An oral yohimbine/L-arginine combination (NMI 861) for the treatment of male erectile dysfunction: a pharmacokinetic, pharmacodynamic and interaction study with intravenous nitroglycerine in healthy male subjects.

AIMS: Interaction of phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction with organic nitrates could lead to severe hypotension. NMI 861 is a combination of 7.7 mg yohimbine tartrate and 6 g l-arginine glutamate. A similar oral combination, which contains the same amount of yohimbine and L-arginine, has been shown to improve erectile function in previous studies. METHODS: In two placebo-controlled, randomized, double-blind, two-way crossover design studies we aimed to assess first the pharmacokinetics and pharmacodynamics of a single oral dose of NMI 861 administered in 16 healthy male subjects, and then the pharmacodynamics of orally administered NMI 861 in combination with intravenous nitroglycerine (GTN) in 12 healthy male subjects. Systolic (SBP) and diastolic (DBP) blood pressures, pulse rate and adverse events were measured in each study. RESULTS: NMI 861 was well tolerated by all subjects with no significant adverse reactions reported. For L-arginine, mean C(max) +/- SEM (range) was 42 +/- 2.2 (28-63) microg ml(-1) and t(max) (range) was 0.88 (0.50-1.5) h. AUC and t(1/2) were not calculated for L-arginine because of the presence of endogenous concentrations and the contribution from food sources. For yohimbine, mean C(max) was 42 +/- 11 (2.8-128) ng ml(-1); t(max) was 0.57 (0.25-1.0) h; mean AUC(0,8 h) was 65 +/- 24 (5.4-332), ng ml(-1) h and t(1/2) was 1.0 +/- 0.34 (0.40-6.0) h. There was a small but significant difference in the mean change from baseline for SBP from 0 to 6 h after NMI 861 treatment compared with placebo (0.8 +/- 1.4 vs-4.1 +/- 2.1 mmHg, respectively; 95% CI 0.0, 9.8 mmHg (P = 0.047)). There was no significant difference in SBP between treatments for the studied periods 6-12 h and 12-24 h. There was no significant difference in DBP or pulse between NMI 861 and placebo treatments for the three studied time periods. In the study designed to investigate the interaction of organic nitrate with NMI 861, subjects were infused intravenously with increasing doses of GTN (15 min each dose) at 2.5, 5, 10, 20 and 40 microg min(-1) starting 40 min after a single oral dose of either NMI 861 or placebo. There was no significant difference in the hypotensive response induced by GTN between the NMI 861 and placebo treatments. The mean maximum changes from baseline during GTN infusion for subjects administered with either NMI 861 or placebo were a decrease of 16.9 +/- 3.4 vs 13.6 +/- 2.4 mmHg (mean difference between treatments -3.3 mmHg, 95% CI -12.7, 6.0 mmHg (P = 0.460)) for SBP, a decrease of 14.7 +/- 2.0 vs 14.0 +/- 2.0 mmHg for DBP (mean difference -0.7 mmHg, 95% CI -8.2, 6.8 mmHg (P = 0.835)), and an increase of 11.8 +/- 1.9 vs 14.1 +/- 2.4 beats min(-1) for pulse, respectively (mean difference -2.3 beats min(-1), 95% CI -9.3, 4.5 beats min(-1) (P = 0.464)). CONCLUSIONS: Acute oral administration of NMI 861 was found to be well tolerated and bioavailable in healthy male subjects and no significant hypotensive interaction with intravenous GTN was detected at the doses investigated.

Judging jury service: results of the North Carolina administrative office of the courts juror survey.

This study examined venirepersons' and jurors' levels of satisfaction with jury service. Surveys were distributed to all persons who reported for state court jury service during two one-week periods in each North Carolina county. Questions concerned satisfaction with various aspects of jury service, the effects of service, hardships experienced, details of and reactions to cases heard, and basic demographic information. Responses were obtained from 82 of the 100 counties and 4,654 venirepersons (of whom 1,478 served as jurors). Consistent with prior research on juror experiences, results generally revealed high levels of satisfaction and positive opinions about various aspects of jury service. Service did not influence opinions about the courts for most respondents, and those whose opinions changed tended to become more positive about jury service. Suggestions for future research emphasize giving higher priority to publishing unpublished research on jury experience, explaining the high satisfaction levels observed in samples of jurors, and examining the impact of trial reform on juror satisfaction levels.

Overt signs of toxicity to dogs and cats of dietary deoxynivalenol.

Studies were conducted to determine the dietary amounts of deoxynivalenol (DON; vomitoxin) in dog and cat food that are required to produce overt signs of toxicity (e.g., vomiting or reduced food intake). Wheat naturally contaminated with 37 mg of DON/kg was used to manufacture pet foods containing 0, 1, 2, 4, 6, 8, and 10 mg of DON/kg. Deoxynivalenol concentration in pet food following manufacture was unchanged, indicating that the toxin was stable during conventional extrusion processing. Dogs previously fed DON-contaminated food were able to preferentially select uncontaminated food. Dogs not previously exposed to DON-contaminated food consumed equal quantities of contaminated and uncontaminated food. There was no effect of 6 mg of DON/kg on dog food digestibility. Food intake of dogs was significantly reduced by DON concentrations greater than 4.5 +/- 1.7 mg/kg, and DON greater than 7.7 +/- 1.1 mg/kg reduced cat food intake. Vomiting by dogs and cats was commonly observed at the 8 and 10 mg DON levels.

Monosomy X as the sole cytogenetic abnormality in acute lymphoblastic leukemia: a report of two new patients.

Monosomy X as the sole acquired cytogenetic abnormality is usually found in myeloid hematological malignancies, especially those with myelodysplastic features. Only three cases of acute lymphoblastic leukemia (ALL) with this abnormality have been previously reported. We add two cases to this series and comment on the likelihood of a tumor suppressor gene being located on the X chromosome.

Hybridization between wapiti (Cervus elephus manitobensis) and sika deer (Cervus nippon): a comparison of two artificial insemination techniques.

The present study compared pregnancy rates of sika deer (Cervus nippon) hinds artificially inseminated with frozen-thawed wapiti (Cervus elephus manitobensis) semen by laparoscopic intrauterine or transvaginal/cervical artificial insemination (AI) techniques. Estrous cycles of 59 sika hinds were synchronized with one-half of a norgestomet ear implant. Fourteen days after implant insertion, norgestomet ear implants were removed and hinds received 50 IU of PG-600 intramuscularly, a combination of 50 IU PMSG and 25 IU hCG. Hinds were then randomly allotted for laparoscopic (n = 25) or transvaginal/cervical (n = 34) AI. AI of the hinds with frozen-thawed wapiti semen (40 x 10(6) spermatozoa) was time-fixed to occur at 55 hr for transvaginal/cervical AI and 65 hr for laparoscopic AI postnorgestomet implant removal. Semen deposition for hinds inseminated by transvaginal/cervical AI occurred as follows: vagina. 8.8% (3/34); os cervix, 67.6% (23/34); intracervical, 20.5% (7/34); and uterus, 2.9% (1/34). On day 42 post-AI, transrectal ultrasonography was performed to determine pregnancy rates. Pregnancy rates were not significantly different (P > 0.10) between laparoscopic (8/25, 32.0%) and transvaginal/cervical AI (9/34, 26.4%), with an overall conception rate of 28.8% (17/59). These results indicate that transvaginal/cervical AI techniques can be as effective as laparoscopic AI under some circumstances. Further refinement of the transvaginal/cervical AI technique to improve pregnancy rates might lead to more widespread use of this technique when laparoscopic AI is not possible.

Abuse characteristics among childhood sexual abuse survivors in therapy: a gender comparison.

OBJECTIVE: The goal of this investigation was to examine similarities and differences in childhood sexual abuse (CSA) characteristics between men and women survivors in outpatient psychotherapy utilizing a substantial sample size of men, while examining an extensive range of abuse characteristics. METHOD: Abuse characteristics of 48 men from an outpatient treatment program for adult survivors of CSA in a university-based community mental health center were compared with those of 257 women from the same program. Data on abuse history were collected at admission or as soon thereafter as possible using a structured clinical interview with established reliability. RESULTS: Women were significantly more likely to have been sexually abused by a family member. Men were significantly more likely to report having oral sex performed upon them. Otherwise, no significant gender differences not attributable to anatomical differences (e.g., vaginal vs. anal intercourse) were found. CONCLUSIONS: The findings suggest that very few differences exist in the nature and extent of CSA reported by men and women. Thus CSA perpetrated on boys appears largely comparable in nature and extent to that committed against girls.

Violence and verbal abuse against staff in accident and emergency departments: a survey of consultants in the UK and the Republic of Ireland.

OBJECTIVES: To determine the incidence of verbal abuse and physical violence in accident and emergency (A&E) departments and to discover the extent of provision of security measures and instructions for staff on how to deal with these problems. DESIGN: A postal questionnaire. SETTING: A&E departments in the UK and the Republic of Ireland. SUBJECTS: Two hundred and seventy three consultants named in charge of 310 departments. MAIN OUTCOME MEASURES: Frequency of physical violence and verbal abuse, injuries sustained, perceived precipitating factors, security measures instituted, and legal action taken. RESULTS: Two hundred and thirty three replies were received. Alcohol, waiting times, recreational drug usage, and patients' expectations were perceived as the chief causes. Patients were the chief perpetrators with nurses being the commonest victims. Staff sustained 10 fractures, 42 lacerations, and 505 soft tissue injuries. There were 298 arrests and 101 court appearances that resulted in 76 convictions. Panic buttons and video cameras were the most common security measures. CONCLUSIONS: Staff within A&E departments are regularly abused, both verbally and physically. Inner city departments appear to be most affected. Documentation is poor. Perpetrators are seldom convicted. There do appear to be actions which hospitals could undertake that might help to ameliorate these problems.

A pediatric case of pigeon breeder's disease in Nova Scotia.

Pigeon breeder's disease has been reported sporadically in the pediatric population since it was first described in children in 1967. Because of its infrequent occurrence in children, a high level of suspicion is often required before a diagnosis is made. A case of pigeon breeder's disease in a child in Nova Scotia, where the disease is virtually unseen or at least unrecognized, is described. The need for prompt recognition of the condition is paramount because its complications may be irreversible.

Community youth development: learning the new story.

Community youth development is a challenging approach to youth work that focuses on the incorporation of new values at the practice, management, and community levels. This article explores the implementation of a community youth development approach within the context of learning organization theory, and describes the experiences of three youth-focused agencies making the transition to a community youth development approach.

Raw and rendered animal by-products as ingredients in dog diets.

Approximately 25 to 40% of the DM in premium dog diets is animal by-product. However, limited information is available regarding the composition and digestibility of these by-products, especially small intestinal digestibility. The effects of raw and rendered animal by-products incorporated into dog diets on nutrient digestion at the ileum and in the total tract were studied in this experiment. Diets fed contained various animal by-products including a rendered beef meat and bone meal (RMBM); fresh beef (FB); poultry by-product meal (PBPM); fresh poultry (FP); a plant-based control protein source, defatted soy flour (DS); and an animal-based control protein source, dehydrated whole egg (WE). The diets were extruded and kibbled. By-products varied widely in concentrations of OM, CP, amino acids, and fat. Nutrient intakes were numerically higher for FB than for all other treatments. All nutrient intakes were higher (P < .03) for the FB treatment than for the RMBM treatment. Digestibilities of DM, OM, CP, fat, and GE at the ileum were higher (P < .06) when dogs were fed diets containing FP than when fed diets containing PBPM. Amino acids were highly digestible at the ileum; however, digestibilities of all amino acids except cystine were higher (P < .04) for the diets incorporating FP vs PBPM. Total tract digestion was different among treatments for DM (P < .02), OM (P < .01), and GE (P < .02), and diets containing animal by-products were similar in total tract digestibility, greater than the DS control, and lower than the WE control. Rendering of poultry, but not beef, seemed to have a slight negative influence on small intestinal, but not total tract, digestibility by dogs.

Violence against women in Belgrade, Serbia: SOS Hotline 1990-1993.

PIP: The findings of a study conducted on violence against women by the staff at the SOS Hotline for Women and Children Victims of Violence in Belgrade, Serbia, is reported in this paper. For each call reporting an incident of violence, a data form was completed with the details of the call. Findings revealed that almost all callers were victims of violence from family members or intimate partners (94%). Many reported incidents of physical, verbal, and emotional violence (70.0%), while only few reported sexual and economic violence. Furthermore, the frequency and duration of violence were very high. Callers were often forced to live with perpetrators because of the lack of available housing, which was worsened due to privatization, economic sanctions against Serbia, and the influx of refugees. Men involved in the wars in Croatia and Bosnia had increased their violent tendency against women at home, especially those cases of sons beating their mothers. Lastly, most refugees were housed in private homes, resulting in increased violence against women refugees and women hosts.^ieng

Artificial insemination, hybridization and pregnancy detection in sika deer (Cervus nippon ).

Artificial insemination (AI) was performed on sika hinds (Cervus nippon ) receiving various dosages of pregnant mare serum gonadotropin (PMSG; Year 1: 0, 50 and 100 IU; Year 2: 100 and 150 IU) and using semen collected from elk and 1 2 elk x 1 2 sika stags. The time from synchronization device removal (CIDR vs norgestomet) to estrus was determined through observations of mounting activity. Methods for pregnancy detection, serum progesterone (P4), estrone sulfate (E1S), pregnancy-specific protein B (PSPB) and ultrasonography, following AI (Year 1: AI, Days 28 and 48 after AI; Year 2: AI, Days 42, 53 and 100 after AI) and a 90-d natural breeding season were investigated. From available production data, body weights were compared among sika and 1 4 elk x 3 4 sika hybrids relative to age. Pregnancy rates tended (P < 0.10) to differ relative to PMSG treatment and sire; administration of 0 IU PMSG resulted in fewer hinds becoming pregnant to AI than 50 or 100 IU of PMSG. Hinds receiving 100 IU of PMSG had higher (P < 0.05) pregnancy rates than hinds receiving 150 IU PMSG. Time to standing estrus did not differ (P > 0.10) between the CIDR and norgestomet groups. Pregnancy rates 50 d after a 90-d breeding season were similar (P > 0.10) between ultrasound (70.9%) and PSPB (61.6%). Serum P4 after 90 d in breeding groups and 50 d after stag removal were higher (P < 0.05) for pregnant than open hinds. Pregnancy rates (Year 1) 48 d after AI were similar (P > 0.10) between ultrasound (49.0%) and PSPB (37.3%). Serum P4 28 and 48 d after AI were higher (P < 0.05) for pregnant than open hinds. Serum E1S was higher (P < 0.01) for pregnant than open hinds 48 d after AI. Pregnancy rates (Year 2) 100 d after AI did not differ (P > 0.10) between ultrasound and PSPB (66.7%). Serum P4 was higher (P < 0.03) in pregnant than open hinds at 42, 53 and 100 d after AI. At 100 d after AI, pregnant hinds had higher (P < 0.002) serum E1S than open hinds. At 6 to 8 and 11 to 13 mo of age, 1 4 elk x 3 4 sika males tended (P < 0.08) to be heavier than sika males, while 1 4 elk x 3 4 sika females were heavier (P < 0.05) than sika females at all ages. In summary, this study documents the use of AI and methods for pregnancy detection in sika hinds as well as preliminary information regarding the production of elk-x-sika hybrids.

Characteristics of childhood sexual abuse among female survivors in therapy.

Characteristics of the abuse experience by 135 women entering an outpatient treatment program for survivors of childhood sexual abuse were assessed utilizing a structured clinical interview. Areas assessed included: nature, frequency and duration of the abuse; participant's age at onset of abuse; perpetrator characteristics; childhood physical abuse experiences; and circumstances leading to abuse cessation. Participants who had been molested by more than one perpetrator were administered questions about the abuse committed by each perpetrator separately. Abuse by the first individual to molest a participant was found to be more likely to be incestuous, of higher frequency, and more extensive and invasive than that by later perpetrators. Survivors seeking therapy indicated experiencing considerably more severe abuse, at a younger age, for longer duration, and at the hands of more perpetrators than previously reported in the literature on nonclinical samples of survivors.

Classification of deletions and identification of cryptic translocations involving 7q by fluorescence in situ hybridization (FISH).

Monosomy 7 (-7) and deletion of the long arm of chromosome 7, del(7q), are frequent non-random findings in the myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), particularly associated with therapy-related disease (t-MDS and t-AML). The cytogenetic breakpoints of 7q deletions are variable, with both terminal and interstitial deletions reported. It is now believed that most deletions are interstitial, and that the variability in reported breakpoints may be due to the difficulty in determining whether the terminal, pale staining G band is present. It has also been suggested that some reported deletions of 7q may be cryptic translocations. To address these questions, we carried out fluorescence in situ hybridization (FISH) studies on leukaemic cells from a large series of patients using a chromosome 7-specific paint and a 7q telomere-specific probe. Of the 26 cases studied, seven were 'pure' deletions (ie without the involvement of other chromosomes); four were interstitial and two terminal. One further patient had two clones each with a different deletion: one with a terminal del(7)(q22) and the second with an interstitial del(7)(q32-qter). A further nine cases had unbalanced translocations with deletion of 7q terminal sequences. The remaining 10 cases were translocations and complex rearrangements, some involving interstitial deletions of 7q. In two cases in which del(7q) was reported as the sole cytogenetic abnormality by G-banding, FISH revealed cryptic translocations involving 7q.

The Effects of Age on the Pharmacokinetics and Pharmacodynamics of Cardiovascular Drugs: Application of Concentration-Effect Modeling. 1. Tolmesoxide.

The effects of age on the disposition and hemodynamic responses to the direct acting vasodilator tolmesoxide were examined in an integrated manner using a combined pharmacokinetic--pharmacodynamic (PKPD) modeling approach. Thirty subjects were studied to represent, as far as was possible, an age continuum. Single doses of tolmesoxide (100 mg) and placebo were administered intravenously and blood was withdrawn and heart rate and blood pressure were measured at frequent intervals up to 10 h post dose. No significant effects of age on the disposition of tolmesoxide and its sulfone metabolite were apparent. Tolmesoxide when compared with placebo produced significant changes in blood pressure and heart rate but PKPD modeling failed to demonstrate any significant effects of age on the blood pressure response to tolmesoxide.

The Effects of Age on the Pharmacokinetics and Pharmacodynamics of Cardiovascular Drugs: Application of Concentration-Effect Modeling. 2. Acebutolol.

The effects of age on the disposition and hemodynamic responses to the selective beta(1) adrenoceptor antagonist were examined in an integrated manner using a combined pharmacokinetic--pharmacodynamic (PKPD) modeling approach. Thirty subjects were studied to represent, as far as was possible an age continuum. Single doses of acebutolol (20 mg) and placebo were administered intravenously and blood was withdrawn and heart rate and blood pressure were measured at frequent intervals up to 10 h post dose. No significant effects of age on the disposition of acebutolol and its major acetylated metabolite were apparent. Acebutolol when compared with placebo produced significant changes in blood pressure and heart rate and application of PKPD modeling demonstrated a significant negative correlation between blood pressure responsiveness to acebutolol and age.

Effects of Age on the Pharmacokinetics and Pharmacodynamics of Cardiovascular Drugs: Application of Concentration-Effect Modeling. 3. Trimazosin.

The effects of age on the disposition and hemodynamic responses to the selective post-synaptic alpha(1) adrenoceptor antagonist trimazosin were examined in an integrated manner using a combined pharmacokinetic--pharmacodynamic (PKPD) modeling approach. Thirty subjects were studied to represent, as far as was possible an age continuum. Single doses of trimazosin (100 mg) and placebo were administered intravenously and blood was withdrawn and heart rate and blood pressure were measured at frequent intervals up to 10 h post dose. Based on regression analysis there was a statistically significant decline in the clearance of trimazosin with increasing age. In addition, based on the ratio of the AUC values for the major metabolite and parent drug, there was evidence of a decline in the relative clearance of matabolite with increasing age. Trimazosin when compared with placebo produced significant changes in blood pressure and heart rate that were statistically greater in elderly subjects. PKPD modeling revealed that both trimazosin and its metabolite 1-hydroxy trimazosin contributed significantly to the hemodynamic profile of the drug but the blood pressure responsiveness to both parent drug and metabolite were unaffected by age. Thus the greater response in the elderly subjects could be attributed to the decline in drug clearance with age.

Fatal bronchiolitis obliterans in a patient with juvenile rheumatoid arthritis receiving chrysotherapy.

Bronchiolitis obliterans has been described in adults with rheumatoid arthritis, particularly in association with D-penicillamine treatment, but to our knowledge has not been reported in juvenile rheumatoid arthritis (JRA). We describe a 12-year-old girl with JRA who developed bronchiolitis obliterans after a 6-month course of intramuscular gold. She presented with severe obstructive airway disease (FEV1, 17% predicted) unresponsive to bronchodilators, without obvious pathology on chest radiograph. Despite aggressive immunosuppressive therapy and eventual lung transplantation, she died 3 1/2 years after her initial diagnosis of JRA. Although rare, bronchiolitis obliterans must be considered in the differential diagnosis of respiratory distress in children with JRA.