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.

Trimazosin in normotensive subjects.

Oral and intravenous trimazosin, a quinazoline derivative, resulted in a significant reduction in blood pressure of normal subjects, particularly when the subjects rose from a supine position to standing. This hypotensive effect was maximal between 4 and 6 hr after dosing and was accompanied by a significant increase in heart rate. The responses to intravenous infusions of phenylephrine indicated that trimazosin had significant, selective, peripheral alpha 1-antagonist properties. Kinetic analysis showed oral bioavailability of 63%, a clearance rate of 66 ml/min, and a terminal elimination t1/2 of approximately 3 hr. The correlation between drug levels and hypotensive effect was significantly improved by inclusion of the concentrations of trimazosin's major metabolite, 1-hydroxy-trimazosin (CP 23445), particularly for the period of maximum effect. Our data show that acute administration of trimazosin is associated with a fall in blood pressure, an increase in heart rate, and a significant degree of alpha 1-antagonism and that the overall hypotensive effect may in part be mediated by an active metabolite. It seems 1-hydroxy-trimazosin is a likely candidate for this role, but it is not clear whether this metabolite also has significant alpha-adrenoceptor antagonist properties.

Controlled trial of a home and ambulatory program for asthmatic children.

Care of asthmatic children is often episodic and more therapeutic than preventive. A 2-year randomized, controlled trial involving 95 children measured the impact of a comprehensive home and ambulatory program for pediatric asthma management using objective outcome measures. Interventions for the study group during the first year included 3-month clinic visits, education, and home visits by a specially trained research nurse. Control subjects continued to receive regular care from a family physician or pediatrician. Eight-nine subjects (93%) completed the study. Study subjects had less school absenteeism than control subjects (10.7 vs. 16.0 days, P = .04) and showed significantly better small airway function after 1 year. Asthma severity improved in 13 study subjects and worsened in 5. The reverse was true for control subjects. Study subjects exhibited better metered aerosol technique than control subjects (P = .0005). Fewer days were spent in hospital by the study subjects admitted compared with control subjects (3.67 vs 11.2 days, P = .02). After 1 year, more study than control families (72.1% vs 33.1%, P = .006) reported that their asthmatic child took responsibility for the asthma management. The intervention failed to reduce exposure to secondhand smoke or to household pets. There were no significant differences in medical visits, theophylline levels, or records of asthma symptoms. One year after discontinuing the intervention, a marked "washout" effect was observed. Comprehensive ambulatory programs of childhood asthma management can improve objective measures of illness severity but must be sustained.

Effect of compression pressure on forced expiratory flow in infants.

The effect of the force of compression on expiratory flow was evaluated in 19 infants (2-13 mo of age) with respiratory illnesses of varying severity. An inflatable cuff was used to compress the chest and abdomen. Expiratory flow and volume, airway occlusion pressure, cuff pressure (Pc), and functional residual capacity were measured. Transmission of pressure from cuff to pleural space was assessed by a noninvasive occlusion technique. Close correlations (P less than 0.001) were found between Pc and the change in pleural pressure with cuff inflation (delta Ppl,c). Pressure transmission was found to vary between two cuffs of different design and between infants. Several forced expirations were then performed on each infant at various levels of delta Ppl,c. Infants with low maximal expiratory flows at low lung volumes required relatively gentle compression to achieve flow limitation and showed decreased flow for firmer compressions. Flow-volume curves in each infant tended to become more concave as delta Ppl,c increased. These findings underline the importance of knowledge of delta Ppl,c in interpreting expiratory flow-volume curves in infants.

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.

The role of piperacillin therapy in pulmonary exacerbations of cystic fibrosis: a controlled study.

Piperacillin was evaluated as an antipseudomonas antibiotic in a double-blind controlled trial involving 18 pulmonary exacerbations of cystic fibrosis. Standard antibiotic treatment (flucloxacillin plus tobramycin) was compared with standard treatment plus intravenous piperacillin administered according to two regimens. No added benefit from piperacillin was demonstrable on the basis of improvement in symptoms, physical signs, weight gain, pulmonary function tests, radiologic signs, or sputum Pseudomonas bacterial counts. Some patients experienced sensitivity reactions to piperacillin. In vitro, piperacillin was a potent antibiotic against all beta-lactamase-producing mucoid strains of Pseudomonas aeruginosa; however, in spite of the fact that adequate serum antibiotic concentrations were achieved, sputum bacterial counts did not correlate with either the clinical status or the use of piperacillin therapy.

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.

A novel statistical approach for the comparison of analytical methods to measure angiotensin converting enzyme activity, enalaprilat, and benazeprilat.

Two different analytical techniques were used to measure angiotensin converting enzyme (ACE) activity, and three different methods were used to measure each of the ACE inhibitors enalaprilat and benazeprilat. All measurements were made in human plasma. The groups of methods were compared by two different statistical approaches. First, the means of the methods were compared by the paired t test or analysis of variance, depending on whether two or three different methods were under comparison. Second, the squared coefficients of variation of the methods were compared by the Jackknife technique. The dual statistical approach employed enabled both the accuracy and the variability of the analytical methods to be compared and is a superior approach to the inappropriate use of correlation coefficients that are commonly used to compare analytical techniques. No statistically significant difference was found between the two assays used to measure ACE activity. Differences were found between the three methods to measure enalaprilat, although no obvious reason could be found for this phenomenon. Significant differences were also found between the three methods used to measure benazeprilat and were attributed to the presence of metabolites interfering in the nonspecific assay methods.

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.

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.

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.

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.

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.

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.

Pharmacokinetics of perindopril: therapeutic consequences.

Perindopril has been studied in groups of normal young and elderly subjects, in patients with hepatic cirrhosis and in hypertensive patients. Plasma concentrations of perindoprilat are increased and renal clearance reduced in elderly subjects, resulting in an increase in the acute pharmacodynamic effect of perindopril. Compensated hepatic cirrhosis does not have any independent effect on the pharmacokinetics of perindopril. After intravenous administration, perindoprilat concentrations show multiexponential decay with a terminal half life of over 30 hours associated with sustained inhibition of ACE. During repeated dosing there is little accumulation of drug, and no evidence of increased haemodynamic effect after chronic treatment in hypertensives. The therapeutic consequences of these findings are: binding of perindoprilat to ACE prolongs the haemodynamic effect, giving the option of once daily administration; despite the long terminal elimination half life of the drug, significant accumulation is not a problem during chronic treatment; increased plasma concentrations of active metabolite in the elderly and reduced renal elimination may require reduced doses to be used; further dose adjustment in compensated hepatic cirrhosis is not routinely necessary.

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

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.

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.