Artificially long legs directly enhance long sprint running performance.

This comment addresses the incomplete presentation and incorrect conclusion offered in the recent manuscript of Beck et al. (R. Soc. Open Sci. 9, 211799 (doi:10.1098/rsos.211799)). The manuscript introduces biomechanical and performance data on the fastest-ever, bilateral amputee 400 m runner. Using an advantage standard of not faster than the fastest non-amputee runner ever (i.e. performance superior to that of the intact-limb world record-holder), the Beck et al. manuscript concludes that sprint running performance on bilateral, lower-limb prostheses is not unequivocally advantageous compared to the biological limb condition. The manuscript acknowledges the long-standing support of the authors for the numerous eligibility applications of the bilateral-amputee athlete. However, it does not acknowledge that the athlete's anatomically disproportionate prosthetic limb lengths (+15 cm versus the World Para Athletics maximum) are ineligible in both Olympic and Paralympic track competition due to their performance-enhancing properties. Also not acknowledged are the slower sprint performances of the bilateral-amputee athlete on limbs of shorter length that directly refute their manuscript's primary conclusion. Our contribution here provides essential background information and data not included in the Beck et al. manuscript that make the correct empirical conclusion clear: artificially long legs artificially enhance long sprint running performance.

Model Selection for the Preclinical Development of New Drug-Radiotherapy Combinations.

Radiotherapy plays an essential role in the treatment of more than half of all patients with cancer. In recent decades, advances in devices that deliver radiation and the development of treatment planning software have helped radiotherapy attain precise tumour targeting with minimal toxicity to surrounding tissues. Simultaneously, as more targeted drug therapies are being brought into the market, there has been significant interest in improving cure rates for cancer by adding drugs to radiotherapy to widen the therapeutic window, the difference between normal tissue toxicity and treatment efficacy. The development of new combination therapies will require judicious adaptation of preclinical models that are routinely used for traditional drug discovery. Here we highlight the strengths and weaknesses of each of these preclinical models and discuss how they can be used optimally to identify new and clinically beneficial drug-radiotherapy combinations.

Genetic correlations between wool traits and meat quality traits in Merino sheep.

Genetic correlations between 29 wool production and quality traits and 25 meat quality and nutritional value traits were estimated for Merino sheep from an Information Nucleus (IN). Genetic correlations among the meat quality and nutritional value traits are also reported. The IN comprised 8 flocks linked genetically and managed across a range of sheep production environments in Australia. The wool traits included over 5,000 yearling and 3,700 adult records for fleece weight, fiber diameter, staple length, staple strength, fiber diameter variation, scoured wool color, and visual scores for breech and body wrinkle. The meat quality traits were measured on samples from the and included over 1,200 records from progeny of over 170 sires for intramuscular fat (IMF), shear force of meat aged for 5 d (SF5), 24 h postmortem pH (pHLL; also measured in the , pHST), fresh and retail meat color and meat nutritional value traits such as iron and zinc levels, and long-chain omega-3 and omega-6 polyunsaturated fatty acid levels. Estimated heritabilities for IMF, SF5, pHLL, pHST, retail meat color lightness (), myoglobin, iron, zinc and across the range of long-chain fatty acids were 0.58 ± 0.11, 0.10 ± 0.09, 0.15 ± 0.07, 0.20 ± 0.10, 0.59 ± 0.15, 0.31 ± 0.09, 0.20 ± 0.09, 0.11 ± 0.09, and range of 0.00 (eicosapentaenoic, docosapentaenoic, and arachidonic acids) to 0.14 ± 0.07 (linoleic acid), respectively. The genetic correlations between the wool production and meat quality traits were low to negligible and indicate that wool breeding programs will have little or no effect on meat quality. There were moderately favorable genetic correlations between important yearling wool production traits and the omega-3 fatty acids that were reduced for corresponding adult wool production traits, but these correlations are unlikely to be important in wool/meat breeding programs because they have high SE, and the omega-3 traits have little or no genetic variance. Significant genetic correlations among the meat quality traits included IMF with SF5 (-0.76 ± 0.24), fresh meat color * (0.50 ± 0.18), and zinc (0.41 ± 0.19). Selection to increase IMF will improve meat tenderness and color which may address some of the issues with Merino meat quality. These estimated parameters allow Merino breeders to combine wool and meat objectives without compromising meat quality.

Genetic parameters for wool traits, live weight, and ultrasound carcass traits in Merino sheep.

Genetic correlations between 29 wool production and quality traits and live weight and ultrasound fat depth (FAT) and eye muscle depth (EMD) traits were estimated from the Information Nucleus (IN). The IN comprised 8 genetically linked flocks managed across a range of Australian sheep production environments. The data were from a maximum of 9,135 progeny born over 5 yr from 184 Merino sires and 4,614 Merino dams. The wool traits included records for yearling and adult fleece weight, fiber diameter (FD), staple length (SL), fiber diameter CV (FDCV), scoured color, and visual scores for breech and body wrinkle. We found high heritability for the major yearling wool production traits and some wool quality traits, whereas other wool quality traits, wool color, and visual traits were moderately heritable. The estimates of heritability for live weight generally increased with age as maternal effects declined. Estimates of heritability for the ultrasound traits were also higher when measured at yearling age rather than at postweaning age. The genetic correlations for fleece weight with live weights were positive (favorable) and moderate (approximately 0.5 ± 0.1), whereas those with FD were approximately 0.3 (unfavorable). The other wool traits had lower genetic correlations with the live weights. The genetic correlations for FAT and EMD with FD and SL were positive and low, with FDCV low to moderate negative, but variable with wool weight and negligible for the other wool traits. The genetic correlations for FAT and EMD with postweaning weight were positive and high (0.61 ± 0.18 to 0.75 ± 0.14) but were generally moderate with weights at other ages. Selection for increased live weight will result in a moderate correlated increase in wool weight as well as favorable reductions in breech cover and wrinkle, along with some unfavorable increases in FD and wool yellowness but little impact on other wool traits. The ultrasound meat traits, FAT and EMD, were highly positively genetically correlated (0.8), and selection to increase them would result in a small unfavorable correlated increase in FD, moderately favorable reductions in breech cover and wrinkle, but equivocal or negligible changes in other wool traits. The estimated parameters provide the basis for calculation of more accurate Australian Sheep Breeding Values and selection indexes that combine wool and meat objectives in Merino breeding programs.

Genetic correlations between wool traits and carcass traits in Merino sheep.

Genetic correlations between 29 wool production and quality traits and 14 whole carcass measures and carcass component traits were estimated from the Information Nucleus of 8 flocks managed across a range of Australian sheep production environments and genetically linked. Wool data were from over 5,000 Merino progeny born over 5 yr, whereas carcass data were from over 1,200 wether progeny of over 176 sires, slaughtered at about 21 kg carcass weight, on average. Wool traits included yearling and adult records for wool weight, fiber diameter, fiber diameter variation, staple strength, scoured color, and visual scores for breech and body wrinkle. Whole carcass measures included HCW, dressing percentage (DP), and various measures of fat depth and eye muscle dimensions. Carcass components were obtained by dissection, and lean meat yield (LMY) was predicted. Heritability estimates for whole carcass measures ranged from 0.12 ± 0.08 to 0.35 ± 0.10 and ranged from 0.17 ± 0.10 to 0.46 ± 0.10 for carcass dissection traits, with no evidence of important genotype × environment interactions. Genetic correlations indicated that selection for increased clean wool weight will result in reduced carcass fat (-0.17 to -0.34) and DP (-0.48 ± 0.15), with little effect on carcass muscle. Selection for lower fiber diameter will reduce HCW (-0.48 ± 0.15) as well as carcass fat (0.14 to 0.27) and muscle (0.21 to 0.50). There were high genetic correlations between live animal measures of fat and muscle depth and the carcass traits (generally greater than 0.5 in size). Selection to increase HCW (and DP) will result in sheep with fewer wrinkles on the body (-0.57 ± 0.10) and barer breeches (-0.74 ± 0.12, favorable), with minor deterioration in scoured wool color (reduced brightness and increased yellowness). Selection for reduced fat will also result in sheep with fewer body wrinkles (-0.42 to -0.79). Increasing LMY in Merinos through selection would result in a large reduction in carcass fat and DP (-0.66 to -0.84), with a smaller increase in carcass muscle and some increase in wool weight and wrinkles. Although no major antagonisms are apparent between the wool and carcass traits, developing selection indexes for dual-purpose wool and meat breeding objectives will require accurate estimates of genetic parameters to ensure that unfavorable relationships are suitably considered. The findings will aid development of dual-purpose wool and meat breeding objectives.

Occurrence of methicillin-resistant Staphylococcus aureus in surface waters near industrial hog operation spray fields.

Industrial hog operations (IHOs) have been identified as a source of antibiotic-resistant Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). However, few studies have investigated the presence of antibiotic-resistant S. aureus in the environment near IHOs, specifically surface waters proximal to spray fields where IHO liquid lagoon waste is sprayed. Surface water samples (n=179) were collected over the course of approximately one year from nine locations in southeastern North Carolina and analyzed for the presence of presumptive MRSA using CHROMagar MRSA media. Culture-based, biochemical, and molecular tests, as well as matrix-assisted laser desorption/ionization-time of flight mass spectrometry were used to confirm that isolates that grew on CHROMagar MRSA media were S. aureus. Confirmed S. aureus isolates were then tested for susceptibility to 16 antibiotics and screened for molecular markers of MRSA (mecA, mecC) and livestock adaptation (absence of scn). A total of 12 confirmed MRSA were detected in 9 distinct water samples. Nine of 12 MRSA isolates were also multidrug-resistant (MDRSA [i.e., resistant to ≥3 antibiotic classes]). All MRSA were scn-positive and most (11/12) belonged to a staphylococcal protein A (spa) type t008, which is commonly associated with humans. Additionally, 12 confirmed S. aureus that were methicillin-susceptible (MSSA) were recovered, 7 of which belonged to spa type t021 and were scn-negative (a marker of livestock-adaptation). This study demonstrated the presence of MSSA, MRSA, and MDRSA in surface waters adjacent to IHO lagoon waste spray fields in southeastern North Carolina. To our knowledge, this is the first report of waterborne S. aureus from surface waters proximal to IHOs.

Lamb survival in Australian Merino sheep: a genetic analysis.

Direct and maternal components of variance for lamb survival to birth, 7 d, and weaning (110 d) were estimated by REML procedures in a flock of Australian Merino sheep. A total of 14,142 lambs, the progeny of 421 sires and 3,666 dams, born between 1975 and 1983 were available for analysis. The study has produced some of the most precise estimates of genetic parameters for lamb survival in the Australian Merino. Very low heritabilities for lamb viability (0.03) and the performance of the dam or ewe rearing ability (0.07) suggest that genetic solutions to lamb survival are unlikely to be significant. But, despite the low heritabilities, there is still potential for improvement through selective breeding. The estimated repeatability of at least 0.10 shows that multiple records on the rearing ability of a ewe over its lifetime can increase selection accuracy. More importantly, such repeatabilities indicate that current generation improvement can be achieved by culling ewes from the breeding flock with poor rearing ability. Despite maternal bond score and lamb birth weight being highly repeatable and moderately heritable traits, correlations with lamb survival were essentially zero. These traits therefore have no value as indirect selection criteria for Merino lamb survival.

Phenotypic aspects of lamb survival in Australian Merino sheep.

Lamb survival in Australian Merino sheep was investigated using survival records from 14,142 lambs born between 1975 and 1983. This data set included roll calls of live lambs at birth, 7 d, marking (30 d), and weaning (110 d), which allowed 4 binomial traits (alive or dead) to be recorded for each lamb at each time interval. The average survival to weaning was 72.4% with 23% of singles, 32% of twins, and 45% of multiple-born lambs not surviving to weaning. The timing of lamb loss was consistent across birth types; 6% died within 24 h of birth, a further 14% by 7 d, 3% between 7 and 30 d, and 8% between 30 and 110 d. Partitioning of phenotypic variation revealed that after the first postpartum week, mothering ability of Australian Merino ewes is not an important factor in lamb survival. Some ewes repeatedly lose lambs at birth and in the early postnatal period, but the intraclass correlation decreased by a factor of 10 for survival after 7 d of age (0.096 at birth and 0.100 at 7 d, falling to 0.009 at marking and 0.018 at weaning). This study examined the relationships of lamb survival with lamb birth weight and found varying relationships at each time period. Whereas birth weight had a highly significant curvilinear relationship with survival to weaning, the relationship was flatter for survival to 24 h with only small differences between average birth weights and the birth weight at which survival was optimized (-0.04, 0.28, and 0.54 kg for single-, twin-, and multiple-born lambs, respectively). This suggests that any management interventions to increase birth weight may increase the risk of death to both lamb and ewe during the lambing process due to dystocia. Among twin-born lambs there was a carryover effect of losses at birth on subsequent loss in the first week of life. Survival to 7 d of age was highly dependent on the survival of the littermate, favoring those whose littermate survived, but after the first week, this trend was reversed. Lamb birthcoat score had a small positive impact on survival only at birth.

WITHDRAWN: Antidepressants for depression in medical illness.

BACKGROUND: Depression in the physically unwell is common and an important cause of morbidity. There are problems with diagnosing depression in the physically ill which may lead to under-recognition and under-treatment. In clinical practice antidepressants are available and a feasible option for treating depressive disorders. Therefore we thought it would be a reasonable first step in addressing this problem to describe the literature of randomised controlled trials in this area. OBJECTIVES: To determine whether antidepressants are clinically effective and acceptable for the treatment of depression in people who also have a physical illness. SEARCH STRATEGY: MEDLINE, Cochrane Library Trials Register and Cochrane Depression and Neurosis Group Trials Register were all systematically searched, supplemented by hand searches of two journals and reference searching. SELECTION CRITERIA: All relevant randomised trials comparing any antidepressant drug (as defined in the British National Formulary) with placebo or no treatment, in patients of either sex over 16, who have been diagnosed as depressed by any criterion, and have a specified physical disorder (for example cancer, myocardial infarction). "Functional" disorders where there is no generally agreed physical pathology (e.g. irritable bowel syndrome) were excluded. The main outcome measures are numbers of individuals who recover/improve at the end of the trial and, as a proxy for treatment acceptability, numbers who complete treatment. DATA COLLECTION AND ANALYSIS: Data was extracted independently by the reviewers onto data collection forms and differences settled by discussion. MAIN RESULTS: 18 studies were included, covering 838 patients with a range of physical diseases (cancer 2, diabetes 1, head injury 1, heart 1, HIV 5, lung 1, multiple sclerosis 1, renal 1, stroke 3, mixed 2). Depression was diagnosed clinically in 3 studies, otherwise by structured interview or checklist. Only 5 studies described how they performed randomisation. 1 study compared drug with no treatment, and the rest with placebo: all of the latter said they were double blind.6 studies used SSRIs, 3 atypical antidepressants, and the remainder tricyclics.Patients treated with antidepressants were significantly more likely to improve than those given placebo (13 studies, OR 0.37, 95% CI 0.27-0.51) or no treatment (1 study, OR 3.45, 95% CI 11.1-1.10). About 4 patients would need to be treated with antidepressants to produce one recovery from depression which would not have occurred had they been given placebo (NNT 4.2, 95% CI 3.2-6.4). Most antidepressants (tricyclics and SSRIs together, 15 trials ) produced a small but significant increase in dropout (OR 1.66, 95% CI 1.14-2.40. NNH 9.8, 95% CI 5.4-42.9). The "atypical" antidepressant mianserin produced significantly less dropout than placebo. Only 2 studies used numerical scales designed to measure effects on function and quality of life; in HIV (Karnofsky scale), drug was better than no treatment; in lung disease (Sickness Impact Profile), drug was not significantly different from placebo. Only 7 studies reported looking for changes in the physical disease. Antidepressants produced no change in immune function in HIV relative to placebo (2 studies) or no treatment (1 study). Relative to placebo, antidepressants produced no change in cardiovascular function in heart disease, in respiratory function in lung disease, or in vital signs or laboratory tests in cancer (1 study each). Nortriptyline produced worse control in diabetes. Trends towards tricyclics being more effective than SSRIs, but also more likely to produce dropout were noted, but these are based on non-randomised comparisons between trials. AUTHORS' CONCLUSIONS: The review provides evidence that antidepressants, significantly more frequently than either placebo or no treatment, cause improvement in depression in patients with a wide range of physical diseases. About 4 patients would need to be treated with antidepressants to produce one recovery from depression which would not have occurred had they been given placebo (NNT 4.2, 95% CI 3.2-6.4). Antidepressants seem reasonably acceptable to patients, in that about 10 patients would need to be treated with antidepressants to produce one dropout from treatment which would not have occurred had they been given placebo (NNH 9.8, 95% CI 5.4-42.9).The evidence is consistent across the trials, apart from 2 trials in cancer, where the "atypical" antidepressant mianserin produced significantly less dropout than placebo. Trends towards tricyclics being more effective than SSRIs, but also more likely to produce dropout were noted, but these are based on non-randomised comparisons between trials. Problems with the evidence include most of the trials' use of observers, rather than patients, to decide on improvement, and concentration mainly on symptoms rather than function and quality of life. There is also a possibility of undetected negative trials.Nevertheless, the review provides evidence that use of antidepressants should at least be considered in those with both physical illness and depression. Regarding diagnosis, the existence of a cheap and readily available treatment for depression should encourage detailed assessment of persistent low mood in the physically ill.

Aprotinin and epsilon aminocaproic acid are effective in reducing blood loss after primary total hip arthroplasty--a prospective randomized double-blind placebo-controlled study.

A prospective randomized double-blind placebo-controlled study was undertaken to determine the efficacy and mechanism of action of two antifibrinolytic drugs aprotinin and epsilon aminocaproic acid (EACA) in reducing blood loss in primary unilateral total hip arthroplasty (THA). Aprotinin was administered as a bolus of 2 x 10(6) kallikrein inhibitor units (KIU) followed by 0.5 x 10(6) KIU h(-1) for 3 h, EACA was given as 10 g over 30 min followed by 5 g over 3 h. The median postoperative blood loss 24 h postoperatively was reduced from 450 mL in the placebo group to 180 mL for aprotinin (60% reduction, P < 0.001) and to 210 mL for EACA (53% reduction, P < 0.01). In this population, there was no reduction in the perioperative transfusion requirements. The mechanism of both drugs was independent of platelets as indicated by flow cytometric measurement of change of their expression of P-selectin, platelet-monocyte aggregates, V/Va and CD40 ligand. There were no thrombotic or infective complications and no adverse events were attributable to use of either drug. Infusion of either aprotinin or EACA at the doses described is a safe and effective means of reducing blood loss after THA. These therapies provide a means of reducing blood loss in THA patients.

Feasibility of using the TOSCA telescreening procedures for diabetic retinopathy.

AIMS: The TOSCA project was set up to establish a tele-ophthalmology service to screen for diabetic retinopathy (DR) in Europe. The aim of this study was to determine the feasibility of establishing telemedicine-based digital screening for detecting DR and to evaluate the satisfaction of both patients and healthcare professionals with the screening procedures used within the TOSCA project. METHODS: The study was a non-randomized, multicentre study carried out in four different countries over a period of 3 months. Patients (n = 390) with diabetes aged > 12 years were included. Two digital retinal images per eye (macular and nasal) were taken and exported to a central server. Patients were asked to complete a questionnaire to assess satisfaction. Accredited graders carried out grading remotely and the results were reported back to the referring centre. Previously graded patient data chosen randomly to represent examples of both DR and no DR were also sent anonymously to the grading centre at a frequency of approximately every 10 patients. RESULTS: Most (99%) of the images were assessable enabling a retinopathy grade to be assigned to the patient. Patients found the retinal photography procedures acceptable; only 6% in one centre would not recommend the procedure. Healthcare professionals (photographers and graders) were also satisfied with the overall procedures. The average time taken to grade each patient was approximately 5 min. CONCLUSIONS: This study demonstrated that it is feasible to electronically transmit and grade retinal images remotely using the TOSCA process. Built-in quality assurance procedures proved acceptable.

Physical activity and exercise training prescriptions for patients.

The dominant outcome from exercise prescription is an increase in various markers of exercise capacity. A very large group of studies have demonstrated that the VO2max is increased in response to exercise performed according to well-accepted principles of exercise prescription. Other markers of exercise capacity, such as the VT, also improve substantially following exercise training. Finally, improvement in exercise capacity is generally related to improved quality of life, particularly in patients with exercise capacity limited by various disease processes. Beyond the specific physiologic gains from training, exercise contributes to a better overall clinical outcome. Although there are few data conclusively demonstrating that exercise independently causes favorable changes in other risk factors, it should be recognized that exercise can contribute indirectly to modulation of other risk factors. Exercise represents positive health advice. Since most of our other recommendations to patients are in the nature of negative advice (e.g., don't smoke, don't eat high-fat foods), and since people are infamous for ignoring negative advice, the value of using a positive recommendation that may indirectly lead the patient to discontinue bad behaviors can hardly be overstated.

Antidepressants for depression in medical illness.

OBJECTIVES: To determine whether antidepressants are clinically effective and acceptable for the treatment of depression in people who also have a physical illness. SEARCH STRATEGY: Medline, Cochrane Library Trials Register and Cochrane Depression and Neurosis Group Trials Register were all systematically searched, supplemented by hand searches of two journals and reference searching. SELECTION CRITERIA: All relevant randomised trials comparing any antidepressant drug (as defined in the British National Formulary) with placebo or no treatment, in patients of either sex over 16, who have been diagnosed as depressed by any criterion, and have a specified physical disorder (for example cancer, myocardial infarction). "Functional" disorders where there is no generally agreed physical pathology (e.g. irritable bowel syndrome) were excluded. The main outcome measures are numbers of individuals who recover/improve at the end of the trial and, as a proxy for treatment acceptability, numbers who complete treatment. DATA COLLECTION AND ANALYSIS: Data was extracted independently by the reviewers onto data collection forms and differences settled by discussion. MAIN RESULTS: 18 studies were included, covering 838 patients with a range of physical diseases (cancer 2, diabetes 1, head injury 1, heart 1, HIV 5, lung 1, multiple sclerosis 1, renal 1, stroke 3, mixed 2). Depression was diagnosed clinically in 3 studies, otherwise by structured interview or checklist. Only 5 studies described how they performed randomisation. 1 study compared drug with no treatment, and the rest with placebo: all of the latter said they were double blind. 6 studies used SSRIs, 3 atypical antidepressants, and the remainder tricyclics. Patients treated with antidepressants were significantly more likely to improve than those given placebo (13 studies, OR 0.37, 95% CI 0.27-0.51) or no treatment (1 study, OR 3.45, 95% CI 11.1-1.10). About 4 patients would need to be treated with antidepressants to produce one recovery from depression which would not have occurred had they been given placebo (NNT 4.2, 95% CI 3.2-6.4). Most antidepressants (tricyclics and SSRIs together, 15 trials ) produced a small but significant increase in dropout (OR 1.66, 95% CI 1.14-2.40. NNH 9.8, 95% CI 5.4-42.9). The "atypical" antidepressant mianserinproduced significantly less dropout than placebo. Only 2 studies used numerical scales designed to measure effects on function and quality of life; in HIV (Karnofsky scale), drug was better than no treatment; in lung disease (Sickness Impact Profile), drug was not significantly different from placebo. Only 7 studies reported looking for changes in the physical disease. Antidepressants produced no change in immune function in HIV relative to placebo (2 studies) or no treatment (1 study). Relative to placebo, antidepressants produced no change in cardiovascular function in heart disease, in respiratory function in lung disease, or in vital signs or laboratory tests in cancer (1 study each). Nortriptyline produced worse control in diabetes. Trends towards tricyclics being more effective than SSRIs, but also more likely to produce dropout were noted, but these are based on non-randomised comparisons between trials. REVIEWER'S CONCLUSIONS: The review provides evidence that antidepressants, significantly more frequently than either placebo or no treament, cause improvement in depression in patients with a wide range of physical diseases. About 4 patients would need to be treated with antidepressants to produce one recovery from depression which would not have occurred had they been given placebo (NNT 4.2, 95% CI 3.2-6.4). Antidepressants seem reasonably acceptable to patients, in that about 10 patients would need to be treated with antidepressants to produce one dropout from treatment which would not have occurred had they been given placebo (NNH 9.8, 95% CI 5.4-42.9). The evidence is consistent across the trials, apart from 2 trials in cancer, where the "atypical" antidepressant mianserin produced significantly less dropout than placebo. Trends towards tricyclics being more effective than SSRIs, but also more likely to produce dropout were noted, but these are based on non-randomised comparisons between trials. Problems with the evidence include most of the trials' use of observers, rather than patients, to decide on improvement, and concentration mainly on symptoms rather than function and quality of life. There is also a possibility of undetected negative trials. Nevertheless, the review provides evidence that use of antidepressants should at least be considered in those with both physical illness and depression. Regarding diagnosis, the existence of a cheap and readily available treatment for depression should encourage detailed assessment of persistent low mood in the physically ill.

T-cell lymphoproliferative disorder in an aged rhesus macaque.

A CD8+ T-cell leukemia was diagnosed in an aged female rhesus macaque. Although leukemia and lymphoma in nonhuman primates are commonly associated with simian T-lymphotropic virus, gibbon ape leukemia virus, oncogenic herpesviruses, and types C, D, and E retroviruses, this monkey was not infected with any of these viruses. However, the monkey did have antibodies against herpesvirus saimiri. This likely represents cross-reactivity of the herpesvirus saimiri assay with rhesus monkey rhadinovirus (RRV) antibodies; RRV was first described in rhesus macaques that were identified as having antibodies against herpesvirus saimiri. Rhesus rhadinovirus is a gamma herpesvirus, related antigenically to herpesvirus saimiri and Kaposi's sarcoma-associated herpesvirus (KSHV), which have been linked to lymphoproliferative disorders in primates and humans, respectively. Moreover, an oncogene has been recently identified in the RRV genome that is equivalent in position to the herpesvirus saimiri and KSHV oncogenes. Presently, the association of RRV infection with disease in nonhuman primates is unknown.

Biphenotypic sarcoma with characteristics of both a Ewing sarcoma and a desmoplastic small round cell tumor.

BACKGROUND: The EWS gene, a transcription factor of unknown function, is involved in chromosomal translocations associated with a wide variety of tumors, particularly small round blue cell tumors such as Ewing sarcoma. It has previously been reported that desmoplastic small round blue cell tumor (DSRBCT) frequently has an associated t(11;22) abnormality resulting from fusion of the EWS and WT-1 genes. PROCEDURE: We report a case of a small round blue cell tumor with characteristics of both Ewing sarcoma and DSRBCT with a t(11;22) translocation leading to fusion of the EWS and FLI1genes. RESULTS: The translocation point and fusion products were confirmed by polymerase chain reaction amplification and restriction fragment mapping of the products. CONCLUSIONS: The biphenotypic nature of this case and the apparent promiscuity of the EWS gene in tumor-associated translocations coupled with other reports of biphenotypic childhood sarcomas has potential implications for the relationship between small round blue cell tumors and the mechanism of EWS/FLI1 oncogenesis.

Antidepressants for depression in people with physical illness.

OBJECTIVES: To determine whether antidepressants are clinically effective and acceptable for the treatment of depression in people who also have a physical illness. SEARCH STRATEGY: Medline, Cochrane Library Trials Register and Cochrane Depression and Neurosis Group Trials Register were all systematically searched, supplemented by hand searches of two journals and reference searching. SELECTION CRITERIA: All relevant randomised trials comparing any antidepressant drug (as defined in the British National Formulary) with placebo or no treatment, in patients of either sex over 16, who have been diagnosed as depressed by any criterion, and have a specified physical disorder (for example cancer, myocardial infarction). "Functional" disorders where there is no generally agreed physical pathology (e.g. irritable bowel syndrome) were excluded. The main outcome measures are numbers of individuals who recover/improve at the end of the trial and, as a proxy for treatment acceptability, numbers who complete treatment. DATA COLLECTION AND ANALYSIS: Data was extracted independently by the reviewers onto data collection forms and differences settled by discussion. MAIN RESULTS: 18 studies were included, covering 838 patients with a range of physical diseases (cancer 2, diabetes 1, head injury 1, heart 1, HIV 5, lung 1, multiple sclerosis 1, renal 1, stroke 3, mixed 2). Depression was diagnosed clinically in 3 studies, otherwise by structured interview or checklist. Only 5 studies described how they performed randomisation. 1 study compared drug with no treatment, and the rest with placebo: all of the latter said they were double blind. 6 studies used SSRIs, 3 atypical antidepressants, and the remainder tricyclics. Patients treated with antidepressants were significantly more likely to improve than those given placebo (13 studies, OR 0.37, 95% CI 0.27-0.51) or no treatment (1 study, OR 3.45, 95% CI 11.1-1.10). About 4 patients would need to be treated with antidepressants to produce one recovery from depression which would not have occurred had they been given placebo (NNT 4.2, 95% CI 3.2-6.4). Most antidepressants (tricyclics and SSRIs together, 15 trials ) produced a small but significant increase in dropout (OR 1.66, 95% CI 1.14-2.40. NNH 9.8, 95% CI 5.4-42.9). The "atypical" antidepressant mianserinproduced significantly less dropout than placebo. Only 2 studies used numerical scales designed to measure effects on function and quality of life; in HIV (Karnofsky scale), drug was better than no treatment; in lung disease (Sickness Impact Profile), drug was not significantly different from placebo. Only 7 studies reported looking for changes in the physical disease. Antidepressants produced no change in immune function in HIV relative to placebo (2 studies) or no treatment (1 study). Relative to placebo, antidepressants produced no change in cardiovascular function in heart disease, in respiratory function in lung disease, or in vital signs or laboratory tests in cancer (1 study each). Nortriptyline produced worse control in diabetes. Trends towards tricyclics being more effective than SSRIs, but also more likely to produce dropout were noted, but these are based on non-randomised comparisons between trials. REVIEWER'S CONCLUSIONS: The review provides evidence that antidepressants, significantly more frequently than either placebo or no treatment, cause improvement in depression in patients with a wide range of physical diseases. About 4 patients would need to be treated with antidepressants to produce one recovery from depression which would not have occurred had they been given placebo (NNT 4.2, 95% CI 3.2-6.4). Antidepressants seem reasonably acceptable to patients, in that about 10 patients would need to be treated with antidepressants to produce one dropout from treatment which would not have occurred had they been given placebo (NNH 9.8, 95% CI 5.4-42.9). (ABSTRACT TRUNCATED)

p53 expression and relation to human papillomavirus infection in pingueculae, pterygia, and limbal tumors.

BACKGROUND: The tumor suppressor gene p53 is expressed without apoptosis in the limbal basal stem cells of all pterygia and limbal tumors and most pingueculae from which these growths seem to originate. Oncogenic human papillomaviruses (HPVs) have been found in pterygia and limbal tumors, and HPV and p53 overexpression commonly coexist in oropharyngeal and penile carcinomas. OBJECTIVE: To search for HPV DNA as a cofactor in the development of pingueculae, pterygia, and limbal tumors. METHODS: We examined specimens--1 of pinguecula, 13 of pterygia (7 primary, 1 recurrent, 1 with dysplasia, and 4 primary not tested for p53), and 10 of limbal tumors (2 with actinic keratosis dysplasia, 1 with conjunctival intraepithelial neoplasia, 3 with carcinoma in situ, and 4 with squamous cell carcinoma)-expressing p53. Specimens were tested for the presence of HPV DNA by the polymerase chain reaction using degenerate consensus primers for the highly conserved portion of the L1 region that encodes a capsid protein of the virus. This assay has a wide spectrum with capability of detecting essentially all known HPV types. Nested polymerase chain reaction was performed on all specimens. Primers of the cystic fibrosis gene were used to confirm the presence of genomic DNA and to rule out inhibitors. Purified HPV DNA type 11 was the positive control, and HPV-negative genomic DNA was the negative control. RESULTS: Using consensus primers for the highly conserved portion of the L1 region, all specimens of pingueculae, pterygia, and limbal tumors studied were negative for HPV DNA by nested polymerase chain reaction. CONCLUSIONS: Human papillomavirus DNA is not required as a cofactor in the development of pterygia and limbal tumors. These data support the theory that increased p53 expression in the limbal epithelia of pingueculae, pterygia, and limbal tumors indicates the probable existence of p53 mutations in these cells as an early event in their development, which is consistent with UV irradiation causation. Thus, due to a damaged p53-dependent programmed cell death mechanism, mutations in other genes may be progressively acquired. This would allow for the multistep development of pterygia and limbal tumor cells from p53-mutated limbal epithelial basal stem cells overlying pingueculae.

A systematic review of the treatment of depression with antidepressant drugs in patients who also have a physical illness.

To determine whether antidepressants are clinically effective and acceptable for the treatment of depression in people who also have a physical illness. The method used was a systematic review of all randomised controlled trials (found by computer and hand searches) comparing any antidepressant drug with placebo or no treatment, in depressed adults with a specified physical disorder. The main outcome measures are numbers of individuals who recover/improve at the end of the trial and, as a proxy for treatment acceptability, numbers who complete treatment. 18 studies were included, covering 838 patients with a range of physical diseases. 6 studies used SSRIs, 3 atypical antidepressants, and the remainder tricyclics. Patients treated with antidepressants were significantly more likely to improve than those given placebo: about 4 patients would need to be treated with antidepressants to produce one recovery from depression which would not have occurred had they been given placebo (NNT 4.2, 95% CI 3.2-6.4). Most antidepressants (tricyclics and SSRIs together, 15 trials) produced a small but significant increase in dropout (OR 1.66, 95% CI 1.14-2.40. NNH 9.8, 95% CI 5.4-42.9). The "atypical" antidepressant mianserin produced significantly less dropout than placebo. Trends towards tricyclics being more effective than SSRIs, but also more likely to produce dropout were noted. The review provides evidence that antidepressants, significantly more frequently than either placebo or no treatment, cause improvement in depression in patients with a wide range of physical diseases.

Suicide in Auckland 1989 to 1997.

AIM: The aim of this study was to describe the population of people who had committed suicide in Auckland in the nine years, 1989 to 1997. METHODS: We extracted data from the police records to the coroner and the autopsy reports on people who had killed themselves in the Auckland coronial region. RESULTS: Suicide is common and disproportionately affects young men, the unemployed and sickness beneficiaries. Few people who kill themselves appear to be in contact with the mental health services. CONCLUSIONS: For effective prevention, up to date local information on suicide and deliberate self-harm is needed.

Medicolegal aspects of managing deliberate self-harm in the emergency department.

Deliberate self-harm is a common reason for people to present to hospital. The management of this problem can cause ethical and legal difficulties to clinicians. This article describes a case of deliberate self-harm which we have used to illustrate answers to commonly asked questions about this difficult area. We make a case for such patients to be treated against their will under common law unless the use of the mental health act is clearly indicated. The Privacy Act appears to prohibit clinicians informing families about an episode of deliberate self-harm if the patient refuses consent. Clarification of "imminent threat to life or health" in the Privacy Act is needed.