both self-selected and control diets with females excreting more oxalate and glycolate relative to creatinine than males. A pronounced inter- and intra-individual variability in the excretion of oxalate was observed, even on controlled diets. This suggests that genetic factors and physiological changes such as hormonal fluctuations may contribute more to the variability in oxalate excretion than the dietary intake of protein.

Particle concentration fluorescence immunoassay for measuring interleukin-6 receptor numbers.

Analysis of the number of receptors per cell and the affinity of the ligand/receptor interaction has provided considerable insight into the functioning of numerous cytokines. Interleukin-6 (IL-6) is a multifunctional cytokine which may have considerable clinical relevance in inflammatory or immunodeficiency diseases. Using particle concentration fluorescence immunoassay (PCFIA) technology, an assay is described which calculates the receptor number and affinity on small numbers of human cells. Resting B cells are shown to lack IL-6 receptors but activation of B cells induces up to 1,300 receptors per cell, with Kd of 1 x 10(-11) to 2 x 10(-11) M. Other recombinant mediators do not alter the binding of labeled IL-6 to the cells. PCFIA avoids the use of radioactivity and requires very small numbers of cells (2 x 10(4) per well). Potential application to the study of regulatory mechanisms and to clinical situations where small samples of blood are available is feasible.

The photoreduction of H(2)O(2) by Synechococcus sp. PCC 7942 and UTEX 625.

It has been claimed that the sole H(2)O(2)-scavenging system in the cyanobacterium Synechococcus sp. PCC 7942 is a cytosolic catalase-peroxidase. We have measured in vivo activity of a light-dependent peroxidase in Synechococcus sp. PCC 7942 and UTEX 625. The addition of small amounts of H(2)O(2) (2.5 microM) to illuminated cells caused photochemical quenching (qP) of chlorophyll fluorescence that was relieved as the H(2)O(2) was consumed. The qP was maximal at about 50 microM H(2)O(2) with a Michaelis constant of about 7 microM. The H(2)O(2)-dependent qP strongly indicates that photoreduction can be involved in H(2)O(2) decomposition. Catalase-peroxidase activity was found to be almost completely inhibited by 10 microM NH(2)OH with no inhibition of the H(2)O(2)-dependent qP, which actually increased, presumably due to the light-dependent reaction now being the only route for H(2)O(2)-decomposition. When (18)O-labeled H(2)O(2) was presented to cells in the light there was an evolution of (16)O(2), indicative of H(2)(16)O oxidation by PS 2 and formation of photoreductant. In the dark (18)O(2) was evolved from added H(2)(18)O(2) as expected for decomposition by the catalase-peroxidase. This evolution was completely blocked by NH(2)OH, whereas the light-dependent evolution of (16)O(2) during H(2)(18)O(2) decomposition was unaffected.

Is radiographic evaluation of the chest necessary following flank surgery?

PURPOSE: We determined whether routine postoperative chest radiography is warranted after flank surgery to assess for pneumothorax. MATERIALS AND METHODS: A retrospective study of 253 adult flank operations performed during a 6-year period was conducted. RESULTS: Incidental pleurotomy occurred in 63 cases (24.9%). The performance of rib resection and the level of rib removed as well as female gender had a significant impact on this occurrence. Pleurotomy was treated by a simple evacuation technique and tube thoracostomy was not necessary. Only 2 patients (0.8%) had a postoperative pneumothorax without intraoperative recognition of pleurotomy, which resolved without intervention. CONCLUSIONS: Routine postoperative chest radiography to assess for pneumothorax following open flank surgery is not necessary.

The effect of back closure on detrusor function in neonates with myelomeningocele.

To determine the effect of back closure on the detrusor-external sphincter coordination, we reviewed the medical records of 40 neonates with myelodysplasia studied prospectively with urodynamic assessment and renal ultrasonography before closure of the spinal defect, within 7 days of closure and at 3-month intervals thereafter. Only 31 of the 40 neonates met all criteria for inclusion. All renal sonograms were normal before and after closure. Urodynamic evaluation demonstrated coordinated detrusor-sphincter activity in 18 neonates before and after closure. During prolonged followup 1 patient had detrusor areflexia and 4 had detrusor-sphincter dyssynergia. Of 11 neonates who demonstrated detrusor areflexia and no external sphincter activity before closure 10 were unchanged on initial post-closure evaluation (4 had detrusor-sphincter dyssynergia during followup), while 1 demonstrated detrusor areflexia with external sphincter overactivity and vesicoureteral reflux after closure. The latter patient subsequently had detrusor hyperreflexia, more severe reflux and upper tract deterioration. She was temporized with a cutaneous vesicostomy. One patient demonstrated detrusor-sphincter dyssynergia before closure and detrusor areflexia with no external sphincter activity after closure, the consequence of surgical division of the neural placode during back closure. The remaining patient demonstrated detrusor-sphincter dyssynergia before and after closure. This patient had coordinated detrusor-sphincter activity during followup. Those neonates who presented with or later had detrusor-sphincter dyssynergia were managed initially with neuropharmacological agents and clean intermittent catheterization. An unsuccessful outcome was managed by cutaneous vesicostomy. Our study demonstrates that neonatal closure of the spinal cord defect does not appear to affect detrusor-sphincter coordination adversely, and re-emphasizes the need for careful and regular followup in children with myelodysplasia to detect deterioration of the urinary tract.

Evaluation of tumor regression and other prognostic factors for early and late metastasis after proton irradiation of uveal melanoma.

The authors examined the relationship of change in tumor height after proton beam irradiation with the risk of metastasis in 700 patients treated for uveal melanoma before July 1, 1986. Rates of change in tumor height were computed for each patient using follow-up ultrasonographic measures during the first 2 years after treatment. Risk of metastasis was evaluated separately in the first 2 years after treatment when tumor decline was assessed (concurrent metastasis), and 2 years or later after treatment (subsequent metastasis). Using Cox proportional hazards models to adjust for other known risk factors, tumors regressing rapidly were significantly more likely to metastasize concurrently with their regression (P less than 0.05). The opposite was found for subsequent metastasis: tumors with a slow annual decline were more likely to metastasize after 2 years after treatment (P less than 0.05). Substantial changes also were noted in the ability of previously described prognostic factors (largest tumor diameter, tumor height, ciliary body involvement, and patient's age) to predict early and late metastasis. Characteristics placing individuals at high risk of metastasis may change markedly with time after treatment.

Establishment of a rabbit model of extrascleral extension of ocular melanoma.

PURPOSE: To establish an animal model of extrascleral extension of choroidal melanoma. METHODS: Pigmented choroidal tumors were established in nine New Zealand albino rabbit eyes using B16F10 melanoma cell line. The sclerotomy site was not closed in the subgroup of six rabbits where extrascleral extension was desired. For the control group, the sclerotomy site was sutured with 8-0 nylon. Animals were treated with daily injections of cyclosporine and followed by serial fundus examinations, color Doppler imaging, and fundus photography. All tumor-bearing eyes were enucleated at the end of the follow-up period and examined for extrascleral extension. RESULTS: Extrascleral extension of choroidal melanoma occurred in all six animals with open sclerotomy sites. No extrascleral extension was observed in the control group. Color Doppler imaging identified extrascleral extension which was confirmed on gross histology. CONCLUSIONS: Our animal model of extrascleral extension of choroidal melanoma requires minimal surgery to establish, and is reproducible and easy to follow with standard diagnostic equipment.

The combined effects of shock waves and cisplatin therapy on rat prostate tumors.

The effects of focused high energy shock waves (SW) generated by the Dornier experimental XL-1 lithotripter alone or in combination with cisplatin (CDDP) on the AT-2 prostate tumor were examined. They were assessed by measuring 1) clonogenic cell survival 24 hours after treatment, 2) tumor growth delay, and 3) the number of lung metastases. The survival of clonogenic cells was reduced 38% by exposure to 2000 SW and tumor growth was delayed by 1.5 days. The limb bearing the tumor was excised in all animals when the tumor reached seven cm.3 The subsequent occurrence of lung metastases in three out of 13 unshocked animals and two out of 14 shocked animals indicated that SW did not promote the dissemination of tumor cells. At doses of one to four mg. CDDP/kg. body weight, SW exposure increased the effectiveness of the chemotherapy measured by a clonogenic assay. The fractional survival was 0.62 after 2000 SW alone, 0.23 with four mg. cisplatin/kg. alone and 0.10 after the combination treatment. At higher doses of CDDP, there was no added effect of SW over that of CDDP therapy alone. Tumor growth to one cm.3 was delayed by seven days after treatment with four mg. CDDP/kg., in comparison to untreated controls. SW exposure combined with CDDP treatment delayed the time taken for the tumor to reach one cm.3 by 13 days in comparison with untreated controls. However, the combination treatment increased animal mortality from 9% with CDDP alone to 29%. These results indicate that SW could be used focally to enhance the cell killing effects of CDDP.

Production of factors with B-cell growth and differentiation activities by peripheral blood mononuclear cells from patients with hypogammaglobulinemia.

BACKGROUND: The maturation of normal B lymphocytes proceeds through a growth phase and a differentiation phase. These two phases appear to be under the influence of mediators released by immune cells, B-cell growth factor(s), which induce proliferation of B cells; and B-cell differentiation factor(s), which induce B-cell differentiation. METHODS: We analyzed the ability of peripheral blood mononuclear cells from patients with hypogammaglobulinemia to produce B-cell growth factor and B-cell differentiation factor activity in comparison with normal peripheral blood mononuclear cells. RESULTS: Of 27 patients tested, 26 had normal production of B-cell growth factor activity. A quantitative but not absolute defect in B-cell growth factor production was demonstrable in one boy with hypogammaglobulinemia. Interleukin-2 and interleukin-4 levels, as determined antigenically in these supernatants, had a similar distribution pattern from patients' or from control peripheral blood mononuclear cells; that is, undetectable levels of interleukin-2 were produced by cells from 4 of 16 patients tested and from 4 of 13 control subjects, and undetectable levels of interleukin-4 produced by cells from 6 of 16 patients and 4 of 13 control subjects. B-cell differentiation factor activity was absent in only one child tested but present in all other patients. Two patients had quantitatively low secretion of B-cell differentiation factor, but all others were within normal range. The two patients with quantitatively depressed B-cell differentiation factor activity had normal levels of B-cell growth factor activity, interleukin-2, and interleukin-4 produced from their cells. CONCLUSION: Peripheral blood mononuclear cells from the majority of patients with hypogammaglobulinemia appear to have the capacity to produce B-cell growth factors and B-cell differentiation factor activity in vitro.