Dementia in veterans and non-veterans in England: a cross-sectional survey.

BACKGROUND: Concerns have been raised that military veterans are at greater risk of dementia due to increased rates of depression, post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) found in this population. The prevalence of dementia in English veterans and whether this is different to non-veterans, however, are currently unknown. AIMS: To study the risk of dementia in the English veteran population, we aimed to calculate the prevalence of dementia in a group of veterans and compare this with a similar group, with no history of military service. METHODS: Male veterans and non-veterans aged over 64 years old were identified from the 2007 Adult Psychiatric Morbidity Survey, a national survey of community-dwelling adults in England. This survey was conducted via face-to-face interviews and incorporated questions on previous military service. Dementia was screened by using the modified Telephone Interview of Cognitive Status (TICS-M). RESULTS: A total of 496 male veterans and 294 non-veterans were identified. TICS-M scores indicated possible dementia in 24% of veterans and 26% non-veterans; after adjusting for age, the odds of possible dementia was significantly lower in veterans than non-veterans (adjusted OR 0.56; 95% CI 0.38-0.84, P < 0.01). CONCLUSIONS: English male veterans were less likely to have dementia than similar male non-veterans. This study did not find any evidence to support the view that dementia is more common in veterans than non-veterans.

Do antidepressants influence the disease course in inflammatory bowel disease? A retrospective case-matched observational study.

BACKGROUND: Depression, like adverse events and psychological stress, can trigger relapse in inflammatory bowel disease (IBD); however, the effects of psychoactive drugs on disease course are unclear. METHODS: Using retrospective electronic case note review, after exclusion of five patients on low-dose tricyclic antidepressants we compared the course of IBD in 29 patients (14 ulcerative colitis and 15 Crohn's disease), during the years before (year 1) and after (year 2) they were started on an antidepressant for a concomitant mood disorder to that of controls matched for age, sex, disease type, medication at baseline, and relapse rate in year 1. RESULTS: Patients had fewer relapses and courses of steroids in the year after starting an antidepressant than in the year before (1 [0-4] (median [range]) vs. 0 [0-4], P = 0.002; 1 [0-3] vs. 0 [0-4], P < 0.001, respectively); the controls showed no changes between years 1 and 2 in relapses (1 [0-4] vs. 1 [0-3], respectively) or courses of steroids (1 [0-2] vs. 0 [0-3]). Although there were no differences in the use of other relapse-related medications, outpatient attendances, or hospital admissions, the number of endoscopies fell significantly in the antidepressant group in year 2 compared with year 1 (P < 0.01). No such changes were seen in the controls. CONCLUSIONS: Antidepressants, when used to treat concomitant mood disorders in IBD, seem to reduce relapse rates, use of steroids, and endoscopies in the year after their introduction. These results suggest the need for a prospective controlled trial to evaluate their effects on disease course in patients with IBD.

Structured triacylglycerol emulsion, containing both medium- and long-chain fatty acids, in long-term home parenteral nutrition: a double-blind randomized cross-over study.

Structured lipid emulsion, an innovative approach in which both medium-chain and long-chain fatty acids are esterified to the same glycerol backbone, has been recently shown to be a safe and efficient way of providing energy to patients requiring parenteral nutrition. As yet, no assessment has been made of its safety and effect on liver functions during long-term treatment. Twenty-two home parenteral nutrition patients with Crohn's disease or short bowel syndrome were enrolled in a double-blind randomized, cross-over study. Twenty patients who completed the study were treated for 4 wk with a structured lipid emulsion and for 4 wk with long-chain triacylglycerol emulsion. Determined every 1 or 2 wk were blood pressure, body weight, respiratory rate, blood count, liver functions, albumin, transferrin, plasma lipids, free fatty acids (FFAs), and, at the end of each treatment period (weeks 4 and 8), plasma dicarboxylic acids and 3-OH-fatty acids. No differences were observed between the groups or within the groups between the two treatments with respect to either clinical safety and adverse event occurrence or laboratory assessments. Plasma dicarboxylic acids and 3-OH-fatty acids were similar and within normal range. No alteration of liver function occurred in any of the patients treated with the structured lipid emulsion, whereas two of the patients receiving long-chain triaclyglycerol emulsion developed abnormal liver function, which resolved after switching to the structured lipid emulsion. In conclusion, structured triacylyglycerols containing both medium- and long-chain fatty acids appear to be safe and well tolerated on a long-term basis in patients on home parenteral nutrition, and it may be associated with possible reduction in liver dysfunction.

Characterization of novel cathepsin K mutations in the pro and mature polypeptide regions causing pycnodysostosis.

Cathepsin K, a lysosomal cysteine protease critical for bone remodeling by osteoclasts, was recently identified as the deficient enzyme causing pycnodysostosis, an autosomal recessive osteosclerotic skeletal dysplasia. To investigate the nature of molecular lesions causing this disease, mutations in the cathepsin K gene from eight families were determined, identifying seven novel mutations (K52X, G79E, Q190X, Y212C, A277E, A277V, and R312G). Expression of the first pro region missense mutation in a cysteine protease, G79E, in Pichia pastoris resulted in an unstable precursor protein, consistent with misfolding of the proenzyme. Expression of five mature region missense defects revealed that G146R, A277E, A277V, and R312G precursors were unstable, and no mature proteins or protease activity were detected. The Y212C precursor was activated to its mature form in a manner similar to that of the wild-type cathepsin K. The mature Y212C enzyme retained its dipeptide substrate specificity and gelatinolytic activity, but it had markedly decreased activity toward type I collagen and a cathepsin K-specific tripeptide substrate, indicating that it was unable to bind collagen triple helix. These studies demonstrated the molecular heterogeneity of mutations causing pycnodysostosis, indicated that pro region conformation directs proper folding of the proenzyme, and suggested that the cathepsin K active site contains a critical collagen-binding domain.

Increase in bone density and plasma osteocalcin during growth hormone therapy in growth hormone deficient children.

UNLABELLED: Bone density in growth hormone (GH) deficient children is decreased more than expected for delayed skeletal maturation. Previous studies suggest GH enhances mineral retention and deposition in bone. Seven GH deficient prepubertal children were studied during 2 years of GH therapy to assess the effect on bone density and plasma osteocalcin. Bone density (radiographic photodensitometry) of the phalanges (cortical and trabecular bone) was expressed as the standard deviation score (SDS) of the mean for sex, bone age and chronological age. Relative osteopenia, less pronounced for bone density/bone age (BD/BA) than bone density/chronological age (BD/CA), improved significantly during GH therapy. After 12 months there was increase over pretreatment levels, significant for BD/CA (-1.65 +/- 0.46 vs -1.15 +/- 0.64; mean +/- SD: p = 0.002), but less pronounced for BD/BA. After 24 months increase in both measurements continued, reaching significance also for BD/BA (Pre: -1.02 +/- 0.55 vs -0.41 +/- 0.29; p = 0.011). Plasma osteocalcin levels were low before GH therapy (11.6 +/- 9.9 ng/ml; n = 7; vs control 24.4 +/- 12.5 ng/ml; n = 21; p < 0.05), rose significantly after one week (31.2 +/- 10.5 ng/ml; p < 0.001), with continued upward trend to plateau between 2-6 months, with elevated levels persisting during 2 years of GH therapy. CONCLUSION: The early and sustained rise in plasma osteocalcin and subsequent increase in bone density with continued gain over 24 months of the study suggests that GH therapy in GH deficient children has a significant prolonged effect on bone formation and mineralization in addition to stimulating linear growth.

Anti-islet autoantibodies detected by monoclonal antibody 1A2: further studies suggesting a role in the pathogenesis of IDDM.

Insulin-dependent diabetes mellitus (IDDM) is associated with autoantibodies to several pancreatic islet antigens. We have described an assay in which autoantibodies displace a radiolabelled monoclonal anti-islet antibody. Sera from 87% of 429 children at time of diagnosis of IDDM were positive, while sera from control groups had much lower prevalences (1.3-19%). Sera from 41.9% of diabetic subjects remained positive after 20 years duration of IDDM. Sera from 23.6% of parents and 37.9% of non-diabetic siblings were positive. Twenty relatives who subsequently developed IDDM had the same prevalence of the antibodies (85%) as did the patients at time of diagnosis. These findings confirm that the autoantibodies detected by monoclonal antibody (mAb) 1A2 are common at the onset of IDDM and their presence prior to the onset of hyperglycaemia suggests that this method may be useful in screening non-diabetic populations. The high prevalence of antibodies in relatives reduces the efficacy for diabetes prediction, but suggests either that generation of these antibodies is an autosomal dominant trait, or that the antigen detected by these antibodies is cross-reactive with a common environmental antigen. Differentiation between these hypotheses will await the identification of the specific islet-cell antigen detected by mAb 1A2.

Transient congenital hypoparathyroidism: resolution and recurrence in chromosome 22q11 deletion.

Transient congenital hypoparathyroidism (TCHP), with spontaneous resolution in infancy and subsequent recurrence in childhood, has not been associated with a specific cause. We report three patients with TCHP, initially with severe but transient neonatal hypocalcemia. During childhood, recurrence of hypoparathyroidism and recognition of phenotypic features suggested a diagnosis of velocardiofacial syndrome (VCFS). Features specific for the DiGeorge syndrome, with known clinical and genetic overlap with VCFS, were not present except for hypoparathyroidism. Genetic analysis confirmed chromosome 22q11 deletion in each patient. TCHP may be the earliest specific finding in 22q11 deletion/VCFS subgroup, with other diagnostic features emerging in later childhood. Infants with resolved TCHP need continued observation of parathyroid sufficiency, genetic analysis, and examination for anomalies associated with chromosome 22q11 deletion.

Decreased T3 and T4 levels following topical application of povidone-iodine in premature neonates.

Thyroid function and iodine levels of 30 preterm neonates were examined before and up to five days after topical exposure to 10% povidone-iodine application. Urinary iodine excretion significantly increased in the group closest to term (8.9 +/- 1.2 mg I/g creatinine x 10) vs controls (3.5 +/- 0.5 mg; p < 0.01). T3 levels significantly decreased at all sub-group gestational ages vs controls (p < 0.01-0.05). Similarly, both FT4 and TT4 levels were lower in the subgroups vs controls (p < 0.01-0.05). TSH levels however did not rise in any group. These data suggest partial failure of thyroid hormone synthesis, in a population of high-risk infants possibly already exhibiting features of the euthyroid-sick syndrome. Topical iodine-containing antiseptic solutions should be used with caution in this population since these antiseptics may modify serum thyroid hormone concentrations rapidly.

Severely deficient binding of 1,25-dihydroxyvitamin D to its receptors in a patient responsive to high doses of this hormone.

A 1.6-yr-old Hispanic boy with sparse hair, muscle weakness, severe growth retardation, and rickets was found to have hypocalcemia, secondary hyperparathyroidism, and high circulating 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels. One year of treatment with a high dose of 1,25-(OH)2D3 (20 micrograms, orally, daily) resulted in marked subjective and radiological improvement; there was a parallel improvement in serum calcium, phosphorus, PTH, alkaline phosphatase, and osteocalcin concentrations. Soluble extracts from cultured skin fibroblasts did not bind [3H]1,25-(OH)2D3 using standard methods. To evaluate the possibility of receptors with abnormally low affinity, we tested for binding with [3H]1,25-(OH)2D3 concentrations higher than those usually used. In one experiment, there was a suggestion of low affinity binding. Hormone receptors with abnormally low affinity for 1,25-(OH)2D may explain this patients resistance to 1,25-(OH)2D. Therapy to maintain extremely high serum 1,25-(OH)2D3 concentrations markedly improved mineral homoeostasis, but did not affect the hair disorder.

Percutaneous transluminal renal angioplasty in the treatment of renovascular hypertension in children.

We report five young patients who underwent percutaneous transluminal renal angioplasty (PTRA) for the treatment of hypertension related to renal artery stenosis. Four had fibromuscular disease and one had probable Takajasu's arteritis; two had solitary kidneys. Following PTRA, a prompt decrease in blood pressure was observed in all patients. Further, four of five patients long after PTRA remained normotensive, and in all patients plasma renin levels declined. These results indicate that PTRA can be a safe and effective alternative to surgery in the treatment of renovascular hypertension in childhood.

Evaluation of percutaneous transluminal renal angioplasty in childhood hypertension.

Percutaneous transluminal renal angioplasty (PTRA) has been infrequently used in the treatment of children with hypertension due to renal artery stenosis. We report our results in five patients aged 4 to 22 years with hypertension diagnosed at ages 1 1/2 to 10 years. Four of the five patients had been on antihypertensive medication prior to angioplasty. Four had fibromuscular disease and one had probable Takajasu's arteritis; two had solitary kidneys. Following angioplasty, a prompt decrease in blood pressure was observed in all patients. Further, four of five patients after PTRA were normotensive without antihypertensive medications, and in all PRA declined. PTRA can be a safe and effective alternative to surgical treatment in the management of renovascular hypertension in childhood. We suggest that PTRA should be the first procedure attempted to correct renovascular hypertension in children.

Duplication 11 (q22----qter) in an infant. A case report with review.

A male infant with partial duplication of the long arm of chromosome 11 (11q22----qter) is described with a hitherto unreported translocation. In most cases 11q trisomy is associated with 11q/22q translocation and a 3:1 meiotic disjunction with 47 chromosomes. In a few cases the 11q translocation is associated with a partial deletion of other autosomes and a total of 46 chromosomes. In the present case, translocation to 9p is involved and no apparent deletion of 9p was noted, providing an opportunity to delineate the phenotypic features due to duplication of 11q. A comparison is made between the findings of partial 11q trisomy and 11q/22q translocation.

Recovery of adrenal function after treatment of adrenocortical carcinoma with o,p'-DDD.

The adrenolytic agent, 2,2-bis[2-chlorophenyl-4-chlorophenyl] 1,1 dichloroethane (o,p'-DDD), was used over a 20-month period following surgery in a 2 3/12-year-old girl for treatment of adrenocortical carcinoma. The child remained free of disease and was maintained on glucocorticoid and mineralo-corticoid supplements for 7 years. Hormonal evaluation was undertaken at 9 9/12 years of age to determine remaining adrenal steroidogenic capacity. Following discontinuation of both hydrocortisone and 9 alpha-fludrocortisone, she remained stable and asymptomatic. Immediately after discontinuing 9 alpha-fludrocortisone, the adrenal glomerulosa was able to respond to stimulation by the renin-angiotensin system as shown by the ability to achieve renal sodium conservation on a restricted sodium intake (less than 10 mEq/d for 5 d). The response of the adrenal fasciculata to ACTH stimulation showed a slower recovery. Baseline levels of cortisol were in the low normal range, but there was no increase in plasma cortisol or urinary 17-hydroxysteroids following stimulation with ACTH. The responses of cortisol, deoxycorticosterone, and corticosterone to ACTH stimulation gradually improved to achieve normal stimulated levels 18 months after stopping medications. Serum testosterone and delta 4-androstenedione were initially increased for level of puberty, while levels of dehydroepiandrosterone were prepubertal. Testosterone and delta 4-androstenedione did not suppress with dexamethasone (2 mg/d for 2 d; 4 mg/d for 2 d), and dehydroepiandrosterone decreased only slightly. However, administration of norethindrone (Norlutin) (10 mg orally, three times a day for 3 d) resulted in suppression while human chorionic gonadotrophin (hCG; 5000 U i.m. daily for 3 d) produced stimulation of testosterone, delta 4-androstenedione and dehydroepiandrosterone. Thus the androgens were felt be predominantly of ovarian origin. Dehydroepiandrosterone rose to low normal levels by 18 months after discontinuation of hydrocortisone. We thus demonstrate for the first time that both the adrenal glomerulosa and fasciculata have the capacity to recover normal function following treatment with o,p'-DDD. Further, we suggest that early exposure to excess adrenal androgens may result in mild alteration of gonadal function.

Metabolic and blood pressure responses to hydrocortisone in the syndrome of apparent mineralocorticoid excess.

A syndrome of low renin hypertension in childhood with apparent mineralocorticoid excess associated with a defect in the peripheral metabolism of cortisol has been described previously in 2 patients. In these patients, decreased secretion rates of glucocorticoids, mineralocorticoids, and sex steroids have been demonstrated. In a 10(10/12)-yr-old girl with this disorder, continuous iv administration of hydrocortisone in doses of 5, 10, 15, and 20 mg/day resulted in an increase in blood pressure and a decrease in serum potassium concentration. The addition of spironolactone during the continued administration of 20 mg/day hydrocortisone did not result in a decrease in blood pressure. Withdrawal of hydrocortisone and continued administration of spironolactone alone resulted in a decrease in blood pressure, a rise in serum potassium concentration, and a fall in serum sodium concentrations. These studies suggest that an abnormality in cortisol action or metabolism causing cortisol to behave as a potent mineralocorticoid may account for this syndrome of apparent mineralocorticoid excess.

Adrenal glomerulosa function in patients with dexamethasone-suppressible hyperaldosteronism.

The response of the adrenal glomerulosa to renin stimulation was determined in 10 patients with dexamethasone-suppressible hyperaldosteronism. The patients were treated continuously with 2 mg/day dexamethasone (DEX) and were studied on a regular sodium diet (87 meq/m2 . day) and on a 10 meq/day sodium diet. With DEX treatment all patients showed a prompt suppression of adrenal fasciculata function as evidenced by suppression of serum cortisol, corticosterone, desoxycorticosterone, and urinary 18-OH-desoxycorticosterone. The complete suppression of urinary pH 1 aldosterone (aldo) by DEX, unique to this disorder, was paralleled by a prompt suppression of urinary 18-OH-corticosterone. With continued DEX administration, plasma renin activity rose to the normal or supranormal range. Dietary sodium restriction resulted in a further rise in plasma renin activity and a rise in urinary pH 1 aldo and 18-OH-corticosterone. We conclude that in DEX-suppressible hyperpaldosteronism, although ACTH appears to be the primary stimulus for aldo secretion in the untreated state, when ACTH is suppressed, the adrenal glomerulosa responds normally to the stimulation of renin-angiotensin II.