The natural history of Peyronie's disease

The natural history of Peyronie's disease was evaluated in 97 men by means of a questionnaire. Disease duration ranged from 3 months to 8 years. Questions addressed pain, bending, ability for intercourse, over-all effect of the disease, psychological effects, treatments received and degree of disease progression. Approximately 40% of the patients found pain, bending, ability for intercourse and over-all effects to be unchanged during the course of the disease. Bending and ability for relations worsened in 40% of the patients during the same interval, while only 6% had worsening of pain. Of the patients 77% reported psychological effects due to Peyronie's disease, which improved in 28%, did not change in 36% and worsened in 36%. Over-all, 13% of the patients believed the disease to be one of gradual resolution, 47% believed there had been little or no change and 40% believed that the disease pattern was one of gradual progression. We found no statistically significant association between disease duration and spontaneous improvement in penile bending. A similar lack of statistical significance was found when improvement in a variety of categories was compared in patients who received no therapy versus those who received a variety of conventional medical therapies.     

Correlation between penile angiography and duplex scanning of cavernous arteries in impotent men

During the diagnostic evaluation of patients with vasculogenic impotence duplex scanning has been proposed as a reliable noninvasive method to evaluate the cavernous arteries. However, the sensitivity and specificity of this test have never been elucidated. To provide insight into the clinical value of this test 25 men who presented with impotence and failed to respond to 60 mg. intracavernous papaverine were evaluated with duplex scanning and the results of this modality were compared to penile angiography. The cavernous arteries were considered normal by duplex scanning if the artery demonstrated either a 60% or greater increase in diameter and/or a peak flow velocity of greater than 25 cm. per second 5 minutes after papaverine injection. Penile angiography was considered normal if both cavernous arteries were visualized and appeared to be normal radiographically (after intracorporeal papaverine). In the 25 patients studied there was no significant difference in peak flow velocity between patients with normal or abnormal cavernous arteries by angiography. In addition, arterial dilatation (more than 60%) after papaverine injection did not correlate with the results of the angiogram. These data demonstrate that duplex scanning of the cavernous arteries does not correlate well with what is observed by penile angiography in a selected population of men with vasculogenic erectile dysfunction. Since penile angiography itself has limitations in the evaluation of the penile arteries, the reliability of duplex scanning to identify cavernous artery dysfunction needs additional confirmation.     

High- and low-affinity receptors regulate platelet responses to phorbol diesters and teleocidin

We examined binding of ³H-phorbol dibutyrate (³H-PDBu) to gel filtered human platelets (GFP) and discovered that GFP possess two classes of receptors for phorbol diesters (PDE). High-affinity (HA) receptors, approximately 5000/GFP, bound ³H-PDBu with an apparent dissociation constant (K_D) of approximately 12 nM. Low-affinity receptors were approximately 5 times more numerous (2.4 × 10⁴/GFP) and had a 10-fold lower affinity for ³H-PDBu (apparent K_D = 115 nM). The potencies of phorbol myristate acetate (PMA) and PDBu paralleled their binding affinities to the PDE receptors. Teleocidin (Tel), although structurally distinct from PDE, competed with ³H-PDBu for its HA-receptors (K_I Tel = 1.9 nM). Binding of PDE to HA- or LA- receptors was rapid, reversible, saturable and stereospecific. The HA- and LA-receptors modulated different platelet responses. HA-receptors regulated the secretion of β-thromboglobulin from -granules and the release of N-acetyl-β-D-hexosaminidases from lysosomes. LA-receptors mediated both platelet aggregation and the release of serotonin from dense granules. This is the first demonstration of two physiologically active classes of PDE/Tel receptors in human platelets, and demonstrates that particular platelet responses may be directed by distinct classes of receptors for specific agonists.     

Effectiveness of montelukast in the treatment of cough variant asthma.

BACKGROUND: Antileukotriene agents have been shown to be beneficial in chronic asthma. Although patients with cough variant asthma have cough with minimal wheezing and dyspnea, airway hyperresponsiveness from chronic inflammation is believed to be the underlying mechanism. OBJECTIVE: To evaluate the effectiveness of montelukast, a leukotriene receptor antagonist, in the treatment of cough variant asthma. METHODS: Fourteen patients with cough variant asthma participated in a randomized, double-blind, placebo-controlled trial with a 7- to 10-day baseline period and a 4-week treatment period with montelukast, 10 mg, or placebo daily. Inclusion criteria were (1) chronic cough with a duration of at least 4 weeks with minimal or no wheezing or dyspnea and (2) forced expiratory volume in 1 second of 50% to 85% of predicted and reversibility of 12% with use of an inhaled beta-agonist or forced expiratory volume in 1 second greater than 85% and positive methacholine challenge results. Patients fulfilled the minimum criteria for cough frequency and symptom scores for randomization. RESULTS: Eight patients received montelukast and 6 received placebo. The primary efficacy variable, mean percentage change from baseline in cough frequency, was significantly improved by the second week, and by the fourth week the mean percentage change from baseline was 75.7% for the treatment group and 20.7% for the placebo group. CONCLUSIONS: The leukotriene receptor antagonist montelukast seems to be effective in the treatment of cough variant asthma. Larger studies are recommended to confirm this effect.     

A tracer kinetic model for 18F-FHBG for quantitating herpes simplex virus type 1 thymidine kinase reporter gene expression in living animals using PET.

Reporter probe 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine (18F-FHBG) and reporter gene mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) have been used for imaging reporter gene expression with PET. Current methods for quantitating the images using the percentage injected dose per gram of tissue do not distinguish between the effects of probe transport and subsequent phosphorylation. We therefore investigated tracer kinetic models for 18F-FHBG dynamic microPET data and noninvasive methods for determining blood time-activity curves in an adenoviral gene delivery model in mice. METHODS: 18F-FHBG (approximately 7.4 MBq [approximately 200 microCi]) was injected into 4 mice; 18F-FHBG concentrations in plasma and whole blood were measured from mouse heart left ventricle (LV) direct sampling. Replication-incompetent adenovirus (0-2 x 10(9) plaque-forming units) with the E1 region deleted (n = 8) or replaced by HSV1-sr39tk (n = 18) was tail-vein injected into mice. Mice were dynamically scanned using microPET (approximately 7.4 MBq [approximately 200 microCi] 18F-FHBG) over 1 h; regions of interest were drawn on images of the heart and liver. Serial whole blood 18F-FHBG concentrations were measured in 6 of the mice by LV sampling, and 1 least-squares ratio of the heart image to the LV time-activity curve was calculated for all 6 mice. For 2 control mice and 9 mice expressing HSV1-sr39tk, heart image (input function) and liver image time-activity curves (tissue curves) were fit to 2- and 3-compartment models using Levenberg-Marquardt nonlinear regression. The models were compared using an F statistic. HSV1-sr39TK enzyme activity was determined from liver samples and compared with model parameter estimates. For another 3 control mice and 6 HSV1-sr39TK-positive mice, the model-predicted relative percentage of metabolites was compared with high-performance liquid chromatography analysis. RESULTS: The ratio of 18F-FHBG in plasma to whole blood was 0.84 +/- 0.05 (mean +/- SE) by 30 s after injection. The least-squares ratio of the heart image time-activity curve to the LV time-activity curve was 0.83 +/- 0.02, consistent with the recovery coefficient for the partial-volume effect (0.81) based on independent measures of heart geometry. A 3-compartment model best described 18F-FHBG kinetics in mice expressing HSV1-sr39tk in the liver; a 2-compartment model best described the kinetics in control mice. The 3-compartment model parameter, k3, correlated well with the HSV1-sr39TK enzyme activity (r2 = 0.88). CONCLUSION: 18F-FHBG equilibrates rapidly between plasma and whole blood in mice. Heart image time-activity curves corrected for partial-volume effects well approximate LV time-activity curves and can be used as input functions for 2- and 3-compartment models. The model parameter k3 from the 3-compartment model can be used as a noninvasive estimate for HSV1-sr39TK reporter protein activity and can predict the relative percentage of metabolites.     

Health Care Markets, the Safety Net, and Utilization of Care among the Uninsured

Objective. To quantify the relationship between utilization of care among the uninsured and the structure of the local health care market and safety net.
Data Sources/Study Setting. Nationally representative data from the 1996 to 2000 waves of the Medical Expenditure Panel Survey (MEPS) linked to data from multiple secondary sources.
Study Design. We separately analyze outpatient care utilization and whether an individual incurred any medical expenditure among uninsured adults living in urban and rural areas. Safety net measures include distances between each individual and the nearest safety net providers as well as a measure of capacity based on local government and hospital health expenditures. Other covariates include the managed care presence in the local health care market, the percentage of individuals who are uninsured in the area, and local primary care physician supply. We simulate utilization using standardized predictions.
Principal Findings. Distances between the rural uninsured and safety net providers are significantly associated with utilization. In urban areas, we find that the percentage of individuals in the area who are uninsured, the pervasiveness and competitiveness of managed care, the primary care physician supply, and safety net capacity have a significant relationship with health care utilization.
Conclusions. Facilitating transport to safety net providers and increasing the number of such providers are likely to increase utilization of care among the rural uninsured. Our findings for urban areas suggest that the uninsured living in areas where managed care presence is substantial, and especially where managed care competition is limited, could be a target for policies to improve the ability of the uninsured to obtain care. Policies oriented toward enhancing funding for the safety net and increasing the capacity of safety net providers are likely to be important to ensuring the urban uninsured are able to obtain health care.     

Asbestosis occurring after brief inhalational exposure: usefulness of bronchoalveolar lavage in diagnosis

A case of clinically and radiologically typical asbestosis manifesting in a 55 year old man occurred 36 years after a brief exposure period of less than one year. A transbronchial lung biopsy was performed but the samples were considered non-diagnostic. The diagnosis was supported by the use of bronchoalveolar lavage to obtain alveolar samples and scanning electron microscopy-energy dispersive x ray analysis of fibres found in the bronchoalveolar lavage fluid which showed a predominance of amosite.     

Time course of metabolic findings in coronary occlusion and reperfusion and their role for assessing myocardial salvage

The techniques currently used to assess myocardial infarction are limited in their ability to determine the amount of viable myocardium after a temporary ischemic event. Blood flow and segmental function may not necessarily demonstrate salvage, whereas metabolic parameters will determine cell survival. In an open chest dog model, short occlusion times of 20 min and subsequent reperfusion using C-11 palmitate as an index of fatty acid metabolism showed depression of fatty acid oxidation, which recovered after 3 hours of reperfusion, indicating the partial reversibility of the ischemic condition. In more extensive studies, using positron emission tomography (PET) and, as an indicator of glucose metabolism, fluoro-F-18-deoxyglucose (FDG); N-13 ammonia in addition to C-11 palmitate for the determination of blood flow; and ultrasonic crystals to measure shortening in the reperfused and control territories, the duration of occlusion was 3 h. Metabolic studies were repeated 24 h, 1 week, and 4 weeks after the ischemic injury. Reperfused viable myocardium exhibited residual glucose metabolism with FDG, whereas fatty acid oxidation remained impaired for a longer period. Gradual metabolic recovery during a 4-week period was associated with the prolonged recovery of regional function, whereas a lack of residual metabolic activity indicated that little change in function was likely to occur. Increased FDG uptake and impaired C-11 palmitate turnover are characteristic of reversibly injured tissue. Therefore, PET studies may offer a unique potential for the evaluation of therapeutic measures such as thrombolysis and early revascularization.

     

Surgical treatment of lymph nodes with metastatic melanoma from unknown primary site

To determine the prognosis of patients with lymph node metastases from an unknown primary melanoma, we retrospectively reviewed the clinicopathologic features of 188 such patients treated from 1971 through 1986 and compared their records with those of patients with clinical stage II melanoma with known primary lesions. Patients with lymph node metastases from an unknown primary melanoma represented 4.6% of all patients with melanoma treated during that period. The five- and ten-year survival rates were 42% and 40%, respectively (median, 37 months). When stratified by number of tumor-containing lymph nodes, there was no significant difference in survival between patients with an unknown primary melanoma and lymph node metastases and those with clinical stage II melanoma and known primary sites. The prognosis of the former patients is no worse than that of patients with lymph node metastases from a known primary site and should be treated in a comparable manner.