"If I don't use a condom I would be stressed in my heart that I've done something wrong": Routine Prevention Messages Preclude Safer Conception Counseling for HIV-Infected Men and Women in South Africa.

Intended conception likely contributes to a significant proportion of new HIV infections in South Africa. Safer conception strategies require healthcare provider-client communication about fertility intentions, periconception risks, and options to modify those risks. We conducted in-depth interviews with 35 HIV-infected men and women accessing care in South Africa to explore barriers and promoters to patient-provider communication around fertility desires and intentions. Few participants had discussed personal fertility goals with providers. Discussions about pregnancy focused on maternal and child health, not sexual HIV transmission; no participants had received tailored safer conception advice. Although participants welcomed safer conception counseling, barriers to client-initiated discussions included narrowly focused prevention messages and perceptions that periconception transmission risk is not modifiable. Supporting providers to assess clients' fertility intentions and offer appropriate advice, and public health campaigns that address sexual HIV transmission in the context of conception may improve awareness of and access to safer conception strategies.

Benefits of a Physician-Scientist-Tailored Curriculum at a Medical Student-Run Free Clinic.

We designed a curriculum to help sustain pre-clinical knowledge for MD/PhD trainees in their graduate training phase while securing regular providers for our student-run free clinic. MD/PhD involvement increased from 1.91 to 2.45 students-per-clinic-day following implementation, and participants affirmed increased preparedness and comfort entering medical school clinical clerkships.

Comparison of proximal isovelocity surface area method with pressure half-time and planimetry in evaluation of mitral stenosis.

OBJECTIVES: This study sought to 1) compare the accuracy of the proximal isovelocity surface area (PISA) and Doppler pressure half-time methods and planimetry for echocardiographic estimation of mitral valve area; 2) evaluate the effect of atrial fibrillation on the accuracy of the PISA method; and 3) assess factors used to correct PISA area estimates for leaflet angulation. BACKGROUND: Despite recognized limitations of traditional echocardiographic methods for estimating mitral valve area, there has been no systematic comparison with the PISA method in a single cohort. METHODS: Area estimates were obtained in patients with mitral stenosis by the Gorlin hydraulic formula, PISA and pressure half-time method in 48 patients and by planimetry in 36. Two different factors were used to correct PISA estimates for leaflet angle (theta): 1) plane-angle factor (theta/180 [theta in degrees]); and 2) solid-angle factor [1-cos(theta/2)]. RESULTS: After exclusion of patients with significant mitral regurgitation, the correlation between Gorlin and PISA areas (0.88) was significantly greater (p < 0.04) than that between Gorlin and pressure half-time (0.78) or Gorlin and planimetry (0.72). The correlation between Gorlin and PISA area estimates was lower in atrial fibrillation than sinus rhythm (0.69 vs. 0.93), but the standard error of the estimate was only slightly greater (0.24 vs. 0.19 cm2). The average ratio of the solid- to the plane-angle correction factors was approximately equal to previously reported values of the orifice contraction coefficient for tapering stenosis. CONCLUSIONS: 1) The accuracy of PISA area estimates in mitral stenosis is at least comparable to those of planimetry and pressure half-time. 2) Reasonable accuracy of the PISA method is possible in irregular rhythms. 3) A simple leaflet angle correction factor, theta/180 (theta in degrees), yields the physical orifice area because it overestimates the vena contracta area by a factor approximately equal to the contraction coefficient for a tapering stenosis.

Combined posteroanterior subepicardial fat simulating the echocardiographic diagnosis of pericardial effusion.

The location and relative size of echo-free spaces observed by cardiac ultrasound have been considered reliable signs for distinguishing pericardial fat from fluid; spaces that are exclusively anterior have been considered to represent fat, while spaces that are exclusively or predominantly posterior have been considered to represent fluid. In the present study, the location and relative size of echo-free spaces in eight patients suggested the diagnosis of pericardial effusion; evaluation by computed tomography or thoracotomy, or both, in six and necropsy in two, however, disclosed that these echo-free spaces--posterior as well as anterior--were exclusively due to fat. Age appeared to be as important a predisposing factor as obesity in the accumulation of excess subepicardial fat. No M-mode or two-dimensional features were found to be reliable in differentiating fat from fluid, although excessive amplitude of the posterior pericardial echo on the M-mode study favored the diagnosis of fat. Thus, the finding of echo-free spaces by cardiac ultrasound, even when the posterior space is isolated or larger than an accompanying anterior space, is not necessarily indicative of pericardial fluid. In elderly patients, in particular, posterior echo-free spaces due to fat may invite an incorrect diagnosis of pericardial effusion or pericarditis. In patients in whom echo-free spaces represent an unexpected finding of cardiac ultrasound examination, computed tomography of the chest may be helpful in establishing whether they are due to fat or fluid.

Comparison with radionuclide angiography of two new geometric and four nongeometric models for echocardiographic estimation of left ventricular ejection fraction using segmental wall motion scoring.

Two new echocardiographic methods for estimating left ventricular ejection fraction, both based on segmental wall motion scoring on a continuous scale, were developed and compared to radionuclide angiography in 50 patients. The first method used a geometric model in which the ventricle was represented by a tubular base section joined to a hemielliptical apex section, each containing 4 quadrants. Contraction was scored visually in 12 regions of the ventricle. The 12 scores were converted to dimensional shortenings, which were then used to calculate separate ejection fractions for each of the 8 quadrants. These 8 values were averaged to obtain the global ejection fraction. Assuming an elliptical end-systolic cross-section shape for each quadrant, the correlation between the echocardiographic and radionuclide ejection fractions was 0.917 with a regression slope of 0.93 and an intercept of 1.5. Results were identical assuming circular end-systolic quadrant shapes. The second approach used a linear combination of the mean wall motion score at the base, midleft ventricle and apex to predict ejection fraction. Coefficients for the 3 mean scores were optimized by least squares best fit with radionuclide ejection fraction in all 50 patients. The simplest linear model showed a correlation of 0.90 between the echocardiographic and radionuclide ejection fraction but underestimated low, and overestimated high, ejection fractions. However, these systematic errors could be removed by regression, which added a constant term of 8.1 and a slope factor of 0.87 to the linear model, improving the correlation with radionuclide ejection fraction to 0.91.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary calcification in the diagnosis of coronary artery disease.

Clinical, postmortem and angiographic studies of coronary calcification are reviewed to define the value of fluoroscopy in the diagnosis and management of coronary artery disease. Autopsy studies consistently show a unique association between calcification of the coronary arteries and atherosclerosis. The relation of coronary calcification to the presence of major stenosis is more variable but is strong enough to be of clinical value, particularly in the younger subject. The diagnostic value of fluoroscopy can be improved by attention to the detailed features of calcification observed with the technique. Combined use of fluoroscopy and exercise testing appears to be a valid and as yet unexploited approach to the noninvasive diagnosis of coronary stenosis. Fluoroscopy has been a neglected method of noninvasive diagnosis and is sufficiently promising to warrant greater clinical use.

De novo deletion of chromosome 18q in a baby with harlequin ichthyosis.

Harlequin ichthyosis, (MIM 242500), is a rare, autosomal recessive skin disorder due to an inborn error of epidermal keratinization. The gene for this condition has not been localized. We present a case of HI in which there was a de novo deletion of chromosome 18q: the karyotype was 46, XY, del(18)(q21.3). We postulate that the gene for HI may lie at, or distal to 18q21.3 and that the deletion observed in this case may have unmasked this autosomal recessive disorder.

The relationship between somatostatin binding and cyclic AMP-stimulated protein kinase inhibition.

Somatostatin binding and the ability to inhibit cyclic AMP stimulated protein kinase were investigated utilizing isolated pancreatic islets, anterior pituitary plasma membranes, adipocytes, erythrocyte ghosts, hepatic plasma membranes, and anterior pituitary secretion vesicles. Three types of response were observed. With type I response, somatostatin bound specifically to pancreatic islets and anterior pituitary secretion vesicles and inhibited cyclic AMP stimulated protein kinase. In type II response, adipocytes and anterior pituitary plasma membranes exhibited somatostatin binding but no effect of the ligand on the kinase. In erythrocyte membrane ghosts and hepatic plasma membranes, there was neither specific somatostatin binding nor protein kinase inhibition (type III response). The absence of somatostatin binding in erythrocytes or hepatic plasma membranes cannot be explained by degradation of the ligand per se. Secretory vesicles isolated from the anterior pituitary gland bind somatostatin with an average affinity which exceeds that observed in plasma membrane (for pituitary secretory vesicles Kd1 = 8.5 X 10(-8)M, Kd2 = 5.2 X 10(-7)M; for pituitary membranes Kd1 = 1.9 X 10(-8)M, Kd2 = 8.1 X 10(-7)M). The molar concentration of high affinity binding sites (Ro) for plasma membranes was 6.9 X 10(-10)M; for secretory vesicles 3.6 X 10(-9)M. Calculated in terms of somatostatin binding per U 5'nucleotidase activity, the binding for plasma membranes becomes 8.4 X 10(-14) mole/U 5'nucleotidase; secretory vesicles 4.4 X 10(-13) mole/U 5'nucleotidase. Thus, secretory vesicles are fivefold richer in high affinity receptor sites than plasma membranes. It is suggested that in order for somatostatin to act, both a receptor and an effector unit must be present. In the case of tissues secreting polypeptide hormones by granule extrusion, the secretory vesicle may possess both the receptor and the effector units. It is postulated that during the process of fusion of the plasma and secretory vesicle membranes, a high affinity binding site for somatostatin is incorporated into the plasma membrane, thereby allowing somatostatin to act at a specific locus in the cell in inhibiting hormone release.

Multiple granular cell tumors. A familial occurrence in children.

A 23-year-old black woman and her 6-year-old son, both with multiple granular cell tumors, are described herein. The mother and son both presented as children with multiple granular cell tumors. This is the first reported case of multiple lesions arising in childhood in successive generations. Only two other case studies of familial granular cell tumors have been reported, but in neither of these cases did multiple tumors present initially in both family members during childhood. A preponderance of multicentric lesions is reported in blacks. The tumors recurred locally in some of the sites where there were inadequate surgical margins, emphasizing the need for complete excision.

Echocardiography allows safer venous cannulation during excision of large right atrial masses.

BACKGROUND: Excision of large right atrial masses requires bicaval cannulation and cardiopulmonary bypass. Safe venous cannulation can be accomplished only by knowing the exact intracavitary location and extension of the mass to avoid fragmentation. Transthoracic echocardiography and intraoperative transesophageal echocardiography, although helpful, cannot always define the exact intracavitary relationships of the tumor. METHODS: We have used both intraoperative transesophageal and epicardial echocardiography to guide venous cannulation in 4 patients with large right atrial masses. Both echo images are used by the surgeon to select the exact site and method of cannulation to avoid fragmentation of the mass. Epicardial echocardiography complemented the images obtained by transesophageal echocardiography. RESULTS: The technique of combined transesophageal and epicardial echocardiography allowed safe venous cannulation in all 4 patients. Each of the right atrial masses was safely excised using case-specific cannulation techniques guided by the echocardiographic images. CONCLUSIONS: We propose the routine use of both intraoperative transesophageal and epicardial echocardiography in guiding venous cannulation for safe excision of large right atrial masses.

Photodynamic therapy using SnET2 for basal cell nevus syndrome: a case report.

A 26-year-old man with basal cell nevus syndrome presented to the Rocky Mountain Cancer Center (Denver, Colorado) for treatment of several basal cell carcinomas with photodynamic therapy using tin ethyl etiopurpurin (SnET2). The patient was of northern European descent, had type I skin (always burns, never tans), and had a 10-year history of multifocal basal cell carcinomas. The patient had a family history of Gorlin's syndrome (basal cell nevus syndrome); the syndrome had been diagnosed in this patient in 1985. The patient was enrolled in a Phase I/II clinical trial. He was given 1.2 mg/kg (94 mg total) of SnET2 via intravenous infusion; he returned to the clinic the following day for red light application. Thirteen lesions, in 12 treatment fields, were illuminated with light totaling 200 J/cm2 at a fluence of 150 mW/cm2. At the 3-month follow-up examination, all tumors were graded as having a complete response by modified AIDS Clinical Trial Guidelines oncologic standards. No evidence of recurrence has been noted during the 6-month follow-up period.

Mitoxantrone and fludarabine in the treatment of patients with non-Hodgkin's lymphoma failing primary therapy with a doxorubicinor mitoxantrone-containing regimen.

Patients with recurrent lymphoma of any grade were treated with mitoxantrone (12 mg/m2 given intravenously (IV) over 15-30 minutes on day 1) followed by fludarabine at a dose of (25 mg/m 2 given IV over 30 minutes on days 1-3) every 28 days fludarabine at a dose of (25 mg/m2 given IV over 30 minutes on days 1-3) every 28 days. All patients had failed one prior chemotherapy regimen that contained either doxorubicin or mitoxantrone, total dose not exceeding 350 mg/m2 doxorubicin or 80 mg/m2 mitoxantrone. mitoxantrone. Thirty one patients (22 with intermediate- or high-grade and 9 with low-grade NHL) were enrolled. Median age was 63 years (range: 21 to 87). The objective response rate for patients with intermediate/high-grade NHL was 55% (27% with CR) and 89% (56% with CR) for patients with low-grade NHL. Median time to disease progression was 5.1 months for patients with intermediate/high-grade NHL and 10.8 months for patients with low-grade NHL. Median time to death for patients with intermediate/high-grade disease was 11.4 months. Median time to death for patients with low-grade NHL was not calculable as only one death (due to respiratory failure) occurred in this group 6.5 months after study start. The regimen was well tolerated. Grade 3/4 neutropenia was reported in 80% (24 of 30) of patients and Grade 3/4 thrombocytopenia in 19% (6 of 31) of patients. Nine hospitalizations for adverse events (primarily fever and neutropenia) occurred among eight patients, all with intermediate/high-grade NHL, during a total of 118 cycles of therapy. Further studies of this combination regimen in patients with intermediate/high-grade NHL and studies combined with monoclonal antibodies in low-grade NHL are warranted.

Delphi-panel analysis of appropriateness of high-dose therapy and bone marrow autotransplants in newly diagnosed multiple myeloma.

There is controversy whether high-dose therapy and a bone marrow autotransplant or conventional chemotherapy is a better treatment for newly diagnosed multiple myeloma. Data from 1 comparative study and 1 randomized trial provide insufficient subject-level data to advise specific people whether to have an autotransplant. We analyzed appropriate use of high-dose therapy and bone marrow autotransplants in people with newly diagnosed, multiple myeloma using a modified Delphi-panel group judgment process. The panel consisted of 9 myeloma experts from diverse geographic sites and practice settings who reviewed Boolean MEDLINE searches of multiple myeloma and chemotherapy or autotransplants. The panel rated a metric of 64 clinical setting developed by permuting age, performance score, disease-stage and disease-related prognostic variables and response to initial therapy. Each panelist rated appropriateness of high-dose therapy and an autotransplant versus conventional-dose chemotherapy on a 9-point ordinal scale (1, most inappropriate, 9, most appropriate). An appropriateness index was developed based on median rating and amount of disagreement. Relationship of appropriateness indices to the permuted clinical variables was considered by analysis of variance and recursive partitioning. Autotransplants were rated appropriate in persons <55 years old with stage 3 disease and a complete or partial response or stable disease after initial chemotherapy, inappropriate in persons with stage 1 or 2 disease, a performance score <70% and a complete or partial response or stable disease after initial chemotherapy and uncertain in all other settings.

Inhibitory effect of inositol phosphates on parathyroid hormone-induced bone resorption in organ cultures.

This study investigates the ability of phytic acid, its inositol phosphate derivatives (inositol penta-, tetra-, tri-, di-, and monophosphate), and inorganic phosphate to inhibit parathyroid hormone (PTH)-induced resorption of fetal rat long bones in organ culture. Pregnant rats injected with 45Ca on the 18th day of gestation were killed the next day and their fetuses removed. Half of each pair of dissected long bones was incubated in a chemically defined control medium, while the contralateral half was incubated in medium containing PTH or PTH plus the phosphate compound to be tested. 45Ca released into the medium was indicative of the amount of bone resorption. All phosphate compounds tested inhibited resorption. The inositol phosphates should be studied further to assess their suitability as therapeutic agents for treatment of metabolic bone diseases involving increased turnover.

Maximum Shannon information content of diagnostic medical testing. Including application to multiple non-independent tests.

The increase in Shannon information available from a diagnostic test associated with grading of the test results into many outcomes, rather than simply positive or negative, was examined to determine its upper limit as the number of test outcomes is increased indefinitely. Numerical methods were employed to find the optimal locations of outcome boundaries when a single normally distributed test variable is classified into 2, 3, 4, 5, 6, 8, 14, or 20 outcome categories. In each case Shannon information was computed for values of prior probability between 0.01 and 0.99 and for distances between the means in diseased and nondiseased populations ranging from 0.5 to 5.0 standard deviations. There is an important improvement in Shannon information as the number of outcomes defined is increased, but the increment in information diminishes rapidly with each additional category. A 20%-30% increment in information may be achieved with three outcomes instead of two. A further important increase in information occurs with four to seven outcomes, but beyond this the increment in inforation is negligible. The findings were similar over a wide range of prior probabilities and distances between the means. The analysis was extended to the case of multiple nonindependent tests by demonstrating their application to a Fisher discriminant function incorporating such tests. It was concluded that for normally distributed test variables: grading of test results significantly improves the information content of both single and multiple tests; the value of information content for 8-20 outcomes represents very nearly the maximum information content of a test; there is little value in using more than five to seven test outcomes; multiple grading should not be neglected for discriminant functions.

Classical statistical considerations in medical decision models.

The influence of sampling error on decision-analytic models was investigated to determine how these errors affect model reliability. Formulas were developed to relate statistical error in the probability decision threshold and gain in expected utility to the error in the data samples upon which such models are based. The formulas were validated in a simulation experiment and then applied to a hypothetical decision model and to the clinical problem of immediate surgery versus continued observation in suspected acute appendicitis. The results of this analysis show that modest statistical error affecting any variable in a decision model may be amplified into a substantially larger error in both the probability decision threshold and the gain in utility predicted by the model. In addition, when errors are present simultaneously in several variables, they may compound to unexpectedly large magnitudes, rendering the model unreliable over a wide range of disease probability. The interpretation of the results of a decision analysis should be viewed along a continuum that takes into account both the magnitude of the gain or loss in expected utility predicted by the model and a quantitative measure of the reliability of this prediction. Whenever possible, a determination of statistical error should be an integral part of any formal decision analysis.

Physiological basis of flow dependence of Gorlin formula valve area in aortic stenosis: analysis using an hydraulic model of pulsatile flow.

BACKGROUND AND AIM OF THE STUDY: The study aim was to clarify the basis of the cardiac output dependence of aortic valve area calculated with the Gorlin formula which has been reported in patients with aortic stenosis. Clinical and experimental studies which have attempted to differentiate between a change in physical orifice area, versus a defect in the Gorlin formula as the cause of cardiac output related variations in Gorlin valve area in aortic stenosis have yielded conflicting results. METHODS: We employed a numerical model of pulsatile flow in which the total instantaneous transvalvular gradient was the sum of the convective and viscous pressure losses and pressure recovery beyond the stenosis. By analogy with other hydraulic devices, viscous losses due to stenosis were modeled by the term KfV(EXP), where V is flow velocity. Kf and EXP were determined for various orifices by adjusting these two parameters to obtain excellent fit between curves of the orifice discharge coefficient based upon the expression KfV(EXP), and empirically measured orifice discharge coefficient curves which have been published in the engineering literature. Mean systolic transvalvular gradient was calculated from the total instantaneous transvalvular gradient values for an assumed jet area, and an assumed systolic time-velocity flow profile. This mean gradient was substituted into the Gorlin equation to find the apparent Gorlin valve area at cardiac outputs varying from 0 to 10 l/min for a range of where V is assumed true areas between 0.5 and 2.0 cm2. RESULTS: For functional valve areas <1.5 cm2, viscous losses resulted in at most a 10-12% fall in apparent Gorlin valve area when cardiac output was decreased from 5 to 2.5 l/min. In addition, maximum viscous losses did not result in a pressure-flow relationship which was closer to linear than to quadratic. which the CONCLUSION: Clinically significant changes in valve area with flow are due to orifice area changes rather than Gorlin formula flow variability. Moreover beyond the Gorlin valve area is preferred over valve 'resistance' for assessing stenosis severity. In low cardiac output states, output should be increased to the normal range before Gorlin valve area is measured.

Detection of coronary artery disease by vasodilator thallium imaging of the heart with amyl nitrite inhalation: a pilot study.

Thallium imaging of the heart using dipyridamole-induced coronary arteriolar vasodilation has proven to be an effective means of detecting significant coronary stenosis. However, intravenous dipyridamole has not yet been made available for general use. We therefore examined the feasibility of substituting amyl nitrite inhalation as an arteriolar vasodilator prior to thallium imaging. Seventeen patients, all of whom had catheterization-proven coronary stenosis, inhaled amyl nitrite for 2-5 min. Thallium was injected after 45-60 s of inhalation. Completion of inhalation was followed immediately by planar imaging. Of 6 patients who inhaled amyl nitrite for at least 4 min, 5 had moderate or severe image defects on immediate scans which completely resolved on delayed scans. Only 3 of 11 who inhaled amyl nitrite for 2 min or less prior to scanning had similarly positive tests. Overall sensitivity for significant stenosis was 8 of 17 (47%). Inhalation was well tolerated with only one episode of angina and hypotension. We conclude that amyl nitrite inhalation for at least 4 min may offer an effective and readily available alternative to intravenous dipyridamole for vasodilator imaging of the heart.

Facial analysis: a comprehensive approach to treatment planning in aesthetic dentistry.

Patient aesthetic expectations and smile enhancement can be achieved through the use of facial analysis. This process allows each member of the restorative team (i.e., clinician, specialist, dental technician) to diagnose the patient and develop a comprehensive treatment plan for his or her specific needs. Treatment planning according to facial architecture and dental configuration allows function and harmonious aesthetics to be improved. This article demonstrates a predictable means to evaluate the components of an attractive face for use as a guide during aesthetic dental treatment.

Considerations in the use of polymer and fiber-based indirect restorative materials.

Restorative materials and techniques are constantly refined in order to address the aesthetic expectations of patients. Second-generation laboratory-fabricated composite materials have recently been developed to combine the advantages of porcelain with composite resin. This class of biomaterial can be utilized in a variety of direct and indirect clinical applications than include inlay/onlay restorations, full-coverage crowns, fixed partial dentures, and implant-supported prostheses. This article reviews considerations for the use of these materials from clinical indications through cementation.