Risk factors of persistent adolescent thinness: findings from the UK Millennium Cohort Study.

BACKGROUND: Thinness during adolescence can increase the risk of adverse health outcomes across the life-course and impede development. There is limited research examining the prevalence and determinants of persistent adolescent thinness in the United Kingdom (UK). We used longitudinal cohort data to investigate determinants of persistent adolescent thinness. METHODS: We analyzed data from 7,740 participants in the UK Millennium Cohort Study at ages 9 months, 7, 11, 14 and 17 years. Persistent thinness was defined as thinness at ages 11, 14 and 17; thinness was defined as an age- and sex-adjusted Body Mass Index (BMI) of less than 18.5 kg/m2. In total, 4,036 participants, classified either as persistently thin or at a persistent healthy weight, were included in the analyses. Logistic regression analyses were conducted to examine associations between 16 risk factors and persistent adolescent thinness by sex. RESULTS: The prevalence of persistent thinness among adolescents was 3.1% (n = 231). Among males (n = 115), persistent adolescent thinness was significantly associated with non-white ethnicity, low parental BMI, low birthweight, low breastfeeding duration, unintended pregnancy, and low maternal education. Among females (n = 116), persistent adolescent thinness was significantly associated with non-white ethnicity, low birthweight, low self-esteem, and low physical activity. However, after adjusting for all risk factors, only low maternal BMI (OR: 3.44; 95% CI:1.13, 10.5), low paternal BMI (OR: 22.2; 95% CI: 2.35, 209.6), unintended pregnancy (OR: 2.49; 95% CI: 1.11, 5.57) and low self-esteem (OR: 6.57; 95% CI: 1.46,29.7) remained significantly associated with persistent adolescent thinness among males. After adjustment for all risk factors, not reaching the recommended physical activity levels (OR: 4.22; 95% CI: 1.82, 9.75) remained significantly associated with persistent adolescent thinness among females. No appreciable associations were found between persistent adolescent thinness and sex, premature birth, smoking during pregnancy, income, maternal postnatal depression, mother-infant attachment or socio-emotional difficulties (p > 0.05). CONCLUSION: Persistent adolescent thinness is not rare and appears to be associated with both physical and mental health factors, with some sex specific differences. Healthy weight initiatives should consider the full weight spectrum. Further research is required to understand thinness at a population level, including among those whose BMI changes during child and adolescent development.

Medical negligence in urology: an untapped database.

INTRODUCTION: The aim of this study was to identify the causes of urological litigation in the NHS and to make recommendations how to reduce the burden of litigation to both injured patients and urologists. METHODS: Under the Freedom of Information Act, the National Health Service Resolution (NHSR) was asked to provide the figures for the number of cases of litigation in urology reported between 2010 and 2020. RESULTS: The number of urological claims more than doubled between 2011 and 2020. Many of the claims that are made result from avoidable errors. CONCLUSION: More education is needed, of both urologists in training and consultant urologists, on the causes of errors that lead to litigation and how many of them can be avoided.

For debate: the short report - legal and ethical implications.

At the outset of an alleged medical negligence case, it is common for medical expert witnesses to be asked to write a brief report, sometimes called a short report or a screening report. Such requests may come from solicitors acting for a claimant or for the defence. Reassurances may be offered that the opinion given will not be disclosed. However, this is very often not the case. Doctors and the instructing solicitors need to be aware of the legal and ethical implications of providing such instructions. The medical expert must be aware that their duty to the court begins from the time of receipt of a letter from a solicitor requesting such a report.

Foundation Year Doctors need more support.

The introduction of new rotas, rota gaps, poor handover arrangements, the junior hospital doctors' strike, the imposition of a new contract after a four-year period of contract negotiation, the Bawa-Garba case, the abolition of the "Firm", poor rest facilities and bullying have all contributed to eroding the morale of junior doctors. The retention of newly registered doctors is falling. Recent evidence shows that in 2010 83% of Foundation Year 2's went straight into training compared to 38% in 2018. This study was undertaken to assess the extent to which the plans and intentions of current Foundation Year Doctors have been influenced by recent history. With the large volume of complaints and their associated costs on the NHS, the study included questions to identify whether junior doctors feel prepared to deal with the medico-legal issues.

Comparative aspects of phytase and xylanase effects on performance, mineral digestibility, and ileal phytate degradation in broilers and turkeys.

Two experiments were performed, using broilers or turkeys, each utilizing a 3 × 2 factorial arrangement, to compare their response to phytase and xylanase supplementation with growth performance, nutrient digestibility, and ileal phytate degradation as response criteria. For both experiments, 960 Ross 308 or 960 BUT 10 (0-day-old) birds were allocated to 6 treatments: (1) control diet, containing phytase at 500 FTU/kg; (2) the control diet with xylanase (16,000 BXU/kg); (3) the control diet supplemented on top with phytase (1,500 FTU/kg); (4) diet supplemented with 1,500 FTU/kg phytase and xylanase (16,000 BXU/kg); (5) the control diet supplemented with phytase (3,000 FTU/kg); and (6) diet supplemented with 3,000 FTU/kg phytase and xylanase (16,000 BXU/kg). Each treatment had 8 replicates of 20 birds each. Water and diets based on wheat, soybean meal, oilseed rape meal, and barley were available ad libitum. Body weight gain and feed intake were measured from 0 to 28 D, and feed conversion ratio (FCR) corrected for mortality was calculated. Ileal digestibility for dry matter and minerals on day 7 and 28 were analyzed in addition to levels of inositol phosphate esters (InsP6-3) and myo-inositol. Statistical comparisons were performed using ANOVA. Xylanase supplementation improved 28D FCR in broilers and turkeys. Increasing doses of phytase reduced FI and improved FCR only in broilers. In broilers, the age × phytase interaction for phosphorous digestibility showed that increasing phytase dose was more visible on day 7, than on day 28. Mineral digestibility was lower in 28-day-old turkey compared with 7-day-old turkey. InsP6 disappearance increased with increasing phytase levels in both species, with lower levels analyzed in turkeys. InsP6 disappearance was greater in younger turkeys (day 7 compared with day 28). In conclusion, although broilers and turkeys shared several similarities in their growth and nutrient utilization responses, the outcomes of the 2 trials also differed in many aspects. Whether this is because of difference in diets (InsP or Ca level) or differences between species needs further investigation.

Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase, and mineralocorticoid receptor gene expression in rat brain. Therapeutic implications.

Imipramine is the prototypic tricyclic antidepressant utilized in the treatment of major depression and exerts its therapeutic efficacy only after prolonged administration. We report a study of the effects of short-term (2 wk) and long-term (8 wk) administration of imipramine on the expression of central nervous system genes among those thought to be dysregulated in imipramine-responsive major depression. As assessed by in situ hybridization, 8 wk of daily imipramine treatment (5 mg/kg, i.p.) in rats decreased corticotropin-releasing hormone (CRH) mRNA levels by 37% in the paraventricular nucleus (PVN) of the hypothalamus and decreased tyrosine hydroxylase (TH) mRNA levels by 40% in the locus coeruleus (LC). These changes were associated with a 70% increase in mRNA levels of the hippocampal mineralocorticoid receptor (MR, type I) that is thought to play an important role in mediating the negative feedback effects of low levels of steroids on the hypothalamic-pituitary-adrenal (HPA) axis. Imipramine also decreased proopiomelanocortin (POMC) mRNA levels by 38% and glucocorticoid receptor (GR, type II) mRNA levels by 51% in the anterior pituitary. With the exception of a 20% decrease in TH mRNA in the LC after 2 wk of imipramine administration, none of these changes in gene expression were evident as a consequence of short-term administration of the drug. In the light of data that major depression is associated with an activation of brain CRH and LC-NE systems, the time-dependent effect of long-term imipramine administration on decreasing the gene expression of CRH in the hypothalamus and TH in the LC may be relevant to the therapeutic efficacy of this agent in depression.

CBED contrast in the lower order Laue zone.

Contrast in a systematic arrangement of lower order Laue zone (LOLZ) beams is reported and analysed using a Bloch wave description. Observations are reported for hexagonal barium ruthenium zirconate (Ba4Ru3ZrO12) and barium ruthenium titanate (Ba3Ti2RuO9), both near the c-axis orientation. The specific scattering dynamics invoked by this diffraction geometry may have novel uses in the exploration of crystallographic parameters.

Cerebrospinal fluid immunoreactive corticotropin-releasing hormone and adrenocorticotropin secretion in Cushing's disease and major depression: potential clinical implications.

To explore whether possible differences in central nervous system neuromodulators contribute to the differential presentation of affective symptomatology in Cushing's disease and major depression, we examined the levels of immunoreactive CRH and ACTH in the cerebrospinal fluid (CSF) of 11 patients with Cushing's disease, a patient with ectopic ACTH secretion, 34 patients with major depression, and 60 healthy subjects. We elected to measure these peptides not only because both are classically involved in pituitary-adrenal regulation, but also because their primarily arousal-producing and anorexigenic behavioral effects in experimental animals suggest that they may play a role in the symptom complex of depressive syndromes. We also explored whether the CSF levels of these peptides were more helpful in determining the often difficult differential diagnosis between major depression and Cushing's disease than the plasma ACTH response to ovine CRH, a currently used but somewhat insensitive laboratory means of distinguishing these disorders. CSF levels of immunoreactive CRH and ACTH were significantly lower in Cushing's disease patients [21.9 +/- 2.7 and 15.4 +/- 1.8 pg/mL, (mean +/- SEM), respectively] compared to patients with major depression [38.4 +/- 2.3 pg/mL (P less than 0.01) and 24.5 +/- 1.6 pg/mL (P less than 0.01), respectively] and controls [38.4 +/- 1.6 pg/mL (P less than 0.001) and 26.3 +/- 1.1 pg/mL (P less than 0.001), respectively]. The coexistence of high plasma ACTH and low CSF ACTH in Cushing's disease yielded a CSF/plasma ACTH ratio consistently less than that in depressed patients, with only 2 of 31 subjects comprising both groups showing values that overlapped. In contrast, 9 of the combined patients showed ACTH responses to ovine CRH that overlapped. These data suggest that differences in centrally directed CRH secretion may account for the differential presentation of the dysphoric syndromes seen in major depression and Cushing's disease. Hence, the classic form of major depression (melancholia), is often associated with evidence of pathological hyperarousal, such as intense anxiety, sleeplessness, and anorexia, while that of Cushing's disease is associated with evidence of pathological hyperarousal, including hyperphagia, fatigue, and inertia. Moreover, measurement of the CSF/plasma ACTH ratio may serve as a clinically useful adjunct to the ovine CRH stimulation test and other laboratory measures in determining the differential diagnosis between major depression and Cushing's disease.

Radionuclide evaluation pre- and postextracorporeal shock wave lithotripsy for renal calculi.

Forty-two patients were evaluated pre- and postextracorporeal shock wave lithotripsy (ESWL) using [99mTc]DTPA renography. A quantitative evaluation showed that the relative renal function decreased 2-3 days post-ESWL on the treated side, and the parenchymal transit time index (PTTI) increased 2-3 days post-ESWL (p less than 0.001) on the treated side and returned to the pretreatment level by 3 wk post-ESWL. The untreated side showed an increase in PTTI 2-3 days post-ESWL (p less than 0.01), which returned to normal by 3 wk post-ESWL. A significantly greater increase in PTTI was seen in patients who received greater than 1,000 shocks as compared with those who received less than 1,000 shocks. Five patients developed obstructing uropathy post-ESWL, when stone fragments caused ureteric obstruction.

The human mineralocorticoid receptor gene promoter: its structure and expression.

The structure and expression of a clone containing the promoter region, all of exon 1, and part of the first intron of the human mineralocorticoid receptor (hMR) gene is presented. The clone has three sets of CAAT and TATA elements, one located at the very 5'-end of the clone, one located just 5'- to the start of transcription, and one set located in intron A, approximately 300 bp into the intron. The major start of transcription site by primer extension analysis and ribonuclease protection assays is located 26 bp downstream of a TATA-like box (TTTAA) and 90 and 143 bp downstream, respectively, of two CCAAT boxes. Putative cis-transcription factor binding sites are as follows: two potential AP1 sites, one potential AP2 site, two ATF/CREB sites, six potential GC boxes or SP1 sites, one potential perfect half-palindromic estrogen response element, and three potential PEA3 sites. Therefore, the hMR promoter region contains elements characteristic of both regulated genes and "housekeeping" genes. CAT assays of overlapping deletions of the promoter region demonstrated tissue-specific regulation in human neuroepithelioma (SK-N-MC-IXC) and non-neuronal, peripheral choriocarcinoma cell lines (JEG-3).

Initial human clinical experience with diode laser interstitial treatment of benign prostatic hyperplasia.

OBJECTIVES: To report the initial results of treatment of outlet obstruction induced by benign prostatic hyperplasia (BPH) using interstitial laser coagulation performed with the Indigo 830 nm diode laser system. METHODS: A group of 112 men with lower urinary tract symptoms caused by BPH underwent treatment with the Indigo 830 nm laser system between October 1994 and November 1995. Patients were assessed prior to treatment and at specified post-treatment intervals for symptom score, uroflow, postvoid residual, and prostate volume. Adverse events and changes in laboratory parameters were monitored at each post-treatment visit to investigate safety of the procedure. RESULTS: Symptom score decreased from 20.9 at initial measurement to 9.6 at 3 months after procedure and 7.9 at 6 months. Uroflow rate increased from 8.0 mL/s initially to 15.2 and 14.2 mL/s at 3 and 6 months, respectively. Residual bladder volumes decreased from 105 mL initially to 59 and 38 mL at 3 and 6 months, respectively. There were no major complications (impotence, sustained incontinence, significant blood loss). Minor complications occurred in a small number of patients but were generally associated with urinary tract infection in patients with catheters. Three patients (2.7%) required retreatment and underwent transurethral resection of the prostate. CONCLUSIONS: Interstitial laser coagulation using an 830-nm diode laser system appears to be a promising new treatment, with substantial improvements in objective and subjective parameters of obstruction and a favorable side-effect profile.

The antidepressants fluoxetine, idazoxan and phenelzine alter corticotropin-releasing hormone and tyrosine hydroxylase mRNA levels in rat brain: therapeutic implications.

Various classes of antidepressant drugs with distinct pharmacologic actions are differentially effective in the treatment of classic melancholic depression--characterized by pathological hyperarousal and atypical depression--associated with lethargy, hypersomnia, and hyperphagia. All antidepressant agents exert their therapeutic efficacy only after prolonged administration. In situ hybridization histochemistry was used to examine in rats the effects of short-term (2 weeks) and long-term (8 weeks) administration of 3 different classes of activating antidepressant drugs which tend to be preferentially effective in treating atypical depressions, on the expression of central nervous system genes thought to be dysregulated in major depression. Daily administration (5 mg/kg, i.p.) of the selective 5-hydroxytryptophan (5-HT) reuptake inhibitor fluoxetine, the selective alpha 2-adrenergic receptor antagonist idazoxan, and the nonspecific monoamine oxidase A and B inhibitor phenelzine increased tyrosine hydroxylase mRNA levels by 70-150% in the locus coeruleus after 2 weeks of drug and by 71-115% after 8 weeks. The 3 drugs decreased corticotropin-releasing hormone mRNA levels by 30-48% in the paraventricular nucleus of the hypothalamus. The decreases occurred at 8 weeks but not at 2 weeks. No consistent change in steroid hormone receptor mRNA levels was seen in the hippocampus with the 3 drugs, but fluoxetine and idazoxan increased the level of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA, respectively, after 8 weeks of drug administration. Proopiomelanocortin (POMC) mRNA levels in the anterior pituitary and plasma adrenocorticotropic-hormone (ACTH) levels were not altered after 2 or 8 weeks of drug treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Schizophrenic deficits: neuroleptics and the prefrontal cortex.

Modern techniques have been applied to brain modeling, based on recent approaches in the artificial intelligence field that use brain-like "connectionistic" computational architectures. The model proposed by Cohen and Servan-Schreiber uses a gain parameter which they identify with dopamine function. They apply their model to neuroleptically treated schizophrenia patients who show improved task performance which they link to increased dopamine function and increased gain in the prefrontal cortex. However, evidence indicates that antipsychotic medications block dopamine (especially D2) receptors, decreasing mesolimbic and mesocortical dopamine function. If therapeutic dosages of neuroleptics diminish dopamine function, this would decrease gain in context modules needed for adequate task performance. Schizophrenia patients would perform more poorly by further reducing gain in their already compromised context modules. The current investigators suggest three possible ways to resolve this difficulty, to explain why normals perform more poorly when taking neuroleptics, although acute schizophrenia patients' performance may be enhanced in several areas. Evidence would suggest that multiple processes occur simultaneously in neuroleptically treated patients with some processes counterbalancing others.

Arthritis-susceptible Lewis rats fail to emerge from the stress hyporesponsive period.

Susceptibility to streptococcal cell wall (SCW)-induced arthritis in 4- to 6-week-old Lewis (LEW/N) rats is associated with blunted glucocorticoid production secondary to a profound defect in inflammatory mediator-induced hypothalamic corticotropin-releasing hormone (CRH) biosynthesis and secretion. The relative SCW arthritis resistance in histocompatible Fischer (F344/N) rats, on the other hand, is associated with robust hypothalamic-pituitary-adrenal (HPA) axis responses to inflammatory mediators. In this study, we investigated HPA axis responses to SCW during the postnatal developmental period in LEW/N and F344/N rats. We found that SCW-induced plasma corticosterone (CORT) responses do not significantly increase during development in LEW/N, while such responses clearly appear at postnatal day 14 in F344/N and outbred Harlan-Sprague-Dawley (HSD) rats. Additionally, LEW/N rats fail to exhibit the normal ontogenic increase in CRH mRNA levels in the paraventricular nucleus (PVN), whereas their SCW-induced PVN CRH mRNA responses are blunted compared to F344/N at postnatal day 14. Taken together, these results suggest that LEW/N rats fail to emerge completely from their stress hyporesponsive period. This may account for the lack of stress responsiveness in young adult LEW/N rats, and consequently, for their susceptibility to SCW-induced arthritis and other inflammatory diseases.

The effects of a gonadotropin-releasing hormone agonist on testicular histology.

We have described the histologic changes in the testes of men treated with buserelin for prostatic cancer. If these changes are reversible, then the agonist analogues, together with testosterone replacement therapy, could be used safely for male contraception. If the changes are irreversible, then boys with central precocious puberty treated with such compounds would be of normal height, but sterile.

Catheter associated urinary tract infection and encrustation.

This paper examines the relationship between urinary pH, infection and urinary catheter encrustation and discusses the current management and problems of catheter associated urinary infection and encrustation.

Urinary encrustation of alloplastic materials.

Currently, all alloplastic materials placed within the urinary tract are susceptible to encrustation, and devices made from these biomaterials are prone to the associated complications. Encrustation is affected by such surface properties as roughness and irregularity, hydrophobicity and wetability, charge, polymer chemistry, and coatings. The composition of the surface may also influence reactivity at the interface. A raised urinary pH as a result of infection with urease-producing bacteria is an important mechanism of encrustation, but encrustation can take place in the absence of infection. Individual variations in the risk of encrustation have been identified. Better device designs are required, as are better models for examining biomaterials and biofilm formation. With a coordinated multidisciplinary approach and adequate resources, we may solve the problem of encrustation, which has such an adverse effect on patient quality of life and on healthcare costs.

Use of image enhancement during lithotripsy.

Renal excursion during breathing is inevitable and is a cause of poor localization during extracorporeal shock-wave lithotripsy (SWL), which in theory might lead to poor treatment results. Eighty-one patients underwent lithotripsy treatment with and without the use of an image enhancement system designed for use with the Dornier MPL9000 lithotripter. This device contains a memory incorporated into a separate differential grayscale monitor, which allows the stone image to be stored. Shockwave release is enabled only when this image corresponds to the real-time image on the lithotripter ultrasound monitor. No improvement in success rates was found using this system, although upper-pole stones appeared to be fragmented more successfully. Overall, the results were favorable in both groups after a single treatment. Further work is needed to establish whether image enhancement is capable of improving the success rates and reducing the side effects of lithotripsy by better targeting.

Extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy in children.

The possibilities for treating children with renal stone disease by extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrolithotomy (PCNL) have not been widely explored. We report ten children, aged between 5 and 16 years, treated by PCNL, and six children, aged between 6 and 15 years, treated by ESWL alone. A 16-year-old spina bifida child with a staghorn calculus was treated electively by a combination of the two methods. Hospital stay was 3 to 8 days for treatment by PCNL or ESWL, and was only 11 days for the combination treatment. Complete stone clearance was achieved in 12 children followed for 3 months. No significant complications occurred. ESWL and PCNL are suitable methods for the management of renal calculi in children.

The diagnosis of pelviureteric junction obstruction.

The distinction between a dilated upper urinary tract which is obstructed and a dilated but unobstructed system is of fundamental importance. This differentiation may be difficult to make with methods of diagnosis currently available. Standard intravenous urography provides good morphological information about the collecting system but is unreliable in the assessment of urodynamic upper tract function and renal parenchymal function. Pressure/flow studies may provide useful urodynamic information but the method has certain disadvantages. Standard probe renography is unreliable in differentiating upper urinary tract stasis from obstruction. A quantitative method of diuretic urography and a new quantitative gamma-camera renal radionuclide investigation are described and the results of these investigations are compared with urodynamic studies in patients with upper urinary tract obstruction at the level of the pelviureteric junction.