Contribution of muscle MRI for diagnosis of myopathy.

Inherited myopathies are a group of disease, which, although distinct from a genetic and prognostic point of view, can lead to non-specific clinical pictures due to phenotypic overlap. Acquired immuno-mediated myopathies may also pose the problem of clinically accurate etiological orientation. The assessment of fatty infiltration and pathological increase in water volume of the muscle contingent on whole-body muscle MRI is becoming increasingly important in aiding the initial diagnosis of inherited and acquired myopathies. MRI helps orientating the clinical diagnostic hypotheses thanks to the patterns of muscle involved (more or less specific according to the entities), which led to the development of decision-making algorithms proposed in the literature. The aim of this article is to specify the proper MRI protocol for the evaluation of myopathies and the basis of the interpretation and to provide a summary of the most frequently inherited and acquired myopathies described in the literature.

Application of the DAWN clinical imaging mismatch and DEFUSE 3 selection criteria: benefit seems similar but restrictive volume cut-offs might omit potential responders.

BACKGROUND AND PURPOSE: An external validation of the selection criteria of diffusion-weighted imaging or computerized tomography perfusion assessment with clinical mismatch in the triage of wake-up and late-presenting strokes undergoing the Neurointervention with Trevo (DAWN) and the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke (DEFUSE3) trials was conducted in a cohort of unknown onset stroke (UOS) patients treated with thrombectomy. METHODS: A validation cohort of UOS patients was selected from a prospectively collected thrombectomy database to match the inclusion criteria of DAWN and DEFUSE 3. Patients with an initial National Institutes of Health Stroke Scale (NIHSS) ≥10 were stratified according to the DAWN selection criteria. Patients ≤90 years old with an initial NIHSS ≥6 were stratified according to the DEFUSE 3 selection criteria. The proportions of patients with a modified Rankin Scale (mRS) ≤2 at 3 months follow-up were compared between DAWN-eligible patients and the DAWN trial thrombectomy group, and between DEFUSE 3-eligible patients and the DEFUSE 3 trial thrombectomy group. RESULTS: Of the 60/102 (59%) DAWN-eligible patients, 26 patients (43%) reached a mRS ≤2 at 3 months follow-up [versus 52/107 patients (49%) in the DAWN trial thrombectomy group; P = 0.52]. Of the 100/117 (85%) DEFUSE 3-eligible patients, 48 patients (48%) reached a mRS ≤2 at 3 months follow-up [versus 41/92 patients (45%) in the DEFUSE 3 trial thrombectomy group; P = 0.67]. Of the DAWN-ineligible and DEFUSE 3-ineligible patients who underwent thrombectomy, 38% (16/42) and 41% (7/17) of patients reached a mRS ≤2, respectively. CONCLUSION: The results of the DAWN and DEFUSE 3 trials were externally validated in a UOS cohort where the trials' selection criteria identified a similar proportion of responders to thrombectomy.

One-hour post-load plasma glucose level during the OGTT predicts mortality: observations from the Israel Study of Glucose Intolerance, Obesity and Hypertension.

AIMS: The relationship between 1- and 2-h glucose levels following an oral glucose tolerance test (OGTT) and long-term mortality was evaluated. METHODS: Over a 33-year period, 2138 individuals were followed for all-cause mortality. Fasting and post-OGTT glucose parameters categorized the cohort according to baseline glycaemic status. Four categories were established according to 1- and 2-h glucose levels (in mmol/l): group A = 1 h ≤ 8.8 and 2 h < 7.8; group B = 1 h > 8.6 and 2 h < 7.8; group C = 1 h ≤ 8.6 and 2 h = 7.8-11.1 (impaired glucose tolerance); group D = 1 h > 8.6 and 2 h = 7.8-11.1 (impaired glucose tolerance). Individuals with diabetes at baseline were excluded from the cohort. RESULTS: By August 2013, 51% of the study cohort had died. The worst prognosis occurred in group D (73.8% mortality), followed by groups C (67.5%), B and A (57.9% and 41.6%, respectively). When the 2-h glucose value is 'normal' (< 7.8 mmol/l), the 1-h glucose value > 8.6 mmol/l is an important predictor of mortality (28% increased risk) compared with group A, controlling for sex, age, smoking, BMI, systolic and diastolic blood pressures. A gradual increased hazard for mortality was seen by study group (hazard ratio = 1.28, 1.60 and 1.76, for groups B, C and D, respectively; group A = reference). CONCLUSIONS: A 1-h glucose value > 8.6 mmol/l predicts mortality even when the 2-h level is < 7.8 mmol/l. However, when the 2-h level is in the impaired glucose tolerance range, the hazard for mortality rises significantly independent of the 1-h value. Individuals at risk for developing diabetes could be identified earlier using the 1-h threshold value of 8.6 mmol/l, which could avert progression to diabetes and increased mortality.‬.

The joint association of self-rated health and diabetes status on 14-year mortality in elderly men and women.

PURPOSE: Low self-rated health (SRH) has been found to be associated with increased risk of type 2 diabetes (T2D) and with mortality. We examined the possible interaction between SRH and diabetic state on all-cause mortality in a large cohort of elderly subjects, followed for 14 years. METHODS: During the years 2000-2004, survivors of the nationwide longitudinal Israel Study of Glucose Intolerance, Obesity and Hypertension were interviewed and examined for the third follow-up. The 1037 participants (mean age 72.4 ± 7.2 years) were asked to rate their health as: excellent, good, fair, poor, or very poor. Glucose categories were as follows: Normoglycemic, Prediabetes, T2D and Undiagnosed diabetes. Survival time was defined as the time from interview to date of death or date of last vital status follow-up (August 1, 2013). Multivariate Cox proportional hazards models were performed in order to assess whether SRH interacts with glycemic state in the association with mortality. RESULTS: A better SRH was reported by those with undiagnosed than known diabetes, and best for normoglycemic and prediabetic individuals. While all individuals with fair or poor/very poor SRH were at increased risk of mortality compared to those with excellent/good SRH, in the known diabetic individuals a greater hazard was observed in the excellent/good SRH (HR 3.32, 95 % CI 1.71-6.47) than in those with fair or poor/very poor SRH (HR 2.19, 95 % CI 1.25-3.86), after adjusting for age, sex, ethnic origin, marital status, education, BMI, physical activity, CVD, tumors, and creatinine level (p for interaction = 0.01). CONCLUSIONS: Self-rated health is not a sensitive tool for predicting mortality in elderly men and women with known T2D.

Basal state hyperinsulinemia in healthy normoglycemic adults heralds dysglycemia after more than two decades of follow up.

BACKGROUND: In a preliminary report, we found an association between hyperinsulinemia in the basal (fasting) state and the development of diabetes. OBJECTIVES: The current analysis further explored the long term link between basal hyperinsulinemia and conversion to dysglycemia. METHODS: This is a prospective study with up to 24 years of follow-up of 515 normoglycemic individuals (mean age at follow up = 70.3 ± 7.0; range 58-94) of an Israeli cohort. Fasting glucose and insulin were measured, and dysglycemia was defined as fasting glucose > 100 mg/dL. RESULTS: At the end of the follow-up period, almost half had progressed to dysglycemia. Male sex and elevated baseline levels of basal insulin, body mass index, blood glucose and blood pressure each favoured progression to dysglycemia over the subsequent two decades. A multivariate logistic regression model identified basal hyperinsulinemia as the strongest predictor for progression to dysglycemia (odds ratio = 1.79; 95% confidence interval 1.12-2.88), while controlling for ethnicity, blood pressure, fasting glucose, male sex, body mass index and age. CONCLUSIONS: Basal hyperinsulinemia in normoglycemic adults constitutes an independent risk factor for metabolic deterioration to dysglycemia over adulthood, and may help to identify apparently healthy subjects at increased risk for diabetes.

Adult-onset diabetes among Arabs and Jews in Israel: a population-based study.

AIMS: To study the age at presentation and factors associated with adult-onset diabetes (≥ 20 years) among Arabs and Jews in Israel. METHODS: Participants (n = 1100) were randomly selected from the urban population of the Hadera District in Israel. The study sample was stratified into equal groups according to sex, ethnicity (Arabs and Jews) and age. Information on age at diabetes presentation, family history of diabetes, history of gestational diabetes, socio-demographic and lifestyle characteristics was obtained through personal interviews. Self reports of diabetes were compared with medical records and were found reliable (κ = 0.87). The risk for diabetes was calculated using Kaplan-Meier survival analysis. Factors associated with diabetes in both ethnic groups were studied using Cox proportional hazard model. RESULTS: The prevalence of adult-onset diabetes was 21% among Arabs and 12% among Jews. Arab participants were younger than Jews at diabetes presentation. By the age of 57 years, 25% of Arabs had diagnosed diabetes; the corresponding age among Jews was 68 years, a difference of 11 years (P < 0.001). The greater risk for diabetes among Arabs was independent of lifestyle factors, family history of diabetes and, among women, history of gestational diabetes; adjusted hazard ratio 1.70; 95% confidence interval 1.19-2.43. CONCLUSIONS: Arabs in Israel are at greater risk for adult-onset diabetes than Jews and are younger at diabetes presentation. Culturally sensitive interventions aimed at maintaining normal body weight and active lifestyle should be targeted at this population. Possible genetic factors and gene-environmental interactions underlying the high risk for diabetes among Arabs should be investigated.

Wireless phone use in childhood and adolescence and neuroepithelial brain tumours: Results from the international MOBI-Kids study.

In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20-24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15-19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk.

Risk of brain tumours in relation to estimated RF dose from mobile phones: results from five Interphone countries.

OBJECTIVES: The objective of this study was to examine the associations of brain tumours with radio frequency (RF) fields from mobile phones. METHODS: Patients with brain tumour from the Australian, Canadian, French, Israeli and New Zealand components of the Interphone Study, whose tumours were localised by neuroradiologists, were analysed. Controls were matched on age, sex and region and allocated the 'tumour location' of their matched case. Analyses included 553 glioma and 676 meningioma cases and 1762 and 1911 controls, respectively. RF dose was estimated as total cumulative specific energy (TCSE; J/kg) absorbed at the tumour's estimated centre taking into account multiple RF exposure determinants. RESULTS: ORs with ever having been a regular mobile phone user were 0.93 (95% CI 0.73 to 1.18) for glioma and 0.80 (95% CI 0.66 to 0.96) for meningioma. ORs for glioma were below 1 in the first four quintiles of TCSE but above 1 in the highest quintile, 1.35 (95% CI 0.96 to 1.90). The OR increased with increasing TCSE 7+ years before diagnosis (p-trend 0.01; OR 1.91, 95% CI 1.05 to 3.47 in the highest quintile). A complementary analysis in which 44 glioma and 135 meningioma cases in the most exposed area of the brain were compared with gliomas and meningiomas located elsewhere in the brain showed increased ORs for tumours in the most exposed part of the brain in those with 10+ years of mobile phone use (OR 2.80, 95% CI 1.13 to 6.94 for glioma). Patterns for meningioma were similar, but ORs were lower, many below 1.0. CONCLUSIONS: There were suggestions of an increased risk of glioma in long-term mobile phone users with high RF exposure and of similar, but apparently much smaller, increases in meningioma risk. The uncertainty of these results requires that they be replicated before a causal interpretation can be made.

Determinants of mobile phone output power in a multinational study: implications for exposure assessment.

OBJECTIVES: The output power of a mobile phone is directly related to its radiofrequency (RF) electromagnetic field strength, and may theoretically vary substantially in different networks and phone use circumstances due to power control technologies. To improve indices of RF exposure for epidemiological studies, we assessed determinants of mobile phone output power in a multinational study. METHODS: More than 500 volunteers in 12 countries used Global System for Mobile communications software-modified phones (GSM SMPs) for approximately 1 month each. The SMPs recorded date, time, and duration of each call, and the frequency band and output power at fixed sampling intervals throughout each call. Questionnaires provided information on the typical circumstances of an individual's phone use. Linear regression models were used to analyse the influence of possible explanatory variables on the average output power and the percentage call time at maximum power for each call. RESULTS: Measurements of over 60,000 phone calls showed that the average output power was approximately 50% of the maximum, and that output power varied by a factor of up to 2 to 3 between study centres and network operators. Maximum power was used during a considerable proportion of call time (39% on average). Output power decreased with increasing call duration, but showed little variation in relation to reported frequency of use while in a moving vehicle or inside buildings. Higher output powers for rural compared with urban use of the SMP were observed principally in Sweden where the study covered very sparsely populated areas. CONCLUSIONS: Average power levels are substantially higher than the minimum levels theoretically achievable in GSM networks. Exposure indices could be improved by accounting for average power levels of different telecommunications systems. There appears to be little value in gathering information on circumstances of phone use other than use in very sparsely populated regions.

Ovarian carcinoma apparently confined to the ovaries--the accuracy of surgical staging in Israel.

BACKGROUND: In order to allot an ovarian malignancy to FIGO Stage I, in addition to abdominal exploration and the basic operation, it is also necessary to do peritoneal washings for cytological examination, random peritoneal biopsies (including diaphragmatic assessment) and omental and retroperitoneal lymph node assessment. OBJECTIVE: The aim of the study was to assess the accuracy of surgical staging of ovarian carcinoma classified as Stage I in Israel. METHODS: Included were all patients with histologically confirmed epithelial ovarian carcinoma (EOC) classified as Stage I in a data base of a nationwide incidence case control epidemiological study of ovarian carcinoma conducted in Israeli Jewish women during the period 1994-1999. Surgical staging data of these patients were retrieved from pathological reports, and from clinical records when available. RESULTS: A total of 182 EOC patients were classified as Stage I. About 86% of the patients underwent hysterectomy and bilateral salpingo-oophorectomy. The most commonly performed staging procedure was omental assessment (85.2%) while peritoneal biopsy was the least common one (34.1%). In 17 (9.3%) of the patients none of the staging procedures were done and only 34 (18.7%) had optimal staging. CONCLUSION: Although the data are from a decade ago, they seem to indicate the need for an increased awareness of the necessity for accurate surgical staging of tumors apparently confined to the ovaries since it can identify a group of patients who require surgical therapy alone and who can be spared the complications, inconvenience and cost of adjuvant chemotherapy.

Effects of a copper-medicated intrauterine device on ovarian artery, uterine artery, and intrauterine blood flow.

AIM: To determine the effect of a copper-medicated intrauterine device (IUD) on ovarian, uterine, arcuate, radial and subendometrial Doppler-derived indices of blood flow. METHOD: 23 regularly menstruating patients requested insertion of an IUD. All patients had a copper T (Nova T) IUD inserted between days 8 and 11 of the menstrual cycle. Ovarian, uterine, arcuate, radial and subendometrial artery pulsatility indices (PIs) were assessed by transvaginal color Doppler prior to insertion between days 8 and 11 of the menstrual cycle, and after 2 months in the same period of the cycle. Ovarian, uterine, arcuate, radial and subendometrial artery PIs were considered prior to and following IUD insertion. RESULTS: No differences were recorded in any of the blood vessels sampled between pre- and post-insertion PIs. CONCLUSION: No significant change in ovarian or in uterine system vascular impedance is associated with the presence of a copper-medicated IUD.

Validation of short term recall of mobile phone use for the Interphone study.

AIM: To validate short term recall of mobile phone use within Interphone, an international collaborative case control study of tumours of the brain, acoustic nerve, and salivary glands related to mobile telephone use. METHODS: Mobile phone use of 672 volunteers in 11 countries was recorded by operators or through the use of software modified phones, and compared to use recalled six months later using the Interphone study questionnaire. Agreement between recalled and actual phone use was analysed using both categorical and continuous measures of number and duration of phone calls. RESULTS: Correlations between recalled and actual phone use were moderate to high (ranging from 0.5 to 0.8 across countries) and of the same order for number and duration of calls. The kappa statistic demonstrated fair to moderate agreement for both number and duration of calls (weighted kappa ranging from 0.20 to 0.60 across countries). On average, subjects underestimated the number of calls per month (geometric mean ratio of recalled to actual = 0.92, 95% CI 0.85 to 0.99), whereas duration of calls was overestimated (geometric mean ratio = 1.42, 95% CI 1.29 to 1.56). The ratio of recalled to actual use increased with level of use, showing underestimation in light users and overestimation in heavy users. There was substantial heterogeneity in this ratio between countries. Inter-individual variation was also large, and increased with level of use. CONCLUSIONS: Volunteer subjects recalled their recent phone use with moderate systematic error and substantial random error. This large random error can be expected to reduce the power of the Interphone study to detect an increase in risk of brain, acoustic nerve, and parotid gland tumours with increasing mobile phone use, if one exists.

Drinking, micturition habits, and urine concentration as potential risk factors in urinary bladder cancer.

Investigation of micturition and drinking habits in urban (n = 475) and rural (n = 156) working populations demonstrated less frequent micturition, decreased fluid intake, and a higher urine concentration in the urban as compared to the rural group. All these differences were significant (P less than .01) by multivariate analysis, adjusting for age and sex differences. Drinking and micturition habits were similar in both sexes, but urine concentration was significantly lower in females (P less than .01) in both the urban and rural groups. Incidence of bladder cancer is reportedly higher in urban versus rural populations and in males versus females, the differences being apparently unaccountable for by differences in smoking, an important risk factor for bladder cancer. Our findings of greater urine concentration and less frequent micturition (which augments urine contact with bladder epithelium) in high-risk groups for bladder cancer are consistent with the "urogenous contact hypothesis." This hypothesis associates the etiology of bladder cancer with prolonged exposure to urine, on the basis of studies indicating carcinogenicity of urine. Further studies should indicate whether frequent drinking and urination are effective preventive measures against bladder cancer.

Effect of BRCA mutations on the length of survival in epithelial ovarian tumors.

PURPOSE: To study the role of BRCA mutations in ovarian cancer survival. PATIENTS AND METHODS: Blood samples and specimens of ovarian tumors (whenever blood samples were not available) at the time of the primary surgery were obtained in the course of a nationwide case-control study of women with ovarian cancer in Israel. The three common BRCA mutations in Israel (185delAG, 5382insC, and 6174delT) were analyzed with a multiplex polymerase chain reaction to amplify the exons containing the three mutations using fluor-labeled primers in a single reaction. Because each mutation is a small insertion or deletion, they can be detected as length polymorphisms. Patients were followed for up to 5 years (range, 20 to 64 months). Statistical analysis was performed using the Kaplan-Meier method and the log-rank test. Stepwise Cox regression analysis was used for determination of independent prognostic factors. RESULTS: This report is based on 896 blood or tumor specimens analyzed for the presence of the BRCA mutations. Of these, 234 women (26.1%) were found to be positive. A significant difference in survival pattern was found between BRCA1/BRCA2 carriers and noncarriers among the women with invasive ovarian cancer (median survival, 53.4 months v. 37.8 months; 3-year survival, 65.8% v. 51.9%, respectively). These differences were independent of age at diagnosis or stage of the disease. CONCLUSION: Our data indicate that the survival of patients with ovarian cancer is affected by BRCA germline mutation, at least in the early years after diagnosis.

Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation.

PURPOSE: Recipients of allogeneic bone marrow transplants (BMTs) who have relapsed may attain complete remissions when treated with transfusions of leukocytes obtained from the original bone marrow donor. We performed a retrospective study to characterize better this new treatment modality. PATIENTS AND METHODS: We surveyed 25 North American BMT programs regarding their use of donor leukocyte infusions (DLI). Detailed forms were used to gather data regarding the original BMT, relapse, DLI, response to DLI, complications of DLI, and long-term follow-up evaluation. Reports of 140 patients were thus available for analysis. RESULTS: Complete responses were observed in 60% (95% confidence interval [CI], 51.9% to 68.1%) of chronic myelogenous leukemia (CML) patients who received DLI and did not receive pre-DLI chemotherapy; response rates were higher in patients with cytogenetic and chronic-phase relapse (75.7%; 95% CI, 68.2% to 83.2%) than in patients with accelerated-phase (33.3%; 95% CI, 19.7% to 46.9%) or blastic-phase (16.7%; 95% CI, 1.9% to 31.9%) relapse. The actuarial probability of remaining in complete remission at 2 years was 89.6%. Complete remission rates in acute myelogenous leukemia (AML) (n = 39) and acute lymphocytic leukemia (ALL) (n = 11) patients who had not received pre-DLI chemotherapy were 15.4% (95% CI, 9.6% to 21.2%) and 18.2% (95% CI, 6.6% to 29.8%), respectively. Complete remissions were also observed in two of four assessable myeloma patients and two of five assessable myelodysplasia patients. Complications of DLI included acute graft-versus-host disease (GVHD) (60%; 95% CI, 51.4% to 68.6%), chronic GVHD (60.7%; 95% CI, 50.3% to 71.1%), and pancytopenia (18.6%; 95% CI, 12.2% to 25.0%). Pre-DLI characteristics predictive of complete response in CML patients were post-BMT chronic GVHD, pre-DLI disease status of chronic phase, and time interval between BMT to DLI less than 2 years. Acute and chronic GVHD post-DLI were highly correlated with disease response (P < .00001). CONCLUSION: DLI results in complete remissions in a high percentage of patients with relapsed chronic-phase CML. Complete remissions are observed less frequently in patients with advanced CML and acute leukemia. GVHD and pancytopenia occur commonly; GVHD is highly correlated with response.

Prognostic significance of precordial ST segment depression on admission electrocardiogram in patients with inferior wall myocardial infarction.

OBJECTIVES: This study assessed retrospectively the correlation between the pattern of precordial ST segment depression on the admission electrocardiogram (ECG) and hospital mortality in patients with an inferior myocardial infarction treated with intravenous thrombolytic therapy. BACKGROUND: Previous studies have shown that in acute inferior myocardial infarction, ST segment depression in the precordial leads is associated with increased hospital mortality. However, the significance of the different patterns of precordial ST segment depression has been evaluated in only two previous studies. METHODS: The study included 1,321 patients (1,020 men) who enrolled in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) trial in Israel and received intravenous thrombolytic therapy. Patients with an ST segment elevation > or = 0.1 mV in at least two of the inferior leads were included. Patients were classified into four groups on the basis of their admission ECG: group I = patients with no precordial ST segment depression (n = 346); group II = those for whom the sum of ST segment depression in leads V1 to V3 was greater than that in leads V4 to V6 (n = 700); group III = those for whom the sum of ST depression in leads V1 to V3 was equal to that in leads V4 to V6 (n = 162); group IV = those with maximal ST depression in leads V4 to V6 (n = 113). RESULTS: The overall hospital mortality rate was 3.6% (48 patients): for groups I, II, III and IV it was 2.9%, 2.8%, 4.3% and 9.7%, respectively. Multivariable logistic regression analysis confirmed that hospital mortality was independently associated with the pattern of precordial ST segment depression. The odd ratios in group IV relative to group I was 2.78 (95% confidence interval 1.26 to 6.13, p = 0.007). CONCLUSIONS: The risk of mortality is higher in patients with an inferior myocardial infarction and maximal ST segment depression in precordial leads V4 to V6 versus precordial leads V1 to V3 on the admission ECG.

Prognostic significance of the admission electrocardiogram in acute myocardial infarction.

OBJECTIONS: We sought to access the ST segment and the terminal portion of the QRS complex in the initial electrocardiogram (ECG) as tools to predict outcome in patients with acute myocardial infarction given thrombolytic therapy. BACKGROUND: Previous studies assessing early risk stratification of patients with acute myocardial infarction by ECG criteria have focused on the number of leads with ST segment elevation or the absolute magnitude of ST deviation. A new classification independent of the absolute values of ST deviation was pursued. METHODS: Patients with ST elevation and positive T waves in at least two adjacent leads who received thrombolytic therapy were classified into two groups based on the absence (1,232 patients) or presence (1,371 patients) of distortion of the terminal portion of the QRS complex on the admission ECG. RESULTS: There were no differences between groups in the prevalence of previous angina, hypertension, current smoking, anterior infarction, time from onset of symptoms to therapy of type of thrombolytic regimen. Patients with QRS distortion were less likely to have had a previous infarction (12.0% vs. 18.4%, p = 0.02) or diabetes mellitus (16.9% vs. 21.4%, p = 0.003). They had higher peak creatine kinase levels (1,617 +/- 1,670 vs. 1,080 +/- 1,343 IU, p = 0.00001). Hospital mortality for those with and without QRS distortion was 6.8% and 3.8%, respectively (p = 0.0008). Multivariable logistic regression analysis confirmed that hospital mortality was independently associated with distortion of terminal portion of the QRS complex (odds ratio 1.78, 95% confidence interval 1.19 to 2.68, p = 0.004). CONCLUSIONS: Distortion of the terminal portion of the QRS complex on the admission ECG is independently associated with a higher hospital mortality rate in patients with acute myocardial infarction given thrombolytic therapy.

Diagnosis delay in familial Mediterranean fever (FMF): social and gender gaps disclosed.

OBJECTIVE: To characterize the factors contributing to a greater than 10 year delay in the diagnosis of familial Mediterranean fever (FMF). METHODS: 50 patients, in whom diagnosis of FMF was delayed by more than 10 years, comprised the study population. The clinical, demographic and molecular genetic characteristics were compared to a control group of 50 FMF patients, in whom the diagnosis was made within a reasonable time period (less than 5 years from onset). Additional factors contributing to a delayed diagnosis in the study group, including physician-related factors, patient-related factors, disease-factors and other factors, were studied as well. RESULTS: Overall, attack sites, duration and severity were comparable among study and control groups. No differences in ethnic origin or family history of FMF were noted between the groups. There were significantly more females (p = 0.009), newly-arrived immigrants (p = 0.005) and carriers of unidentified MEFV mutations (p = 0.04) in the study group. Delayed diagnosis of FMF stemmed from misdiagnosis and physician negligence (70%), as well as from patient negligence (70%). The diagnosis was ultimately made mainly due to a change in disease pattern and other causes, such as diagnosis of FMF in a relative. CONCLUSION: The study unveils unexpected causes behind a prolonged delay in the diagnosis of FMF such as social status (immigrant), female gender, physician negligence and lack of patient awareness. The possibility that the delay stems from a milder disease pattern was dismissed.

Cytokine-mediated regulation of rat ovarian function: interleukin-1 stimulates the accumulation of a 92-kilodalton gelatinase.

It is known that the mammalian ovary possesses a complete interleukin-1 (IL-1) system replete with ligands, receptors, and a receptor antagonist. To further assess the hypothesis that IL-1 may play an intermediary role in gonadotropin-triggered ovulation, we have set out to determine whether IL-1 is capable of promoting ovarian collagenase biosynthesis, an established component of the ovulatory cascade. Untreated cultured whole ovarian dispersates from immature (25 day old) rats constitutively elaborated several collagenolytic species as assessed in a gelatin matrix. A major 72 kilodalton (kDa) gelatinase (GL) was particularly apparent. Treatment with IL-1 beta produced selective dose- and cell density-dependent increments in the accumulation of a 92-kDa GL species. Administration of an IL-1 receptor antagonist neutralized the IL-1-induced stimulation of the 92-kDa GL in a dose-dependent fashion thereby supporting the presumption that the IL-1 effect is receptor mediated. Studies of comparable cellular densities of granulosa or enriched theca-interstitial cultures demonstrated the IL-1 induced 92-kDa GL to be highly expressed in the enriched theca-interstitial but not in the isolated granulosa cell preparations. Treatment with transforming growth factor-beta 1, a putative regulator of IL-1 action, significantly attenuated IL-1-induced 92-kDa GL accumulation thereby suggesting a potential regulatory paracrine/autocrine role for this agent in ovarian gelatinase economy. Initial characterization revealed the 92-kDa GL species to be a metalloproteinase present in its proenzyme zymogenic form. Taken together, our present findings reveal the ovarian expression of a constitutive 72-kDa GL and of an IL-1-stimulated 92-kDa GL the accumulation of which is particularly marked in enriched theca-interstitial preparations. These observations, along with the demonstration of the gonadotropin-dependent preovulatory induction of ovarian IL-1 gene expression, provide strong indirect support for the view that IL-1 may be the centerpiece of an intraovarian regulatory loop concerned with the promotion of the ovulatory cascade.

Cerebrovascular events in patients with significant stenosis of the carotid artery are associated with hyperhomocysteinemia and platelet antigen-1 (Leu33Pro) polymorphism.

BACKGROUND AND PURPOSE: Although risk factors for carotid artery stenosis caused by atherosclerosis are known, it is unclear what triggers "activation" of the atherosclerotic plaques and the ensuing thromboembolic cerebral events. The aim of this study was to evaluate whether thrombophilic factors, platelet glycoprotein (GP) polymorphisms, and homocysteine are associated with a risk of ischemic events in patients with significant carotid stenosis. METHODS: Consecutive patients with >/=50% carotid stenosis, whether symptomatic (with ipsilateral ischemic events) or asymptomatic, who were evaluated and followed in a neurovascular clinic were tested for plasma levels of homocysteine, C677T mutation in methylenetetrahydrofolate reductase, G20210A mutation of factor II, factor V Leiden, antiphospholipid antibodies, and polymorphisms of platelet membrane GP: human platelet antigen (HPA)-1, GP Ia (C807T), and GP Ib (variable number of tandem repeats, Kozak, and HPA-2). RESULTS: Eighty-six asymptomatic and 67 symptomatic patients were evaluated. The former group was older (73.7+/-6.9 versus 69.5+/-9.1 years, P=0.02). Major risk factors for stroke were similar in both groups. In symptomatic patients versus asymptomatic patients, hyperhomocysteinemia was 3-fold more frequent (34.3% versus 12.8%, respectively; P=0.002) and HPA-1a/b was almost 2-fold more common (38.8% versus 20.9%, respectively; P=0.01). All other thrombophilic factors and platelet polymorphisms studied did not differ significantly between the 2 groups. Multivariate analysis revealed that hyperhomocysteinemia and the HPA-1a/b genotype conferred a significant risk of cerebral ischemic events, with odds ratios (95% CI) of 4.07 (1.7 to 9.7) and 3.4 (1.5 to 7.8), respectively. CONCLUSIONS: Hyperhomocysteinemia and HPA-1a/b are independent risk factors for ischemic events in patients with significant carotid stenosis.