Recurrent ischemic colitis in a patient with leiden factor V mutation and systemic lupus erythematous with antiphospholipid syndrome

Ischemic colitis results from insufficient blood supply to the large intestine and is often associated with hypercoagulable states. The condition comprises a wide range presenting with mild to fulminant forms. Diagnosis remains difficult because these patients may present with non-specific abdominal symptoms. We report a 51- year-old female patient with known Leiden factor V mutation as well as systemic lupus erythematous along with antiphospholipid syndrome suffering from recurrent ischemic colitis. At admission, the patient complained about abdominal pain, diarrhea and rectal bleeding lasting for 24 hours. Laboratory tests showed an increased C-reactive protein (29.5 mg/dl), while the performed abdominal CT-scan revealed only a dilatation of the descending colon along with a thickening of the bowel wall. Laparotomy was performed showing an ischemic colon and massive peritonitis. Histological examination proved the suspected ischemic colitis. Consecutively, an anti-coagulation therapy with coumarin and aspirin 100 was initiated. Up to the time point of a follow up examination no further ischemic events had occurred. This case illustrates well the non-specific clinical presentation of ischemic colitis. A high index of suspicion, recognition of risk factors and a history of non-specific abdominal symptoms should alert the clinicians to the possibility of ischemic disease. Early diagnosis and initiation of anticoagulation therapy or surgical intervention in case of peritonitis are the major goals of therapy.

[Chronic anterior tibial syndrome]

In two young athletic men we made the diagnosis of chronic tibialis anterior syndrome. Pain during strenuous exercise was localized in the anterolateral aspect of both calves. After stopping exercise the complaints disappeared within 15-20 minutes and not in 2-3 minutes as it would be typical for patients with atherosclerotic peripheral arterial occlusive disease. Diagnosis is based on patient history, normal clinical examination (systolic ankle pressure determined by Doppler-Sonography, electronic segmental oscillography) and increased intramuscular pressure at rest (> 10 mmHg) and after exercise (42 and 35 mmHg). Bilateral fasciotomy was performed in both patients. They are free of pain after 3 respectively 6 months postoperatively.

TINF2, a component of the shelterin telomere protection complex, is mutated in dyskeratosis congenita

Patients with dyskeratosis congenita (DC), a heterogeneous inherited bone marrow failure syndrome, have abnormalities in telomere biology, including very short telomeres and germline mutations in DKC1, TERC, TERT, or NOP10, but approximately 60% of DC patients lack an identifiable mutation. With the very short telomere phenotype and a highly penetrant, rare disease model, a linkage scan was performed on a family with autosomal-dominant DC and no mutations in DKCI, TERC, or TERT. Evidence favoring linkage was found at 2p24 and 14q11.2, and this led to the identification of TINF2 (14q11.2) mutations, K280E, in the proband and her five affected relatives and TINF2 R282H in three additional unrelated DC probands, including one with Revesz syndrome; a fifth DC proband had a R282S mutation. TINF2 mutations were not present in unaffected relatives, DC probands with mutations in DKC1, TERC, or TERT or 298 control subjects. We demonstrate that a fifth gene, TINF2, is mutated in classical DC and, for the first time, in Revesz syndrome. This represents the first shelterin complex mutation linked to human disease and confirms the role of very short telomeres as a diagnostic test for DC.

Transient apical ballooning syndrome--clinical characteristics, ballooning pattern, and long-term follow-up in a Swiss population

BACKGROUND: Transient apical ballooning syndrome (TABS) or Takotsubo cardiomyopathy mimics acute ST-elevation myocardial infarction, but is considered to have a good prognosis with only moderate elevation of myocardial enzymes and full recovery of left ventricular function. Although it is increasingly reported, its exact incidence, clinical presentation, and prognosis in non-Asian populations remain largely unknown. OBJECTIVE: To describe the clinical characteristics and long-term follow-up of patients who presented with TABS at our institution over a 3 year-period. METHODS: Patients were retrospectively retrieved from our local database. Patient charts were carefully reviewed and the diagnosis of TABS was based on the Mayo Clinic diagnostic criteria. Moreover, psychosocial stress or gastrointestinal disease was recorded. RESULTS: During the study period, 13,715 coronary angiographies were performed at our institution, including 2459 patients presenting with an acute coronary syndrome (ACS). Forty-one TABS were diagnosed, which represents an incidence of 1.7% of ACS-patients and 0.3% of all coronary angiographies performed, respectively. Mean age was 65 years, with 85% women. Clinical presentations included chest pain, dyspnoea, and cardiogenic shock. A preceding psychological or physical condition perceived as "stress" was reported in 61%. At a mean follow-up of 675+/-288 days, none of the patients died of cardiac causes, but two patients had a recurrence of symptoms. CONCLUSIONS: This is the largest cohort of TABS patients reported out of Europe so far. The good overall prognosis and low likelihood of recurrence were confirmed.

Nondermatomal somatosensory deficits in patients with chronic pain disorder: clinical findings and hypometabolic pattern in FDG-PET

Patients with chronic pain disorders often show somatosensory disturbances that are considered to be functional. This paper aims at a more precise clinical description and at a documentation of functional neuroimaging correlates of this phenomenon. We examined 30 consecutive patients with unilaterally accentuated chronic pain not explained by persistent peripheral tissue damage and ipsilateral somatosensory disturbances including upper and lower extremities and trunk. The patients were assessed clinically and with conventional brain CT or MRI scan. In the last 11 patients functional neuroimaging was carried out (18-fluordeoxyglucose positron emission tomography=FDG-PET). Depressive symptoms were assessed with the Hamilton depression scale (HAMD-17) and pain intensity was rated with a visual analogue scale for pain (VAS). All patients suffered from mild to moderate depressive symptoms. All patients had experienced a prolonged antecedent phase of severe emotional distress; most of them remembered a "trigger episode of somatic pain" on the affected side. Somatosensory deficits were a replicable hyposensitivity to touch and heat perception of nondermatomal distribution. Conventional imaging procedures (brain CT or MRI scans) showed no structural changes. However, in 11 patients functional imaging with FDG-PET showed a significant hypometabolic pattern of changes in cortical and subcortical areas, mainly in the post-central gyrus, posterior insula, putamen, and anterior cingulate cortex. In summary, pain-related nondermatomal somatosensory deficits (NDSDs) are a phenomenon involving biological as well as psychosocial factors with replicable neuroperceptive clinical findings and a complex neurodysfunctional pattern in the FDG-PET.

Ventricular tachycardia in a Brugada syndrome patient caused by a novel deletion in SCN5A

The aim of the present study was to identify the molecular mechanism behind ventricular tachycardia in a patient with Brugada syndrome. Arrhythmias in patients with Brugada syndrome often occur during sleep. However, a 28-year-old man with no previously documented arrhythmia or syncope who experienced shortness of breath and chest pain during agitation is described. An electrocardiogram revealed monomorphic ventricular tachycardia; after he was converted to nodal rhythm, he spontaneously went into sinus rhythm, and showed classic Brugada changes with coved ST elevation in leads V(1) to V(2). Mutation analysis of SCN5A revealed a novel mutation, 3480 deletion T frame shift mutation, resulting in premature truncation of the protein. Heterologous expression of this truncated protein in human embryonic kidney 293 cells showed a markedly reduced protein expression level. By performing whole-cell patch clamp experiments using human embryonic kidney 293 cells transfected with the mutated SCN5A, no current could be recorded. Hence, the results suggest that the patient suffered from haploinsufficiency of Na(v)1.5, and that this mutation was the cause of his Brugada syndrome.

Unilateral hypoplastic breast in a male-to-female transsexual with Poland syndrome after gender reassignment--reconstructive considerations

Gender reassignment procedures are performed more frequently nowadays due to a multidisciplinary approach and improved techniques and selection process. Many male-to-female patients require bilateral breast augmentation as part of the transformation following the gender reassignment if they fail to develop female breast features after hormonal treatment. We report on a very rare incidence of male-to-female gender reassignment in a patient with Poland syndrome. A male-to-female transsexual on hormonal therapy for gender reassignment developed one normal female-shaped breast whereas the other breast remained hypoplastic. As a male, he was not aware of his chest wall deformity but it became a major issue after successful gender reassignment surgery. Our experience with the specific reconstructive considerations and recommendations regarding our surgical approach to this complex reconstructive problem are discussed.

Comparative efficacy of pharmacological and non-pharmacological interventions in fibromyalgia syndrome: network meta-analysis

OBJECTIVES To synthesise the available evidence on pharmacological and non-pharmacological interventions recommended for fibromyalgia syndrome (FMS). METHODS Electronic databases including MEDLINE, PsycINFO, Scopus, the Cochrane Controlled Trials Registry and the Cochrane Library were searched for randomised controlled trials comparing any therapeutic approach as recommended in FMS guidelines (except complementary and alternative medicine) with control interventions in patients with FMS. Primary outcomes were pain and quality of life. Data extraction was done using standardised forms. RESULTS 102 trials in 14 982 patients and eight active interventions (tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors (SNRIs), the gamma-amino butyric acid analogue pregabalin, aerobic exercise, balneotherapy, cognitive behavioural therapy (CBT), multicomponent therapy) were included. Most of the trials were small and hampered by methodological quality, introducing heterogeneity and inconsistency in the network. When restricted to large trials with ≥100 patients per group, heterogeneity was low and benefits for SNRIs and pregabalin compared with placebo were statistically significant, but small and not clinically relevant. For non-pharmacological interventions, only one large trial of CBT was available. In medium-sized trials with ≥50 patients per group, multicomponent therapy showed small to moderate benefits over placebo, followed by aerobic exercise and CBT. CONCLUSIONS Benefits of pharmacological treatments in FMS are of questionable clinical relevance and evidence for benefits of non-pharmacological interventions is limited. A combination of pregabalin or SNRIs as pharmacological interventions and multicomponent therapy, aerobic exercise and CBT as non-pharmacological interventions seems most promising for the management of FMS.

Ranking of tests for pain hypersensitivity according to their discriminative ability in chronic neck pain

BACKGROUND AND OBJECTIVES Quantitative sensory testing (QST) is widely used to investigate peripheral and central sensitization. However, the comparative performance of different QST for diagnostic or prognostic purposes is unclear. We explored the discriminative ability of different quantitative sensory tests in distinguishing between patients with chronic neck pain and pain-free control subjects and ranked these tests according to the extent of their association with pain hypersensitivity. METHODS We performed a case-control study in 40 patients and 300 control subjects. Twenty-six tests, including different modalities of pressure, heat, cold, and electrical stimulation, were used. As measures of discrimination, we estimated receiver operating characteristic curves and likelihood ratios. RESULTS The following quantitative sensory tests displayed the best discriminative value: (1) pressure pain threshold at the site of the most severe neck pain (fitted area under the receiver operating characteristic curve, 0.92), (2) reflex threshold to single electrical stimulation (0.90), (3) pain threshold to single electrical stimulation (0.89), (4) pain threshold to repeated electrical stimulation (0.87), and (5) pressure pain tolerance threshold at the site of the most severe neck pain (0.86). Only the first 3 could be used for both ruling in and out pain hypersensitivity. CONCLUSIONS Pressure stimulation at the site of the most severe pain and parameters of electrical stimulation were the most appropriate QST to distinguish between patients with chronic neck pain and asymptomatic control subjects. These findings may be used to select the tests in future diagnostic and longitudinal prognostic studies on patients with neck pain and to optimize the assessment of localized and spreading sensitization in chronic pain patients.

Acute coronary syndrome in patients younger than 30 years--aetiologies, baseline characteristics and long-term clinical outcome

BACKGROUND Coronary atherosclerosis begins early in life, but acute coronary syndromes in adults aged <30 years are exceptional. We aimed to investigate the rate of occurrence, clinical and angiographic characteristics, and long-term clinical outcome of acute coronary syndrome (ACS) in young patients who were referred to two Swiss hospitals. METHODS From 1994 to 2010, data on all patients with ACS aged <30 years were retrospectively retrieved from our database and the patients were contacted by phone or physician's visit. Baseline, lesion and procedural characteristics, and clinical outcome were compared between patients in whom an underlying atypical aetiology was found (non-ATS group; ATS: atherosclerosis) and patients in whom no such aetiology was detected (ATS group). The clinical endpoint was freedom from any major adverse cardiac event (MACE) during follow-up. RESULTS A total of 27 young patients with ACS aged <30 years were admitted during the study period. They accounted for 0.05% of all coronary angiograms performed. Mean patient age was 26.8 ± 3.5 years and 22 patients (81%) were men. Current smoking (81%) and dyslipidaemia (59%) were the most frequent risk factors. Typical chest pain (n = 23; 85%) and ST-segment elevation myocardial infarction (STEMI; n = 18 [67%]) were most often found. The ATS group consisted of 17 patients (63%) and the non-ATS group of 10 patients (37%). Hereditary thrombophilia was the most frequently encountered atypical aetiology (n = 4; 15%). At 5 years, mortality and MACE rate were 7% and 19%, respectively. CONCLUSION ACS in young patients is an uncommon condition with a variety of possible aetiologies and distinct risk factors. In-hospital and 5-year clinical outcome is satisfactory.

Regional myocardial wall thinning at multidetector computed tomography correlates to arrhythmogenic substrate in postinfarction ventricular tachycardia: assessment of structural and electrical substrate

BACKGROUND A majority of patients undergoing ablation of ventricular tachycardia have implanted devices precluding substrate imaging with delayed-enhancement MRI. Contrast-enhanced multidetector computed tomography (MDCT) can depict myocardial wall thickness with submillimetric resolution. We evaluated the relationship between regional myocardial wall thinning (WT) imaged by MDCT and arrhythmogenic substrate in postinfarction ventricular tachycardia. METHODS AND RESULTS We studied 13 consecutive postinfarction patients undergoing MDCT before ablation. MDCT data were integrated with high-density 3-dimensional electroanatomic maps acquired during sinus rhythm (endocardium, 509±291 points/map; epicardium, 716±323 points/map). Low-voltage areas (<1.5 mV) and local abnormal ventricular activities (LAVA) during sinus rhythm were assessed with regard to the WT. A significant correlation was found between the areas of WT <5 mm and endocardial low voltage (correlation-R=0.82; P=0.001), but no such correlation was found in the epicardium. The WT <5 mm area was smaller than the endocardial low-voltage area (54 cm(2) [Q1-Q3, 46-92] versus 71 cm(2) [Q1-Q3, 59-124]; P=0.001). Among a total of 13 060 electrograms reviewed in the whole study population, 538 LAVA were detected and analyzed. LAVA were located within the WT <5 mm (469/538 [87%]) or at its border (100% within 23 mm). Very late LAVA (>100 ms after QRS complex) were almost exclusively detected within the thinnest area (93% in the WT<3 mm). CONCLUSIONS Regional myocardial WT correlates to low-voltage regions and distribution of LAVA critical for the generation and maintenance of postinfarction ventricular tachycardia. The integration of MDCT WT with 3-dimensional electroanatomic maps can help focus mapping and ablation on the culprit regions, even when MRI is precluded by the presence of implanted devices.

A novel C-terminal truncation SCN5A mutation from a patient with sick sinus syndrome, conduction disorder and ventricular tachycardia.

OBJECTIVES Individual mutations in the SCN5A-encoding cardiac sodium channel alpha-subunit cause single cardiac arrhythmia disorders, but a few cause multiple distinct disorders. Here we report a family harboring an SCN5A mutation (L1821fs/10) causing a truncation of the C-terminus with a marked and complex biophysical phenotype and a corresponding variable and complex clinical phenotype with variable penetrance. METHODS AND RESULTS A 12-year-old male with congenital sick sinus syndrome (SSS), cardiac conduction disorder (CCD), and recurrent monomorphic ventricular tachycardia (VT) had mutational analysis that identified a 4 base pair deletion (TCTG) at position 5464-5467 in exon 28 of SCN5A. The mutation was also present in six asymptomatic family members only two of which showed mild ECG phenotypes. The deletion caused a frame-shift mutation (L1821fs/10) with truncation of the C-terminus after 10 missense amino acid substitutions. When expressed in HEK-293 cells for patch-clamp study, the current density of L1821fs/10 was reduced by 90% compared with WT. In addition, gating kinetic analysis showed a 5-mV positive shift in activation, a 12-mV negative shift of inactivation and enhanced intermediate inactivation, all of which would tend to reduce peak and early sodium current. Late sodium current, however, was increased in the mutated channels. CONCLUSIONS The L1821fs/10 mutation causes the most severe disruption of SCN5A structure for a naturally occurring mutation that still produces current. It has a marked loss-of-function and unique phenotype of SSS, CCD and VT with incomplete penetrance.

Flow-R, a model for susceptibility mapping of debris flows and other gravitational hazards at a regional scale

The development of susceptibility maps for debris flows is of primary importance due to population pressure in hazardous zones. However, hazard assessment by process-based modelling at a regional scale is difficult due to the complex nature of the phenomenon, the variability of local controlling factors, and the uncertainty in modelling parameters. A regional assessment must consider a simplified approach that is not highly parameter dependant and that can provide zonation with minimum data requirements. A distributed empirical model has thus been developed for regional susceptibility assessments using essentially a digital elevation model (DEM). The model is called Flow-R for Flow path assessment of gravitational hazards at a Regional scale (available free of charge under http://www.flow-r.org) and has been successfully applied to different case studies in various countries with variable data quality. It provides a substantial basis for a preliminary susceptibility assessment at a regional scale. The model was also found relevant to assess other natural hazards such as rockfall, snow avalanches and floods. The model allows for automatic source area delineation, given user criteria, and for the assessment of the propagation extent based on various spreading algorithms and simple frictional laws. We developed a new spreading algorithm, an improved version of Holmgren's direction algorithm, that is less sensitive to small variations of the DEM and that is avoiding over-channelization, and so produces more realistic extents. The choices of the datasets and the algorithms are open to the user, which makes it compliant for various applications and dataset availability. Amongst the possible datasets, the DEM is the only one that is really needed for both the source area delineation and the propagation assessment; its quality is of major importance for the results accuracy. We consider a 10 m DEM resolution as a good compromise between processing time and quality of results. However, valuable results have still been obtained on the basis of lower quality DEMs with 25 m resolution.

Fear-learning deficits in subjects with fibromyalgia syndrome?

BACKGROUND: Fibromyalgia syndrome (FMS) is frequently associated with psychiatric conditions, particularly anxiety. Deficits in contingency learning during fear conditioning have been hypothesized to increase anxiety and, consequently, pain sensation in susceptible individuals. The goal of this study was to examine the relationship between contingency learning and pain experience in subjects with FMS and rheumatoid arthritis (RA). METHODS: Fourteen female FMS subjects, 14 age-matched female RA subjects and 14 age-matched female healthy controls (HCs) were included in a fear-conditioning experiment. The conditioned stimulus (CS) consisted of visual signs, the unconditioned stimulus (US) of thermal stimuli. CS- predicted low-temperature exposure (US), while CS+ was followed by low or high temperature. RESULTS: In the FMS group, only 50% of the subjects were aware of the US-CS contingency, whereas 86% of the RA subjects and all of the HCs were aware of the contingency. CS+ induced more anxiety than CS- in RA subjects and HCs. As expected, low-temperature exposure was experienced as less painful after CS- than after CS+ in these subjects. FMS subjects did not show such adaptive conditioning. The effects of the type of CS on heart rate changes were significant in the HCs and the aware FMS subjects, but not in the unaware FMS subjects. CONCLUSIONS: Contingency learning deficits represent a potentially promising and specific, but largely unstudied, psychopathological factor in FMS. Deficits in contingency learning may increase anxiety and, consequently, pain sensation. These findings have the potential to contribute to the development of novel therapeutic approaches for FMS.

Symptom experience during acute coronary syndrome and the development of posttraumatic stress symptoms

There is growing evidence for the development of posttraumatic stress symptoms as a consequence of acute cardiac events. Acute coronary syndrome (ACS) patients experience a range of acute cardiac symptoms, and these may cluster together in specific patterns. The objectives of this study were to establish distinct symptom clusters in ACS patients, and to investigate whether the experience of different types of symptom clusters are associated with posttraumatic symptom intensity at six months. ACS patients were interviewed in hospital within 48 h of admission, 294 patients provided information on symptoms before hospitalisation, and cluster analysis was used to identify patterns. Posttraumatic stress symptoms were assessed in 156 patients at six months. Three symptom clusters were identified; pain symptoms, diffuse symptoms and symptoms of dyspnea. In multiple regression analyses, adjusting for sociodemographic, clinical and psychological factors, the pain symptoms cluster (β = .153, P = .044) emerged as a significant predictor of posttraumatic symptom severity at six months. A marginally significant association was observed between symptoms of dyspnea and reduced intrusive symptoms at six months (β = -.156, P = .061). Findings suggest acute ACS symptoms occur in distinct clusters, which may have distinctive effects on intensity of subsequent posttraumatic symptoms. Since posttraumatic stress is associated with adverse outcomes, identifying patients at risk based on their symptom experience during ACS may be useful in targeting interventions.