Influence of hypothermic cardiopulmonary bypass on atrial natriuretic factor levels

Atrial natriuretic factor (ANF) is a peptide released from the heart in response to atrial distension. This peptide causes diuresis, vasodilatation, decreased blood pressure, and antagonizes the renin-aldosterone and antidiuretic hormone neuraxes. The influence of cardiopulmonary bypass and cardiac surgery on the circulation and release of ANF is unknown. Plasma ANF concentrations were therefore determined in patients undergoing coronary artery revascularization (CABG) and mitral valve replacement (MVR). Peptide levels were unchanged following anaesthetic induction. Plasma ANF concentrations decreased significantly during hypothermic (less than or equal to 28 degrees C) cardiopulmonary bypass in both patient groups. After 60 minutes of cardiac bypass, ANF declined from (mean +/- SEM) 512 +/- 132 to 20 +/- 6 pg.ml-1 (P less than 0.05) during MVR, and from 178 +/- 41 to 110 +/- 48 pg.ml-1 during CABG (P less than 0.05). Rewarming during bypass was associated with an increase in ANF concentration in both groups. Heparin anticoagulation and protamine reversal had no effect on immunoreactive ANF levels. In patients undergoing CABG, there was a linear relationship between plasma ANF concentration (pg.ml-1) and right atrial pressure (mmHg) prior to cardiopulmonary bypass (r = 0.86, P less than 0.005). However, one and three hours after cardiopulmonary bypass there was no significant relationship between right atrial pressure and ANF plasma levels. These results suggest that reduction in plasma ANF concentration occurs during hypothermic cardiopulmonary bypass. Furthermore, the proportional relationship between atrial distension and circulating ANF concentration was altered following cardiac surgery.     

The halo-Milwaukee brace. Case series of a revived technique

STUDY DESIGN: A case series in which the halo-Milwaukee brace was used for postoperative immobilization in children with complex congenital and developmental spinal deformities. OBJECTIVES: To describe the use of halo-Milwaukee orthosis in a pediatric population for stabilization of the cervical and upper thoracic spine. SUMMARY AND BACKGROUND DATA: Postoperative immobilization of the neck and upper thorax can be achieved with cervical orthoses, cervicothoracic lumbar orthosis, halo cast, Minerva jacket, or halo vest. In the young child or in individuals with severe deformities, prefabricated braces often do not provide adequate stability or predictable fit. The halo-Milwaukee brace has proven to be an effective and versatile technique in the management of complex pediatric spinal deformities. METHODS: Halo-Milwaukee brace immobilization was used in 12 patients after surgical stabilization of the upper thoracic or cervical spine. Technique and indications are discussed in this report. Surgical outcomes and complications were reviewed retrospectively in all cases. RESULTS: Application of the halo-Milwaukee brace was a clinically effective and safe means of controlling the upper thoracic and cervical spine. The orthosis was well tolerated and allowed access to the posterior incision. The brace is easily converted to a standard Milwaukee brace with neck ring. The pelvic segment of the brace is molded before surgery, and in most instances did not require postoperative modification. CONCLUSION: The halo-Milwaukee brace is a simple and convenient method of intraoperative and postoperative immobilization. The technique is applicable in patients who cannot be treated with more conventional off-the-shelf orthoses. The brace was well tolerated and allowed for early patient mobilization.     

Use of a continuous alfentanil infusion for extracorporeal shock wave lithotripsy in the treatment of renal calculi

Extracorporeal shock wave lithotripsy (ESWL) is the most widely used treatment for renal calculi. Newer second generation lithotripters are being produced, which are considered to be less painful than their prototypes. Thus, the trend in anesthesia for ESWL is away from general endotracheal and regional anesthesia and toward less involved and more easily monitored techniques such as intravenous analgesia (IVA). This report relates our experience with a continuous alfentanil infusion for ESWL treatment of renal calculi with a nonimmersion second generation Dornier HM-4 lithotripter model. Thirty-five patients treated pre-operatively with droperidol and midazolam, followed by a continuous infusion of alfentanil, reported excellent pain relief via a numerical pain score and manifested little, if any, hypertension or tachycardia. Stone fragmentation, fluoroscopy, and recovery time did not differ between patients receiving IVA or general anesthesia. Potential disadvantages of IVA include elevation of transcutaneous CO 2, bradycardia in 14 patients requiring the use of atropine, slightly longer ESWL time, increased number of shocks needed for fragmentation, and a small failure rate, with 11% of patients requiring general anesthesia. With proper patient selection and respiratory monitoring, IVA is highly recommended for ESWL in the treatment of renal calculi.     

The male contraceptive regimen of testosterone and levonorgestrel significantly increases lean mass in healthy young men in 4 weeks,but attenuates a decrease in fat mass induced by testosterone alone

In hypogonadal men, testosterone (T) in replacement dosages is known to increase fat-free mass (lean mass) and decrease fat mass. In young eugonadal men, similar dosages of T increase lean mass, but much higher dosages of T are required to decrease total body fat mass. Current T-based male hormonal contraceptive regimens include a second agent, such as a progestin, to maximize inhibition of pituitary gonadotropins and improve efficacy. To study the effect of such combinations on body composition, we randomized healthy, young, eugonadal men into four combinations of exogenous T and the progestin, levonorgestrel (LNG): 1) 100 mg T enanthate, im, weekly plus 125 micro g LNG, orally, daily (T+LNG); 2) T plus placebo LNG (T alone); 3) placebo T plus LNG (LNG alone); and 4) placebo T plus placebo LNG (placebo). We then analyzed body composition by dual energy x-ray absorptiometry after 4 and 8 wk of treatment. T+LNG significantly increased total lean mass after 4 and 8 wk of treatment (3.5 +/- 0.9% and 4.2 +/- 1.2%, respectively; P < 0.05) and truncal lean mass after 4 and 8 wk of treatment (4.7 +/- 0.9% and 5.0 +/- 0.9%, respectively; P < 0.05) compared with baseline and placebo. T alone also increased total and truncal lean mass significantly compared with placebo after 4 wk of treatment, but not compared with baseline (3.3 +/- 1.4% and 3.2 +/- 2.3%, respectively; P < 0.05 vs. placebo), suggesting an additive effect of T and LNG to increase lean mass. Fat mass significantly decreased in the abdomen in men administered T alone compared with LNG alone (-4.9 +/- 2.8%; P < 0.05). Fat mass significantly increased in the abdomen with LNG alone (4.1 +/- 1.0%; P < 0.05) compared with baseline and was unchanged with the combination of T+LNG, suggesting that LNG attenuates the decrease in fat mass seen with T alone. There was no change in weight or body mass index in any group during the study. This study shows that in young eugonadal men 1) T alone rapidly increases lean mass and decreases fat mass in 4-8 wk; 2) T+LNG rapidly increases lean mass, but has no effect on fat mass; and 3) LNG alone increases fat mass. The favorable profile on body composition by T is, therefore, partially attenuated by the progestin, LNG. These findings suggest that androgen-based male hormonal contraceptives might have favorable effects on body composition. The impact of these changes on cardiovascular risk in normal men needs further study.     

Advances in male contraception

Despite significant advances in contraceptive options for women over the last 50 yr, world population continues to grow rapidly. Scientists and activists alike point to the devastating environmental impacts that population pressures have caused, including global warming from the developed world and hunger and disease in less developed areas. Moreover, almost half of all pregnancies are still unwanted or unplanned. Clearly, there is a need for expanded, reversible, contraceptive options. Multicultural surveys demonstrate the willingness of men to participate in contraception and their female partners to trust them to do so. Notwithstanding their paucity of options, male methods including vasectomy and condoms account for almost one third of contraceptive use in the United States and other countries. Recent international clinical research efforts have demonstrated high efficacy rates (90-95%) for hormonally based male contraceptives. Current barriers to expanded use include limited delivery methods and perceived regulatory obstacles, which stymie introduction to the marketplace. However, advances in oral and injectable androgen delivery are cause for optimism that these hurdles may be overcome. Nonhormonal methods, such as compounds that target sperm motility, are attractive in their theoretical promise of specificity for the reproductive tract. Gene and protein array technologies continue to identify potential targets for this approach. Such nonhormonal agents will likely reach clinical trials in the near future. Great strides have been made in understanding male reproductive physiology; the combined efforts of scientists, clinicians, industry and governmental funding agencies could make an effective, reversible, male contraceptive an option for family planning over the next decade.     

Acute testosterone deprivation reduces insulin sensitivity in men

Objective In men with prostate cancer, androgen deprivation reduces insulin sensitivity; however, the relative roles played by testosterone and estradiol are unknown. To investigate the respective effects of these hormones on insulin sensitivity in men, we employed a model of experimental hypogonadism with or without hormone replacement. Design Placebo‐controlled, randomized trial. Participants Twenty‐two healthy male volunteers, 18–55 years old. Methods Following screening, subjects received the gonadotrophin‐releasing hormone antagonist acyline plus one of the following for 28 days: Group 1, placebo transdermal gel and placebo pills; Group 2, transdermal testosterone gel 10 g/day plus placebo pills; Group 3, transdermal testosterone gel 10 g/day plus the aromatase inhibitor anastrozole 1 mg/day to normalize testosterone while selectively reducing serum estradiol. Fasting insulin, glucose, adipokines and hormones were measured bi‐weekly. Results With acyline administration, serum testosterone was reduced by >90% in all subjects in Group 1. In these men, mean fasting insulin concentrations were significantly increased compared with baseline (P = 0·02) at 28 days, despite stable body weight and no changes in fasting glucose concentrations. Decreased insulin sensitivity was also apparent in the insulin sensitivity indices homeostasis model of insulin resistance (P = 0·03) and quantitative insulin sensitivity check index (P = 0·04). In contrast, in Groups 2 and 3, testosterone concentrations remained in the physiologic range, despite significant reduction in mean estradiol in Group 3. In these groups, no significant changes in insulin sensitivity were observed. Conclusions Acute testosterone withdrawal reduces insulin sensitivity in men independent of changes in body weight, whereas estradiol withdrawal has no effect. Testosterone appears to maintain insulin sensitivity in normal men.     

Cognitive effects of short-term manipulation of serum sex steroids in healthy young men

We examined the effects of sex steroids on cognitive functioning by exogenously manipulating circulating T levels in a group of healthy young men. Thirty-two men were randomized to receive 8 wk of treatment including: 1) im T enanthate 100 mg/wk plus daily oral placebo (T); 2) im placebo/wk plus 125 microg daily oral levonorgestrel (LNG); 3) im T enanthate 100 mg/wk plus 125 microg daily oral LNG (T + LNG); 4) im placebo/wk plus daily oral placebo. Cognitive functions were assessed at baseline and twice during treatment. Serum T and E2 levels were significantly increased in the T and T + LNG groups compared with baseline (P < 0.01) and T levels were significantly decreased in the LNG group (P < 0.05). Verbal memory significantly decreased in the LNG group (P < 0.01) and was maintained by coadministration of T in the T + LNG group. Divided attention was unaffected in the LNG group but improved significantly in the T + LNG group. In summary, decreased serum T levels induced by LNG or direct effects of the progestin, LNG, adversely affects verbal memory in normal young men. These results suggest that short-term changes in sex steroid levels have effects on cognitive function in healthy young men.     

Male Hormonal Contraceptives

Because of the shortcomings of currently available methods of male contraception, efforts have been made to develop additional forms of contraception for men. The most promising approach to male contraceptive development involves hormones, and requires the administration of exogenous testosterone. When administered to a healthy man, testosterone functions as a contraceptive by suppressing the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary, thereby depriving the testes of the signals required for normal spermatogenesis. After 2-3 months of treatment, low levels of pituitary gonadotropins lead to markedly decreased sperm counts and effective contraception in the majority of men. Treatment with exogenous testosterone has proven not to be associated with serious adverse effects and is well tolerated by men. In addition, sperm counts uniformly normalize when testosterone is discontinued. Thus, male hormonal contraception is safe, effective, and reversible; however, spermatogenesis is not suppressed to zero in all men, meaning that some diminished potential for fertility persists. Because of this, recent studies have combined testosterone with progestogens and/or gonadotropin-releasing hormone antagonists to further suppress pituitary gonadotropins and optimize contraceptive efficacy. Current combinations of testosterone and progestogens completely suppress spermatogenesis in 80-90% of men without severe adverse effects, with significant suppression in the remainder of individuals. Recent trials with newer, long-acting forms of injectable testosterone, which can be administered every 8 weeks, combined with progestogens, administered either orally or by long-acting implant, have yielded promising results and may soon result in the marketing of a safe, reversible, and effective hormonal contraceptive for men.