Malignant hyperthermia

Malignant hyperthermia refers to covert myopathies, which do not affect the individual during daily life activities, but may lead to life-threatening tachycardia, rigor, labile blood pressure and most importantly high-grade temperature when exposed to general anaesthesia. This conditions is mimicked by thyroid storm, neuroleptic malignant syndrome, phaeochromocytoma and sepsis. We present a presumptive case of malignant hyperthermia.     

Meckel's diverticulum causing exsanguinating haemorrhage

A seven month old male baby presented to emergency room in shock. Patient had 3 hours history of massive fresh bleeding per rectum. Emergency laparotomy revealed Meckel's diverticulum (MD) with large vitello-intestinal artery responsible for massive bleeding. Diverticulectomy was performed.     

Flat and polypoid adenocarcinomas of the colorectum: A comparative histomorphologic analysis of 47 cases

"Flat" colorectal adenomas and adenocarcinomas are well documented in the Japanese literature but only sporadically reported in the English literature. The present study involved systematic morphological analysis of a large series of colorectal carcinomas (CRCs) to determine the frequency of these "flat" CRCs (FCRCs) and analyze their pathological characteristics and associated patient survival. The study group comprised 47 patients (19 females and 28 males) with primary CRC who underwent colorectal resection at the H. Lee Moffitt Cancer Center between 1997 and 2002. These cases were selected based on the gross appearance of the tumors and after review of all of the hematoxylin and eosin-stained tumor sections in a series of 190 consecutive colorectal resections for CRCs. Application of strict morphological criteria classified 22 tumors as FCRCs. For comparison, 25 "polypoid" CRCs (PCRCs) were also identified. Cases of ulcerative fungating annular CRCs and CRCs with mixed gross appearance were excluded from this analysis. Clinicopathologic data, including patient survival, were compared for FCRCS and PCRCs. Statistical analyses were carried out using the chi(2) or Fisher's exact test and log-rank tests. Overall, 22 of 190 CRCs (11%) were found to meet the morphological criteria of FCRCs. Mean patient age was 70.6 years (range, 55 to 87) for FCRCs versus 68.5 years (range, 54 to 91) for PCRCs, and mean tumor size was 4.7 cm (range, 1.6 to 9) for FCRCs versus 4.4 cm (range, 0.5 to 10) for PCRCs. None of the 22 FCRCs and only 1 of 25 (4%) PCRCs were well differentiated; 17 of 22 (77%) FCRCs and 23 of 25 (92%) PCRCs were moderately differentiated; and 5 of 22 (22%) FCRCs and 1 of 25 (4%) PCRCs were poorly differentiated (P = 0.0087). FCRC cases were staged as 0 stage T1, 3 (14%) stage T2, and 19 (86%) stage T3; PCRC cases, as 4 (16%) stage T1, 14 (56%) stage T2, and 7 (28%) stage 3 (P = 0.000031). Similarly, angiolymphatic invasion was identified in 12 of 22 (54%) FCRCs versus 4 of 25 (16%) PCRCs (P = 0.0123). Although some differences between FCRCs and PCRCs were observed on resection in terms of nodal status (N), presence of metastases (M), and perineural invasion, these differences were not statistically significant. In comparison with PCRCs, FCRCs were associated with significantly shorter postresection patient survival at 1 to 5 years (P = 0.028). We have demonstrated in this report that a proportion of primary CRCs resected at our institution were indeed "flat." Furthermore, these FCRCs exhibited higher histological grades, higher T stage, more frequent angiolymphatic invasion, and shorter patient survival compared with PCRCs. Based on these data, FCRC appears to be a worse subtype of colon cancer than PCRC. Further appraisal of FCRCs and additional studies to further elucidate the molecular mechanisms underlying their morphogenesis are warranted.     

Multiple synchronous fibrovascular polyps of the hypopharynx

PURPOSE OF THE STUDY: To evaluate the clinical, radiological presentation and surgical management of fibrovascular polyps of the hypopharynx. METHODS: Retrospective medical analysis of a case report. We report the case of a 66-year-old man, who presented with an incarcerated left inguinal hernia, vomiting and regurgitation of a large mass into the oral cavity resulting in syncope. MRI and cine-esophagram demonstrated a large mass in the cervical esophagus. At the time of herniorrhaphy, endoscopy revealed an 11.8-cm hypopharyngeal mass that completely obstructed the oropharynx. RESULTS: The airway was secured by tracheostomy and the lesion was subsequently removed via open pharyngotomy. Postoperatively, a second polyp was found ball-valving into the airway, and an endoscopic resection was performed prior to decannulation. Histopathology of both lesions confirmed the diagnosis of a fibrovascular polyp. CONCLUSION: Fibrovascular polyps are rare benign intraluminal esophageal lesions resulting in mild symptoms of dysphagia that may also cause significant morbidity such as syncope and asphyxia. This is the first report of synchronous fibrovascular polyps of the hypopharynx.     

Body image perception, dietary practices and physical activity of overweight and normal weight Malaysian female adolescents

Body image plays an important role in the management of body weight, especially among female adolescents. This study examined the differences in body image perception, weight management knowledge, eating behaviour and physical activity between overweight and normal weight Malaysian female adolescents. Body mass index screening was done on 588 secondary school students to identify overweight (OW) and normal weight (NW) subjects. A BMI-for-age of => 85th percentile and between => 5th and <85th percentile were used as cut-offs for identifying suitable subjects of overweight and normal weight, respectively. Fifty girls identified as being OW were matched for age and ethnicity with 50 NW students. Subjects completed a self-administered questionnaire on demographics, eating behaviour and physical activity, a weight management knowledge inventory (WMKI) and the Body Silhouette Chart. The study sample comprised Malays (40%), Chinese (30%) and Indians (30%) with a mean age of 14.76 ± 1.15 years. The majority of them were from families with a monthly household income of less than RM1,000. Significantly more NW subjects (χ2=6.112, p=0.013) than OW subjects had incorrect perception of their current body weight status. The WMKI revealed that more OW subjects (64%) than NW subjects (52%) had a low level of weight management knowledge. Eating behaviour patterns were not significantly different between OW and NW subjects, but more OW subjects skipped one or more daily meals as compared to their NW counterparts (χ2=0.174, p=0.010). Physical activity patterns were similar in both groups. Healthy eating and physical activity promotion programmes in schools should include sound weight management practices.     

Interspecies differences in the nephrotoxic response to cyclooxygenase inhibition

In contrast to cyclooxygenase-1 (COX-1), the basal expression of renal cyclooxygenase-2 (COX-2) varies among species. High basal levels of COX-2 in the renal cortex and papilla in dogs compared with monkeys suggest that COX-2 inhibition may lead to distinct nephrotoxic responses. In this study, we compared the renal effects of COX inhibition between dogs and cynomolgus monkeys (n = 6/group) following the administration of naproxen sodium, a non-selective COX-1/COX-2 inhibitor. Dogs and monkeys were treated with 50 or 150 mg/kg/day naproxen sodium, respectively, for 2 to 6 weeks. Naproxen doses used in this study resulted in equivalent inhibition of COX activity in both species as measured by reductions in urinary prostaglandin E2 (PGE2) and 6-keto-PGF1-alpha levels. There was prominent reduction in renal blood flow (43%) and urinary sodium excretion (62%) in dogs but no alterations in renal blood flow and only minimal change (19%) in urinary sodium excretion in monkeys. The canine but not monkey kidney showed prominent COX-2 expression in the macula densa, thick ascending limb of Henle and papillary interstitial cells by immunohistochemistry. After treatment, the canine but not monkey kidneys had mild to moderate renal tubular atrophy and interstitial fibrosis and renal papillary necrosis. Obstructive nephropathy secondary to intra-tubular drug accumulation was seen in monkeys but not in dogs. Collectively, these data demonstrate species differences in the renal response to COX inhibition. The nature of functional and morphologic changes suggests a more prominent role of COX-2 in renal hemodynamics and natriuresis in dogs than in monkeys.     

Identification and characterisation of SB-366791, a potent and selective vanilloid receptor (VR1/TRPV1) antagonist

Vanilloid receptor-1 (TRPV1) is a non-selective cation channel, predominantly expressed by peripheral sensory neurones, which is known to play a key role in the detection of noxious painful stimuli, such as capsaicin, acid and heat. To date, a number of antagonists have been used to study the physiological role of TRPV1; however, antagonists such as capsazepine are somewhat compromised by non-selective actions at other receptors and apparent modality-specific properties. SB-366791 is a novel, potent, and selective, cinnamide TRPV1 antagonist isolated via high-throughput screening of a large chemical library. In a FLIPR-based Ca(2+)-assay, SB-366791 produced a concentration-dependent inhibition of the response to capsaicin with an apparent pK(b) of 7.74 +/- 0.08. Schild analysis indicated a competitive mechanism of action with a pA2 of 7.71. In electrophysiological experiments, SB-366791 was demonstrated to be an effective antagonist of hTRPV1 when activated by different modalities, such as capsaicin, acid or noxious heat (50 degrees C). Unlike capsazepine, SB-366791 was also an effective antagonist vs. the acid-mediated activation of rTRPV1. With the aim of defining a useful tool compound, we also profiled SB-366791 in a wide range of selectivity assays. SB-366791 had a good selectivity profile exhibiting little or no effect in a panel of 47 binding assays (containing a wide range of G-protein-coupled receptors and ion channels) and a number of electrophysiological assays including hippocampal synaptic transmission and action potential firing of locus coeruleus or dorsal raphe neurones. Furthermore, unlike capsazepine, SB-366791 had no effect on either the hyperpolarisation-activated current (I(h)) or Voltage-gated Ca(2+)-channels (VGCC) in cultured rodent sensory neurones. In summary, SB-366791 is a new TRPV1 antagonist with high potency and an improved selectivity profile with respect to other commonly used TRPV1 antagonists. SB-366791 may therefore prove to be a useful tool to further study the biology of TRPV1.     

Acupuncture

With the increasing availability of acupuncture in the United States, it is possible that patients will increasingly seek and use acupuncture for diverse indications. Research into acupuncture is still in its infancy, and much of the scientific evidence surrounding it is fragmentary and often contradictory. As is the case even in well-researched therapies, physicians often have to make decisions about patient care based on a mixture of available scientific evidence, anecdote, and patient preference. As investigations into this therapy continue, and patients, practitioners, and the medical system become more familiar with its integration into mainstream medical treatment settings [108], the role of acupuncture in the treatment of disease will become clearer.     

Identification and quantification of antigens associated with HLA class I molecules on a bladder tumour cell line. Implications for vaccine design

The aim of this study was to isolate and identify antigenic peptides associated with HLA class I molecules on a bladder tumour cell line. HLA-A1 molecules were purified using an immunobead-purification technique and following elution of nonapeptides associated with the complex, their HPLC profile was determined by Tandem mass spectrometry (MS/MS). Three peptides were identified namely: (1) P991 (VTDPGNLLY); (2) P1041.5 (LTDLGFLVY), and (3) P1057.7 (LTDPHLLSY); these sequences matched elements of hepatitis B, MAGE1-A1 and herpes simplex viruses. These antigens had half-lives of approximately 120 min which is within the theoretical range of such short peptides. These results indicate that identification of MHC-associated peptides is possible without using an assay for cytotoxic T cells. Although this approach was applied on a relatively small scale, broader applications can be foreseen.     

Pharmacokinetics and bioequivalence evaluation of two simvastatin 40 mg tablets (Simvast and Zocor) in healthy human volunteers

The pharmacokinetics of two brands of simvastatin 40 mg tablets were compared in 24 healthy human volunteers after a single oral dose in a randomized cross-over study, conducted at IPRC, Amman, Jordan. Reference (Zocor, MSD, Netherlands) and test (Simvast, Julphar, UAE) products were administered to fasted volunteers; blood samples were collected at specified time intervals, plasma separated and analyzed for simvastatin and its active metabolite (beta-hydoxy acid) using a validated LC-MS/MS method at Cartesius Analytical Unit, Institute of Biomedical Sciences - USP, Sao Paulo, Brazil. The pharmacokinetic parameters AUC(0-t), AUC(0-variant), C(MAX), T(MAX), T(1/2) and elimination rate constant were determined from plasma concentration-time profile for both formulations and were compared statistically to evaluate bioequivalence between the two brands, using the statistical modules recommended by FDA. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals fell within the acceptable range for bioequivalence. Based on these statistical inferences it was concluded that the two brands exhibited comparable pharmacokinetic profiles and that Julphar's Simvast is bioequivalent to Zocor of MSD, Netherlands.