Increased sexual desire with exogenous testosterone administration in men with obstructive sleep apnea: a randomized placebo-controlled study.

Testosterone (T) deficiency, sexual dysfunction, obesity and obstructive sleep apnea (OSA) are common and often coexist. T prescriptions have increased worldwide during the last decade, including to those with undiagnosed or untreated OSA. The effect of T administration on sexual function, neurocognitive performance and quality of life in these men is poorly defined. The aim of this study was to examine the impact of T administration on sexual function, quality of life and neurocognitive performance in obese men with OSA. We also secondarily examined whether baseline T might modify the effects of T treatment by dichotomizing on baseline T levels pre-specified at 8, 11 and 13 nmol/L. This was a randomized placebo-controlled study in which 67 obese men with OSA (mean age 49 ± 1.3 years) were randomized to receive intramuscular injections of either 1000 mg T undecanoate or placebo at baseline, week 6 and week 12. All participants were concurrently enrolled in a weight loss program. General and sleep-related quality of life, neurocognitive performance and subjective sexual function were assessed before and 6, 12 and 18 weeks after therapy. T compared to placebo increased sexual desire (p = 0.004) in all men, irrespective of baseline T levels. There were no differences in erectile function, frequency of sexual attempts, orgasmic ability, general or sleep-related quality of life or neurocognitive function (all p = NS). In those with baseline T levels below 8 nmol/L, T increased vitality (p = 0.004), and reduced reports of feeling down (p = 0.002) and nervousness (p = 0.03). Our findings show that 18 weeks of T therapy increased sexual desire in obese men with OSA independently of baseline T levels whereas improvements in quality of life were evident only in those with T levels below 8 nmol/L. These small improvements would need to be balanced against potentially more serious adverse effects of T therapy on breathing.

Recombinant human erythropoietin as an adjunct to radiation therapy and cisplatin for stage IIB-IVA carcinoma of the cervix: a Southwest Oncology Group study.

OBJECTIVE: The survival of cervix cancer patients is associated with their hemoglobin (Hgb) level during radiotherapy. The Southwest Oncology Group (SWOG) conducted a phase II trial to determine whether recombinant human erythropoietin (rHuEPO) safely corrects anemia during chemoradiotherapy for cervix cancer. METHODS: Patients had stage IIB-IVA cervix cancer and a Hgb between 8.0 and 12.5 g/dl. All patients received rHuEPO thrice weekly and oral iron starting 10-15 days before their 5-week course of whole pelvic irradiation and weekly cisplatin followed by intracavitary brachytherapy. RESULTS: Fifty-three patients from 26 institutions received the protocol treatment. The mean Hgb was 10.4 +/- 1.3 g/dl on the first day of rHuEPO administration (baseline), 11.0 +/- 1.6 g/dl on the first day of chemoradiotherapy, 11.6 +/- 1.9 g/dl at the midpoint of chemoradiotherapy, and 11.8 +/- 2.2 g/dl at the end of chemoradiotherapy. The target Hgb level of 12.5 g/dl was achieved in 40% of patients (95% CI 26-56%) by the midpoint of Chemoradiotheraphy. Change in Hgb was associated with baseline serum iron (P = 0.008) and transferrin saturation (P = 0.05) levels, but not with baseline Hgb or serum ferritin, or patient age. Seven patients developed deep vein thrombosis. Two-year progression-free survival (PFS) was 43% and overall survival (OS) was 51%. Survival was significantly associated with Hgb level at the end of chemoradiotherapy, but not with the baseline Hgb level. CONCLUSIONS: rHuEPO and iron gradually increased Hgb levels in anemic women with local advanced cervix cancer during chemoradiotherapy. There was a higher than expected incidence of deep vein thrombosis. The progression-free and overall survival rates were lower than reported for women with normal Hgb levels.

Long-term outcomes of elective human sperm cryostorage.

BACKGROUND: Sperm cryopreservation allows men with threatened fertility to preserve their progenitive potential, but there is little data on long-term outcomes of elective sperm cryostorage programmes. METHODS AND RESULTS: Over 22 years, 930 men sought semen cryostorage in a single academic hospital, of which 833 (90%) had spermatozoa cryostored. Among 692 (74%) men surviving their illness, sperm samples were discarded for 193 (21% of all applicants, 28% of survivors) and cryostored spermatozoa were used for 64 men (7% of all applicants, 9% of survivors) in 85 treatment cycles commencing at a median of 36 months post-storage (range 12-180 months) with nearly 90% of usage started within 10 years of storage and none after 15 years. Pregnancy was most efficiently produced by intracytoplasmic sperm injection (median three cycles) compared with conventional IVF (median eight cycles) or artificial insemination (median more than six cycles; P < 0.05). A total of 141 (15%) of men had died and of these, 120 (85% of those dying) had their spermatozoa discarded; requests to prolong cryostorage were received from relatives of 21 men (2% of all applicants, 15% of deceased) of which three cases had spermatozoa transferred for use with no pregnancies reported. Sperm concentration was lower for all cryostorage groups compared with healthy sperm donor controls (P < 0.05). Following orchidectomy, men with testicular cancer had sperm density approximately half that of all other groups of men seeking cryostorage (P < 0.05), the lowering attributable to removal of one testis rather than in defects in spermatogenesis. CONCLUSION: Elective sperm cryopreservation is an effective, if sparsely used, form of fertility insurance for men whose fertility is threatened by medical treatment and is an essential part of any comprehensive cancer care programme.

Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix.

PURPOSE: To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma. PATIENTS AND METHODS: Patients with clinical stage IA(2), IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m(2) and a 96-hour infusion of fluorouracil 1,000 mg/m(2)/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT. RESULTS: Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 (P =.003) and 1.96 (P =. 007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group. CONCLUSION: The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix.

A phase II evaluation of all-trans-retinoic acid plus interferon alfa-2a in stage IV melanoma: a Southwest Oncology Group study.

BACKGROUND: Interferon alfa has modest but definite activity in the treatment of metastatic melanoma and is the only agent currently available for adjuvant therapy of high-risk resected disease. A variety of retinoic acid derivatives have been shown to be synergistic with interferon alfa in vitro and in vivo, with nonoverlapping toxicities. If promising combinations of interferon alfa and retinoids could be developed for melanoma patients, they would have clinical relevance for the treatment of advanced as well as localized disease. PURPOSE: To determine the efficacy and toxicity of a combination of interferon alfa-2a and all-trans-retinoic acid in patients with measurable metastatic melanoma, the South-west Oncology Group conducted a phase II clinical trial. PATIENTS AND METHODS: Fifty-seven patients with measurable metastatic melanoma (American Joint Committee on Cancer stage IV) were entered; five patients were unevaluable. Treatment consisted of oral all-trans-retinoic acid (37.5 to 75 mg/m2 orally twice daily for 21 days followed by 7 days' rest) plus subcutaneously administered interferon alfa-2a (6 MU/m2 three times a week). RESULTS: Two complete and three partial responses were observed among 52 evaluable patients, for an objective response rate of 10% (95% confidence interval 3% to 21%). Responses were seen only in patients with pulmonary, nodal, or subcutaneous metastases, and lasted from 4 to 23+ months. Median survival for the 52 patients was 8 months. Side effects were tolerable but significant, with one case of grade IV anemia and 92% of patients experiencing at least grade II toxicity. Flu-like symptoms were the most commonly reported side effects. There was one case of grade III hyperlipidemia. CONCLUSION: The combination of recombinant human interferon alfa-2a with all-trans-retinoic acid did not result in a greater percentage of objective responses or a longer overall survival than that associated with interferon alfa alone. This combination cannot be recommended for further evaluation in melanoma in either the advanced disease or the adjuvant settings.

The effectiveness of weekly iron supplementation regimen in improving the iron status of Chinese children and pregnant women.

It is evident that intermittent iron supplementation is better than daily supplementation in two aspects: iron absorption is more efficient and has insignificant side effects in contrast to the daily dose. The significantly higher daily iron loss observed in the daily iron supplemented groups rats also suggests alterations in total body iron metabolism. Based on serum ferritin distribution patterns, intermittent iron supplementation avoids temporary iron overload with daily iron supplemented. We conclude that weekly iron supplementation scheme is safer and easier to administer. This feasible strategy for the control of iron deficient anemia in pregnant women and children would be an effective iron-supplementation program (Baily et al., 1993).

PIP: Most governmental programs to control widespread iron deficiency in the developing world involve providing daily supplements of iron to all children and pregnant women. This approach has generally poor results due in part to dose-related undesirable gastrointestinal side effects and the lack of effective absorption and retention of iron consumed on a daily basis. However, recent evidence indicates that iron is absorbed significantly better when consumed only at intervals coinciding with gut mucosal renewals. That approach also prevents constant high iron concentrations in the gut which may cause undesirable side effects. Much lower iron doses administered intermittently are as effective in correcting iron nutrition and safer than daily doses in iron deficient anemic rats. 246 healthy 3-6 year olds and 405 pregnant women were enrolled in two studies to determine whether intermittent iron supplementation in humans is more efficient than daily iron administration. Weekly iron supplementation proved to be better than daily supplementation, producing more efficient iron absorption with fewer side effects. Serum ferritin distribution patterns indicate that intermittent iron supplementation avoids the iron overload which results from daily iron supplemented.

Debridement of porcine burns with a highly purified, ananain-based cysteine protease preparation.

A novel enzymatic debriding agent was evaluated on experimental full-thickness porcine contact burns. This agent consists of a highly purified, ananain-based, cysteine protease preparation formulated in a hydrophilic cream vehicle. Debridement of full-thickness burns was found to be dependent on several factors including the concentration of enzyme in the vehicle, the duration of treatment, and the hydration status of the burn wound before treatment. With an optimized debridement regimen, burns were consistently debrided of all gelatinized tissue with two 5-hour treatments. Histologic evaluation of the debrided wounds revealed an acellular deeper dermis that was debrided of necrotic cellular debris; however, the collagen matrix of the deeper dermis remained intact. This observation was consistent with a demonstrated in vitro specificity of the ananain-based protease for gelatin over collagen. A direct comparison of debridement efficacy with sutilains ointment, showed the ananain-based, debriding enzyme preparation to provide more rapid debridement of gelatinized tissue. Enzymatically debrided wounds exhibited graft take only after surgical excision of approximately 1 mm of the remaining acellular, avascular dermis. This highly purified enzyme preparation offers the potential for rapid nonsurgical debridement of gelatinized burn tissue, but required additional surgical debridement for graft take in this porcine model.

Randomized trial of vitamin A versus observation as adjuvant therapy in high-risk primary malignant melanoma: a Southwest Oncology Group study.

PURPOSE: A national cooperative group trial was conducted in patients with early-stage cutaneous malignant melanoma to determine if oral vitamin A can increase disease-free survival or survival. PATIENTS AND METHODS: Two hundred forty-eight patients with completely resected melanoma of Breslow's thickness greater than 0.75 mm and clinically negative lymph nodes were randomized to oral vitamin A (100,000 IU/d) for 18 months or to observation. Patients were stratified by Breslow's thickness of primary lesion (0.76 to 1.50 mm, 1.51 to 3.00 mm, or > 3.00 mm), sex, and type of therapy (excision, excision plus node dissection, excision plus perfusion, or excision plus both). The median duration of follow-up observation of living patients is greater than 8 years. The relative risk (RR) in disease-free survival and overall survival in the treatment compared with the observation group was calculated using Cox proportional hazards models. RESULTS: Overall, there was no difference in disease-free survival or overall survival between the two groups. Examination of treatment by stratification interactions and subset analysis did not show any treatment-effect differences based on sex or type of therapy. There was also no difference between groups in disease-free survival based on Breslow's thickness of the primary lesion. Overall, 12% of patients who received vitamin A experienced grade 3 or 4 toxicities. CONCLUSION: Based on the lack of overall survival benefit, further evaluation of vitamin A as adjuvant therapy for melanoma does not appear warranted.

Prenatal administration of methadone in the rat: acoustic startle amplitude and the rest-activity cycle at 30 days of age.

Two doses of methadone were administered by osmotic minipump from Day 8 of gestation through parturition, a dosing technique previously shown to produce physical dependence in the dams. A pair-fed control group received sterile water via minipump and was allowed to eat and drink only the amount consumed by the high-dose group on the same gestation days. A nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. The effects of methadone on maternal and offspring toxicity replicated our previous findings. At 29-31 days of age each treated and control animal was tested either for changes in acoustic startle amplitude or the rest-activity cycle. Methadone treated offspring were no different from the controls on either measure. These findings support the hypothesis derived from our earlier research that prenatal exposure to methadone produces a prolonged but transitory opioid abstinence. This is evidenced by increased startle amplitude and a disturbed rest-activity cycle that peaks at approximately 3 weeks of age. We demonstrate that these effects are no longer evident at 4 weeks of age. Together, these findings define a state of hyperexcitability in the young rat that resolves by 1 month of age. This transitory state parallels clinical descriptions of human infants undergoing opiate abstinence.