Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts.

BACKGROUND: Subclinical hyperthyroidism (SHyper) has been associated with increased risk of hip and other fractures, but the linking mechanisms remain unclear. OBJECTIVE: To investigate the association between subclinical thyroid dysfunction and bone loss. METHODS: Individual participant data analysis was performed after a systematic literature search in MEDLINE/EMBASE (1946-2016). Two reviewers independently screened and selected prospective cohorts providing baseline thyroid status and serial bone mineral density (BMD) measurements. We classified thyroid status as euthyroidism (thyroid-stimulating hormone [TSH] 0.45-4.49 mIU/L), SHyper (TSH < 0.45 mIU/L) and subclinical hypothyroidism (SHypo, TSH ≥ 4.50-19.99 mIU/L) both with normal free thyroxine levels. Our primary outcome was annualized percentage BMD change (%ΔBMD) from serial dual X-ray absorptiometry scans of the femoral neck, total hip and lumbar spine, obtained from multivariable regression in a random-effects two-step approach. RESULTS: Amongst 5458 individuals (median age 72 years, 49.1% women) from six prospective cohorts, 451 (8.3%) had SHypo and 284 (5.2%) had SHyper. During 36 569 person-years of follow-up, those with SHyper had a greater annual bone loss at the femoral neck versus euthyroidism: %ΔBMD = -0.18 (95% CI: -0.34, -0.02; I2 = 0%), with a nonstatistically significant pattern at the total hip: %ΔBMD = -0.14 (95% CI: -0.38, 0.10; I2 = 53%), but not at the lumbar spine: %ΔBMD = 0.03 (95% CI: -0.30, 0.36; I2 = 25%); especially participants with TSH < 0.10 mIU/L showed an increased bone loss in the femoral neck (%Δ BMD = -0.59; [95% CI: -0.99, -0.19]) and total hip region (%ΔBMD = -0.46 [95% CI: -1.05, -0.13]). In contrast, SHypo was not associated with bone loss at any site. CONCLUSION: Amongst adults, SHyper was associated with increased femoral neck bone loss, potentially contributing to the increased fracture risk.

Short medial approach harvesting of hamstring tendons.

Harvesting the hamstring tendons for anterior cruciate ligament reconstruction is not straightforward to perform or to teach: the incision is small, the work-space is narrow and the surgeon's tactile feedback using the stripper is difficult to explain to juniors. The purpose of this short note is to describe a reliable means of harvesting the semitendinosus, gracilis or both. Patient and tourniquet positioning, instrumentation and landmarks are detailed; then the 6 steps (speed-bump 1, speed-bump 2, bubble, hook, expansions, stripper) are explained.

The emergence of Leptospira borgpetersenii serovar Arborea as the dominant infecting serovar following the summer of natural disasters in Queensland, Australia 2011.

The following research reports the emergence of Leptospira borgpetersenii serovar Arborea as the dominant infecting serovar following the summer of disasters and the ensuing clean up in Queensland, Australia during 2011. For the 12 month period (1 January to 31 December) L. borgpetersenii serovar Arborea accounted for over 49% of infections. In response to a flooding event public health officials need to issue community wide announcements warning the population about the dangers of leptospirosis and other water borne diseases. Communication with physicians working in the affected community should also be increased to update physicians with information such as clinical presentation of leptospirosis and other waterborne diseases. These recommendations will furnish public health officials with considerations for disease management when dealing with future disaster management programs.

[How do Swiss family physicians treat subclinical hypothyroidism?]. / Comment tes médecins de famille prennent-ils en charge l'hypothyroïdie infraclinique?

Subclinical hypothyroidism is a common condition, and its prevalence increases with age. Currently, guidelines regarding the screening and treatment of subclinical hypothyroidism are controversial. An international survey of general practitioners (GPs), to which Swiss GPs also contributed, showed large inter-country variations in treatment strategies for subclinical hypothyroidism. These differences are mainly explained by the lack of strong evidence for the management of this condition. The European randomized-controlled clinical trial TRUST should help clarify recommendations for screening and thyroxin replacement for the elderly with subclinical hypothyroidism. Working in close collaboration with GPs in Switzerland for the recruitment of patients will ensure that the findings from this study will be applicable to primary care settings.

Neutrophil counts in leptospirosis patients infected with different serovars.

In leptospirosis patients, haematological abnormalities have been reported. The aim of this study was to determine if neutrophil counts were different between patients known to be infected with a range of leptospiral serovars. The study retrospectively compared the neutrophil counts from the first blood samples taken from 210 leptospirosis patients at first presentation to a Queensland Health hospital. Significant differences (p <0.001) were observed in neutrophil counts across the 11 different infecting serovars. These findings suggest that neutrophil counts may be useful in the development of an algorithm determining the infecting serovar in suspected leptospirosis patients. Further studies are required to delineate host cytokine responses which may suggest the underlying aetiology of the observed differences in neutrophil counts. Such studies would also provide valuable therapeutic insights into treating the disease.

[2011 findings from literature on general internal ambulatory medicine]. / Acquisitions thérapeutiques en médecine ambulatoire en 2011.

In 2011 several articles seemed significant for the practice of general medicine. Diagnosis of hypertension needs several measurements and may need 24-hour ambulatory blood pressure monitoring. Glycosylated hemoglobin is a reliable tool to diagnose diabetes mellitus. The ABCD2 score with neurological imaging help the triage of transient ischemic attacks. Pulmonary embolism can be treated as outpatient for low risk patients. Gluten-free diet may be tried in irritable bowel syndrome. Nitrofurantoin is a reasonable alternative for simple urinary tract infection in women, but antibiotics are not needed after drainage of an uncomplicated skin abscess. Subclinical thyroid dysfunction is a risk factor of osteoporosis in older men. Sequential use of MMSE and ACE scores is a promising approach to assess medical decision-making capacity.

Genetic structure of Africanized honeybee populations (Apis mellifera L.) from Brazil and Uruguay viewed through mitochondrial DNA COI-COII patterns.

Mitochondrial genotypes of Africanized honeybees from Brazil and Uruguay were surveyed by DraI restriction of the COI-COII region. Eleven mitotypes were found, three of which had not previously been described (A28-A30). Out of 775 samples (725 from Brazil, 50 from Uruguay), 197 were A1 and 520 were A4. A1 frequency increases toward the north of Brazil, whereas A4 frequency increases toward the south, a pattern echoing the African distribution. The origin of the A4 and most of the A1 African patterns can be attributed to the introduction of Apis mellifera scutellata into Brazil in 1956. The A29 and A30 patterns have the P1 sequence observed in many Iberian Peninsula samples, which represent the traces of the introductions into Brazil and Uruguay by settlers.

[Subfascial lipomatous tumors: management in a series of 37 consecutive cases]. / Tumeurs graisseuses sous-aponévrotiques: stratégie de prise en charge à propos d'une série continue de 37 cas.

PURPOSE OF THE STUDY: The prognosis of subfascial lipomatous soft tissue tumors depends greatly on their histological type ranging from benign lipomas that cause little local or general problems to the severe prognosis of liposarcomas that exhibit both local and distant extension. However, the clinical presentation of the two types of tumors may be similar and thus quite misleading, sometimes leading to inappropriate management and severe consequences. The main objective of this study was to determine whether the preoperative work-up in patients treated for musculoskeletal tumors within our recruitment zone is adequate, allowing appropriate therapeutic decisions. In addition, we wanted to know what explorations are most pertinent for the differential diagnosis between benign and malignant subfascial lipomatous soft tissue tumors. MATERIAL AND METHODS: Thirty-seven patients with subfascial tumors were included in this study. There were 16 with benign lipomas and 21 with liposarcomas. All the patients with benign lipomas but only 9 (43%) of those with liposarcoma had received initial care within our recruitment zone before final diagnosis. Two cases had been referred after biopsy and 1 after resection by morcellation; the 9 others were secondary referrals after tumor recurrence. Only 5 of these 12 referred patients had had an MRI exploration prior to surgery, 2 with an erroneous interpretation. An MRI series was obtained for all the patients with benign lipoma and for the 9 with liposarcomas who attended our units directly. A biopsy was also obtained in case of suspected liposarcoma. Two radiologists blinded to the final diagnosis reviewed the available MRI to assess their diagnostic value for subfascial lipomatous soft tissue tumors. RESULTS: No case of recurrence, after marginal resection (10 cases) was noted for lipomas. Six are under observation with regular MRI (with no change in size or signal). Four patients with liposarcoma died from their disease (19%) and 2 who had undergone "curative" resection had a recurrence (12%). Incorrect or imprecise (incomplete, incorrectly interpreted or no MRI) preoperative diagnosis led to additional morbidity with 3.4 surgical procedures (mean per patient) compared with 1 in patients who had had undergone a complete work-up and whose diagnosis was established after multidisciplinary discussions. Among the diagnostic elements available before pathology, only MRI findings had diagnostic value for subfascial lipomatous soft tissue tumors: for benign lipoma positive predictive value=92% and negative predictive value=93%. DISCUSSION: The clinical course of the benign lipomas and the sarcomas in this series confirm the radically different prognosis of these two tumors, both in terms of local extension and survival. Inadequate management in the initial diagnostic stages-i.e. lack of MRI with contrast injection, biopsy and multidisciplinary interpretation prior to treatment-raises the risk of higher morbidity, particularly a significantly greater number of reoperations, and progression to a higher grade of malignancy for two tumors. Our retrospective analysis enabled us to develop a decision making tree for patients with subfascial lipomatous tumors. Prospective validation will be necessary.

Risk factors for symptomatic urinary tract infection in women with diabetes.

OBJECTIVE: Women with diabetes have urinary tract infections (UTIs) more often than women without diabetes. The aim of the present multicenter study was to evaluate which clinical characteristics are associated with the development of a symptomatic UTI during an 18-month follow-up period. RESEARCH DESIGN AND METHODS: Patients with either type 1 or type 2 diabetes who were between 18 and 75 years of age were included. Follow-up results were available for 589 of the 636 women included in this study. All patients were interviewed, their medical history was noted, and at least one uncontaminated urine culture was collected at the moment of study entry. RESULTS: Of the 589 women, 115 (20%) developed a symptomatic UTI, 96 (83%) of whom were prescribed antimicrobial therapy A total of 34 women (14%) with type 1 diabetes developed a UTI. The most important risk factor for these women was sexual intercourse during the week before entry into the study (44% without vs. 53% with sexual intercourse, relative risk [RR] = 3.0, P = 0.01). A total of 81 (23%) women with type 2 diabetes developed a UTI. The most important risk factor for these women was the presence of asymptomatic bacteriuria (ASB) at baseline (25% without vs. 42% with ASB, RR = 1.65, P = 0.04). CONCLUSIONS: Risk factors for developing a UTI are the presence of ASB for women with type 2 diabetes and sexual intercourse during the week before entry into the study for women with type 1 diabetes.

High prevalence of hepatitis C virus infection in Belgian intravenous drug users and potential role of the "cotton-filter" in transmission: the GEMT Study.

AIMS: To estimate viral seroprevalences for HCV, HBV and HIV among belgian intravenous (IVDU) and non intravenous (non-IVDU) drug users; to assess risk factors for HCV infection in IVDU; to assess feasibility of chronic hepatitis C follow-up in this population. DESIGN: Cross-sectional study. Demographic and behavioural characteristics were obtained by a standardized questionnaire. Serum samples were tested for HCV, HBV and HIV. SUBJECTS AND SETTING: 329 patients (244 IVDU and 85 non-IVDU) attending ten general practitioners in 1995. RESULTS: HCV seroprevalence was 78.3%; it was 35.7% for HBV and 0.9% for HIV in IVDU, vs 2.4%, 8.3% and 0%, respectively, in non-IVDU. In logistic regression analysis, independent risk factors for HCV infection were: 1/sharing of syringes and/or of "cottons" used as filters (adjusted prevalence odds ratio [POR] = 31.7; 95% confidence interval [CI] = 9.8-102.5), 2/duration of injecting upper than one month (adjusted POR = 8.6; CI = 3.0-24.7) and 3/age (adjusted POR = 1.2 by year of difference; CI = 1.0-1.3). A biochemical follow-up was obtained in 70% of HCV seropositive users; 79.5% of them had chronic hepatitis C (mean value of ALT = 3.5 times upper normal value, range 1.1-23.0). Among these, 24.7% went through liver biopsy during the three years follow-up period of the study. CONCLUSIONS: HCV seroprevalence is very high among belgian IVDU. Prevention strategies have to focus on neophytes injectors. They must be urgently revisited for what concern needles/syringes exchange programs: "cottons" must be included. Follow-up and treatment of chronic hepatitis C seem to be poorly effective among drug users.

Prevalence of electrocardiographic and echocardiographic abnormalities in ambulatory ischemic colitis.

The aim of this study was to evaluate the prevalence of cardiac arrhythmia and intracardiac embolic process in ambulatory ischemic colitis. From November 1994 to November 1997, 33 consecutive cases of ambulatory ischemic colitis were detected. This study included 21 women and 12 men with a mean age of 71 years. All patients underwent a cardiovascular investigation including questioning, electrocardiogram, 24-hr ambulatory electrocardiography and transthoracic echocardiography. A prior history of ischemic colitis was found in four cases (12%). Cardiac arrhythmia was detected in eight cases. Transthoracic echocardiography showed an intracardiac process, potentially responsible for a peripheral embolism, in four cases. In conclusion, the aggregate, in 33% of the patients, there was potential cardiac etiology. This suggests that when ambulatory ischemic colitis occurs, it is necessary to perform an exhaustive cardiovascular evaluation similar to those performed in other ischemic diseases.

Characterization of Nasutitermes globiceps (Isoptera: Termitidae) esterases.

Esterases of Nasutitermes globiceps termites which occur on the Upper Paraná River floodplain (Brazil) were characterized. The electrophoretic pattern of the termite esterases Nasutitermes globiceps was obtained by starch gel electrophoresis. Six esterase activity zones were obtained and numbered, with esterase-1 being the most anodall one and esterase-6 the most cathodal one. Esterase-2 was detected only with substrates derived from the 4-methylumbelliferyl radical. The esterases of N. globiceps present wide substrate specificity, having been observed with substrates derived from alpha-naphthyl (acetate, propionate, and butyrate) and beta-naphthyl (acetate, butyrate) and from 4-methylumbelliferyl (acetate, propionate and butyrate). Esterase-6 is a caste-specific enzyme detected in soldiers. Only esterases 1, 3 and 5 were detected in nymphs. No genetic polymorphism has been detected thus far in the esterases of Nasutitermes globiceps. This study suggests that allozyme variation can be explored to understand Nasutitermes social structure.

[Castleman's disease of the abdomen]. / Maladie de Castleman à localisation abdominale.

Plasmocytic variants of Castleman's disease are uncommon. We report a new case of abdominal location with a rapidly fatal outcome. Another particularity of that case was the negativity of Kaposi's sarcoma associated herpesvirus, a virus recently implicated in human immunodeficiency virus associated Castleman's disease.

Granulocyte function in women with diabetes and asymptomatic bacteriuria.

OBJECTIVE: To study whether diabetic women with asymptomatic bacteriuria have impaired granulocyte function and compare them with nonbacteriuric diabetic women. RESEARCH DESIGN AND METHODS: A prevalence study with granulocyte function testing in a randomly selected number of patients was conducted; the setting was the university. The patients consisted of 63 women visiting the outpatient clinic for routine control of their diabetes. Measurements of routine blood controls and urine cultures were conducted in all patients. Granulocyte function testing (chemotaxis, opsonization, oxidative burst, phagocytosis, and killing) was performed in the first 20 patients (10 with and 10 without asymptomatic bacteriuria) and in 7 healthy control subjects. RESULTS: The prevalence of bacteriuria was 32%. Demographic characteristics were not significantly different between bacteriuric and nonbacteriuric women. Leukocytes were found more often in the urine of bacteriuric women (P < 0.05). No differences in any of the granulocyte function tests were documented among diabetic women with true asymptomatic bacteriuria, nonbacteriuric women, and healthy control subjects. CONCLUSIONS: The prevalence of asymptomatic bacteriuria is increased in women with diabetes. Granulocyte function impairment, however, cannot be the explanation for this finding.

[Epidemiology of hepatocellular carcinoma in the department of Calvados]. / Epidémiologie du carcinome hépatocellulaire dans le département du Calvados.

OBJECTIVES: The aim of this study was to determine the epidemiological characteristics of hepatocellular carcinoma in a non-selected population. METHODS: Between 1984 and 1990, all cases of hepatocellular carcinoma were registered at the Registry of Digestive Tumors of Calvados. Standardized incidence rates were calculated for males and females. Prognostic factors were determined by the Cox multivariate method. RESULTS: 213 patients with hepatocellular carcinoma were registered. Standardized incidence rates were 7.5/100,000 in men and 0.4/100,000 in women. Sex-ratio was 18.3. Mean age was 66.4 years; hepatocellular carcinoma was uncommon (3%) before the age of 50. Cirrhosis was associated in 85.9% of patients. The cause of cirrhosis was known in 150 cases: alcoholic: 73.3%, cryptogenetic: 8.7%, viral B or C: 7.3%, alcoholic and viral B or C: 5.3%, and genetic hemochromatosis: 4.7%. The overall survival rate in 203 patients was 21%, 8% and 3% at 1 year, 3 years and 5 years, respectively. The multivariate study identified 4 prognostic factors: number of tumors < or = 2, lack of ascites, serum alpha-fetoprotein < or = 10 mg/mL, and hepatocellular carcinoma revealing a well-compensated liver disease until the time of diagnosis. CONCLUSION: The occurrence of hepatocellular carcinoma seems to be linked to cirrhosis, male sex, and age > 50, which could be used as the main selection criterias for the screening of hepatocellular carcinoma.

Molecular profile of an antibody response to HIV-1 as probed by combinatorial libraries.

A large number (33) of human Fab fragments reacting with HIV-1 surface glycoprotein gp120 have been generated by selection from a combinatorial IgG1 kappa library displayed on the surface of phage. The library was prepared from a long term asymptomatic HIV-seropositive donor. Analysis of the sequences from these Fabs shows the heavy chains can be placed in groups, many of which contain intraclonal variants, almost certainly corresponding to chains used in vivo. Further variants can be accessed via chain shuffling experiments in which a given light chain is recombined with a library of heavy chains. Heavy chain promiscuity, i.e. the ability of heavy chains to pair with different light chains with retention of antigen binding, is dependent on the particular heavy chain considered and probably excludes the identification of in vivo light chain partners. The antibodies examined here are primarily to the CD4 binding site on gp120 and broadly reflect the serum profile of the donor. The antibodies show evidence of extensive somatic modification indicative of an antigen-driven response. The heavy chain CDR3 regions of the antibodies show a remarkably conserved extended length. A number also show strong sequence conservation in CDR3 against a background of considerable diversity in the rest of the VH gene supporting a central role for this region in antigen recognition.

A binary plasmid system for shuffling combinatorial antibody libraries.

We have used a binary system of replicon-compatible plasmids to test the potential for promiscuous recombination of heavy and light chains within sets of human Fab fragments isolated from combinatorial antibody libraries. Antibody molecules showed a surprising amount of promiscuity in that a particular heavy chain could recombine with multiple light chains with retention of binding to a protein antigen. The degree to which a given heavy chain productively paired with any light chain to bind antigen varied from 43% to 100% and depended strongly on the heavy-chain sequence. Such productive crosses resulted in a set of Fab fragments of similar apparent binding constants, which seemed to differ mainly in the amount of active Fab fragment produced in the bacterial cell. The dominance of the heavy chain in the antibody-antigen interaction was further explored in a set of directed crosses, in which heavy and light chains derived from antigen-specific clones were crossed with nonrelated heavy and light chains. In these crosses, an Fab fragment retained antigen binding only if it contained a heavy chain from an antigen-specific clone. In no case did the light chain confer detectable affinity when paired with indifferent heavy chains. The surprising promiscuity of heavy chains has ramifications for the evaluation of the diversity of combinatorial libraries made against protein antigens and should allow the combination of one such promiscuous heavy chain with an engineered light chain to form an Fab fragment carrying synthetic cofactors to assist in antibody catalysis.