PHEOCHROMOCYTOMA, THE GREAT MASQUERADER, PRESENTING AS REVERSIBLE CARDIOMYOPATHY: PRIMUM NON NOCERE.

Background: Pheochromocytoma, the great masquerader, can have a varied spectrum of clinical manifestations. It can often cause a diagnostic challenge despite the availability of modern investigation modalities. Case: We present the case of a 38-year-old male who presented with uncontrolled hypertension for the past 10 years and heart failure for one year. The diagnosis of pheochromocytoma was missed in the initial setting, leading to a biopsy of the retroperitoneal mass. Fortunately, the patient survived the procedure. Subsequently, with the involvement of a multi-disciplinary team, he was optimized for surgery under strict cardiac monitoring. After the complete excision of the tumour, he showed significant improvement not only in his clinical symptoms but also in his cardiac status. Conclusions: This case emphasizes the age-old medical phrase of 'Primum non nocere or first, do no harm'. Any invasive procedure in a pheochromocytoma can lead to a massive release of catecholamines causing a hypertensive crisis, pulmonary oedema, and even cardiac arrest. Any young patient presenting with hypertension or heart failure should be investigated for secondary causes. Cardiomyopathy due to pheochromocytoma is because of catecholamine overload and usually reverses or improves after curative surgery.

An observational study of the efficacy of azithromycin in erythema annulare centrifugum.

Erythema annulare centrifugum (EAC) is a form of figurate erythema consequent to a cutaneous hypersensitivity reaction to an underlying agent. In the present study, we aimed to assess the role of oral azithromycin in cases of idiopathic EAC. We performed an open trial of azithromycin in 10 patients with idiopathic EAC. Histopathological examination of biopsies was performed to exclude any alternative diagnosis and to assess the depth of the infiltrate. Patients were administered oral azithromycin 250 mg once daily until clinical resolution of the disease, and followed up regularly to monitor for possible relapse. Histopathological examination of the 10 biopsies revealed superficial pattern in 3, deep pattern in 2 and mixed pattern in the remaining 5. Of the 10 patients, 8 responded to azithromycin 250 mg, with no relapse during follow-up. Oral azithromycin might be a promising therapy in cases of idiopathic EAC. Cases with a superficial pattern respond earlier than cases with a deep pattern.

Outcomes of combined tibial tuberosity transfer and medial patellofemoral ligament reconstruction for recurrent patellar instability.

Patellofemoral instability is multifactorial and is associated with pathomechanics secondary to anatomical variance. Surgical management of this problem must be tailored to each patient and a thorough clinical and radiological assessment of the anatomical alignment should be carried out pre-operatively. The aim of this study is to assess the role of medial patellofemoral ligament reconstruction combined with tibial tuberosity transfer in patients with increased tibial tuberosity to trochlear groove (TT-TG) distance. Twenty-four patients (27 knees) over 2-years were operated on by a single surgeon, with standardised post-operative rehabilitation and follow up. Mean follow up was 31-months. Two patients had problems with recurrent instability, 1 had a -traumatic re-dislocation at 2 years and a total of 4 required further operation for complications. Mean post--operative Kujala scores were 87.4 (SD 9.8). Combined medial patellofemoral ligament reconstruction and tibial tuberosity transfer is an appropriate treatment for patients with increased TT-TG distance.

Determinants of survival in sudden cardiac arrest manifesting with pulseless electrical activity.

OBJECTIVE: The proportion of sudden cardiac arrests (SCA) manifesting with pulseless electrical activity (PEA) has increased significantly, and the survival rate remains lower than ventricular fibrillation (VF). However, a subgroup of PEA-SCA cases does survive and may yield key predictors of improved outcomes when compared to non-survivors. We aimed to identify key predictors of survival from PEA-SCA. METHODS: Our study sample is drawn from two ongoing community-based, prospective studies of out-of-hospital SCA: Oregon SUDS from the Portland, OR metro area (Pop. approx. 1 million; 2002-2017) and Ventura PRESTO from Ventura County, CA (Pop. approx. 850,000, 2015-2021). For the present sub-study, we included SCA cases with PEA as the presenting rhythm where emergency medical services (EMS) personnel attempted resuscitation. RESULTS: We identified 1,704 PEA-SCA cases, of which 173 (10.2%) were survivors and 1,531 (89.8%) non-survivors. Patients whose PEA-SCA occurred in a healthcare unit (16.9%) or public location (18.1%) had higher survival than those whose PEA-SCA occurred at home (9.3%) or in a care facility (5.7%). Young age, witness status, PEA-SCA location and pre-existing COPD/asthma were independent predictors of survival. Among witnessed cases the survival rate was 10% even if EMS response time was >10 minutes. CONCLUSIONS: Key determinants for survival from PEA-SCA were young age, witnessed status, public location and pre-existing COPD/asthma. Survival outcomes in witnessed PEA cases were better than expected, even with delayed EMS response.

'Congenital follicular melanocytic naevi': a more appropriate term for spotted grouped pigmented naevi.

We report two patients with an uncommon form of pigmented naevus consisting of grouped follicular papules. A biopsy taken from the lesions showed multiple naevus cells, predominantly around the hair follicles, with sparing of the eccrine glands. The clinicohistopathological term given for this condition is 'spotted grouped pigmented naevi type I', and has rarely been reported. We discuss the unusual morphology and differential diagnosis of this condition, and suggest that the term 'congenital follicular melanocytic naevi' is more appropriate for this presentation.

Reversible atrioventricular blocks in thyroid storm.

Atrioventricular blocks or sinoatrial blocks are rarely described in patients with thyrotoxicosis or thyroid storm. The mechanism of these blocks remains obscure. Thyroid storm, being an emergency situation requires early diagnosis and management because if left untreated, it may prove fatal. Usually patients with AV blocks require pacing (temporary or permanent). Here we describe a case who developed AV blocks, did not undergo pacing, but recovered only on antithyroid treatment.

Evaluation of endothelial function and effect of glycemic control (excellent vs. poor / fair control) on endothelial function in uncontrolled type 2 diabetes mellitus.

OBJECTIVE: To evaluate the endothelial functions before and after glycemic control in type II diabetes mellitus. MATERIAL AND METHODS: It was an open, randomized and comparative study on 30 patients of type 2 diabetes mellitus. The study was of 12 weeks spread over 5 visits. The initial visit (visit 1) is for screening of patients. Other visits (visits 2 to 5) constituted the follow up of patients. The primary efficacy parameters included blood sugar (fasting and postprandial) done on each visit and glycosylated hemoglobin (HbA1c) done at visits 1 and 5. Based on glycosylated hemoglobin (HbA1c) only poorly controlled and fairly controlled patients were included in the study. Brachial artery flow mediated vasodilatation (FMD) was studied in all these patient at visits 1 and 5 to see the effect of glycemic control on endothelial functions. Results obtained were statistically analyzed with appropriate method. RESULTS: There was a significant improvement in endothelial functions in patients with fair, good and excellent control of diabetes. During uncontrolled state (HbA1c 10.08 +/- 0.48%) FMD was lowest, i.e., 2.88 +/- 0.53 at 1st week which improved to 11.94 +/- 3.33 at 12th week with control of diabetes (HbA1c 6.74 +/- 0.16%). The FMD in patients who had fair control (HbAlc 8.45 +/- 0.30%) in the beginning was 6.74 +/- 2.43% and after excellent control in these patients FMD rises to 12.81 +/- 3.16%. CONCLUSION: Our data showed that the endothelial functions improved sequentially with control of diabetes from fair to good to excellent glycemic control.

Dissociable dopaminergic and pavlovian influences in goal-trackers and sign-trackers on a model of compulsive checking in OCD.

RATIONALE: Checking is a functional behaviour that provides information to guide behaviour. However, in obsessive-compulsive disorder (OCD), checking may escalate to dysfunctional levels. The processes underpinning the transition from functional to dysfunctional checking are unclear but may be associated with individual differences that support the development of maladaptive behaviour. We examined one such predisposition, sign-tracking to a pavlovian conditioned stimulus, which we previously found associated with dysfunctional checking. How sign-tracking interacts with another treatment with emerging translational validity for OCD-like checking, chronic administration of the dopamine D2 receptor agonist quinpirole, is unknown. OBJECTIVES: We tested how functional and dysfunctional checking in the rat observing response task (ORT) was affected by chronic quinpirole administration in non-autoshaped controls and autoshaped animals classified as sign-trackers or goal-trackers. METHODS: Sign-trackers or goal-trackers were trained on the ORT before the effects of chronic quinpirole administration on checking were assessed. Subsequently, the effects on checking of different behavioural challenges, including reward omission and the use of unpredictable reinforcement schedules, were tested. RESULTS: Prior autoshaping increased checking. Sign-trackers and goal-trackers responded differently to quinpirole sensitization, reward omission and reinforcement uncertainty. Sign-trackers showed greater elevations in dysfunctional checking, particularly during uncertainty. By contrast, goal-trackers predominantly increased functional checking responses, possibly in response to reduced discrimination accuracy in the absence of cues signalling which lever was currently active. CONCLUSIONS: The results are discussed in terms of how pavlovian associations influence behaviour that becomes compulsive in OCD and how this may be dependent on striatal dopamine D2 receptors.

Nephritogenic mAb 5-1-6 is directed at the extracellular domain of rat nephrin.

mAb 5-1-6 identifies an antigen on rat podocyte slit-diaphragms and induces severe proteinuria when injected into rats. Nephrin, an Ig-like transmembrane protein that is mutated in congenital nephrotic syndrome of the Finnish type, has been localized to the slit-diaphragm on human podocytes. Here we document that the mAb 5-1-6 antigen is rat nephrin. After incubation of rat glomeruli with this mAb, the antibody/antigen complex was chemically cross-linked, extracted, and immunoprecipitated, prior to Western analysis. By mass spectrometry and 2D gel electrophoresis, we identified several peptides with complete identity to human nephrin. In addition, the 185-kDa protein immunoprecipitated by mAb 5-1-6 from rat glomerular extracts reacts with a rabbit anti-mouse nephrin antibody. Finally, nephrin and the mAb 5-1-6 antigen have identical glomerular localization patterns on immunofluorescence of rat kidney. These results demonstrate that the nephritogenic mAb 5-1-6 identifies the extracellular domain of nephrin, thereby documenting the importance of the slit-diaphragm and its component, nephrin, in the regulation of glomerular permselectivity.

Transfer-free multi-layer graphene as a diffusion barrier.

Graphene is a promising ultra-thin barrier against undesired mass transport, however, the high deposition temperatures or the defect inducing post-deposition transfer processes limit its widespread applicability. Herein we report on the successful blocking of copper (Cu) ion diffusion by large area multi-layer graphene (MLG) membranes deposited directly on silicon oxide (SiO2) via low temperature plasma-enhanced chemical vapor deposition. The barrier strength of MLG is compared to evaporated tantalum (Ta) by applying positive bias-temperature stress (BTS) to Cu/barrier/SiO2/Si test structures. After constant BTS of 4 × 106 V cm-1 at 400 K for 50 min, the MLG barrier device exhibits a negligible flat band voltage shift in capacitance-voltage measurements and no discernible current peak in triangular voltage scans, whereas the Ta barrier allows significant Cu ion transport. Highly limited Cu ion diffusion through MLG suggests that lower energy diffusion paths, like grain boundaries and defects of individual graphene layers, do not align in the direction of an applied stress field. In general, the presented low-temperature direct growth MLG membranes can block undesirable diffusion in many applications, and are especially suitable as Cu diffusion barriers in integrated circuit chips, photovoltaic cells and flexible electronic devices.

Sudden cardiac death with apparently normal heart.

BACKGROUND: Mechanisms of sudden cardiac death (SCD) in subjects with apparently normal hearts are poorly understood. In survivors, clinical investigations may not establish normal cardiac structure with certainty. Large autopsy series may provide a unique opportunity to confirm structural normalcy of the heart before reviewing a patient's clinical history. METHODS AND RESULTS: We identified and reexamined structurally normal hearts from a 13-year series of archived hearts of patients who had sudden cardiac death. Subsequently, for each patient with a structurally normal heart, a detailed review of the circumstances of death as well as clinical history was performed. Of 270 archived SCD hearts identified, 190 were male and 80 female (mean age 42 years); 256 (95%) had evidence of structural abnormalities and 14 (5%) were structurally normal. In the group with structurally normal hearts (mean age 35 years), SCD was the first manifestation of disease in 7 (50%) of the 14 cases. In 6 cases, substances were identified in serum at postmortem examination without evidence of drug overdose; 2 of these chemicals have known associations with SCD. On analysis of ECGs, preexcitation was found in 2 cases. Comorbid conditions identified were seizure disorder and obesity (2 cases each). In 6 cases, there were no identifiable conditions associated with SCD. CONCLUSIONS: In 50% of cases of SCD with structurally normal hearts, sudden death was the first manifestation of disease. An approach combining archived heart examinations with detailed review of the clinical history was effective in elucidating potential SCD mechanisms in 57% of cases.

Epidemiology and natural history of atrial fibrillation: clinical implications.

With a substantial impact on morbidity and mortality, the growing "epidemic" of atrial fibrillation (AF) intersects with a number of conditions, including aging, thromboembolism, hemorrhage, hypertension and left ventricular dysfunction. Currently, the epidemiology and natural history of AF govern all aspects of its clinical management. The ongoing global investigative efforts toward understanding AF are also driven by epidemiologic findings. New developments, by affecting the natural history of the disease, could eventually alter the nature of decision making in patients with AF. The crucial issue of rate versus rhythm control awaits completion of the AF Follow-up Investigation of Rhythm Management trial. The processes of electrical and structural remodeling that perpetuate AF appear to be reversible. In the era of functional genomics, the molecular basis of this ubiquitous arrhythmia is in the process of being defined. Unraveling the molecular genetics of AF might provide new insights into the structural and electrical phenotypes resulting from genetic mutations and, as such, new approaches to treatment of this arrhythmia at the ion channel and cellular levels. Thus, current adverse trends are superimposed on a background of a rapidly developing knowledge base and potentially exciting new therapeutic options. Consequently, an understanding of the epidemiology and natural history of AF is crucial to the future allocation of resources and the utilization of an expanding range of therapies aimed at reducing the impact of this disease on a changing patient population.

Altered response to ibutilide in a heart failure model.

OBJECTIVE: Despite the frequent use of anti-arrhythmic drugs in the general population, the electrophysiologic effects of these agents have not been elucidated in congestive heart failure (CHF). METHODS: To examine the impact of left ventricular dysfunction on actions of type III anti-arrhythmic drugs, we evaluated the actions of ibutilide in a canine model of pacing-induced dilated cardiomyopathy. Following ablation of the atrioventricular node, effects on action potential duration at 90% (APD(90)) were compared in vivo, between eight CHF animals and seven controls. Monophasic action potential recordings were obtained from right and left ventricular endocardium/epicardium during and after three doses of ibutilide (0. 01, 0.02 and 0.05 mg/kg), at pacing cycle lengths of 300-1000 ms. RESULTS: APD(90) prolongation with ibutilide (0.01 mg/kg) was significantly greater in CHF vs. controls (P=0.0026, ANOVA). However, plasma ibutilide levels at this dose, were not significantly different between the two groups. In CHF, maximal effects were observed at the lowest dose, whereas effects were gradual and dose-dependent in controls. With ibutilide administration (0.01 mg/kg), an increased dispersion of left-right ventricular APD(90) was observed in CHF, but not in controls (P=0.03). A trend was observed, for increased incidence of non-sustained polymorphic ventricular tachycardia in CHF. CONCLUSIONS: In the presence of CHF, the actions of ibutilide are altered significantly. These findings may reflect altered tissue effects, as a consequence of myocardial electrical remodeling in CHF.

Variola virus F1L is a Bcl-2-like protein that unlike its vaccinia virus counterpart inhibits apoptosis independent of Bim.

Subversion of host cell apoptosis is an important survival strategy for viruses to ensure their own proliferation and survival. Certain viruses express proteins homologous in sequence, structure and function to mammalian pro-survival B-cell lymphoma 2 (Bcl-2) proteins, which prevent rapid clearance of infected host cells. In vaccinia virus (VV), the virulence factor F1L was shown to be a potent inhibitor of apoptosis that functions primarily be engaging pro-apoptotic Bim. Variola virus (VAR), the causative agent of smallpox, harbors a homolog of F1L of unknown function. We show that VAR F1L is a potent inhibitor of apoptosis, and unlike all other characterized anti-apoptotic Bcl-2 family members lacks affinity for the Bim Bcl-2 homology 3 (BH3) domain. Instead, VAR F1L engages Bid BH3 as well as Bak and Bax BH3 domains. Unlike its VV homolog, variola F1L only protects against Bax-mediated apoptosis in cellular assays. Crystal structures of variola F1L bound to Bid and Bak BH3 domains reveal that variola F1L forms a domain-swapped Bcl-2 fold, which accommodates Bid and Bak BH3 in the canonical Bcl-2-binding groove, in a manner similar to VV F1L. Despite the observed conservation of structure and sequence, variola F1L inhibits apoptosis using a startlingly different mechanism compared with its VV counterpart. Our results suggest that unlike during VV infection, Bim neutralization may not be required during VAR infection. As molecular determinants for the human-specific tropism of VAR remain essentially unknown, identification of a different mechanism of action and utilization of host factors used by a VAR virulence factor compared with its VV homolog suggest that studying VAR directly may be essential to understand its unique tropism.

Electrophysiologic characteristics of diverse accessory pathway locations of antidromic reciprocating tachycardia.

This study assessed antidromic reciprocating tachycardia (ART) in patients with paraseptal accessory pathways (APs). Previous clinical experience suggests that paraseptal APs are unable to serve as the anterograde limb during ART. Based on the reentry wavelength concept, we hypothesized that anatomic location of a paraseptal AP may not preclude occurrence of ART. If wavelength criteria were met due to prolonged conduction time retrogradely in the atrioventricular node or anterogradely in the AP, ART may be sustained. All patients who had ART in the electrophysiologic laboratory at our institution (1991 to 1998) were studied. Based on fluoroscopically guided electrophysiologic mapping and radiofrequency ablation, AP location was classified as paraseptal, posterior, or lateral. Conduction time and refractoriness measurements were made for all components of the ART circuit. Of 24 patients with ART, 5 (21%) had ART utilizing a paraseptal AP. Anterograde conduction time through the AP and retrograde atrioventricular nodal conduction time were significantly longer in patients with paraseptal versus lateral pathways. Isoproterenol was required for ART induction in 38% of patients with a posterior AP, 36% with lateral AP location, but not in patients with a paraseptal AP. There were no significant differences in tachycardia cycle length or refractoriness of anterograde and/or retrograde components of the macroreentry circuit between the 3 pathway locations. Thus, ART can occur in patients with a paraseptal AP. Slower anterograde pathway conduction, or retrograde atrioventricular nodal conduction renders the wavelength critical for completion of the antidromic re-entrant circuit.

Evaluation of oxidative stress before and after control of glycemia and after vitamin E supplementation in diabetic patients.

The present study evaluates the presence of oxidative stress in the uncontrolled diabetic state. Glycemic control reduced the oxidative stress, but total normalization of the parameters of oxidative stress was not achieved, indicating continued oxidant injury despite optimal control of the diabetes. Vitamin E supplementation for 4 weeks in these patients further reduced the oxidative stress, suggesting that vitamin E supplementation might be helpful in reducing free-radical-induced oxidant injury.

Antibody-dependent macrophage-mediated cytotoxicity against Entamoeba histolytica.

Interactions between trophozoites of Entamoeba histolytica and peritoneal exudate macrophages from unsensitised and antigen-sensitised animals were studied in vitro. Normal macrophages killed trophozoites to some extent. This killing capacity was enhanced by prior sensitisation of the animals with specific antigen. Incorporation of anti-amoebic antiserum in the amoeba-macrophage mixture greatly enhanced the killing capacity of macrophages. Fraction one (F-I) of a crude amoebic extract was most effective in enhancing the cytotoxicity of macrophages by prior sensitisation and anti-F-I serum was the most effective antiserum. The cytotoxicity-inducing capacity of the immune serum resided in the IgG but not in the IgM fraction.

Virulence of Entamoeba histolytica in rat and its comparison with the serological responses of the amoebic patients.

The virulence of 70 isolates of Entamoeba histolytica was studied in the Wistar strain of albino rat by intracaecal inoculation of amoebae. The results were evaluated by the Neal scoring system, histopathological grading of ulcers and virulence indices. It was found that isolates from acute amoebic cases could infect and produce ulcers in significantly more animals than could the isolates from asymptomatic cyst passers. The virulence indices of isolates from acute cases were also significantly higher as compared to those from asymptomatic cyst passers. However, there was no significant difference between virulence indices of isolates from acute cases and non-dysenteric amoebic colitis. This study also showed that Neal scores failed to correlate with the type of pathology produced by the amoebae in the caecum. It is felt that virulence indices which depend upon the histopathological lesions should also be taken into consideration. The serological response of the patients tended to correlate with the virulence indices of isolates but only minimally. The results thus contradict a common belief amongst clinicians that higher levels of anti-amoebic antibodies reflect severe disease, as compared to low levels of antiamoebic antibodies.

Silent myocardial ischemia in diabetics with normal autonomic function.

Twenty male diabetic patients (age range, 40-60 years) with normal autonomic function were studied to determine the prevalence of silent myocardial ischemia on exercise as well as ambulatory electrocardiography. The presence and extent of silent myocardial ischemia was also correlated with the severity of atherosclerotic coronary artery disease as determined by coronary angiography. A cohort of 20 matched non-diabetic patients were also included in the study. Silent myocardial ischemia was detected in 50% of the diabetic patients on exercise electrocardiography and in 35% on ambulatory electrocardiography compared with 10% and 5% in non-diabetics by the two methods, respectively (P < 0.01 and P < 0.05, respectively). On exercise testing in diabetic patients, silent myocardial ischemia was detected in 64% of the patients with three-vessel disease, 50% of the patients with two-vessel disease and 20% of the patients with one-vessel disease whereas in non-diabetic patients silent myocardial ischemia was detected in only 18% of the patients with three-vessel disease (P < 0.05) and in none of the patients with two- or one-vessel disease. On ambulatory electrocardiography, only patients (both diabetic and non-diabetic) with three-vessel disease manifested silent myocardial ischemia. Total ischemic burden was similar in both the diabetic and non-diabetic patients. We conclude that silent myocardial ischemia occurs in diabetic patients with coronary artery disease more frequently even in the absence of autonomic dysfunction and the prevalence of silent myocardial ischemia is higher in patients with severe degree of coronary artery disease.

Autologous bone grafting in staged scoliosis surgery. The patient as bone bank.

STUDY DESIGN: A prospective clinical study in which autologous rib graft, harvested during the thoracotomy in staged scoliosis correction, is stored within the patient for use during the second stage (posterior intrumentation and fusion). OBJECTIVE: To determine whether the bone stored by this technique is biologically viable and microbiologically safe. SUMMARY OF BACKGROUND DATA: To the authors' knowledge, this method of storage of bone has never been described previously. METHODS: During the first operation, the excised rib was divided into 3-5 cm fragments and stored in a sub-muscular plane adjacent to the posterior elements of the spine before closure. The graft was then retrieved at the second stage. Samples were sent for histologic and microbiologic examination before implantation. RESULTS: On histologic examination, more than 50% of the osteocytes retained their basophilic staining, indicating that they were viable. In addition, osteoclastic activity was notably absent. There was no significant bacterial contamination of the samples. Clinically, all patients achieved satisfactory bone fusion. CONCLUSION: Homeostatic equilibrium in humans provides the ideal environment in which bone graft can be stored. There is no increased risk of infection, and the osteogenic potential of the graft is retained.