The new Ghent criteria for Marfan syndrome: what do they change?

The diagnosis of Marfan syndrome (MFS) is challenging and international criteria have been proposed. The 1996 Ghent criteria were adopted worldwide, but new diagnostic criteria for MFS were released in 2010, giving more weight to aortic root aneurysm and ectopia lentis. We aimed to compare the diagnosis reached by applying this new nosology vs the Ghent nosology in a well-known series of 1009 probands defined by the presence of an FBN1 mutation. A total of 842 patients could be classified as MFS according to the new nosology (83%) as compared to 894 (89%) according to the 1996 Ghent criteria. The remaining 17% would be classified as ectopia lentis syndrome (ELS), mitral valve prolapse syndrome or mitral valve, aorta, skeleton and skin (MASS) syndrome, or potential MFS in patients aged less than 20 years. Taking into account the median age at last follow-up (29 years), the possibility has to be considered that these patients would go on to develop classic MFS with time. Although the number of patients for a given diagnosis differed only slightly, the new nosology led to a different diagnosis in 15% of cases. Indeed, 10% of MFS patients were reclassified as ELS or MASS in the absence of aortic dilatation; conversely, 5% were reclassified as MFS in the presence of aortic dilatation. The nosology is easier to apply because the systemic score is helpful to reach the diagnosis of MFS only in a minority of patients. Diagnostic criteria should be a flexible and dynamic tool so that reclassification of patients with alternative diagnosis is possible, requiring regular clinical and aortic follow-up.

What do French patients and geneticists think about prenatal and preimplantation diagnoses in Marfan syndrome?

OBJECTIVES: Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with manifestations mainly involving the skeletal, ocular, and cardiovascular systems. The phenotypic variability observed in MFS makes genetic counselling difficult. Prenatal diagnosis (PND) and preimplantation genetic diagnosis are technically feasible when a causal mutation is identified, but both raise many ethical questions in this condition. Little is known about opinions and practices in such reproductive issues in MFS. The goal of this study was to report on patients' points of view and geneticists' standard practices. METHODS: Two different questionnaires were produced. RESULTS: Fifty geneticists filled in the questionnaire. Twenty-two per cent thought that PND was acceptable, 72% debatable and 6% not acceptable. Preimplantation genetic diagnosis was more often reported acceptable (34% of answers). Results varied according to the physician's experience with the disease. Fifty-four answers were collected for patients' questionnaires. Most of them (74%) were favourable to the development of prenatal testing, and believed that the choice should be given to parents. However, only a minority would opt for prenatal diagnosis for themselves. CONCLUSION: This study showed that the majority of patients were in favour of PND and that opinions among practitioners varied widely, but that overall, practitioners favoured a systematic multidisciplinary evaluation of the couple's request.

Loss of chromatic sensitivity in AMD and diabetes: a comparative study.

BACKGROUND: Abnormalities in rod and cone photoreceptor morphology have been reported in normal aging retinas in the absence of known pathology and have been taken as an indicator of susceptibility to retinal disease. Some loss of visual performance may therefore precede retinal structural changes that can be detected reliably using conventional fundus imaging techniques. Red/green (RG) and yellow/blue (YB) colour discrimination thresholds are sensitive measures of normal retinal function and poor YB discrimination is often taken as an indicator of retinal disease, though it is generally acknowledged that RG loss is also present in most cases of acquired deficiency. Although structural changes in age-related macular degeneration (AMD) and diabetes share some similarities, significant differences remain and this may result in different patterns of RG and YB loss. AIM: The aim of this study was to quantify and compare the severity of RG and YB loss of chromatic sensitivity in patients with AMD and diabetes. METHODS: Patients with varying severity of AMD and diabetes and normal subjects of similar age were recruited for the study. RG and YB colour detection thresholds were measured in the two groups of patients and the control group, using the Colour Assessment and Diagnosis (CAD) test. RESULTS: Each AMD subject investigated showed significant, but unequal loss of YB and RG chromatic sensitivity, with YB discrimination showing the greatest loss. Diabetic subjects also exhibited reduced chromatic sensitivity, but with almost equal and highly correlated RG and YB thresholds (R(2) = 0.99). The severity of colour vision loss measured with the CAD test also correlates well with a clinical classification index of disease progression in AMD, and with the level of hyperglycaemic control in diabetes. CONCLUSIONS: These findings suggest that accurate measurements of RG and YB colour thresholds can provide a sensitive measure of functional change in diseases of the retina with patterns of loss that differ significantly in AMD and diabetes.

Pathogenic FBN1 mutations in 146 adults not meeting clinical diagnostic criteria for Marfan syndrome: further delineation of type 1 fibrillinopathies and focus on patients with an isolated major criterion.

Mutations in the FBN1 gene cause Marfan syndrome (MFS) and have been associated with a wide range of milder overlapping phenotypes. A proportion of patients carrying a FBN1 mutation does not meet diagnostic criteria for MFS, and are diagnosed with "other type I fibrillinopathy." In order to better describe this entity, we analyzed a subgroup of 146 out of 689 adult propositi with incomplete "clinical" international criteria (Ghent nosology) from a large collaborative international study including 1,009 propositi with a pathogenic FBN1 mutation. We focused on patients with only one major clinical criterion, [including isolated ectopia lentis (EL; 12 patients), isolated ascending aortic dilatation (17 patients), and isolated major skeletal manifestations (1 patient)] or with no major criterion but only minor criteria in 1 or more organ systems (16 patients). At least one component of the Ghent nosology, insufficient alone to make a minor criterion, was found in the majority of patients with isolated ascending aortic dilatation and isolated EL. In patients with isolated EL, missense mutations involving a cysteine were predominant, mutations in exons 24-32 were underrepresented, and no mutations leading to a premature truncation were found. Studies of recurrent mutations and affected family members of propositi with only one major clinical criterion argue for a clinical continuum between such phenotypes and classical MFS. Using strict definitions, we conclude that patients with FBN1 mutation and only one major clinical criterion or with only minor clinical criteria of one or more organ system do exist but represent only 5% of the adult cohort.

[Recurrent delayed pericarditis after pacemaker implantation: a post-pericardiotomy-like syndrome?]. / Une péricardite retardée récidivante après implantation de pacemaker: un équivalent de syndrome de Dressler?

INTRODUCTION: Pacemaker implantation is a usual technique in cardiology which may be followed by acute pleural effusion and delayed unusual pericarditis. CASE REPORT: We reported the case of a 67 year-old man hospitalized for faintness. Rhythmical auricular disease was diagnosed and pacemaker was implanted without immediate complication. Though pericarditis with tamponade at the day 21 will require emergency pericardiotomy surgery. A recurrent pericarditis at day 45 was treated with anti-inflammatory drugs without relapse at the end of the treatment. DISCUSSION: Repeated delayed pericarditis after pacemaker surgery may be compared to the Dressler syndrome which occurs after myocardial infarction.

Antigenic changes of DBA/2J mastocytoma cells when grown in the BALB/c mouse.

A 10-day growth period of the DBA/2J strain-specific P815-X2 mastocytoma in the BALB/c mouse altered the antigenicity of the tumor cell surface. The in vivo-modified mastocytoma cells differed from mastocytoma cells grown in the original DBA/2J mice in suspectibility to lysis by immune peritoneal exudate cells, in vitro antigenic recognition by cytotoxic T-cells, and immunizing capacity in allogeneic C57BL/6 mice. Propagation of the altered tumor cells in the original host or maintenance in tissue culture for 40 hours restored complete susceptibility to lymphocyte-mediated cytotoxicity.

[Acute heart failure and preserved systolic function: can we explain all only by the diastolic dysfunction? A prospective study on 145 patients hospitalized for acute pulmonary edema]. / Insuffisance cardiaque aiguë et fonction systolique préservée: peut-on tout expliquer par la seule dysfonction diastolique? Etude prospective sur 145 patients hospitalisés pour OAP.

INTRODUCTION: Heart failure with conserved systolic function is frequent and attributed to the diastolic dysfunction. The diagnosis of diastolic heart failure requires the association of clinical signs of heart failure, a conserved left ventricular systolic function and a diastolic dysfunction. OBJECTIVE: To determine the proportion of cases of isolated diastolic heart failure among patients hospitalized for acute pulmonary edema. METHODS: The left ventricular ejection fraction (LVEF), the diastolic function and levels of NT-proBNP have been assessed at admission of 145 patients hospitalized for acute pulmonary edema. RESULTS: 49% of patients included were older than 80 years (mean age 78.6 + 0.9 years). Among the 83 patients with conserved LVEF, 25% had an ischemic heart disease, 24% a severe valvular disease, 22% an atrial fibrillation, 5% a severe bradycardia, 2% a severe hypertrophic obstructive cardiomyopathy. Only 15 patients presented an isolated diastolic heart failure. The level of NT-proBNP was correlated to LVEF but was not able to identify those with isolated diastolic heart failure in the group with "conserved systolic function". CONCLUSION: Among patients hospitalized for acute pulmonary edema, the prevalence of heart failure with conserved systolic function is high, but only 10% of them presented an isolated diastolic heart failure. The NT-proBNP levels do not permit to identify them.

Progressive decreases in nuclear retinoid receptors during skin squamous carcinogenesis.

Retinoids are essential for normal skin growth, differentiation, and apoptosis and are active pharmacologically in the prevention and treatment of skin cancers and other lesions. Retinoid effects are mediated mainly by retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which act as transcription factors to alter gene expression. Using in situ hybridization, we analyzed the expression of RARs and RXRs in normal sun-exposed skin (n = 85), squamous cell carcinoma (SCC; n = 28), and actinic keratosis [AK (a precursor to SCC); n = 38]. The expressions of five receptors (RAR-alpha and -gamma and RXR-alpha, -beta, and -gamma) were moderate to very strong in normal skin, with higher expressions in spinous and granular layers than in the basal layer. RAR-beta expression was weak or absent in normal and lesion samples. All five receptors expressed in the skin were suppressed progressively from normal skin to premalignant skin (AK) to invasive skin SCC. Specific receptor decreases in lesions relative to normal skin ranged from 75% (RXR-beta) to 96% (RAR-alpha) in SCC and from 37% (RAR-gamma) to 68% (RXR-beta) in AK. The degree of suppression of RXR-alpha and RAR-gamma, the two predominant retinoid receptors in skin, was relatively less for RXR-alpha (58% versus 86%; P = 0.015) and relatively greater for RAR-gamma (37% versus 89%; P = 0.0001) between AK and SCC, suggesting that suppression of RXR-alpha may be an earlier event and expression of RAR-gamma may be a later event of multistep squamous skin carcinogenesis. Our results indicate that suppressed expression of retinoid receptors occurs early (in AK) and is associated with progression of squamous skin carcinogenesis to SCC.

Prognostic value of thallium-201 single-photon emission computed tomographic myocardial perfusion imaging according to extent of myocardial defect. Study in 1,926 patients with follow-up at 33 months.

OBJECTIVES: This study was designed to assess the prognostic value of thallium-201 single-photon emission computed tomographic (thallium SPECT) perfusion imaging in patients evaluated for stable angina pectoris and to examine the relation, if any, between the presence and extent of myocardial defect and future fatal or nonfatal cardiovascular events (revascularization, secondary myocardial infarction). BACKGROUND: Compared with planar scintigraphy, thallium SPECT enables better evaluation of the extent of myocardial perfusion defect. However, its prognostic value has not yet been studied in a large population of patients. METHODS: Between 1987 and 1989 we studied 3,193 patients. After exclusion of patients with unstable angina, myocardial infarction during the previous month or earlier revascularization, 1,926 patients were followed up for 33 +/- 10 (mean +/- SD) months after stress thallium SPECT imaging (performed after exercise in 1,121 patients or during dipyridamole infusion in 805 patients). Thallium SPECT imaging of the left ventricle was divided into six segments. RESULTS: After normal thallium SPECT imaging (715 patients), the annual total and cardiovascular mortality rates were, respectively, 0.42%/year and 0.10%/year and were significantly higher after abnormal thallium SPECT imaging (respectively, 2.1%, relative risk 5, p = 0.012; 1.5%, relative risk 15, p < 0.0001 [log-rank test]). There was a significant relation between the number of abnormal segments and cardiovascular mortality during follow-up (p < 0.02) or the occurrence of nonfatal events (p < 0.001). The extent of defect on the initial scan provided the best SPECT variable for long-term prognosis. Thallium SPECT imaging provided additive prognostic information compared with other clinical variables (gender, previous myocardial infarction) and exercise electrocardiogram. CONCLUSIONS: In patients with stable angina, normal thallium SPECT imaging indicates a low risk patient, and the extent of myocardial defect is an important prognostic predictive factor.

Phase I study of cinchonine, a multidrug resistance reversing agent, combined with the CHVP regimen in relapsed and refractory lymphoproliferative syndromes.

Overexpression of P-glycoprotein (P-gp) in cancer cells reduces intracellular accumulation of various anticancer drugs including anthracyclines and vinca alkaloids. This multidrug resistance (MDR) phenotype can be reversed in vitro by a number of non-cytotoxic drugs. We have identified the quinine's isomer cinchonine as a potent MDR reversing agent, both in vitro and in animal models. Here, we report an open phase I dose escalation trial in patients with refractory or relapsed malignant lymphoid diseases. Cinchonine dihydrochloride was administered by continuous i.v. infusion for 48 h and escalated over five dose levels ranging from 15 to 35 mg/kg/d. Cinchonine infusion started 24 h before i.v. doxorubicin (25 mg/m2), vinblastine (6 mg/m2), cyclophosphamide (600 mg/m2) and methylprednisolone (1 mg/kg/d) (CHVP regimen) and lasted for 24 h after chemotherapy infusion. Thirty-four patients received 87 cycles of CHVP/cinchonine. The MTD of cinchonine administered by continuous i.v. infusion was 30 mg/kg/d. Prolonged cardiac repolarization was the main dose-limiting toxicity. No ventricular arrhythmia including 'torsade de pointes' was observed. An MDR reversing activity was identified in the serum from every patient and correlated with cinchonine serum level. When infused at 30 mg/kg/d, cinchonine demonstrated a limited influence on doxorubicin pharmacokinetic. We conclude that i.v. infusion of cinchonine might be started 12 h before MDR-related chemotherapy infusion and requires continuous cardiac monitoring but no reduction of cytotoxic drug doses.

[Risk stratification in pre-hospital management of myocardial infarction with ST elevation: value of a risk score profile]. / Stratification du risque dans la prise en charge préhospitalière des infarctus du myocarde avec sus-décalage du segment ST: intérêt du profil de score de risque.

The aims of this study were to evaluate new tools of risk stratification in an unselected population of myocardial infarction (MI), usable in a pre-hospital situation, and to compare the risk profile of these patients with those of other clinical trials or myocardial infarction registries. The risk scores of death at 30 days (TIMI score and TIMI risk index) based on data available in the context of coronary emergencies, were applied to the population base of the MI observatory of myocardial infarction in the Côte d'Or (RICO). The risk profile was expressed by the smoothed graph of frequency distribution of each score. The TIMI score applied to the RICO population had a high discriminating power (c = 0.80) for mortality whereas TIMI risk index was less powerful (c = 0.57). The risk profile of the RICO population was comparable to that of InTIME II, ASSENT 2 and the NRMI with reperfusion registry. The NRMI without reperfusion and the MAGIC studies had different profiles characterised by a shift in the graph towards high risk patients. The authors conclude that risk stratification scores, like the TIMI score, are valuable tools for early triage in the management of MI patients. The risk profiles allow comparative analysis of risk levels of populations notably with respect to other registries and also with respect to randomised clinical trials.

[Role of visual analysis of first-pass contrast-enhanced MRI in reperfused myocardial infarction]. / Intérêt de l'IRM de perfusion avec analyse visuelle a la phase aiguë de l'infarctus du myocarde reperfusé.

The aim of this work is to evaluate the relationship between improvement of regional myocardial function and visual analysis of contrast-enhanced (CE) MRI in patients after acute myocardial infarction. MRI was performed on 19 patients 1 and 11 weeks after a reperfused acute myocardial infarction. Perfusion data (first-pass images [FPI] and delayed CE images) were acquired after an intravenous bolus of gadolinium-DTPA and visually analyzed using a 17 segment model. Each segment was then classified in 3 groups, according to the presence or absence of FPI and CE patterns at baseline study: group 0: normal-appearing segments; group 1: segments with delayed hyper-enhancement but no early hypo-enhancement; group 2: segments with early hypoenhancement. Relative Wall thickening (RWT) was analyzed in each segment and its improvement evaluated in each group. Between first MRI and follow-up study, a significant improvement of RWT occurred in group 1 (mean +/- SD) [from 43.43 +/- 26.59% to 76.71 +/- 47.38%; p = 0.001] but not in group 2 (from 32.73 +/- 25.58% to 39.57 +/- 30.57%; p = NS). In group 0, RWT despite normal value at baseline study exhibited a significant improvement at follow-up (from 65.23 +/- 46.52% to 79.73 +/- 48.46%; p = 0.0015). In conclusion, the combined analysis of early and delayed perfusion abnormalities in MRI in the week following myocardial infarction can predict myocardial viability and allows in the future an evaluation of the efficacy of perfusion therapy.

[Atrial fibrillation during myocardial infarction with and without ST segment elevation]. / Fibrillation auriculaire au cours de l'infarctus du myocarde avec et sans sus-decalage du segment ST: Données de l'observatoire des infarctus de Côte-d'or (RICO).

INTRODUCTION: The occurrence of atrial fibrillation (AF) in the acute phase of myocardial infarction with ST segment elevation is common and responsible for an excess hospital mortality. The aim of this work was to define the incidence, predictive factors, and the prognostic impact of AF during MI with and without raised ST segment in the RICO study. PATIENTS AND METHODS: Between January 2001 and July 2003, 1701 patients were included in this study: 130 (7.6%) had AF in the first 24 hours of management (AF+ group); 1571 (92.4%) remained in sinus rhythm (AF- group). RESULTS: Among the 1701 patients included in this study, 1197 (70.4%) had MI with raised ST and 504 (29.6%) had MI without raised ST. The incidence of AF was identical whatever the type of MI (7.6% with raised ST versus 7.7% without, p=0.334). The presence of Killip class >2 on admission and chronic obstructive pulmonary disease were independent predictive factors for the occurrence of AF (OR=3.84, p=0.007, and OR=2.47, p=0.014 respectively). The presence of AF was significantly associated with the occurrence of ventricular arrhythmia and/or cardiovascular mortality during admission in the non-selected MI population whatever the type of MI (raised ST ; AF+; 34% and AF-; 18%, p<0.01 versus without raised ST; AF+; 36% and AF-; 16%, p = 0.01). CONCLUSION: This study provides evidence that the incidence of AF during the first 24 hours of MI, as well as its poor prognosis, are identical whether or not there is ST segment elevation.

[Brugada syndrome]. / Syndrom brugada.

Brugada syndrome is believed to be responsible for 4 to 12% of all sudden deaths and for 20% of deaths in patients with structurally normal hearts. As a distinct clinical entity with a high risk of sudden cardiac death it was first described in 1992. The syndrome characterized by ST segment elevation in right precoardial leads V1 to V3 unrelated to ischemia and by electrolyte disturbance without obvious structural heart disease. The clinical findings are based on ECG and syncope or sudden death. The arrhythmia leading to sudden death is a rapid polymorphic ventricular tachycardia. The electrocardiographic signature of the syndrome is dynamic and often concealed, but can be unmasked by potent sodium channel blockers such as flecainde, ajmaline. The Brugada syndrome is a familial disease displaying an autosomal dominant mode of transmission with incomplete penetration and with incidence ranging between 5 and 66 per 10,000. The syndrome has been linked to mutations in SCNA5, the gene encoding for the a subunit of the sodium channel. Implantation of an automatic cardiverter-defibrillator is the only currently proven effective therapy.

Excision repair of pyrimidine dimers induced by simulated solar radiation in the skin of patients with basal cell carcinoma.

One prominent lesion induced in DNA by ultraviolet (UV) radiation is the cyclobutyl pyrimidine dimer formed between adjacent pyrimidines on the same DNA strand. We investigated whether people who have developed basal cell carcinoma on sun-exposed skin have an altered ability to repair UV-induced pyrimidine dimers in DNA. Twenty-two patients with at least one basal cell carcinoma, aged 31-84 years, and 19 healthy volunteers, aged 25-61 years, took part in the study. Both groups were given one minimal erythema dose (MED) of simulated solar radiation on the lower back. DNA was extracted from the irradiated skin 0 to 6 h later, and the number of UV-induced pyrimidine dimers was determined using a dimer-specific endonuclease. At time 0, the average number of dimers per unit of DNA was similar in the two groups. After 6 h, an average of 22 +/- 4% of the dimers were removed in the group with basal cell carcinoma compared to 33 +/- 4% in the cancer-free group. In the basal cell carcinoma group, only 23% of the patients repaired more than 30% of the dimers after 6 h, compared with 53% of the cancer-free subjects (p less than 0.05). We conclude that patients who develop basal cell carcinoma on sun-exposed skin may have a decreased ability to repair pyrimidine dimers induced in skin exposed to simulated solar radiation.

Ultraviolet radiation-induced damage to human Langerhans cells in vivo is not reversed by ultraviolet A or visible light.

Exposure of human skin in vivo to UVB radiation induces pyrimidine dimers in DNA and alters the morphology and function of epidermal Langerhans cells. Cells in human skin have been reported to contain a photoreactivation repair mechanism that, following exposure to UVA or visible light, repairs UVB-induced pyrimidine dimers. The purpose of this study was to determine whether exposure to photoreactivating light would also reverse the UVB-induced morphologic alterations in human Langerhans cells. The skin of eight healthy volunteers was exposed to a low dose of UVB radiation (between 0.75 and 1.5 times the minimal erythema dose), and immediately thereafter exposed to photoreactivating light from either BLB fluorescent lamps (UVA radiation) or incandescent bulbs (visible light). After exposure to UVB radiation, the number of ATPase+ epidermal Langerhans cells was reduced in all subjects to between 21% and 65% of that in unirradiated skin, and the majority of the remaining cells exhibited morphologic alterations. Exposure of the UVB-irradiated skin to photoreactivating light did not reverse or reduce these effects. We conclude that UVB-induced morphologic alterations of human Langerhans cells are not subject to photoreactivation. These results imply either that pyrimidine dimers are not involved in these effects of UVB irradiation, or that photoreactivation does not occur in human Langerhans cells in situ.

The sensitivity of Langerhans cells to simulated solar radiation in basal cell carcinoma patients.

The role of Langerhans cells (LC) in host resistance against the induction and growth of nonmelanoma skin cancers is still obscure. The purpose of this study was to investigate the sensitivity of LC to simulated solar radiation in patients with basal cell carcinoma (BCC). Thirty-four patients (31-74 years old) with at least one histologically diagnosed BCC on a sun-exposed area and 21 healthy volunteers (29-62 years old) were included in the study. Patients and control subjects were given 10 graded doses of simulated solar UV radiation (10-75 mJ/cm2) on the lower back using a 12S solar simulator with a WG 320 filter. Twenty-four hours later, the minimal erythema dose (MED) was determined and shave biopsies were taken from the site given 1.25 X MED and from adjacent, unirradiated skin. Epidermal sheets were stained for LC using the ATPase method. The mean value of the MED of the BCC patients was 25 +/- 2 mJ/cm2 and that of controls was 29 +/- 3 mJ/cm2 (p greater than 0.05). The number of ATPase+ LC was significantly decreased (p less than 0.05), and their morphology was altered in the irradiated skin of nearly all individuals. However, there was no significant difference in the average reduction of LC in the patients (32% +/- 3%) compared with that of control subjects (32% +/- 4%). The depletion of LC ranged from 0% to 74% in different individuals, all of whom were given 1.25 MED. Furthermore, no correlation was found between the percentage decrease in ATPase+ cells and the dose of UV radiation required to produce erythema. Our results indicate that the ability of UV radiation to cause erythema was unrelated to the magnitude of its effects on LC number or morphology. Second, the morphologic alterations of LC in BCC patients after UV irradiation do not differ from those observed in normal individuals. Third, as a group, patients with BCC do not have a significantly lower MED than cancer-free subjects.

Exercise stress testing for detection of silent myocardial ischemia in human immunodeficiency virus-infected patients receiving antiretroviral therapy.

The prevalence of silent myocardial ischemia (SMI) and the factors associated with SMI were evaluated in patients infected with human immunodeficiency virus (HIV) who had been receiving highly active antiretroviral therapy (HAART) for > or =12 months and did not have known coronary artery disease or cardiac symptoms. Patients prospectively underwent exercise stress testing. The prevalence of SMI was 11% (11 of 99 patients). Patients who had SMI were significantly older than were patients who did not (mean+/-SD, 51+/-8 years vs. 42+/-9 years; P=0.001) and were more likely to have trunk obesity (54% of patients vs. 17%; P=.004). A significant correlation was found between a positive exercise test result and obesity (correlation,.006), waist-to-hip ratio (.007), and glucose and cholesterol levels (.04; P=.03). In multivariate analysis, age, central fat accumulation, and cholesterol level were independent variables associated with the detection of SMI. Exercise testing might be recommended for patients with HIV who have central fat accumulation and hypercholesterolemia.

Adverse effects of outpatient parenteral antibiotic therapy.

PURPOSE: Although home parenteral antimicrobial therapy has become common, few studies have carefully examined its adverse effects. SUBJECTS AND METHODS: We retrospectively reviewed the medical records of 269 patients who received 291 courses of home parenteral antimicrobial therapy through a hospital-based home infusion program during a 2-year period. Patients with human immunodeficiency virus (HIV) infection were not included. RESULTS: The majority (59%) of patients were treated for bone and joint infections. Patients had a mean age of 47 years. The mean duration of antibiotic therapy was 40 days. Of monitored courses, leukopenia occurred in 16%, neutropenia in 7%, thrombocytopenia in 4%, and eosinophilia in 12%, usually after a month of therapy; these adverse effects were most frequently associated with the use of beta-lactam antibiotics. Nephrotoxicity occurred in 8% of monitored courses at a mean of 27 days and was most commonly associated with amphotericin B. Diarrhea occurred in 7% and rash in 4% of patients, and both were most commonly seen with beta-lactam antibiotics. Of those patients with permanent indwelling catheters, 11% of those with central catheters and 9% of those with peripherally inserted central catheters (PICCs) developed line complications. Overall, 8% of patients required rehospitalization. CONCLUSION: Home infusion antibiotic therapy exposes patients to the complications associated with inpatient antibiotic therapy and needs to be monitored closely to prevent serious complications and rehospitalizations.

Myocardial uptake of metaiodobenzylguanidine in patients with left ventricular hypertrophy secondary to valvular aortic stenosis.

UNLABELLED: The time course of myocardial uptake of metaiodobenzylguanidine ([123I]MIBG) was studied in 26 patients: seven control subjects (Group 1) and 13 patients with left ventricular hypertrophy secondary to valvular aortic stenosis. Seven of these had received no treatment (Group 2) and six were receiving amiodarone or digoxin (Group 3); six heart transplant recipients were investigated for extra neuronal myocardial uptake of [123I]MIBG (Group 4). The index of myocardial [123I]MIBG uptake was lower in Groups 2 and 3 than in Group 1 (Group 2: 1.42 +/- 0.07, p < 0.001; Group 3: amiodarone, 1.30 +/- 0.10, p < 0.05; digoxin, 1.22 +/- 0.06, p < 0.01; Group I: 1.83 +/- 0.18) and lower in Group 3 than in Group 2. Patients of Group 4 showed a much lower mean index of myocardial [123I]MIBG uptake than the control group (1.07 +/- 0.08, p < 0.001). IN CONCLUSION: 1. Patients with left ventricular hypertrophy secondary to valvular aortic stenosis were found to have lower myocardial [123I]MIBG activity and rapid washout than the control subjects. 2. Amiodarone and digoxin partially inhibited myocardial [123I] MIBG uptake. 3. Extra neuronal myocardial uptake of [123I]MIBG in humans only accounts for 13% of the total cardiac activity.