Takotsubo cardiomyopathy triggered by alcohol withdrawal

Takotsubo cardiomyopathy is a reversible cardiomyopathy frequently precipitated by a sudden emotional or physical stress. The exact physiopathology is still debated and may involve catecholamine-induced myocardial stunning. Alcohol withdrawal is associated with an hyperadrenergic state and may be a period at risk of cardiac events. We report a 56-year-old man with Takotsubo cardiomyopathy triggered by alcohol withdrawal.     

Treatment by Lenalidomide in lower risk myelodysplastic syndrome with 5q deletion--the GFM experience

We treated 95 RBC transfusion dependent lower risk MDS with del 5q with Lenalidomide (10 mg/day, 3 weeks/4 weeks). Median age was 70.4, median interval from diagnosis 29 months. IPSS was low in 31% and intermediate-1 in 69% patients. Del 5q was isolated, with 1 additional and >1 additional abnormality in 79%, 14%, and 6% patients, respectively. 62 (65%) patients achieved transfusion independence (TI). The only significant factor predicting TI was baseline platelet count >150 G/L and platelet decrease by at least 50% during the first weeks of treatment (p = 0.001). Grade III-IV neutropenia and thrombocytopenia were seen in 74% and 37.9% of the cases, respectively, and 3 deaths were attributed to cytopenias. Eight (8%) patients developed deep venous thrombosis (DVT). Platelet decrease by less than 50% predicted a higher risk of DVT. Only 6 patients (6.3%) patients progressed to AML, but median follow-up time was short (18 months). We confirm the high rate of TI with Lenalidomide in lower risk MDS with del 5q. Very close patient monitoring for cytopenias and DVT is mandatory, especially during the first weeks of treatment.     

Opposing function of the proprotein convertases furin and PACE4 on breast cancer cells' malignant phenotypes: role of tissue inhibitors of metalloproteinase-1

Proteolytic cleavage of various cancer-related substrates by the proprotein convertases (PC) was reported to be important in the processes of neoplasia. These enzymes are inhibited by their naturally occurring inhibitors, the prosegments (ppPC), and by the engineered general PC inhibitor, the serpin variant alpha1-PDX. In the present study, we sought to compare the effect of these PC inhibitors on malignant phenotypes of breast cancer cells. Overexpression in a stable manner of alpha1-PDX and the prosegment ppPACE4 in MDA-MB-231 breast cancer cells resulted in increased matrix metalloproteinase (MMP)-9 (but not MMP-2) activity and a reduced secretion of tissue inhibitor of metalloproteinase 1 (TIMP-1). This was associated with significant enhancement in cell motility, migration, and invasion of collagen in vitro. In contrast, ppFurin expression in these cells decreased MMP-9 activity and diminished these biological functions, but had no significant effect on TIMP-1 secretion. Taken together, these data showed the specific and opposing roles of Furin and PACE4 in the regulation of MMP-9/TIMP-1-mediated cell motility and invasion.     

Stepwise process for the development of entecavir resistance in a chronic hepatitis B virus infected patient

BACKGROUND/AIMS: Complex mutants may be selected under sequential anti-VHB pressures. We analyzed the genotypic and phenotypic evolution of the viral quasi-species of a patient who developed resistance to entecavir following lamivudine breakthrough. METHODS: The polymerase gene was amplified, cloned and sequenced at different time points. Hepatoma cell lines were transfected to compare the replication capacity of HBV mutants and their drug susceptibility. RESULTS: A mixture of lamivudine-resistant HBV strains coexisted following viral breakthrough to lamivudine, all harboring the rtM204V mutation. The rtV173L+L180M+M204V dominant mutant displayed strong lamivudine-resistance and the highest replication capacity. Following the switch to entecavir, the viral load dropped but the lamivudine-resistant strains continued to be selected. Three years later, the viral load rose again, and a complex mixture of entecavir-resistant strains, all harboring the lamivudine-resistance signature rtL180M+M204V and the rtS202G mutation were observed. Although the rtL180M+S202G+M204V variant, that prevailed at the end of entecavir therapy, did not show the highest viral genome replication capacity, it conferred one of the strongest resistance levels to entecavir. CONCLUSIONS: We report the selection of complex HBV mutants that escaped lamivudine and entecavir antiviral pressures. Genotypic and phenotypic analysis provided additional information to understand the process of HBV variant selection.     

Prospective evaluation of a new ultrathin one-plane bending videoendoscope for transnasal EGD: a comparative study on performance and tolerance

BACKGROUND: EGD, with small-diameter endoscopes, is routinely performed via a nasal route in adults. OBJECTIVE: To evaluate a new ultrathin one-plane bending videoendoscope for transnasal EGD. DESIGN: Single center, prospective, randomized study. SETTING: Edouard Herriot University Hospital. PATIENTS: A total of 122 outpatients (median age, 49 years [18-81 years], 62 men and 60 women) were randomized into 2 groups (on a 2:1 basis) according to the endoscope used: (1) a standard 5.9-mm-diameter videoendoscope (80 patients) or (2) a one-plane bending high resolution 4.9-mm-diameter videoendoscope (42 patients). MAIN OUTCOME MEASUREMENTS: The operator assessed the quality of examination by using standard scores or a 100-mm visual scale. Patients quantified tolerance by using a 100-mm visual scale. RESULTS: The duration of the procedure was the same in each group. The feasibility of transnasal insertion was significantly higher when using the 4.9-mm-diameter endoscope (97.61% [41/42 patients] vs 88.75% [71/80 patients], P<.05). The tolerance of EGD was significantly better in the group with the small videoendoscope, for global discomfort, pain, belching, and bloating. Similarly, acceptation of a new EGD in similar conditions was higher in group 2 (92.9% vs 80%, P<.05). The quality of examination (global, lavage, inflation, suction) was not different between the 2 groups. LIMITATIONS: Evaluation of patient tolerance and quality of examination was based on subjective features. CONCLUSIONS: Availability of a new ultrathin one-plane bending videoendoscope represents a major technical improvement for transnasal EGD, which significantly improves both feasibility and patient tolerance, without affecting the quality of the examination.     

Long-term follow-up of hypothenar hammer syndrome: a series of 47 patients

Hypothenar hammer syndrome (HHS) is an uncommon form of secondary Raynaud phenomenon, occurring mainly in subjects who use the hypothenar part of the hand as a hammer; the hook of the hamate strikes the superficial palmar branch of the ulnar artery in the Guyon space, leading to occlusion and/or aneurysm of the ulnar artery. In patients with HHS, such injuries of the palmar ulnar artery may lead to severe vascular insufficiency in the hand with occlusion of digital artery. To date, only a few series have analyzed the long-term outcome of patients with HHS. This prompted us to conduct the current retrospective study to 1) evaluate the prevalence of HHS in patients with Raynaud phenomenon and 2) assess the short-term and long-term outcome in patients with HHS.From 1990 to 2006, 4148 consecutive patients were referred to the Department of Internal Medicine at the University of Rouen medical center for evaluation of Raynaud phenomenon using nailfold capillaroscopy. HHS was diagnosed in 47 of these 4148 patients (1.13% of cases).Forty-three patients (91.5%) had occupational exposure to repetitive palmar trauma. The more common occupations were factory worker (21.3%), mason (12.8%), carpenter (10.6%), and metal worker (10.6%); the mean duration of occupational exposure to repetitive palmar trauma at HHS diagnosis was 21 years. One patient (2.1%) had recreational exposure (aikido training) to repetitive trauma of the palmar ulnar artery, and 3 other patients (6.4%) developed HHS related to a single direct injury to the hypothenar area. Clinical manifestations were more often unilateral (87.2%) involving the dominant hand (93%). HHS complications included digital ischemic symptoms (ischemia: n = 21, necrosis: n = 20) and irritation of the sensory branch of the ulnar nerve (n = 11). In HHS patients, angiography demonstrated occlusion of the ulnar artery in the area of the Guyon space (59.6%), aneurysm of the ulnar artery in the area of the Guyon space (40.4%), and embolic multiple occlusions of the digital arteries (57.4%).All patients were advised to change their occupational exposure. They were given vasodilators, including calcium channel blocker (n = 37) and buflomedil (n = 12); 36 patients (76.6%) also received oral platelet aggregation inhibitors. Twenty-one patients with digital ischemia/necrosis were further given hemodilution therapy to reduce the hematocrit level to 35%. In 3 patients with HHS-related digital necrosis who exhibited partial improvement with vasodilators, prostacyclin analog therapy (a 5-day regimen of intravenous prostacyclin analog) was instituted, resulting in complete healing of digital ulcer in these 3 patients. Other conservative treatment options included controlling risk factors (smoking cessation, low-lipid diet, therapy for arterial hypertension) and careful local wound care of fingers in the 20 patients with digital necrosis. Only 2 patients, exhibiting digital necrosis and multiple digital artery occlusions, with nonthrombotic ulnar artery aneurysm underwent reconstructive surgery, that is, resection of the aneurysm with end-to-end anastomosis of the ulnar artery. The median length of follow-up in patients with HHS was 15.9 months. Thirteen patients (27.7%) exhibited clinical recurrences of HHS; the median time of HHS recurrence onset was 11 months. Outcome of HHS relapse was favorable with conservative measures in all cases.Awareness of HHS is required to increase suspicion of the disorder so that further exposure to risk factors like repetitive hypothenar trauma can be avoided for these patients; this is of great importance for their overall prognosis. We found favorable outcomes in most patients after conservative measures were initiated; therefore we suggest that surgery may be undertaken in the subgroup of patients who exhibit partial improvement while receiving conservative therapy. Finally, because we observed recurrence of HHS in 27.7% of patients, we note that HHS patients require close follow-up, including both regular and systematic physical vascular examination.     

Effect of twice-daily nevirapine on adherence in HIV-1-infected patients: a randomized controlled study

OBJECTIVE: For optimal adherence, once-daily dosing is best. Whether this applies to antiretroviral therapy is unknown. We thus aimed to determine the effect of once-daily dosing on adherence to nevirapine. DESIGN: A three-phase (3-month observational, 4-month randomized, 5-month interventional) open-label, clinical trial at four French academic medical centres during 2005-2006 among 62 chronically HIV-1-infected subjects with long-lasting viral suppression under a twice-a-day nevirapine-based antiretroviral combination. METHODS: Adherence was measured using electronic monitoring devices and validated by sequential plasma drug levels. Participants were randomly assigned to switch to nevirapine 400 mg once-daily (n = 31) or continue nevirapine 200 mg twice-a-day (n = 31). After the randomized phase, participants had an opportunity to choose their antiretroviral dosage. Primary outcome was the mean percentage of adherence. RESULTS: Fifty-two patients qualified for electronic data analysis. During the randomized phase, the mean adherence rate was non-significantly superior by 0.5% in once-daily versus twice-a-day dosing (P = 0.68), adjusting for previous twice-a-day adherence rate (P < 0.0001). Once-daily group increased days without dose [odds ratio (OR) 1.7; 95% confidence interval (CI) 1.0, 2.8; P = 0.04], adjusting for previous drug interruptions (P < 0.0001). In the longitudinal analysis, once-daily dosing was significantly associated with at least two consecutive days without dose (OR 4.4; 95% CI 1.9, 10.3; P < 0.001). CONCLUSION: Changing from twice to once-daily nevirapine does not improve adherence. Supporting continuous adherence to antiretroviral therapy in the 'once-a-day era' remains a challenge, even if more potent regimens can achieve viral suppression at lower adherence levels.     

Nephrin mutations can cause childhood-onset steroid-resistant nephrotic syndrome

Classically, infants with mutations in NPHS1, which encodes nephrin, present with nephrotic syndrome within the first 3 mo of life (congenital nephrotic syndrome of the Finnish-type), and children with mutations in NPHS2, which encodes podocin, present later with steroid-resistant nephrotic syndrome. Recently, however, NPHS2 mutations have been identified in children with congenital nephrotic syndrome. Whether NPHS1 mutations similarly account for some cases of childhood steroid-resistant nephrotic syndrome is unknown. In this study, 160 patients who belonged to 142 unrelated families and presented with nephrotic syndrome at least 3 mo after birth were screened for NPHS1 variants once mutations in NPHS2 had been excluded. Compound heterozygous NPHS1 mutations were identified in one familial case and nine sporadic cases. Mutations included protein-truncating nonsense and frameshift mutations, as well as splice-site and missense variants. Mutations were classified as "severe" or "mild" using prediction algorithms and functional assays. Most missense variants trafficked normally to the plasma membrane and maintained the ability to form nephrin homodimers and to heterodimerize with NEPH1, suggesting retained function. The presence of at least one "mild" mutation in these patients likely explains the later onset and milder course of disease. These results broaden the spectrum of renal disease related to nephrin mutations.