Multidisciplinary Responses to the Sexual Victimization of Children: Use of Control Phone Calls.

This descriptive study addresses the question of the value of one-party consent phone calls regarding the sexual victimization of children. The authors reviewed 4 years of experience with children between the ages of 3 and 18 years selected for the control phone calls after a forensic interview by the New York State Police forensic interviewer. The forensic interviewer identified appropriate cases for control phone calls considering New York State law, the child's capacity to make the call, the presence of another person to make the call and a supportive residence. The control phone call process has been extremely effective forensically. Offenders choose to avoid trial by taking a plea bargain thereby dramatically speeding up the criminal judicial and family court processes. An additional outcome of the control phone call is the alleged offender's own words saved the child from the trauma of testifying in court. The control phone call reduced the need for children to repeat their stories to various interviewers. A successful control phone call gives the child a sense of vindication. This technique is the only technique that preserves the actual communication pattern between the alleged victim and the alleged offender. This can be of great value to the mental health professionals working with both the child and the alleged offender. Cautions must be considered regarding potential serious adverse effects on the child. The multidisciplinary team members must work together in the control phone call. The descriptive nature of this study did not allow the authors adequate demographic data, a subject that should be addressed in future prospective study.

Relative resistance of human CD4(+) memory T cells to suppression by CD4(+) CD25(+) regulatory T cells.

Successful expansion of functional CD4(+) CD25(+) regulatory T cells (T(reg)) ex vivo under good manufacturing practice conditions has made T(reg) -cell therapy in clinical transplant tolerance induction a feasible possibility. In animals, T(reg) cells home to both transplanted tissues and local lymph nodes and are optimally suppressive if active at both sites. Therefore, they have the opportunity to suppress both naïve and memory CD4(+) CD25(-) T cells (Tresp). Clinical transplantation commonly involves depleting therapy at induction (e.g. anti-CD25), which favors homeostatic expansion of memory T cells. Animal models suggest that T(reg) cells are less suppressive on memory, compared with naïve Tresp that mediate allograft rejection. As a result, in the context of human T(reg) -cell therapy, it is important to define the effectiveness of T(reg) cells in regulating naïve and memory Tresp. Therefore, we compared suppression of peripheral blood naïve and memory Tresp by fresh and ex vivo expanded T(reg) cells using proliferation, cytokine production and activation marker expression (CD154) as readouts. With all readouts, naïve human Tresp were more suppressible by approximately 30% than their memory counterparts. This suggests that T(reg) cells may be more efficacious if administered before or at the time of transplantation and that depleting therapy should be avoided in clinical trials of T(reg) cells.

Infection and systemic inflammation, not ammonia, are associated with Grade 3/4 hepatic encephalopathy, but not mortality in cirrhosis.

BACKGROUND & AIMS: Patients with cirrhosis are prone to infection which is a frequent precipitant of hepatic encephalopathy (HE). Clinical studies have examined the importance of inflammation and infection in modulating the manifestation of symptoms of HE in acute liver failure and patients with cirrhosis and minimal/low grade HE. It would be logical to presume that this relationship persists in patients who develop severe HE in cirrhosis although this has not been examined to date. METHODS: We report the findings of a prospective audit of 100 consecutive patients with cirrhosis admitted between Jan 2000 and March 2008 to a liver Intensive Care Unit (ICU) where HE was the primary indication for admission (59% Grade 3; 41% Grade 4). Haematological and microbiological data were collected at ICU admission, and organ scores and outcomes were recorded. RESULTS: 46% of patients had positive cultures taken within ± 48h from admission to ICU [25% blood] and a further 22% were culture negative but had evidence of systemic inflammation (SIRS). SIRS score (p=0.03) and SOFA score (p=0.006) were significantly higher in those patients with Grade 4 HE, who were also less likely to survive (p<0.001). HE grade/coma score did not correlate with ammonia, biochemistry or MELD score. Fifty-two percent of patients survived their ICU stay while the remainder developed progressive multiorgan failure and died; 38% survived to discharge, and 16% were transplanted. CONCLUSIONS: These data support an association between infection/SIRS and not ammonia, in patients with cirrhosis that develop severe HE. The presence or absence of infection/SIRS did not determine survival.

Transcriptional regulation of the mucosal immune system mediated by T-bet.

The immune system faces the arduous task of defending the mucosal surfaces from invading pathogens, but must simultaneously repress responses against commensal organisms and other inert antigens that are abundant in the external environment, as inappropriate immune activation might expose the host to increased risk of autoimmunity. The behavior of individual immune cells is governed by the expression of transcription factors that are responsible for switching immune response genes on and off. T-bet (T-box expressed in T cells) has emerged as one of the key transcription factors responsible for controlling the fate of both innate and adaptive immune cells, and its expression in different immune cells found at mucosal surfaces is capable of dictating the critical balance between permitting robust host immunity and limiting susceptibility to autoimmunity and allergy.

The Ontario Osteoporosis Strategy: implementation of a population-based osteoporosis action plan in Canada.

In the last decade, there have been a number of action plans published to highlight the importance of preventing osteoporosis and related fractures. In the province of Ontario Canada, the Ministry of Health provided funding for the Ontario Osteoporosis Strategy. The goal is to reduce morbidity, mortality, and costs from osteoporosis and related fractures through an integrated and comprehensive approach aimed at health promotion and disease management. This paper describes the components of the Ontario Osteoporosis Strategy and progress on implementation efforts as of March 2009. There are five main components: health promotion; bone mineral density testing, access, and quality; postfracture care; professional education; and research and evaluation. Responsibility for implementation of the initiatives within the components is shared across a number of professional and patient organizations and academic teaching hospitals with osteoporosis researchers. The lessons learned from each phase of the development, implementation, and evaluation of the Ontario Osteoporosis Strategy provides a tremendous opportunity to inform other jurisdictions embarking on implementing similar large-scale bone health initiatives.

Significant psychological morbidity occurs in irritable bowel syndrome: a case-control study using a pharmacy reimbursement database.

BACKGROUND: Psychological problems are associated with IBS but the strength of this association is unclear. AIM: To assess co-prescribing of antispasmodic and CNS-acting drugs through a nested case-control study. METHODS: A national dispensing database identified patients who were first dispensed antispasmodic medicines for a continuous 3-month period or more during 2006, using 2005 as a run-in period. Each patient was matched with four control patients and excluded if they received drugs indicated for IBD. RESULTS: Four hundred and seven patients commenced antispasmodic drugs during 2006. These patients were matched with 1628 controls. In 2005, patients subsequently prescribed antispasmodics were 2-3 times more likely to receive CNS-acting drugs than controls. In the year following commencement of IBS therapy, patients were 2-4 times more likely than controls to be prescribed CNS-acting drugs including antidepressants (35.4% vs. 9.3%), anxiolytics (27.8% vs. 8.8%), antipsychotics (9.8% vs. 3.3%) and hypno-sedatives (32.7% vs. 11.3%; P < 0.0001). The adjusted OR (95% CI) for antidepressant, anxiolytic, hypnosedative and antipsychotic prescribing in IBS patients were 3.81 (2.79-5.20), 2.84 (2.12-3.81), 2.62 (1.91-3.60) and 2.58 (1.80-3.66), respectively. CONCLUSIONS: Patients prescribed ongoing therapy for presumed IBS are 2-4 times more likely to be prescribed CNS-acting drugs than controls, providing evidence of psychological comorbidity in IBS.

The effect of portal and peripheral insulin delivery on carbohydrate and lipid metabolism in a miniature pig model of human IDDM.

A pig model of insulin-dependent diabetes was used to examine the importance of the portal-systemic insulin gradient for whole-body metabolic control. Six pigs had jugular vein, portal vein, and carotid artery cannulae implanted before being made diabetic (150 mg kg[-1] streptozotocin). Each animal received 4 weeks of portal and 4 weeks of peripheral insulin delivery in random order. The blood glucose target range was 5-10 mmol x l(-1), and serum fructosamine and fasting and postprandial blood glucose concentrations were not different between peripheral and portal insulin infusion. Insulin requirement was not different between the 4 week infusion periods, but fasting peripheral insulin levels after peripheral delivery (124 +/- 16 (mean +/- SEM) pmol x l[-1]) were significantly higher (p < 0.05) than in portally infused (73.8 +/- 5.4 pmol x l[-1]) or pre-diabetic control animals (68.4 +/- 3.6 pmol x l[-1]). Basal hepatic glucose output was also higher (p < 0.05) in peripherally (4.2 +/- 0.4 mg x kg[-1] x min[-1]) than in portally infused animals (2.9 +/- 0.4 mg x kg[-1] x min[-1]) or controls (3.0 +/- 0.3 mg x kg[-1] x min[-1]). Clamp glucose metabolic clearance rate was, however, not different between the peripheral and portal insulin delivery routes (8.1 +/- 1.0 vs 9.0 +/- 0.7 ml x kg[-1] x min[-1]), although both were significantly lower (p < 0.05) than that measured in prediabetic control animals (11.7 +/- 1.0 ml x kg[-1] x min[-1]). Lipid profiles and subfractions were similar in all three groups. It is concluded that the portal route of delivery is superior to the peripheral in maintaining more appropriate insulin concentrations and control of hepatic glucose output, although in the absence of euglycaemia it is still associated with significant metabolic abnormalities.

Renal enlargement and insulin-like growth factor-1 accumulation in the Wistar rat model of experimental diabetes is not prevented by angiotensin converting enzyme inhibition.

Experimental diabetes is associated with renal enlargement and glomerular hyperfiltration. Possible mechanisms for these changes could be the direct effects of growth factors such as insulin-like growth factor-1 and angiotensin II. We investigated whether treatment with trandolapril, an angiotensin converting enzyme inhibitor, prevented renal enlargement in streptozotocin-diabetic rats. Seven groups of male Wistar rats were studied: C (control + placebo); CL (control + low-dose trandolapril, 0.01 mg.kg-1.day-1); CH (control + high-dose trandolapril, 0.5 mg.kg-1.day-1; DP (diabetic + placebo); DI (diabetic, insulin-treated); DL (diabetic + low-dose trandolapril); DH (diabetic + high-dose trandolapril) and DI (diabetic + insulin). From day 2 glucose concentrations and body weight were similar in the non-diabetic and diabetic animals treated with insulin. Diabetic animals treated with placebo and low-dose trandolapril weighed significantly less compared to the control group. The diabetic groups, not treated with insulin, showed marked hyperglycaemia throughout the study. Kidney weight was greater in the diabetic, non insulin-treated groups compared with the control and insulin-treated groups. After 24 h of diabetes, kidney insulin-like growth factor-1 content was significantly increased from baseline levels in groups DP, DL and DH but by 48 h these levels had returned to normal. Renal tissue angiotensin converting enzyme activity was similar in groups C and DI but significantly reduced in all trandolapril-treated animals. Despite inhibiting renal angiotensin converting enzyme activity renal enlargement with increased tissue insulin-like growth factor-1 still occurred. This suggests that neither angiotensin II nor glomerular hyperfiltration, with raised intraglomerular pressure, play a role in the initial renal enlargement seen in experimental diabetes. Renal accumulation of insulin-like growth factor-1 appears to be an important factor in early renal hypertrophy and its effects are not modulated by angiotensin converting enzyme or angiotensin II.

Thyroid-induced changes in the growth of the liver, kidney, and diaphragm of neonatal rats.

Eu-, hypo- and hyper-thyroid rats were studied 12 days postpartum. Hypothyroidism was induced by administering propylthiouracil (PTU) via the mother's drinking water between late gestation and throughout lactation. This procedure effectively blocked the normal early postnatal surge of T3 and T4. In contrast, hyperthyroidism was induced in the young pups by daily injections of T4 from day 3 postpartum. The effects of these experimental manipulations of thyroid status on the rates of protein turnover and growth of the liver, kidney, and diaphragm were studied and compared with measurements made on appropriate euthyroid control tissues. Tissue rates of protein synthesis were decreased in response to hypothyroidism with consequent growth retardation of all three tissues and the whole animal. In contrast, the three body tissues responded very differently to the induction of hyperthyroidism. Hepatic rates of protein synthesis and growth were completely unaffected by thyroid excess. The response of the diaphragm was essentially the reverse of that seen with hypothyroidism, i.e., the enhanced rates of protein synthesis and protein degradation leading to muscle hypertrophy. The rates of protein turnover in the kidney were also increased, but unlike the diaphragm the net result was renal atrophy. Clearly, thyroid hormones influence the normal rapid growth of the neonate and its individual tissues. However, beyond a certain concentration the threshold of responsiveness to these hormones seems to vary between individual tissues.

The influence of thyroid hormones on the growth of the atria and ventricles of the heart in immature rats.

The normal plasma concentrations of tri-iodothyronine (T3) and thyroxine (T4) increase approximately six- and fourfold respectively between the end of gestation and weaning in the rat. This early postnatal surge of thyroid hormones was experimentally modified to produce either a state of hypo- or hyperthyroidism. The growth and rates of protein turnover in the atria and ventricles of the heart were studied, 12 and 20 days postpartum, both as a function of age and of changing thyroid status. Neonatal hypothyroidism was induced by adding propylthiouracil to the mothers' drinking water late in gestation and throughout lactation. Hyperthyroidism was achieved by giving the suckling pups daily injections of T4 from day 3 postpartum onwards. Between 12 and 20 days the weight and protein mass of the combined ventricles of the euthyroid animals approximately doubled, along with substantial increases (50%) in the RNA and DNA contents. Over this same 8 days, growth in the combined atria was much slower. During the same period, hypothyroidism significantly retarded the growth of these immature rats and their atria and ventricles. Both the rates of protein synthesis and protein degradation were decreased in the atria and ventricles. In contrast, hyperthyroidism significantly increased growth in both types of cardiac tissue, this being more pronounced in the atria than in the ventricles between 12 and 20 days. The rates of protein synthesis were increased accordingly, principally by increases in the ribosomal activities. In conclusion, thyroid hormones clearly influence the early postnatal growth of the atria and ventricles of the heart in the rat.

The influence of thyroid hormones on the growth of the lungs in perinatal rats.

The growth and rates of protein turnover in the perinatal lung have been studied in the rat during normal development between late gestation and weaning, and after altering their thyroid status. The aim was to establish what influence thyroid hormones have on the early stages of growth in the lungs. Perinatal hypothyroidism was induced by administering propylthiouracil (PTU) via the mothers' drinking water from late gestation and throughout lactation. A precocious and elevated surge of thyroid hormones was induced by daily injections of T4 from day 3 postpartum onwards. Hypothyroidism in the neonate, but not the fetus, significantly retarded the growth of the animal and its lungs. This was attributable to a decrease in both the pulmonary rates of protein synthesis and protein degradation; the effect on the former rate exceeding that on the latter. Neonatal hyperthyroidism did not significantly alter protein turnover or the growth of the lungs, compared with euthyroid control tissues. This contrasts with the accelerated growth of some other body tissues in the presence of excess thyroid hormones.

The effects of established diabetes on the growth of the fetal liver and skin in the rat.

1. The effects of uncontrolled maternal diabetes on the growth of the whole rat fetus and its liver and skin were studied over the last 4 days of gestation. 2. Smaller fetuses, with growth-retarded livers and skins, were consistently found between 18 and 21 days in the diabetic pregnancies. 3. The smaller diabetic livers and skins (i.e. combined epidermis and dermis) possessed lower protein, RNA and DNA contents, compared with the same fetal tissues from normal pregnancies. 4. The growth retardation of the livers in diabetic fetuses was attributed to fewer normally sized hepatic cells. 5. Whilst hepatic rates of protein synthesis (measured in vivo) remained largely unchanged, these were actually increased in the skin, compared with normal control tissues. 6. These findings point to an elevated rate of protein degradation in both diabetic tissues as the most likely cause of their retarded growth.

Growth of the rat foetal liver in gestational diabetes.

1. Through a combination of streptozotocin and insulin injections an animal model of gestational diabetes has been established, whereby blood glucose concentrations are elevated over the second-half of pregnancy. 2. Between 18 and 21 days of gestation the diabetic mothers carried smaller foetuses, which in turn possessed growth retarded livers. 3. This suppression of hepatic growth in diabetic foetuses was evident in terms of consistently decreased (7-27%) liver weights and protein and nucleic acid contents. 4. No differences were found between the rates of hepatic protein synthesis (measured in vivo) in control and diabetic foetuses. 5. Hence, the growth retardation of the foetal liver, arising from maternal hyperglycaemia, must necessarily involve an increase in protein degradation.

Beta-adrenergic stimulation of cyclic AMP is defective in cultured dermal fibroblasts of psoriatic subjects.

Epidermal cells from psoriatic lesions demonstrate a very low cAMP response to beta-adrenergic stimuli. We have shown that a similar abnormality occurs in dermal fibroblasts from affected areas of skin. The cells, after 5-12 passages in tissue culture, had a much reduced response to 10(-8) M and 10(-6) M isoproterenol when compared with fibroblasts from control subjects. The abnormality was not abolished by the addition of the phosphodiesterase inhibitor, 3-isobutyl-I-methylxanthine. Other putative agonists tested were vasoactive intestinal peptide and peptide histidine methionine. Neither of these had an effect on dermal fibroblasts from either normal controls or from lesions of psoriasis.

Maternal diabetes in rats. I. Effects on placental growth and protein turnover.

The developmental growth of the rat placenta was investigated between days 14 and 21 of gestation in normal control, gestational-diabetic, established-diabetic, and insulin-maintained-diabetic mothers. While established-diabetic mothers were hyperglycemic for 2 wk before and throughout the pregnancy, gestational-diabetic mothers were only hyperglycemic for the second half of pregnancy. Daily insulin replacements successfully restored normoglycemia. The wet weight and protein content of control placentas increased linearly between days 14 and 21. Although placentas from diabetic animals were initially smaller, placentomegaly was found at full term. Placental glycogen concentrations were also markedly increased in all diabetic animals. These changes were largely prevented by insulin replacement. The changes in placental size during normal development and in association with the diabetic state were explained by measuring placental rates of protein turnover (in vivo). In normal placentas, protein synthetic and degradative rates progressively declined over the last week of gestation. Because synthesis rates were unchanged in placentas of diabetic mothers, it appears that the differences in placental size primarily arise from alterations in protein degradation.

Maternal diabetes in rats. II. Effects on fetal growth and protein turnover.

The developmental growth of the rat fetus was studied between days 14 and 21 of pregnancy in normal control, established-diabetic, gestational-diabetic, and insulin-maintained-diabetic mothers. Measurements of fetal body weights and protein mass revealed a suppression of growth in the diabetic pregnancies, probably arising from reduced hyperplasia. Growth of the liver and skin appeared to be suppressed in proportion to the whole fetus, whereas the lung, brain, and particularly the heart were relatively well protected from growth retardation. Fetal growth during development, and its retardation in association with the hyperglycemic state, was explained by measuring the rates of fetal protein turnover in vivo. Both the protein synthetic and degradative rates gradually declined during normal development. However, in the diabetic pregnancies, fetal protein synthesis was consistently lower than control rates, whereas protein degradation increased sharply toward the end of gestation. These changes in protein synthesis and breakdown probably combine to yield a smaller fetus in the absence of normoglycemia.

Sexual abuse of boys.

In a retrospective review of 145 sexually abused children, 11% were male. The boys were more likely to be assaulted in a public place than were girls, and boys were more prone to physical injury. The relationship of the perpetrator to the child was similar for boys and girls as was the age of the children. This study emphasizes the existence of boys as victims of sexual abuse.