Hormonal Contraception for Men

Between 1971 and 1977, a public-sector contraceptive development program organized 35 clinical studies to test whether progestins, alone or with androgens, could be used to develop a new contraceptive for men. This review presents the principal findings from these studies. The studies demonstrated that when high doses of progestins are administered to men. sperm production is suppressed to very low levels in the majority of cases. But full suppression of sperm production in all men could not be achieved even when high doses of progestins were administered alone or in combination with high doses of an androgen. All of the progestins tested were associated with weight gain and transient decreases in libido in some men. Some of the regimens tested caused additional side effects, including gynecomastia and impairment of liver function. It is concluded that none of the 25 regimens investigated to date is suited for further development as a male contraceptive. However, the finding that several of the regimens suppressed sperm production to very low levels – often to azoospermic levels – without producing substantial side effects is encouraging. Based on these findings, it is suggested that other combined regimens of more ***     

In vitro fertilization in Norfolk,Virginia, 1980–1983

Three years of progress of the Vital Initiation of Pregnancy (VIP) Program in Norfolk is reported. No conception resulted from 41 oocyte aspirations during spontaneous menstrual cycles in 1980. An average of 3.7 oocytes per cycle, or a 73.5% recovery rate, resulted in 362 human menopausal gonadotropin/human chorionic gonadotropin-induced cycles from January 1981 to March 1983. Forty pecent of the oocytes recovered from these cycles were preovulatory, 35% atretic, and 25% immature. Immature oocytes were often matured in vitro, fertilized, and found to produce pregnancies. A total of 62 pregnancies occurred, which represents a 17 or 23% pregnancy rate, based on laporoscopies or embryo transfers, respectively. There were 11 preclinical and 7 clinical miscarriages. Twenty-nine normal babies have been delivered, including a set of twins. The remainder appears to be normally progressing pregnancies. Polyspermia was observed in 8.8% of the fertilizable oocytes.     

Serum prolactin profiles of normal human conceptual cycles

Commencing on day 10 of the menstrual cycle through onset of subsequent menses, or confirmation of pregnancy, daily sera collected from 15 women planning pregnancy were analyzed by radioimmunoassays (RIA) for prolactin (hPRL), estradiol-17β and luteinizing hormone (hLH). Two of the observed subjects became pregnant in the single cycles studied. The profiles of these hormones during the early gestation following spontaneous ovulation were established. No distinct midcycle peaks of hPRL were observed in either subject. Enormous spikes were observed in daily prolactin values, with wide variations between subjects.     

Características clínicas y pronóstico de la neumonía adquirida en la comunidad causada por Staphylococcus aureus resistente a la meticilina

Introduction

The aim of this study is to describe the epidemiological and clinical features, treatment and prognosis of community-acquired pneumonia (CAP) caused by methicillin-resistant Staphylococcus aureus (MRSA) in two different geographic regions where community-acquired MRSA (CA-MRSA) infections have different frequencies.

Methods

Observational study of patients admitted to two hospitals (one in Argentina, the other in Spain) between March 2008 and June 2012.

Results

We documented 16 cases of CAP caused by MRSA. MRSA accounted for 15 of 547 (2.7%) cases of CAP in Hospital Rodolfo Rossi and 1 of 1258 (0,08%) cases at the Hospital Universitari de Bellvitge (P ≤ .001). Most patients were young and previously healthy. Multilobar infiltrates, cavitation and skin and soft tissue involvement were frequent. All patients had positive blood cultures. Five patients required admission to the intensive care unit. Early mortality (≤ 48 hours) was 19%, and overall mortality (≤ 30 days) was 25%.

Conclusion

CAP caused by MRSA causes high morbidity and mortality rates. It should be suspected in areas with a high prevalence of CA-MRSA infections, and especially in young and healthy patients who present with multilobar pneumonia with cavitation. Mortality is mainly related to septic shock and respiratory failure and occurs early in most cases.     

Regulation of Ca2+ release from mitochondria by the oxidation-reduction state of pyridine nucleotides

Mitochondria from normal rat liver and heart, and also Ehrlich tumor cells, respiring on succinate as energy source in the presence of rotenone (to prevent net electron flow to oxygen from the endogenous pyridine nucleotides), rapidly take up Ca(2+) and retain it so long as the pyridine nucleotides are kept in the reduced state. When acetoacetate is added to bring the pyridine nucleotides into a more oxidized state, Ca(2+) is released to the medium. A subsequent addition of a reductant of the pyridine nucleotides such as beta-hydroxybutyrate, glutamate, or isocitrate causes reuptake of the released Ca(2+). Successive cycles of Ca(2+) release and uptake can be induced by shifting the redox state of the pyridine nucleotides to more oxidized and more reduced states, respectively. Similar observations were made when succinate oxidation was replaced as energy source by ascorbate oxidation or by the hydrolysis of ATP. These and other observations form the basis of a hypothesis for feedback regulation of Ca(2+)-dependent substrate- or energy-mobilizing enzymatic reactions by the uptake or release of mitochondrial Ca(2+), mediated by the cytosolic phosphate potential and the ATP-dependent reduction of mitochondrial pyridine nucleotides by reversal of electron transport.     

Walking ability after stroke in patients from Argentina: predictive values of two tests in subjects with subacute hemiplegia

[Purpose] This study aimed to determine the predictive values of the trunk control test (TCT) and functional ambulation category (FAC) for independent walking up to 6 months post stroke. [Subjects] Twenty-seven subjects with hemiplegia secondary to a unilateral hemisphere stroke were included. [Methods] The protocol was started at 45 days post stroke, with the TCT and FAC as walking predictors. At 90, 120, and 180 days post stroke, the subjects’ independent walking ability was assessed by using the Wald test. [Results] The TCT was identified as an independent predictor of ambulation at 90, 120, and 180 days. Subjects who scored ≥ 49 in the initial test had 93.8% probability of achieving independent gait at 6 months. The FAC proved that 100% of the subjects who scored 2 at 45 days post stroke walked independently at 90 days, 100% of the subjects who scored 1 walked independently at 120 days, and only 33.3% of the subjects who scored 0 walked independently at 180 days. [Conclusion] The TCT and FAC can predict independent walking at 45 days post stroke. In subjects with FAC 0, the TCT should be used to predict patients who will be able to walk independently.Key words: Stroke, Predictors, Walking     

The angiotensin receptor type 1-Gq protein-phosphatidyl inositol phospholipase Cbeta-protein kinase C pathway is involved in activation of proximal tubule Na+-ATPase activity by angiotensin(1-7) in pig kidneys

In a previous study, we observed that angiotensin(1–7) (Ang(1–7)) stimulates proximal tubule Na⁺-ATPase activity through the angiotensin receptor type 1 (AT₁R). Here we aimed to study the signalling pathways involved. Our results show that the stimulatory effect of Ang(1–7) on Na⁺-ATPase activity through AT₁R involves a G_q protein–phosphatidyl inositol-phospholipase Cβ(PI-PLCβ) pathway because: (1) the effect was reversed by GDPβS, a non-hydrolysable GDP analogue, and by a monoclonal G_q protein antibody; (2) the effect was similar and not additive to that of GTPγS, a non-hydrolysable GTP analogue; (3) Ang(1–7) induced a rapid decrease (30 s) in phosphatidylinositol 4,5-bisphosphate levels, a PI-PLCβ substrate; and (4) U73122, a specific inhibitor of PI-PLCβ, abolished Ang(1–7)-induced stimulation of Na⁺-ATPase activity. Angiotensin(1–7) increased the protein kinase C (PKC) activity similarly to phorbol-12-myristate-13-acetate (PMA), an activator of PKC. This effect was reversed by losartan, a specific antagonist of AT₁R. The stimulatory effects of Ang(1–7) and PMA on Na⁺-ATPase activity are similar, non-additive and reversed by calphostin C, a specific inhibitor of PKC. A catalytic subunit of PKC (PKC-M) increased the Na⁺-ATPase activity. These data show that Ang(1–7) stimulates Na⁺-ATPase activity through the AT₁R–G_q protein–PI-PLCβ–PKC pathway. This effect is similar to that described for angiotensin II, showing for the first time that these compounds could have similar effects in the renal system.     

Real‐world comparative analysis of bleeding complications and health‐related quality of life in patients with haemophilia A and haemophilia B

Introduction

Clinical severity and impact of haemophilia on quality of life have been generally considered to be lower for haemophilia B (HB) compared with haemophilia A (HA) patients.

Aims

To compare annual bleeding rate (ABR), target joint development and health‐related quality of life (HRQoL) between adult (≥18 years) severe HA and HB patients using recent data from the Cost of Haemophilia in Europe: a Socioeconomic Survey (CHESS) study.

Methods

Multivariate generalized linear models (GLM) were constructed to assess the relationship between haemophilia type, ABR, HRQoL (derived from EQ‐5D index scores) and the presence of target joints while controlling for covariates.

Results

Of the 1225 patients included, 77% (n = 949) had HA and 23% (n = 278) had HB. Of the 514 patients who completed the EQ‐5D, 78% (n = 405) had HA, and 22% (n = 110) had HB. Unadjusted mean ABR was 3.79 in HA and 4.60 in HB. The presence of ≥1 target joint was reported in 59% and 54% of patients with HA and HB, respectively. Unadjusted mean EQ‐5D index score was 0.78 in HA and 0.76 in HB. Haemophilia type was not a significant predictor of ABR, target joints or HRQoL when adjusted for confounding factors such as BMI, age and replacement therapy regimen.

Conclusion

Data suggest comparable ABR, incidence of target joints and HRQoL between patients with HB and HA indicating comparable clinical severity and disease impact on patient quality of life.