The emancipation of testosterone from niche hormone to multi-system player

It is no exaggeration to say that our conceptualization of the (patho-) physiological functions of testosterone has undergone a revolutionary development over the last three decades. The traditional thinking was that the biological functions of testosterone were restricted mainly to the area of reproduction and male sexuality. However, scientific research has clearly demonstrated that testosterone is a multi-system hormone serving a wide range of hitherto unsuspected biological functions.In line with this, it will be argued in this contribution that the physiological role of testosterone has been underestimated, while the risks of testosterone administration have been overstated. Space does not permit to elaborate extensively on all new insights of the role of testosterone in the biology of the male. Three areas will be addressed: (1) the role that testosterone can play in body weight management of hypogonadal men; (2) the role of testosterone in inflammatory processes; (3) the strategy required to let patients benefit from the recent insights that testosterone is a multi-system hormone whose use should not be limited to reproductive/sexual medicine.     

Densitometer type and impact on risk assessment for osteoporosis.

Studies have shown a high correlation between measurements of bone mineral density (BMD) obtained on differentdual-energy X-ray absorptiometry machines. Challenger osteodensitometers (Diagnostic Medical System [DMS],Montpellier, France) are becoming widely used but little is known about their clinical performance. The aim of this study was to compare BMD measurements and the resulting patient classification based on T-scores obtained on a DMS Challenger device to those obtained on Hologic 4500A (Bedford, MA) device. Fifty-three volunteers were studied.The BMD of the spine and of the hip were simultaneously measured on both densitometers. BMD values obtained on the Challenger were significantly higher than those obtained with the Hologic QDR4500 (p<0.001). The correlations coefficients between the Hologic QDR4500 and the DMS Challenger measured BMDs were r=0.70 at the femoral neck, r=0.70 at the trochanter, and r=0.83 at the spine (p<0.001). Among the 35 postmenopausal women, there was discordance in the WHO T-score-based classification in 28 subjects (80%) at the spine, 18 subjects (52%) at the femoral neck, and 14 subjects (42%) at the trochanter. The intermachine agreement was low: The kappa score was -0.10 at the spine, 0.2 at the femoral neck, and 0.3 at the trochanter. In conclusion, this study cautions against the use of non established densitometers that leads to underdiagnosis of patients and, subsequently, to inappropriate treatment strategies.     

Progressive hemolytic anemia due to delayed recognition of a Beall mitral valve prosthesis

In addition to a working knowledge of general complications such as thromboembolism and infective endocarditis, optimal care of the patient with a prosthetic valve requires specific knowledge concerning the characteristics of a given patient's prosthesis. This may need to include the ability to identify the valve roentgenographically when history and records are unavailable. A 53-year-old woman with mitral stenosis secondary to rheumatic heart disease and status post a reported Bjork-Shiley mitral valve (MV) replacement 17 years prior to hospital admission was referred for evaluation of severe hemolytic anemia. Previous cinefluoroscopy in 1986 at the time of a cerebrovascular accident revealed a normally functioning caged disc prosthesis and not the tilting disc of a Bjork-Shiley prosthetic valve. The valve was not further characterized and she continued receiving warfarin therapy until May 1989 when she presented with laboratory findings showing a marked hemolytic anemia with a hemoglobin of 6.5 mg/dl and lactate dehydrogenase (LDH) value of 2100 IU. Echocardiography revealed normal valvular function without evidence of perivalvular leak. The patient was referred for further evaluation with chest roentgenogram at the time of hospital admission revealing a valve configuration characteristic of the Beall model 103/104 series that has been found to manifest progressive disc variance with a high degree of hemolytic anemia (despite normal noninvasive evaluation of MV function), disc tilting with intermittent regurgitation, and catastrophic disc embolization in extreme cases. The precise identification of valvular prosthesis in patients after valve replacement is crucial for optimal management. As in our case, the mere identification of a particular valve may necessitate certain management and therapy based on the natural history of that valve. In the absence of reliable history and/or records, the roentgenographic examination should lead to the precise identification.     

Structure-activity relationship in the gastric cytoprotective effect of several sesquiterpene lactones.

The structural requirements for the gastric cytoprotective activity of several sesquiterpene lactones are reported. A theoretical-experimental study on the potentially active centers is carried out. The biological evaluation of reduced analogues and the simulation of the molecular interactions between these compounds and an endogenous cysteine residue suggest that the presence of a non sterically hindered Michael acceptor seems to be an essential structural requirement for the cytoprotective activity in this family of compounds. This observation suggests that cytoprotection is mediated through a Michael reaction between the sulfhydryl-containing peptides of the mucosa and Michael acceptors present in the molecules under study. This mechanism of action is in addition to and distinct from the one proposed in our previous paper, namely, that these sesquiterpenes stimulate endogenous synthesis of prostaglandins.     

Obesity in Pima Indians. Distribution characteristics and possible thresholds for genetic studies.

We examined distribution characteristics of the body mass index (BMI; weight/height; kg/m2) in a sample of 1128 male and 1372 female Pima Indians aged 15-65 years. We found that women had a higher mean and variance of BMI than men. From commingling analyses, we determined that the distribution of BMI could be accounted for either by a single skewed distribution or by a mixture of multiple normal components. These component distributions may be used to define provisional thresholds in selecting families for genetic studies. To ensure genetic segregation of obesity predisposing genes in Pima families will require that some members have BMIs > or = 40 kg/m2.