Comparison between testosterone oenanthate-induced azoospermia and oligozoospermia in a male contraceptive study. IV. Suppression of endogenous testicular and adrenal androgens

Administration of supraphysiological doses of testosterone to normal men causes inhibition of spermatogenesis, but while most become azoospermic, 30-55% maintain a low rate of spermatogenesis. We have investigated whether there are differences in endogenous androgen production, of testicular and adrenal origin, which may be related to the degree of suppression of spermatogenesis. Thirty-three healthy Caucasian men were given weekly i.m. injections of 200 mg testosterone oenanthate (TE), 18 became azoospermic, while 15 remained oligozoospermic. Urinary excretion of epitestosterone, a specific testicular product, was reduced to <10% of pretreatment values, with no differences between the groups. Similar results were obtained for other markers of testicular steroidogenesis. Urinary and plasma adrenal androgens were also reduced during TE treatment: a statistically significant decrease in both (P < 0.001 and P < 0.05 respectively) was seen in the azoospermic but not oligozoospermic responders. These results suggest that testicular steroidogenesis is decreased to <10% by the administration of supraphysiological doses of exogenous testosterone. Differences in the degree of ongoing steroidogenesis in the testis do not appear to account for incomplete suppression of spermatogenesis, thus differences in androgen metabolism may underlie this heterogeneous response. A small but significant reduction in secretion of adrenal androgens was also detectable, the relevance of which is unclear.      

PAN-811 provides neuroprotection against glutamate toxicity by suppressing activation of JNK and p38 MAPK

In an earlier study, we demonstrated that PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, provides protection against glutamate, staurosporine, veratridine, or hypoxia/hypoglycemia toxicities in primary cortical neuronal cultures by upregulating Bcl-2 expression [R.-W. Chen, C. Yao, X.C. Lu, Z.-G. Jiang, R. Whipple, Z. Liao, H.A. Ghanbari, B. Almassian, F.C. Tortella, J.R. Dave. PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, elicits its function in primary neuronal cultures by upregulating Bcl-2 expression. Neuroscience 135 (2005) 191–201]. Both JNK (c-Jun N-terminal kinase) and p38 MAP (mitogen-activated protein) kinase activation have a direct inhibitory action on Bcl-2 by phosphorylation. In the present study, we continued to explore the mechanism of PAN-811 neuroprotection. Our results indicate that treatment of cultured cortical neurons with glutamate (100 μM) induces phosphorylation of both JNK and p38 MAPK. Specifically, pretreatment of neurons with 10 μM PAN-811 (an optimal neuroprotective concentration) for 1 h, 4 h, or 24 h significantly suppresses glutamate-mediated activation of both JNK and p38 MAPK. Furthermore, the p38 MAPK-specific inhibitor SB203580 and the JNK-specific inhibitor SP600125 prevented glutamate-induced neuronal death in these primary cultures. Our results demonstrate that glutamate-induced phosphorylation of JNK and p38 MAPK is suppressed by PAN-811, which might contribute to Bcl-2 upregulation and PAN-811 neuroprotection.     

Disabling job injuries among urban EMS providers

OBJECTIVE: Nationwide data were collected concerning serious, disabling injuries requiring hospitalization (SDIH) or deaths among urban emergency medical services (EMS) providers. DESIGN AND SETTING: A mail survey of EMS systems was conducted among the 200 most populated U.S. cities. PARTICIPANTS: Participants were training and operations officers of urban EMS systems. MEASUREMENTS AND MAIN RESULTS: Ninety forms (45%) were returned with 88 evaluable (44%). There were 81 SDIHs for a rate of one in 31,616 dispatches. No deaths were reported. Body parts most frequently injured were the hand (22%), head (19%), foot (16%), and eye (14%). Although 90% of fire-based EMS systems (fire-EMS) provided helmets, eye protection, safety shoes, and gloves, less than half (45%) of nonfire-EMS did so. Three (4%) SDIHs resulted from acts of violence. CONCLUSION: Occupational injuries of EMS personnel are at a serious level. Fire-based EMS systems experienced a higher rate of hand SDIHs despite the provision of protective equipment. Few nonfire-EMS staff are provided with safety equipment, which may have resulted in a relatively high number of head and hand SDIHs. Fire-EMS medical directors need to take an active role in verifying that protective equipment is adequate and appropriate to allow the performance of field EMS duties without being too cumbersome. Medical directors of nonfire-EMS must be advocates for the provision of basic protective equipment aimed at mitigating SDIHs of EMS staff.     

Out-of-hospital use of a pulse oximeter to determine systolic blood pressures

STUDY OBJECTIVE: Blood pressure (BP) in the out-of-hospital setting is one of the most important diagnostic tools used by emergency medical services (EMS) providers. Conventional methods of palpation and auscultation can be time consuming, and the measurements often are inaccurate because of the adverse working conditions encountered. Pulse oximetry waveform systolic blood pressure (POWSBP) measurement has been used successfully in emergency departments to monitor BP. The objective of this study was to compare the accuracy of field POWSBP measurements obtained by noninvasive electronic BP measurement (NIBPM), auscultation, and palpation in the out-of-hospital environment. DESIGN: Blood pressure measurements used for this study were obtained by POWSBP, NIBPM (PROPAQ model 102; Protocol Systems, Beaverton, Oregon USA), auscultation, and palpation on patients in moving ambulances. Measurement of POWSBP was accomplished by observing the return of the waveform on the pulse oximeter at the time of cuff deflation. The order in which the readings were obtained as well as the arm chosen for measurement were randomized. SETTING AND PARTICIPANTS: Paramedics and emergency medical technicians in an urban, inner-city emergency medical services (EMS) system. MEASUREMENTS AND MAIN RESULTS: Blood pressure measurements were sampled from 69 patients. Regression analysis identified significant correlation between POWSBP and the four methods utilized, with r = 0.92 for NIPBM, r = 0.95 for auscultation, and r = 0.97 for palpation, all significant at p < 0.0001. CONCLUSIONS: The use of POWSBP measurement is a fast, easy, and accurate technique with which to measure systolic BP in the field. It may have special importance for noisy environments and moving vehicles in which conventional methods of auscultation or palpation may be difficult.     

A comparison of pediatric and adult trauma patients transported by helicopter and ground EMS: managed-care considerations

INTRODUCTION: There is a paucity of data comparing injured pediatric patients transported by helicopter emergency medical services (HEMS) with patients transported by ground ambulance. The purpose of this study was to compare HEMS pediatric trauma patients to: 1) pediatric patients transported by ground to an urban level-1 trauma center (TC), and; 2) a similar cohort of adult patients. The managed-care consequences of these comparisons are highlighted. METHODS: All trauma patients flown directly from the scene by HEMS from January 1, 1990, to April 30, 1993, were compared to a cohort of trauma patients arriving by ground advanced life support (ALS). All patients were transported to the same level-1 TC. The data collected included the mechanism of injury and the prehospital procedures performed, the injury severity score (ISS), and outcome. RESULTS: There was no difference in the ISS between the HEMS (n = 216) and ground ALS (n = 355) pediatric patients (16.8 vs 17.1; p = 0.55). Adult HEMS patients (n = 202) had significantly higher ISS than did injured adults (n = 1652) transported by ground (18.0 vs 13.6; p < 0.0001). Overall, trauma patients transported by air directly from the scene have a higher ISS than patients transported by ground (17.5 vs 13.6; p < 0.001). CONCLUSIONS: Pediatric patients transported by HEMS were as severely injured as those transported by ground, in contrast to adult patients. We conjecture that since trauma triage schemes classically focus on adults, ground personnel are more selective about which patients are flown to a TC, and less selective for pediatric patients. Trauma centers and HEMS programs should develop pediatric trauma triage protocols that do not overemphasize physiologic parameters.     

d-ala2-methionine-enkephalinamide self-administration in the morphine-dependent rat

The self-administration of d-enkephalin was studied in the dependent rat self-administering morphine. The rats were prepared with chronic IV and bilateral intraventricular (IVT) injection cannulae. They were made physically dependent on morphine and trained to lever press for IV morphine self-injections (inj) (10 mg/kg) on a fixed ratio (20) (FR20) schedule of reinforcement. Substitution of d-enkephalin either IVT. (40 g/inj) or IV (10 mg/kg/inj) in the morphinedependent rat maintained consistent lever pressing and self-administration.behavior similar to morphine self-administration. No signs of abstinence were observed during the d-enkephalin substitution. However, saline substitution (0,05 ml/inj IV) for morphine in the self-administering rat produced an abstinence syndrome characterized by extinction of responding, wet-dog shakes, writhes, and diarrhea, which were reversed for 1 h by a single IVT injection of d-enkephalin (40 or 80 g). These results indicate that d-enkephalin will serve as a reinforcer to maintain opiate-seeking behavior and support physical dependence in the rat.     

Hemin enhances the in vitro growth of primitive erythroid progenitor cells

Since exogenous hemin has been shown to exert a variety of stimulatory effects on erythroid cells, including the augmentation of hemoglobin synthesis, we determined its effect on early stages of erythroid development by employing clonal cells assays. The addition of hemin at a concentration of 2 X 10(-4) M to cultures of normal murine marrow substantially increased the observed number of primitive BFU-E, which was in contrast to its lack of an effect on more mature erythroid colony-forming cells. This cell-specific enhancement of primitive BFU-E resulted in marrow frequencies equivalent to or exceeding those reported in the presence of "burst-promoting activity." In the presence of hemin, the number of BFU-E was also observed to be linearly related to the number of cells plated at very low plating densities, and the cell titration curve was observed to extrapolate to the origin. The evidence suggests that hemin may be a primary growth regulator of early developmental stages of erythroid progenitor cells.