Search

In the bodybuilding and fitness communities, anecdotal evidence suggests that some take ‘steroid holidays’, traveling to and living in foreign countries so as to have greater access to performance ...

The Oregon Coast landscape displays strong spatial patterns in air temperature, precipitation, and geology, which can confound our ability to detect relationships among land management, instream conditions, and fish at broad spatial scales. Despite this structure, we found that a suite of immutable or intrinsic attributes (e.g., reach gradient, drainage area, elevation, and percent weak rock geology of the catchments draining to each of our 423 study reaches) could explain much of the variation in pool surface area across the landscape and could contribute to an estimate of how many juvenile coho salmon (Oncorhynchus kisutch) one might expect to find in those pools. Further, we found evidence of differences in pool surface area across land ownership categories that reflect differing management histories. Our results also suggest that historical land and river management activities, in particular splash dams that occurred at least 50 years ago, continue to influence the distribution of juvenile coho salmon and their habitats today.

Key points Oxygen is vital for life-sustaining aerobic respiration in humans and is arguably the most commonly administered drug in anaesthesia and critical care medicine. Within the mitochondrial inner membrane, oxygen acts as the terminal electron acceptor at the end of the electron transport chain whereby oxidative phosphorylation results in the synthesis of adenosine triphosphate (ATP), the coenzyme that supplies energy to all active metabolic processes. This article will discuss the key physiological concepts underpinning the movement of oxygen within the human body and also highlight some clinical applications that serve as examples of these concepts. With respect to human physiology, oxygen transport can be divided into that occurring through convection and that occurring by diffusion. In this context, convection describes the movement of oxygen within the circulation, occurring through bulk transport. This is an active process requiring energy, in this case derived from the pumping of the heart. On the other hand, diffusion describes the passive movement of oxygen down a concentration gradient, for example, from the microcirculation into the tissues (and ultimately the mitochondria). ### Oxygen uptake into the blood Deoxygenated venous blood becomes oxygenated in the pulmonary capillaries after diffusion down a concentration gradient across the alveolar capillary membrane (see Section 2: diffusive oxygen transport). The …

The canine variant of the rabies virus has been eliminated in the United States. Among the public and many healthcare providers, however, dog bites are still associated with risk for rabies transmission. This study examined the risk of rabies in biting dogs and the use of rabies post-exposure prophylaxis (rPEP) for dog bite victims in Tennessee. The study included a retrospective analysis of laboratory testing requisitions for dogs from 2002 to 2016, collection of clinical data on confirmed rabies-positive dogs from 2008 to 2016 and analysis of hospital discharge data for rPEP from 2007 to 2014. Among dogs submitted for rabies testing, those having a recent history of biting were significantly less likely to test positive for rabies than dogs with no reported bite (OR = 0.01; 95% CI [0.003-0.04]). The most common clinical signs reported among rabies-positive dogs were anorexia, dysphagia, ataxia, limb paresis or paralysis, and lethargy; aggressiveness was uncommon. Among hospital patients with an animal-related injury who received rPEP, more than half (52%) presented with dog bites. These data show that laboratory submissions for rabies testing and prescriptions for rPEP do not reflect the epidemiology of rabies in Tennessee. Education and outreach targeting the public and healthcare providers should emphasize the animal species and situations associated with a greater risk for rabies transmission, such as bites from rabies reservoir species or animals exhibiting signs of neurologic disease.

Objective: The largest outbreak of Legionnaires Disease (LD) in the UK for a decade occurred in Edinburgh in June 2012. We describe the clinical and public health management of the outbreak. Setting: Three acute hospitals covering an urban area of ∼480 000. Methods: Data were collected on confirmed and suspected cases and minutes of the Incident Management Team meetings were reviewed to identify key actions. Results: Over 1600 urine samples and over 600 sputum samples were tested during the outbreak. 61 patients with pneumonia tested positive for Legionella pneumophila serogroup 1 by urinary antigen detection, culture, respiratory PCR or serology. A further 23 patients with pneumonia were treated as suspected cases on clinical and epidemiological grounds but had no microbiological diagnosis. 36% of confirmed and probable cases required critical care admission. Mean ICU length of stay was 11.3 (±7.6) days and mean hospital length of stay for those who were admitted to ICU was 23.0 (±17.2) days. For all hospitalized patients the mean length of stay was 15.7 (±14) days. In total there were four deaths associated with this outbreak giving an overall case fatality of 6.5%. Hospital and critical care mortality was 6.1% and 9.1%, respectively. Conclusions: A significant proportion of patients required prolonged multiple organ support or complex ventilation. Case fatality compared favourably to other recent outbreaks in Europe. Access to rapid diagnostic tests and prompt antibiotic therapy may have mitigated the impact of pre-existing poor health among those affected.

Aquatic monitoring programs vary widely in objectives and design. However, each program faces the unifying challenge of assessing conditions and quantifying reasonable expectations for measured indicators. A common approach for setting resource expectations is to define reference conditions that represent areas of least human disturbance or most natural state of a resource characterized by the range of natural variability across a region of interest. Identification of reference sites often relies heavily on professional judgment, resulting in varying and unrepeatable methods. Standardized methods for data collection, site characterization, and reference site selection facilitate greater cooperation among assessment programs and development of assessment tools that are readily shareable and comparable. We illustrate an example that can serve the broader global monitoring community on how to create a consistent and transparent reference network for multiple stream resource agencies. We provide a case study that offers a simple example of how reference sites can be used, at the landscape level, to link upslope management practices to a specific in-channel response. We found management practices, particularly areas with high road densities, have more fine sediments than areas with fewer roads. While this example uses data from only one of the partner agencies, if data were collected in a similar manner they can be combined and create a larger, more robust dataset. We hope that this starts a dialog regarding more standardized ways through inter-agency collaborations to evaluate data. Creating more consistency in physical and biological field protocols will increase the ability to share data.

A high-resolution imaging system, consisting of megapixel mid-IR and visible cameras along the same line of sight, has been prepared for the new W7-X stellarator and was operated during Operational Period 1.1 to view one of the five inboard graphite limiters. The radial line of sight, through a large diameter (184 mm clear aperture) uncoated sapphire window, couples a direct viewing 1344 × 784 pixel FLIR SC8303HD camera. A germanium beam-splitter sends visible light to a 1024 × 1024 pixel Allied Vision Technologies Prosilica GX1050 color camera. Both achieve sub-millimeter resolution on the 161 mm wide, inertially cooled, segmented graphite tiles. The IR and visible cameras are controlled via optical fibers over full Camera Link and dual GigE Ethernet (2 Gbit/s data rates) interfaces, respectively. While they are mounted outside the cryostat at a distance of 3.2 m from the limiter, they are close to a large magnetic trim coil and require soft iron shielding. We have taken IR data at 125 Hz to 1.25 kHz frame rates and seen that surface temperature increases in excess of 350 °C, especially on leading edges or defect hot spots. The IR camera sees heat-load stripe patterns on the limiter and has been used to infer limiter power fluxes (∼1-4.5 MW/m

Postoperative radiotherapy is routinely used in early breast cancer employing either 50 Gy in 25 daily fractions (long course) or 40 Gy in 15 daily fractions (short course). The role of radiotherapy and shorter fractionation regimens require validation.Patients with clinical stage I and II disease were randomised to receive immediate radiotherapy or delayed salvage treatment (no radiotherapy). Patients receiving radiotherapy were further randomised between long (50 Gy in 25 daily fractions) or short (40 Gy in 15 daily fractions) regimens. The primary outcome measure was time to first locoregional relapse. Reported results are at a median follow-up of 16.9 years (interquartile range 15.4-18.8).In total, 707 women were recruited between 1985 and 1992: median age 59 years (range 28-80), 68% postmenopausal, median tumour size 2.0 cm (range 0.12-8.0); 271 patients have relapsed: 110 radiotherapy, 161 no radiotherapy. The site of first relapse was locoregional158 (64%) and distant 87 (36%). There was an estimated 24% reduction in the risk of any competing event (local relapse, distant relapse or death) with radiotherapy (hazard ratio = 0.76; 95% confidence interval 0.65, 0.88). The benefit of radiotherapy treatment for all competing event types was statistically significant (X(Wald)(2) = 36.04, P0.001). Immediate radiotherapy reduced the risk of locoregional relapse by 62% (hazard ratio = 0.38; 95% confidence interval 0.27, 0.53), consistent across prognostic subgroups. No differences were seen between either radiotherapy fractionation schedules.This study confirmed better locoregional control for patients with early breast cancer receiving radiotherapy. A radiotherapy schedule of 40 Gy in 15 daily fractions is an efficient and effective regimen that is at least as good as the international conventional regimen of 50 Gy in 25 daily fractions.

OBJECTIVES: To determine the effect of colony-stimulating factor (CSF) on incidence of febrile neutropenia, infection, and survival in older people with non-Hodgkin's lymphoma (NHL) treated with chemotherapy. DESIGN: Retrospective cohort study. SETTING: The Surveillance, Epidemiology, and End Results–Medicare database. PARTICIPANTS: Thirteen thousand two hundred twenty-three people diagnosed with NHL at age 65 and older (mean age 74.9, range 65–102) in 1992 to 2002 who received chemotherapy within 12 months of diagnosis. MEASUREMENTS: Primary prophylaxis was defined as CSF administered at the start of chemotherapy before febrile neutropenia or infection; secondary prophylaxis was defined as CSF use after febrile neutropenia or infection. RESULTS: Participants with five to nine administrations of primary prophylactic CSF had a 42% lower risk of febrile neutropenia (odds ratio (OR)=0.58, 95% confidence interval (CI)=0.41–0.83), and participants with 10 or more administrations had a 48% lower risk (OR=0.52, 95% CI=0.36–0.76) after adjusting for age, stage, histology, and comorbidity. Results did not differ significantly after adjusting for propensity score of receiving CSF. There was no significant association between primary prophylactic CSF and overall survival, but secondary prophylactic CSF was significantly associated with better survival. Four to 10 administrations of secondary prophylactic CSF was associated with 9% lower mortality risk (hazard ratio (HR)=0.91, 95% CI=0.84–0.99), 11 to 23 administrations was associated with 23% lower mortality risk (HR=0.77, 95% CI=0.71–0.84) and 24 or more administrations was associated with 13% lower mortality risk (HR=0.87, 95% CI+0.79–0.95) than in participants not receiving CSF after neutropenia or infection. CONCLUSION: Primary prophylactic CSF was observed to be effective in reducing the incidence of neutropenia and infection. These findings substantiate the clinical guidelines for recommending prophylactic CSF in older people with NHL receiving chemotherapy.

Deoxyguanosine kinase (DGUOK) deficiency is the commonest type of mitochondrial DNA depletion associated with a hepatocerebral phenotype. In this article, we evaluate predictors of survival and therapeutic options in patients with DGUOK deficiency. A systematic search of MEDLINE, LILAC, and SCIELO was carried out to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and other studies with clinical pertinence. DGUOK deficiency was searched with the terms dGK, DGUOK, mitochondrial DNA depletion, mtDNA, and hepatocerebral. Bibliographies of identified articles were reviewed for additional references. Thirteen identified studies met the inclusion criteria and were used in this study. The analysis revealed that DGUOK deficiency is associated with a variable clinical phenotype. Long-term survival is best predicted by the absence of profound hypotonia, significant psychomotor retardation, or nystagmus. In the presence of these features, there is increased mortality, and liver transplantation does not confer increased survival. In summary, liver transplantation appears to be futile in the presence of specific neurological signs or symptoms in patients affected with DGUOK deficiency. Conversely, in the absence of these neurological features, liver transplantation may be considered a potential treatment.

tAnGo is a large randomised trial assessing the addition of gemcitabine(G) to paclitaxel(T), following epirubicin(E) and cyclophosphamide(C) in women with invasive higher risk early breast cancer. To assess the safety and tolerability of adding G, a detailed safety substudy was undertaken. A total of 135 patients had cardiac, pulmonary and hepatic function assessed at (i) randomisation, (ii) mid-chemotherapy, (iii) immediately post-chemotherapy and (iv) 6 months post-chemotherapy. Skin toxicity was assessed during radiotherapy. No differences were detected in FEV1 or FVC levels between treatment arms or time points. Diffusion capacity (TLCO) reduced during treatment (P < 0.0001), with a significantly lower drop in EC-GT patients (P=0.02). Most of the reduction occurred during EC and recovered by 6-months post treatment. There was no difference in cardiac function between treatment arms. Only 11 patients had echocardiography/MUGA results change from normal to abnormal during treatment, with only five having LVEF < 50%. Transient transaminitis occurred in both treatment arms with significantly more in EC-GT patients post-chemotherapy (AST P=0.03, ALT P=0.003), although the majority was low grade. There was no correlation between transaminitis and other toxicities. Both treatment regimens reported temporary reductions in pulmonary functions and transient transaminitis levels. Despite these being greater with EC-GT, both regimens appear well tolerated.

This paper describes two cases of metaphyseal osteomyelitis in young dogs. The condition was characterised by generalised stiffness, muscle atrophy and reluctance to stand. Pain was evident on deep palpation of the distal extremities of long bones. Radiographic lesions, consisting of diffuse areas of bone lysis and pronounced periosteal reaction, were demonstrated in the metaphyseal regions of multiple long bones, particularly the distal radii and ulnae. Growth plates appeared unaffected and remained open. Biochemical abnormalities included significant increases in the plasma concentrations of fibrinogen and alkaline phosphatase. A pronounced neutrophilia and absolute monocytosis were noted in one dog. A six week course of amoxycil-lin/clavulanic acid in combination with metronidazole resulted in complete resolution of clinical and radiographic signs in each case. Growth disturbances were not observed.

Finger ring avulsion injuries can be functionally, cosmetically and emotionally devastating for the patient. This cadaveric study assessed a simple way to prevent ring avulsion injuries. Fresh cadaver fingers were used to test the incidence of avulsion injury with ordinary rings and when a single slot was cut in the ring. Intact rings mostly produced significant digital injuries, while the rings with slots did not.

Case Description—A 21-year-old neutered male captive California sea lion developed chronic polyuria; polydipsia; polyphagia; accelerated development of existing cataracts; and frequent episodes of gastrointestinal upset including anorexia, signs of abdominal discomfort, diarrhea, and vomiting. Clinical Findings—Chronic hypercholesterolemia, hypertriglyceridemia, hyperglycemia, and glucosuria were identified. During episodes of gastrointestinal abnormalities, transient hyperbilirubinemia and increased serum γ-glutamyltransferase activities developed. Clinical findings strongly suggested chronic pancreatitis with secondary diabetes mellitus and intermittent cholestasis. Multiple diagnostic tests, including abdominal ultrasonography, serial hematologic and serum biochemical analyses, fecal examinations, urinalyses and bacteriologic culture of urine, measurement of serum fructosamine and insulin concentrations, and evaluation of thyroid and adrenal function, did not reveal any specific parasitic, endocrine, hepatic, or neoplastic etiologies. Treatment and Outcome—For 1.5 years, the sea lion received once-daily administration of glargine insulin, gastrointestinal protectants, and a strict high-protein, low-fat diet. Daily monitoring of glucose regulation was achieved by training the sea lion to submit to blood and urine sampling. Glucose regulation ranged from fair to good, and clinical signs of diabetes mellitus lessened. Episodes of gastrointestinal upset still occurred, although the frequency and severity decreased. Ultimately, a severe episode developed, associated with diabetic ketoacidosis and sepsis, and the sea lion died. Severe fibrosing pancreatitis with exocrine and endocrine atrophy and abscesses arising from ectatic pancreatic ducts were found. Peripancreatic fibrosis caused stricture of the common bile duct, resulting in gallbladder distension without cholecystitis. Clinical Relevance—Diabetes mellitus can occur secondary to chronic pancreatitis in California sea lions and insulin therapy should be considered.

Objective:To identify the nature of Woodruff's plexus, which has been frequently mentioned in the rhinological literature but has never been properly characterised.Study design and setting:A study using 21 cadaveric specimens, combining microdissection of the mucosa of the posterior part of the inferior meatus, Spalteholz ‘clearing’ of specimens injected with latex ink, and histological analysis of sections of the inferior meatal mucosa.Results:Microdissection revealed a superficial plexus of thin walled vessels in the inferior meatus, which were also seen in cleared, injected specimens. Histological sections showed these vessels to be large, thin walled veins with very little muscle or fibrous tissue, within a thin mucosa relatively devoid of other structures.Conclusion:Woodruff's plexus is a venous plexus in the posterior part of the inferior meatus.Significance:This is the first time Woodruff's plexus has been properly characterised. Whilst the significance of the plexus itself is uncertain, its long overdue identification as a venous plexus provides a platform for further study and discussion.

Background: Chevron osteotomy, a commonly performed procedure for the treatment of hallux valgus, results in osteonecrosis of the first metatarsal head in 0% to 20% of cases. The aim of this study was to map out the arrangement of the vascular supply to the first metatarsal head and its relationship to the limbs of the chevron osteotomy. Methods: Ten cadaveric lower limbs were injected with an India ink-latex mixture, and the feet were dissected to assess the blood supply to the first metatarsal head. The dissection was carried out by tracing the branches of the dorsalis pedis and posterior tibial vessels. A distal chevron osteotomy was mapped, with the limbs of the osteotomy set at an angle of 60° from the geometric center of the first metatarsal head. The relationship of the limbs of the osteotomy to the blood vessels was recorded. Results: The first metatarsal head was found to be supplied by branches from the first dorsal metatarsal, first plantar metatarsal, and medial plantar arteries. The first dorsal metatarsal artery was the dominant vessel among the three arteries in eight specimens. All of the vessels formed a plexus at the plantar-lateral aspect of the metatarsal neck, just proximal to the capsular attachment, with a varying number of branches from the plexus then entering the metatarsal head. The plantar limb of the proposed chevron cuts exited through this plexus of vessels in all specimens. Contrary to the widely held view, only minor vascular branches could be found entering the dorsal aspect of the neck. Conclusions: The identification of the plantar-lateral corner of the metatarsal neck as the major site of vascular ingress into the first metatarsal head suggests that constructing the chevron osteotomy with a long plantar limb exiting well proximal to the capsular attachment may decrease the postoperative prevalence of osteonecrosis of the first metatarsal head.

Lean Duplex Stainless Steels (LDSS) have been used or are being considered as substitutes for several well-established materials, in various applications. This paper concentrates on AL 2003 TM LDSS (UNS S32003) as a substitute for Type 316L stainless steel. Comparative data are presented including corrosion test data in various media, mechanical test data, and design strength limits. Examples of applications are given.

Eastern equine encephalitis (EEE) was diagnosed in a flock of African penguins. Diagnosis was based on history and clinical signs and confirmed via serologic testing, virus isolation, reverse transcriptase-polymerase chain reaction (RT-PCR) assay, and histologic examination. Clinical signs in penguins included anorexia, behavior changes, depression, regurgitation, ataxia, recumbency, and seizures, and some penguins did not have any clinical signs. Mean +/- SD number of days that affected penguins had clinical signs was 12 +/- 5 days. Abnormalities initially detected on CBC included heterophilic leukocytosis and anemia; lymphocytosis and monocytosis were detected later. Plasma biochemical abnormalities included high activities of aspartate amino-transferase and creatine kinase, hyponatremia, hypochloremia, hyperglycemia, and high concentrations of globulin, triglycerides, and cholesterol. Mean +/- SD number of days required for resolution of CBC and plasma biochemical abnormalities was 67 +/- 24 days after the onset of clinical signs. Treatment consisted of supportive therapy. All penguins survived with the exception of one that was euthanatized; histopathologic findings were consistent with encephalitis. Results of RT-PCR assays performed on tissue from the right cerebrum of the penguin that was euthanatized were positive for EEE viral RNA. An inability to isolate virus several weeks after illness suggested successful viral clearance in recovered penguins. To the authors' knowledge, EEE infection in any penguin species has not been reported.

To examine the epidemiology, treatment patterns, and costs of cytomegalovirus (CMV) retinitis treatment in the post-HAART (highly active antiretroviral therapy) era, a retrospective cohort study was performed using data from US managed-care plans from 1997-2002. Cases with CMV retinitis were defined by requiring diagnosis codes for HIV (or AIDS), CMV, and retinitis and claims for anti-CMV treatment. Costs of oral, intravenous, and intraocular treatment periods were examined. The incidence of enrolled HIV or AIDS cases increased from 7 per million members in 1997 to 150 per million members in 2001. The incidence of CMV retinitis decreased from 23 per 10,000 HIV or AIDS cases in 1997 to 8 per 10,000 HIV or AIDS cases in 2001. The average duration of a CMV episode was 192 days and the average cost was 19,576 US dollars. In a multiple linear regression model adjusting for age, gender, insurance type, geographic region, HAART use, and co-existing AIDS-defining illnesses, intraocular and oral treatment periods saved 7135 and US dollars and 6866 US dollars, respectively, per treatment period compared with intravenous treatment (P < 0.05). The incidence of CMV retinitis decreased in this managed-care population during the post-HAART era. Use of oral or intraocular treatment saves costs compared with intravenous treatment in a managed-care environment.

PURPOSE: To present a case of unilateral hypopyon uveitis that began 15 days after uneventful bilateral LASIK in a 24-year-old man with an undisclosed history of ulcerative colitis. METHODS: Case report. RESULTS: The hypopyon uveitis completely resolved after treatment with aggressive topical and oral steroid agents in combination with topical antibiotic coverage. CONCLUSIONS: Although rare, visually significant hypopyon uveitis may arise after LASIK in the setting of ulcerative colitis and positive human leukocyte antigen (HLA) B27. Early recognition and treatment can result in an excellent outcome. The exact relationship between hypopyon uveitis and LASIK is impossible to ascertain.

Background:Decompression of the endolymphatic sac for Ménière's disease gives unpredictable results. This may be because the sac is difficult to identify and decompress accurately without causing surgical trauma.Methods:In order to test this idea, transmastoid decompression was simulated in 5 cadaver half heads and the anatomy of the endolymphatic sac was reviewed in a further 14 specimens.Results:The endolymphatic sac was found and confirmed by histology in all five simulated decompressions. A newly described feature, a trapezoid thickening of dura, was a useful guide. The review showed that the sac was constant proximally, but variable distally. The posterior semicircular canal, posterior fossa dura and sigmoid sinus are at risk during dissection.Conclusion:The endolymphatic sac may be identified on inspection by an overlying patch of dura, thereby reducing exploratory dissection. It is best to decompress the sac as far proximally as possible, whilst protecting the posterior semicircular canal.

OBJECTIVE: To evaluate a culturally appropriate intervention to increase activity in overweight Mexican American women. METHODS: Participants were randomly assigned to a physical activity program or wait-list control. RESULTS: Treated participants were not more active than controls at 6 or 12 months. In addition, we found no significant differences in the proportion of individuals who met an objective criterion for physical activity from baseline to 6 months in the treatment or control groups. CONCLUSION: The intervention did not increase physical activity in this population. Differences in baseline activity and contamination of the control group may partially account for the outcome.

Core level X-ray Absorption Spectroscopy measurements have been performed at the L 3,2 edges of thin film Fe samples deposited on the (100) surface of Cu. Soft X-rays from five different beamlines have been used to measure spectra from identical samples with very different degrees of transverse coherence in the synchrotron radiation. The degree of source coherence has been characterised by diffraction. The transverse coherence length has been extracted and found to be on the μm length scale at certain beamlines. An increase of the L edge resonance intensities, relative to the continuum states, is observed in spectra measured at these beamlines.

OBJECTIVE To assess the relation between APO E genotype and MRI white matter changes in Alzheimer9s disease. The APO e4 allele is correlated with amyloid angiopathy and other neuropathologies in Alzheimer9s disease and could be associated with white matter changes. If so, there should be a dose effect. METHODS 104 patients with probable Alzheimer9s disease (NINCDS-ADRDA criteria) in this Alzheimer9s Disease Research Centre were studied. Patients received MRI and APO E genotyping by standardised protocols. Axial MRI was scored (modified Schelten9s scale) for the presence and degree of white matter changes and atrophy in several regions by a neuroradiologist blinded to genotype. Total white matter and total atrophy scores were also generated. Data analysis included Pearson9s correlation for regional and total imaging scores and analysis of variance (ANOVA) (or Kruskal-Wallis) and χ 2 for demographic and disease related variables. RESULTS 30 patients had no e4, 53 patients were heterozygous, and 21 patients were homozygous. The three groups did not differ in sex distribution, age of onset, age at MRI, MMSE, clinical dementia rating, or modified Hachinski ischaemia scores. There were no significant correlations between total or regional white matter scores and APO E genotype (Pearson correlation). CONCLUSIONS No correlation between total or regional white matter scores and APO E genotype was found. The pathogenesis of white matter changes in Alzheimer9s disease may be independent of APO E genotype.

The objective of this study is to evaluate the one-year outcome of the first 50 patients who underwent nonsurgical septal reduction for symptomatic hypertrophic obstructive cardiomyopathy at our institution.Left ventricular outflow tract obstruction is an important determinant of clinical symptoms in patients with hypertrophic obstructive cardiomyopathy. Nonsurgical septal reduction is a new therapy that has been shown to result in left ventricular outflow tract gradient reduction and resolution of symptoms immediately after the procedure and on midterm follow-up.Fifty patients with hypertrophic obstructive cardiomyopathy who underwent nonsurgical septal reduction at our institution and completed 1-year follow-up are described. Complete history, physical examination, two-dimensional echocardiography with Doppler and exercise treadmill testing have been analyzed.The mean age of the study group was 53 +/- 17 years. All patients had refractory symptoms before enrollment. Ninety-four percent had class III or IV New York Heart Association class symptoms at baseline compared to none at 1 year (p0.001). The exercise duration increased by 136 s at 1 year (p0.021). Only 20% of patients were either receiving beta-blockers or calcium-channel blockers on follow-up. The resting left ventricular outflow tract gradient decreased from 74 +/- 23 mm Hg to 6 +/- 18 mm Hg (p0.01) and from 84 +/- 28 mm Hg to 30 +/- 33 mm Hg (p0.01) in patients with dobutamine-provoked gradient at one year. These changes are associated with decreased septal thickness and preserved systolic function.Nonsurgical septal reduction therapy is an effective therapy for symptomatic patients with hypertrophic obstructive cardiomyopathy with persistence of the favorable outcome up to one year after the procedure.

OBJECTIVES Our objectives were to determine whether angiotensin-1 converting enzyme (ACE) insertion/deletion (I/D) polymorphism was associated with the severity of coronary artery disease (CAD) and its progression/regression in response to fluvastatin therapy in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) population. BACKGROUND Genetic factors are involved in susceptibility to CAD. Angiotensin-1 converting enzyme I/D polymorphism, which accounts for half of the variance of plasma and tissue levels of ACE, has been implicated in susceptibility to CAD and myocardial infarction (MI). METHODS Angiotensin-1 converting enzyme genotypes were determined by polymerase chain reaction (PCR). Fasting plasma lipids were measured and quantitative coronary angiograms were obtained at baseline and 2.5 years following randomization to fluvastatin or placebo. RESULTS Ninety-one subjects had DD, 198 ID and 75 II genotypes. The mean blood pressure, minimum lumen diameter (MLD), number of coronary lesions and total occlusions were not significantly different at baseline or follow-up among the genotypes. There was a significant genotype-by-treatment interaction for total cholesterol (p = 0.018), low-density lipoprotein cholesterol (LDL-C) (p = 0.005) and apolipoprotein (apo) B (p = 0.045). In response to fluvastatin therapy, subjects with DD, compared with those with ID and II genotypes, had a greater reduction in total cholesterol (19% vs. 15% vs. 13%), LDL-C (31% vs. 25% vs. 21%) and apo B (23% vs. 15% vs. 12%). Definite progression was less (14%) and regression was more common (24%) in DD as compared with those with ID (32% and 17%) and II (33% and 3%) genotypes (p = 0.023). Changes in the mean MLD and lesion-specific MLD also followed the same trend. CONCLUSIONS Angiotensin-1 converting enzyme I/D polymorphism is associated with the response of plasma lipids and coronary atherosclerosis to treatment with fluvastatin. Subjects with DD genotype had a greater reduction in LDL-C, a higher rate of regression and a lower rate of progression of CAD.

Seven dogs with non-regenerative anaemia were diagnosed as having myelofibrosis on the basis of the presence of collagen and increased deposits of reticulin fibre in the haemopoietic spaces of bone marrow core biopsies. A scoring system was used to assess the cellularity of the marrow and the amounts of collagen, reticulin and haemosiderin present. These scores, together with the haematological findings, were compared with the dogs' responses to treatment and their outcome. Treatment consisted of blood transfusions, where required, and anabolic steroids and corticosteroids. Three dogs deteriorated and were euthanased within three months of diagnosis, but the other four recovered fully. There was no correlation between the collagen and reticulin scores, or the degree of anaemia and the outcome, but the four dogs which recovered all had a macrocytosis when first examined. There was no evidence of an underlying lymphoproliferative or myeloproliferative disease in any of the seven cases.

Rett syndrome is a disorder of unknown etiology in females that manifests as severe mental and motor retardation during the first years of life. A postnatal pattern of altered growth is its earliest clinical expression. Head growth decelerates during the first year of age and is followed by a decline in somatic (height/weight) growth. The decreased occipitofrontal circumference (OFC) is reflected in decreased brain size, and measurements of the dendrites of cortical neurons suggest that a developmental and growth arrest have occurred. To further document growth in Rett syndrome, measurements of organ weights, as recorded in 39 postmortem examination studies were compared with normal organ weights for females of comparable age and height. These organ weights suggest that the pattern of growth failure in Rett syndrome, as compared with other forms of mental handicap, such as Down syndrome and Turner's syndrome, may be unique. In Rett syndrome the rate of brain growth, as derived from OFC, decelerates after birth. The increment in normal brain weight after 4 years of age, the age of the first postmortem examinations, is not observed in the Rett brain. The heart, kidneys, liver, and spleen grow at the normally defined rate until 8-12 years of age, when their growth rate decelerates, but their growth continues achieving organ weights that are appropriate for the height of the female. Adrenal weights are normal. These observations suggest that despite a generalized decreased growth in Rett syndrome the brain may be preferentially affected in this syndrome.

Cytomegalovirus (CMV) retinitis is a common opportunistic infection in patients with AIDS. With long-term therapy for CMV retinitis, resistant CMV may develop. In a prospective study of 122 patients with CMV retinitis, 2.4 and 0.8% of patients had foscarnet-resistant blood culture isolates (50% inhibitory concentration [IC50], >400 mM) and urine culture isolates, respectively, at diagnosis of CMV retinitis prior to treatment, whereas 4.1 and 6.6% had cidofovir-resistant (IC50 ,> 2mM) blood and urine culture isolates, respectively. Patients were treated according to best medical judgement. Of 44 foscarnet-treated patients, 26% had a resistant blood or urine culture isolate by 6 months of treatment and 37% had a resistant isolate by 9 months; of 13 cidofovir-treated patients, 29% had a resistant blood or urine culture isolate by 3 months of therapy. The probabilities of developing foscarnet resistance while on foscarnet and developing cidofovir resistance while on cidofovir were not significantly different from that for developing ganciclovir resistance while on ganciclovir (odds ratios, 1.87 [P 5 0.19] and 2.28 [P 5 0.15], respectively). Cytomegalovirus (CMV) retinitis is the most common intraocular infection in patients with AIDS and has been reported to affect approximately 30% of patients with AIDS (9, 10, 12). Left untreated, CMV retinitis is a progressive disease, which spreads throughout the retina, causing total retinal destruction and blindness (12). As of November 1997, three drugs were approved by the United States Food and Drug Administration for the treatment of CMV retinitis: ganciclovir, foscarnet, and cidofovir. All are effective, but none eliminates virus from the retina, and chronic suppressive therapy is required (10, 15, 17). The use of chronic suppressive antiviral therapy is associated with the development of resistant virus (5, 7, 13), and resistant CMV is associated with a poor response to therapy (7, 13, 14). The Cytomegalovirus Retinitis and Viral Resistance Study (8, 11, 13) is a prospective study of CMV resistance to antiviral agents. Herein we report results on the incidence of resistance to foscarnet and to cidofovir.

Injection studies using methylene blue and latex were used in 60 digits from 40 cadavers to study how anaesthetic fluid injected into the flexor tendon sheath might spread around the proximal part of the finger. The injected solution escaped from the flexor tendon sheath around the vincular vessels which are present near the base and head of the proximal phalanx. Outside the digital canal, the dye flowed smoothly through the perivascular loose areolar tissue and spread alongside the main digital vessels and nerves and their palmar and dorsal branches.

Recent data have extended the benefit of lipid lowering therapy to patients with only mildly to moderately elevated LDL-cholesterol, which is typical of patients with coronary artery disease. Meta-analysis of clinical trials of statin therapy with similar sample sizes indicated that the LDL-cholesterol level on treatment was as good a predictor of angiographic benefit as was the percentage reduction in LDL-cholesterol. We review evidence that management of triglyceride-rich lipoproteins, HDL, fibrinogen, lipoprotein particle size, LDL-oxidation, and lipoprotein (a) may also favorably influence atherosclerotic progression. Angiographic and arterial ultrasound trials of lipid lowering therapy have demonstrated benefits on disease progression that are consistent with benefits on myocardial infarction, stroke, and death reported in larger, lengthier trials.

Objective: To assess the effect of estradiol (E2) replacement therapy on cardiac structure and function in healthy postmenopausal women. Methods: We conducted a randomized, double-blind, placebo-controlled, crossover study of 31 healthy postmenopausal female volunteer study subjects (55–65 years) using 12 weeks of micronized E2 replacement therapy (2 mg/day). Echocardiography and Doppler techniques were used to assess the cardiac effects of E2 at rest and during graded bicycle ergometry. Results: Crossover analysis demonstrated no carryover effects of estrogen treatment (which increased serum E2 15-fold to 37.6 pmol/L) on the cardiac characteristics measured. Estradiol treatment did not affect measurements of systolic function, diastolic function, left ventricular mass, or pulmonary artery pressure at rest or during bicycle ergometry. Left ventricular end-diastolic volume at rest was slightly higher with E2 treatment ( P = .03). However, this change was not reflected by changes in stroke volume, ejection fraction, or cardiac output. Conclusions: Estrogen replacement therapy, which results in physiologic serum concentrations, does not affect cardiac structure or function in normal postmenopausal women after 12 weeks of treatment.

A critical problem in the dietary treatment of hypercholesterolemia is the long-term maintenance of cholesterol reduction. A system to maintain contact and provide feedback through a computer-interactive phone system was used with 115 subjects who completed a four-week diet and behavioral cholesterol reduction program. The subjects, mean age 48 years, were 87% non-Hispanic Caucasian and 74.8% were female. They were randomized to a control or maintenance group. The maintenance group received calls twice a month for six months. Total cholesterol (TC) and weight (lb) were obtained before and after a four-week program and after the six-month maintenance period. Neither group of subjects with all cholesterol measurements fully maintained initial cholesterol reductions (mean TC: in maintenance [n = 48) 248, 221, 231 versus control [n = 43] 243, 224, 232 mg/dL). All (n = 59) of the maintenance subjects used the phone system, with 83.3% of a subset evaluating it indicating the phone messages were helpful. Patients (n = 25) with > or = 5 lb weight loss and 10% TC decrease from baseline had a better maintenance of TC reduction in the maintenance versus control group (273,208,231 versus 259,205,246 mg/dL) (P < .05). We conclude that (1) maintenance remains a problem for cholesterol-lowering diet interventions, (2)automated phone calls are capable of maintaining contact and providing patient feedback, and (3) this system may help in the maintenance of TC levels for patients who made greater changes.

To compare the performance of prostate-specific antigen (PSA) levels with the performance of PSA density (PSAD), the ratio of the serum to the size of the prostate, as predictors of the presence of prostate cancer.We analyzed the results of digital rectal examination (DRE), transrectal ultrasonography (TRUS), serum PSA levels, and PSAD in 244 patients who had a needle biopsy of the prostate.Cancer was detected in 110 patients (45%). Compared with DRE, TRUS and serum PSA levels 4.0 ng/mL or higher, PSAD at a cutoff point of 0.15 ng/mL/cm3 was significantly more specific and had a higher positive predictive value than each of the other tests but was significantly less sensitive than TRUS and PSA (P0.05 for each). In a receiver operating characteristic analysis, PSAD was significantly more accurate than PSA (P0.001). In 80 patients with a normal PSA, PSAD added no additional information, and PSAD was not able to identify a subset at low risk. In 82 patients with a high PSA level (10 ng/mL or higher), 15% had a PSAD less than 0.15 and only 8% had a cancer.Overall, PSAD was significantly more accurate than PSA for predicting the results of needle biopsy of the prostate, but in practice PSAD proved useful in only a small subset of patients. If the serum PSA level was high but the PSAD was low, cancer was rarely detected. These patients may be suitable candidates for careful follow-up rather than early repeat biopsy.

The case histories of 60 dogs with hyperadrenocorticism were reviewed. Fifty-four of the dogs were treated with mitotane at a mean daily dose rate of 48.8 mg/kg (range 25.6 to 84 mg/kg) for between four and 21 days. The mean weekly maintenance dose of mitotane was 48.8 mg/kg. An adrenocorticotrophic hormone (ACTH) stimulation test was performed before the treatment began, and in 30 cases at the end of the induction course, and the response to ACTH was measured at regular intervals thereafter. Nine of the treated dogs developed complete hypoadrenocorticism during treatment and required permanent mineralocorticoid replacement therapy. Twelve of the dogs had normal responses to an ACTH stimulation test before treatment, and the diagnosis of hyperadrenocorticism was based on the result of a low-dose dexamethasone suppression test. These 12 dogs had consistently lower cortisol levels before and after stimulation with ACTH and four of them developed complete hypoadrenocorticism. In general the clinical signs were well controlled when the cortisol levels were less than 105 nmol/litre before and after the stimulation test. Dogs in which the clinical signs recurred had cortisol levels between 210 and 580 nmol/litre after the test, a level which is within the normal pretreatment range. Twenty-seven of the treated dogs died and six of these deaths were attributable directly to the disease or therapy. The median survival time of the 54 treated dogs was 30 months; eight dogs died during the first 16 weeks of treatment, and the dogs which survived this period had a median survival time of 39 months (mean 50 months).

The subjects were 25 American and 28 Japanese gymnasts filmed during national championships. Performances were analyzed to determine the effect of grip technique at bar regrasp. It was hypothesized that the new outer grip technique would achieve significantly higher body angle and center of gravity (CG) than the inner grip technique at bar regrasp, qualities that are essential for successful performance of the basket to handstand mount on the parallel bars. It was further hypothesized that the new outer grip technique would achieve significantly (a) greater angular speed of arm rotation and vertical displacement of CG during the upward inverted swing and (b) higher body angle and CG at bar release. The results revealed significant differences in all of the areas hypothesized in favor of the new outer grip technique. Although the technique must be refined to control the tendency for excessive body arching at bar release, the new outer grip has the technical advantage for pursuing virtuosity points and new maneuvers.

The implicational fragment of the logic of relevant implication, R→ is one of the oldest relevance logics and in 1959 was shown by Kripke to be decidable. The proof is based on LR→, a Gentzen-style calculus. In this paper, we add the truth constant t to LR→, but more importantly we show how to reshape the sequent calculus as a consecution calculus containing a binary structural connective, in which permutation is replaced by two structural rules that involve t. This calculus, LT→ⓣ, extends the consecution calculus LT→t formalizing the implicational fragment of ticket entailment. We introduce two other new calculi as alternative formulations of R→t. For each new calculus, we prove the cut theorem as well as the equivalence to the original Hilbert-style axiomatization of R→t. These results serve as a basis for our positive solution to the long open problem of the decidability of T→, which we present in another paper.

Eczema of the nipple is an important symptom presenting to the general surgeon in the out-patient department. The diagnosis of Paget's disease of the nipple has traditionally been made by incision biopsy necessitating at least a local anaesthetic. We present 14 patients with nipple skin change, in whom the technique of scrape cytology was used to identify patients with Paget's disease. In our series eight cases of Paget's disease were successfully identified by scrape cytology with no false negatives or positives. We suggest that this is a quick, easy, non-invasive method of screening eczema of the nipple in the out-patient clinic.

Oral iodized oil is the major alternative to iodized salt for correcting endemic iodine deficiency. This study responds to a need for better guidelines in its use. Schoolchildren, aged 6-11 yr, from a severely iodine-deficient area of Algeria received iodized poppy seed oil (Lipiodol) in a single oral dose containing 120, 240, 480, or 960 mg iodine (groups A-D) or in an im injection of 480 mg iodine (group E). Thyroid volume by ultrasonography had not changed 395 days after treatment in groups A, B, and C, had decreased in groups D and E. Urinary iodine concentration rose rapidly from an initial median of 0.21 mumol/L, but fell below 0.79 mumol/L (the currently accepted level for indicating iodine deficiency) by 150 days for groups A and B, and by 395 days for groups C and D. Median serum TSH and T4 levels were normal before and after treatment, whereas high initial serum thyroglobulin values decreased in all groups after iodized oil treatment. For correcting iodine deficiency in children, we recommend single oral doses of Lipiodol containing 240 mg iodine for 6-month coverage or 480 mg for 12 months. These doses may not completely sustain iodine sufficiency, but will prevent the worst of the iodine deficiency disorders. Additionally, we conclude that the urinary iodine concentration is the most useful epidemiological indicator for assessing current iodine status, and thyroid volume and serum thyroglobulin levels are the best markers for assessing chronic effects.

To determine knowledge, attitudes, behaviors, and self-reported cholesterol measurement in a low-income, urban patient population, we conducted an interview survey of users and potential users of primary care services in a public health care system for low-income Harris County, Texas, residents. The response rate was 93%, with a final sample of 547 randomly selected subjects 18 years of age and older, who were Hispanic (54%), black (28%), non-Hispanic white (14%), and Asian, Native American, or other (4%). Results indicated that 76% had heard of serum or blood cholesterol, and 30% reported past cholesterol measurement. Knowledge that dietary saturated fat can raise blood cholesterol ranged from 11% in Hispanic men to 51% in non-Hispanic white men and women. A lower percentage of Hispanics correctly answered all knowledge questions, and Hispanics reported higher-fat food choices than blacks and non-Hispanic whites. More than 90% of the respondents expressed interest in more information on diet, 60% reported that they read nutrition labels, and 15% said they have been trying to reduce blood cholesterol levels. A lower percentage of Hispanics reported previous cholesterol measurement than blacks or non-Hispanic whites, a difference that persisted after adjusting for multiple factors associated with cholesterol measurement. Older age (older than 50) and more physician visits in the past year also were associated with past cholesterol measurement. Comparisons with national surveys show that cholesterol knowledge and actual measurement in this low-income sample lag behind those of the national population. Yet, despite gaps in knowledge and cholesterol measurement, respondents showed positive attitudes about and interest in cholesterol-lowering interventions.

This paper describes the clinical and pathological features of 11 dogs with insulin-secreting tumours of the pancreas. All the dogs showed episodic weakness or collapse. The diagnosis was made on fasting plasma glucose and serum insulin concentrations, the insulimglucose ratio, and the results of an intravenous glucose tolerance test. Ten of the dogs had exploratory laparotomy, and partial pancreatectomy was performed in nine of the cases. One case was euthanased at surgery because of widespread metastases. The tumours were graded histologically and the results compared with the time to recurrence of clinical signs and postoperative survival time. Postoperative survival time for dogs which died or were euthanased as a direct result of tumour recurrence, and time to recurrence of clinical signs were calculated from actuarial survival curves. The median time to recurrence of clinical signs after surgery was 12 months (range from four to 16 months; mean time to recurrence of clinical signs 12 months). Two cases died of unrelated disease, without recurrence of hypoglycaemic signs. The median postoperative survival time was 14 months (range 10 to 33 months; mean survival time 15 months). There is a suggestion that tumours with a high mitotic count carried a worse prognosis.