Background Enteric fever is very common infectious disease in developing countries like Nepal. Due to lack of resources diagnosis has to be clinical most of the time. Hence a proposal of clinical diagnostic criteria and validation of the same would be very useful. Objective To validate the proposed clinical diagnostic criterion including features characterized as major and minor criteria Methods This study was done in the department of medicine of Kathmandu Medical College Teaching hospital, from June 2009 to January 2012. A total of 114 patients presenting with fever were included in the study. After proposal of clinical diagnostic criteria for enteric fever, by a prior published study, all the fever patients were grouped according to criteria positive or negative. The most significant criteria were validated by calculating sensitivity and specificity along with positive and negative likelihood ratios with blood culture taken as gold standard. Results A total of 114 patients were enrolled. Total patients diagnosed as enteric was 47.3 %. Clinical diagnostic criterion B which included three major (headache, fever and relative bradycardia) and three minor criteria (abdominal pain, vomiting, diarrhea, splenomegaly and chills) was highly significant (p=<.0001) in diagnosing enteric fever and had a sensitivity of 72.2% ( 95% CI 58.1- 83.1) and specificity of 98.3% ( 95% CI 89.8-99-9). The positive likelihood ratio was 43.33 (95 % CI 6.16-304.77) and negative likelihood ratio as 0.28 (95% CI 0.18-0.43). Conclusion Clinical diagnostic criteria can be a very useful tool for diagnosis of enteric fever when culture facility is not available.

Aim:

The aim of this study was to present a hospital intensive care program for patients affected by a severe eating disorders, with a significant loss of weight (BMI<15 and weight less than 25° centile), severe medical complications (orthostatic hypotension, bradycardia <40 bpm or tachycardia >110 bpm or inability to sustain core body temperature), abnormal laboratory data, especially electrolyte imbalance and refusal to take food and fluids.

Methods:

In our study we reported 2 year follow-up of 16 patients treated with the hospital intensive care program between 2007 and 2008 in our department. Result: The proposed program was proved an efficient method in a critical phase of the alimentary behavior disorders. It was possible for all the patients to avoid alternative feeding techniques (enteral or parenteral) and to obtain a correct alimentation with a satisfactory improvement of clinical conditions. Eight patients (50%) fully recovered. 5 patients (31.25%) had a significant improvement reaching a BMI>18.5 and one of them had a regular menstrual cycle, too. However in this group of patients a strict modality to alimentation and concern about weight and physical appearance remain. In 3 patients (18.5%) the BMI is still low and amenorrhea persists.

Conclusions:

The hospital intensive care program, inspired by the cognitive-behavioral model, through a food rehabilitation and a psychotherapeutic and psychoeducational help, lets the patients and their family understand and modify the dysfunctional patterns, experimenting a right modality to approach alimentation, with a satisfactory improvement in clinical conditions.

BACKGROUND:

Crizotinib is used for the treatment of advanced anaplastic lymphoma kinase (ALK)-rearranged nonsmall cell lung cancer (NSCLC). Sinus bradycardia (SB) is a side effect listed in its package insert. We investigated the frequency and timing of SB, patient characteristics associated with SB during crizotinib treatment, and potential correlation between heart rate (HR) changes and clinical response to crizotinib.

METHODS:

A retrospective chart review was conducted of the timing and frequency of SB, patient characteristics, and clinical response of patients to crizotinib treatment.

RESULTS:

Forty-twp patients who had ALK-rearranged or mesenchymal epithelial transition (MET)-amplified NSCLC and received treatment with oral crizotinib 250 mg twice daily who were enrolled in 2 crizotinib trials (PROFILE 1001 and PROFILE 1005) were analyzed. There was an average decrease of 26.1 beats per minute (bpm) from the pretreatment HR among all patients during crizotinib treatment. Twenty-nine patients (69%) experienced at least 1 episode of SB (HR, <60 bpm). The average time to the lowest HR recorded was 18.6 weeks (range, 5-72 weeks). Patients who experienced SB were significantly older (aged 55.8 years vs 47.8 years; P = .0336), had a lower pretreatment HR (mean, 77.9 bpm vs 100.6 bpm; P = .002), and were on crizotinib longer (52.9 weeks vs 24.6 weeks; P = .0050) than patients who did not experience SB. The overall response rate (P = .0195) and the maximum tumor shrinkage (P = .0205) were significantly greater in patients who experienced SB.

CONCLUSIONS:

HR decrease is common during crizotinib treatment. It remains to be determined whether the correlation between HR decrease and clinical response to crizotinib reflects a biomarker of drug efficacy or a time/cumulative dose-dependent phenomenon. Cancer 2013;. © 2013 American Cancer Society.

Kinmen, an offshore island of Taiwan, is a popular location for sightseeing and an important entry port between Taiwan and China. Kinmen is also highly endemic for scrub typhus. The authors aimed to investigate the disease characteristics there, which remained largely unknown.The authors conducted a retrospective study on patients with scrub typhus in Kinmen during 2005-2008. The clinical information was reviewed from medical records for statistical analysis.There were 261 patients with scrub typhus included with a bimodal summer-autumn type of distribution, with most patients (40%) age 20-29 years and a large proportion of patients (26%) older than 60 years. The disease manifestation, laboratory examinations, and treatment outcomes were comparable in summer and autumn. Fever (97%), eschar (93%), and relative bradycardia (67%) were the most common presentations, whereas lymphadenopathy (18%) and skin rash (8%) were infrequent. Elevated liver function, C-reactive protein levels, and low to normal platelet counts were frequent findings. A correct diagnosis was made made in an average 3.7 days after fever or 1.6 visits of medical consultation, and minocycline was prescribed in a timely manner. Most patients had good recovery and only 12 patients (5%) had severe infection with acute renal failure, shock, gastrointestinal bleeding, or respiratory failure; no mortality was found. Older age, longer fever duration, thrombocytopenia, abnormal liver and renal function, hyponatremia, and elevated C-reactive protein levels were significantly associated with severe complications and prolonged treatment duration.A unique summer-autumn type of scrub typhus with milder disease manifestations is identified in Kinmen. The younger patient population, rapid diagnosis, and prompt treatment may be associated with a shortened disease course and lead to a better outcome.

G protein-coupled receptors (GPCRs) are signaling molecules with a wide variety of skills. Members of this large family of membrane protein have been shown to regulate the activities of the different signaling pathways of the ligand specific manner. α2-adrenoceptors (α2-ARs) are one of the GPCRs and the stimulation of them could modulate many classical effects such as hypotension, bradycardia, etc.. Recently, α2A-AR is more and more important for its role in the therapeutic applications in central nervous system (CNS) diseases. High throughput screening of α2A-AR agonists was established by LANCETM cAMP assay from a compound library of 80,000 small-molecule compounds to find out potential human α2A-adrenoceptor (α2A-AR) agonists that might have therapeutic effect in CNS diseases. From the preliminary and secondary screening, 37 compounds were identified as α2A-AR agonists, and six compounds among them presented more pronounced α2A-AR stimulating activity than guanfacine, a selective α2A-AR agonist. The study provided referred data for the development of potent α2A-AR agonists and suggested that the existence of the parent structure (1, 2, 4-benzothiadiazine 1, 1-dioxide) bodes well for pharmaceutical development of α2A-AR agonists.

Background:

Propofol is routinely used for anaesthesia during paediatric heart catheterisation. Propofol infusion syndrome (PRIS) is a rare, but often fatal complication mainly defined as bradycardia with progress to asystolia during propofol infusion. Metabolic acidosis is regarded as an early warning sign of PRIS. In this study the effect of propofol and sevoflurane on serum base excess, pH and lactate have been examined during paediatric heart catheterisation.

Methods:

In this prospective randomised study 40 children have been anaesthetised for paediatric heart catheterisation with propofol (N = 22) or sevoflurane (N = 20) with ethic committee approval. Base excess, pH and lactate were measured by blood gas analysis at the beginning, during and at the end of the procedure. Changes relative to baseline were analysed by paired t-Test with correction for multiple testing. The study was powered to detect a difference of 1.5 mmol.l -1 for base excess and lactate.

Results:

Base excess (-2.59 (2.33) vs. -4.48 (2.88), p = 0,0004, mean(standard deviation)) and pH (7.39 (0.05) vs. 7.36 (0.06), p = 0.0008,) changed significantly in in the propofol group but not in the sevoflurane group. The number of patients with base excess < 5.0 increased in the propofol group only from 2 to 10 (p = 0.016). Lactate decreased in both groups (1.1 (0.3) vs. 0.9 (0.2), p = 0.003 for sevoflurane and (1.0 (0.3) vs. 0.8 (0.3), p = 0.0004 for propofol).

Conclusions:

Propofol but not sevoflurane had an effect on base excess and pH during paediatric heart catheterisation.

The presentation, mechanisms, and incidence of ST elevation myocardial infarction (STEMI) in heart transplant recipients have been characterized only to a limited degree in the current literature. Herein, we present a unique case of STEMI years after heart transplantation with a focus on the salient features of its diagnosis and interventions. We also provide a review of the epidemiology of this phenomenon.A 33-year-old woman who was status post cardiac transplantation for dilated cardiomyopathy presented to the clinic with mild nonspecific fatigue and concern after having noticed relative bradycardia compared with her posttransplantation baseline heart rate. Electrocardiogram (ECG) showed junctional rhythm and inferior ST elevations, likely reflecting nodal ischemia. Troponins were grossly positive and echocardiogram showed marked right ventricular dysfunction.Successful percutaneous coronary intervention (PCI) with aspiration thrombectomy and drug-eluting stent placement was emergently performed. The heart's rhythm soon returned to sinus tachycardia. Right ventricular wall-motion abnormalities resolved. The patient suffered no clinical sequelae of her STEMI.This case illustrated that "classic" symptoms of STEMI may not occur at all in the setting of heart transplantation. To our knowledge, this is the first case of posttransplantation STEMI presenting as asymptomatic bradycardia, and highlights the importance of maintaining high clinical suspicion for ischemia in transplant recipients with subtle changes. In reviewing the epidemiology of this case, we locate and bundle different types of studies that have directly or indirectly looked at STEMI in heart transplantation. For a variety of putative pathophysiological reasons, STEMI is indeed a rare manifestation of the common transplant phenomenon of coronary artery vasculopathy (CAV).

This study examined linkages between 6-month-old infants' (n = 101) orienting response, measured physiologically by brief bradycardia or heart deceleration at the onset of a frustration task (maternal arm-restraint) and mother-infant co-regulation measured during a 15-min unstructured free play episode. Given the socially disruptive nature of the frustration task, we suspected that infants who experienced more positive co-regulated interactions including symmetrical (both partners actively engaged and attending to each other) or asymmetrical (one partner actively engaged while partner attends to the other) with mothers would be more likely to display an orienting response (bradycardia) during the onset of the arm-restraint procedure than infants who experience unilateral (one partner focused on other but the other focused on self), unengaged (neither partner attending to the other) or disruptive interactions. Findings indicate that dyads that experienced more asymmetrical co-regulation had infants who were more likely to experience bradycardia while unengaged interactions predicted the absence of bradycardia. These findings suggest that mother-infant co-regulation may help establish expectations about social interactions and that when these relational expectancies are violated infants are more likely to exhibit bradycardia at the onset of a socially disruptive task. Alternative explanations are also considered.

Reflex syncope is defined by a rapid transient loss of consciousness caused by global cerebral hypoperfusion resulting from vasodilatation and/or bradycardia attributable to inappropriate cardiovascular reflexes. A hereditary component has been suggested, but prevalence of family history may differ among subtypes of reflex syncope, as these have different autonomic responses and pathogeneses may be diverse. The present study aimed to assess the prevalence of a positive family history of syncope and cardiovascular characteristics in patients with cardioinhibitory and vasodepressor reflex syncope. Patients (n=74) were classified into subtypes of reflex syncope - cardioinhibition/asystole (Vasovagal Syncope International Study subtypes II-B [VASIS II-B], n=38) or vasodepressor (VASIS III, n=36) - using the head-up tilt test. Family history was obtained by questionnaires supplemented by interview. Patients with cardioinhibitory syncope had a mean onset of disease 8years earlier than vasodepressor patients (mean±standard deviation 14.5years±12.6 for cardioinhibitory patients compared to 22.4years±11.9 for vasodepressor patients, p<0.001). Thirty-seven (50%) of 74 probands had a positive family history with at least one relative affected with syncope, arrhythmias, known sudden unexpected death, and/or heart disease. The prevalence of a positive family history was higher in patients with cardioinhibitory syncope compared to vasodepressor syncope (24 (63%) compared to 13 (36%); p=0.02). Overall, 40 first-degree relatives (26%) and 27 second- or third-degree relatives (25%) were affected. The most frequent events in families of patients with cardioinhibitory or vasodepressor reflex syncope were severe syncope and/or arrhythmias, known sudden unexpected deaths, and heart disease. In conclusion, prevalence of familial occurrence of syncope is in agreement with previous studies. However, a high occurrence of all-cardiovascular disorders in cardioinhibitory patients may reflect shared genetic susceptibility to these diseases.