Bacteria of human physiological microflora liberate immunomodulating peptides

Human isolates of Propionibacterium acnes and Staphylococcus saprophyticus could be shown to liberate low molecular weight peptides (MW less than 6.500 D) with immunomodulating activity. FACS analyses of BALB/c-mouse lymphoid cells from the thymus and spleen revealed an enhanced percentage of T-helper cells after peptide administration. Intestinal microflora decontamination of BALB/c-mice considerably reduced immune cell function and lymphatic tissue proliferation. Apparently, lack of peptide production or liberation correlated to immunosuppression. Substitution of peptides (from P. acnes or S. saprophyticus) to decontaminated mice reconstituted immune cell function and proliferation. Cortisone-resistant thymocytes were used as an experimental equivalent of functional cells in the thymus. Thus, cortisone treatment of BALB/c-mice significantly reduced the number of thymocytes, however, administration of microbial peptides restored the thymus population.     

Measuring health program effectiveness in the field: an assessment tool

To assist field workers in program evaluation and to explicitly discuss program strengths and weaknesses, a practical method to estimate the effectiveness of public health interventions within the existing program capacity was developed. The method and materials were tested in seven countries (Afghanistan, Zimbabwe, Tanzania, Uganda, Guatemala, the Philippines, and Ghana). In this method, four core components are assessed using a questionnaire: (1) the efficacy of the intervention; (2) the level of existing human resources (i.e., quality of recruitment, training, and continuing education); (3) the infrastructure (i.e., supplies, salary, transportation, and supervision); and (4) the level of community support (i.e., access and demand). Using the assessment tool provided, program staff can determine if all necessary elements are in place for a successful program that can deliver the specific intervention. Based on the results of the assessment program, weaknesses can be identified, explicitly discussed, and addressed. The usefulness of this tool in humanitarian relief may be twofold: (1) to assess the design and implementation of effective programs; and (2) to highlight the inevitable need for capacity building as the disaster situation evolves.     

A one-day method for the diagnosis of pulmonary tuberculosis in rural Ethiopia.

Smear diagnosis of pulmonary tuberculosis (PTB) requires three sputum examinations over 2 days. We evaluated the performance of two sputum specimens obtained on a single day (the second specimen submitted 1 h after the first) against the standard 2-day method in rural Ethiopia. A total of 243 suspects were enrolled; 52 had confirmed PTB: 49 (94%) were detected by the same-day method and 51 (98%) by the standard method (P > 0.5). The same-day approach would reduce the number of visits required for diagnosis, save resources for the health system and the patient, and ultimately improve case detection in poorer countries.     

Respiratory variations in pulse oximetry plethysmographic waveform amplitude to predict fluid responsiveness in the operating room

BACKGROUND: Respiratory variations in pulse oximetry plethysmographic waveform amplitude (DeltaPOP) are related to respiratory variations in pulse pressure (DeltaPP) and are sensitive to changes in preload. The authors hypothesized that DeltaPOP can predict fluid responsiveness in mechanically ventilated patients during general anesthesia. METHODS: Twenty-five patients referred for cardiac surgery were studied after induction of general anesthesia. Hemodynamic data (cardiac index, central venous pressure, pulmonary capillary wedge pressure, DeltaPP, and DeltaPOP) were recorded before and after volume expansion (500 ml hetastarch, 6%). Fluid responsiveness was defined as an increase in cardiac index of 15% or greater. RESULTS: Volume expansion induced changes in cardiac index (2.0+/-0.4 to 2.3+/-0.5 mmHg; P<0.05), DeltaPP (11+/-7 to 6+/-5%; P<0.05), and DeltaPOP (12+/-9 to 7+/-5%; P<0.05). DeltaPOP and DeltaPP were higher in responders than in nonresponders (17+/-8 vs. 6+/-4 and 14+/-7 vs. 6+/-4%, respectively; P<0.05 for both). A DeltaPOP greater than 13% before volume expansion allowed discrimination between responders and nonresponders with 80% sensitivity and 90% specificity. There was a significant relation between DeltaPOP before volume expansion and percent change in cardiac index after volume expansion (r=0.62; P<0.05). CONCLUSIONS: DeltaPOP can predict fluid responsiveness noninvasively in mechanically ventilated patients during general anesthesia. This index has potential clinical applications.     

Hypogonadal Men Nonresponders to the PDE5 Inhibitor Tadalafil Benefit from Normalization of Testosterone Levels with a 1% Hydroalcoholic Testosterone Gel in the Treatment of Erectile Dysfunction (TADTEST Study)

IntroductionAddition of testosterone (T) may improve the action of phosphodiesterase type 5 inhibitors (PDE5‐Is) in patients with erectile dysfunction not responding to PDE5‐Is with low or low‐normal T levels.AimsTo confirm this add‐on effect of T in men optimally treated with PDE5‐Is and to specify the baseline T levels at which such an effect becomes significant.MethodsA multicenter, multinational, double‐blind, placebo‐controlled study of 173 men, 45–80 years, nonresponders to treatment with different PDE5‐Is, with baseline total T levels ≤4 ng/mL or bioavailable T ≤ 1 ng/mL. Men were first treated with tadalafil 10 mg once a day (OAD) for 4 weeks; if not successful, they were randomized in a double‐blind, placebo‐controlled design to receive placebo or a 1% hydroalcoholic T gel (50 mg/5 g gel), to be increased to 10 mg T if results were clinically unsatisfactory.Main Outcomes MeasuresMean change from baseline in the Erectile Function Domain Score of the International Index of Erectile Function and rate of successful intercourses (Sexual Encounter Profile 3 question).ResultsErectile function progressively improved over a period of at least 12 weeks in both the placebo and T treatment groups. In the overall population with a mean baseline T level of 3.37 ± 1.48 ng/mL, no additional effect of T administration to men optimally treated with PDE5‐Is was encountered. The differences between the T and placebo groups were significant for both criteria only in the men with baseline T ≤3 ng/mL.ConclusionsThe maximal beneficial effects of OAD dosing with 10 mg tadalafil may occur only after as many as 12 weeks. Furthermore, addition of T to this PDE5‐I regimen is beneficial, but only in hypogonadal men with baseline T levels ≤3 ng/mL. Buvat J, Montorsi F, Maggi M, Porst H, Kaipia A, Colson MH, Cuzin B, Moncada I, Martin‐Morales A, Yassin A, Meuleman E, Eardley I, Dean JD, and Shabsigh R. Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1% hydroalcoholic testosterone gel in the treatment of erectile dysfunction (TADTEST study).     

A dose-response study of testosterone on sexual dysfunction and features of the metabolic syndrome using testosterone gel and parenteral testosterone undecanoate

The objective of this study was to observe the dose-response effects of testosterone (T) treatment on symptoms of sexual dysfunction and the metabolic syndrome. Two cohorts of elderly men with late-onset hypogonadism were followed over 9 months. Group 1, consisting of 28 men (mean age, 61 years; mean T level, 2.07 +/- 0.50 ng/mL), received long-acting T undecanoate (TU; 1000 mg); group 2, composed of 27 men (mean age, 60 years; mean T level, 2.24 +/- 0.41 ng/mL), received T gel (50 mg/day) for 9 months. In patients treated with T gel, plasma T levels rose from 2.24 +/- 0.41 to 2.95 +/- 0.52 (statistically significant) at 3 months, 3.49 +/- 0.89 (statistically significant) at 6 months, and 3.80 +/- 0.73 ng/mL at 9 months (T level at 6 months was compared with T level at 3 months). With TU, plasma T levels rose from 2.08 +/- 0.56 to 4.81 +/- 0.83 (statistically significant) at 3 months, 5.29 +/- 0.91 at 6 months, and 5.40 +/- 0.77 ng/mL at 9 months. With TU, the plasma T levels were statistically significantly higher than with T gel With TU, there was a greater improvement in sexual symptoms and in symptoms of the metabolic syndrome. With both treatments, changes in waist circumference correlated with changes in total, low-density, and high-density lipoprotein cholesterol. Parameters of safety were not different between the 2 treatments. T administration had a beneficial effect on sexual dysfunction and symptoms of the metabolic syndrome in elderly men. The higher plasma levels of T generated with TU than with T gel were clearly more effective, indicating that there is a T dose-effect relationship.     

Decline of plasma 5alpha-dihydrotestosterone (DHT) levels upon testosterone administration to elderly men with subnormal plasma testosterone and high DHT levels

The study was performed to measure the impact of testosterone (T) administration on circulating levels of 5alpha-dihydrotestosterone (DHT). Group 1 (32 men; mean age 61 years; mean T 6.9 +/- 1.9 nmol l(-1)) were treated for 15 months with long-acting T undecanoate. Group 2 (23 men, mean age 60 years, mean T 7.6 +/- 2.0 nmol l(-1)) were treated for 9 months with T gel. Plasma T and DHT were measured before and after 9 months T administration. In the men treated with T undecanoate plasma T and DHT were also measured after 12 and 15 months. Before T administration, plasma DHT ranged from 0.39 to 1.76 nmol l(-1) (0.30-1.90 nmol l(-1)). Mean DHT declined upon T administration from 0.95 +/- 0.50 to 0.55 +/- 0.30 nmol l(-1) (P < 0.05). With an arbitrary cut-off at 0.60 nmol l(-1), all 21 values of DHT > 0.60 nmol l(-1) had fallen from 1.29 +/- 0.50 to 0.70 +/- 0.60 nmol l(-1) (P < 0.01). Below this cut-off point 13 values rose and 21 fell upon T administration. Below this cut-off point values on average declined from 0.39 +/- 0.12 to 0.30 +/- 0.14 nmol l(-1) (P < 0.05). The study revealed that in a cohort of elderly men with subnormal plasma T levels plasma DHT levels declined upon T administration when they were in the higher range of normal (>0.6 nmol l(-1)), with a profound shift of DHT/T ratios presumed to be an indicator of a reduced 5alpha-reductase activity. Below plasma DHT levels of 0.6 nmol l(-1), responses of plasma DHT to T administration varied.     

Metabolic syndrome, testosterone deficiency and erectile dysfunction never come alone

Until a decade ago the ailments of elderly men, such as atherosclerosis, hypertension, diabetes mellitus, lower urinary tract symptoms and erectile dysfunction (ED), were regarded as distinct diagnostic/therapeutic entities but there is a growing awareness that these entities are not disparate and, to improve the health of the ageing male, require an integral approach. There is an inter-dependence between the metabolic syndrome, ED and patterns of testosterone in ageing men. The main features of the metabolic syndrome are abdominal obesity, insulin resistance, hypertension and dyslipidaemia, significant factors in the aetiology of erectile function. The metabolic syndrome is associated with lower-than-normal testosterone levels. A new concept of the role of testosterone in male physiology suggests that testosterone plays also a significant role in the development and maintenance of bone and muscle mass and is a determinant of glucose homeostasis and lipid metabolism. Testosterone is not only a factor in libido but exerts also essential effects on the anatomical and physiological substrate of penile erection. With these recent insights, the health problems of elderly men must be placed in a context that allows an integral approach. Treatment of testosterone deficiency is to become part and parcel of this approach.