Otolaryngological manifestations of ‘Muckle-Wells syndrome’

We present a follow-up of a cohort of three cases of Muckle-Wells syndrome (MWS). The aim of this report is to characterise the symptoms of this rare autosomal dominant condition with respect to the ENT practice. A retrospective analysis of the clinical features of MWS from our outpatient follow-up record of the three patients diagnosed with MWS. An extensive literature search was performed, using Medline through Pub Med (1950-2010), EMBASE (1980-2009) and Ovid (1958-2009). Retrospective case note study. In the present cohort, progressive sensorineural hearing loss was the main presentation and has been followed up over 10 years (median). The spectrum of head and neck presentation from the world literature was reviewed and includes hypothyroidism, amyloid goitre, cervical lymphadenopathy, and facial rash. This is the first documented report of the Otolaryngological features of the MWS in the English ENT literature. An awareness of this rare syndrome is essential in order to diagnose this uncommon syndrome and thus to plan for a long-term follow-up.     

Multianalyte profiling of serum antigens and autoimmune and infectious disease molecules to identify biomarkers dysregulated in epithelial ovarian cancer

Ovarian cancer is the deadliest gynecologic cancer in the United States. When detected early, the 5-year survival rate is 92%, although most cases remain undetected until the late stages where 5-year survival rates are 30%. Serum biomarkers may hold promise. Although many markers have been proposed and multivariate diagnostic models were built to fit the data on small, disparate sample sets, there has been no systematic evaluation of these markers on a single, large, well-defined sample set. To address this, we evaluated the dysregulation of 204 molecules in a sample set consisting of serum from 294 patients, collected from multiple collection sites, under a well-defined Gynecologic Oncology Group protocol. The population, weighted with early-stage cancers to assess biomarker value for early detection, contained all stages of ovarian cancer and common benign gynecologic conditions. The panel of serum molecules was assayed using rigorously qualified, high-throughput, multiplexed immunoassays and evaluated for their independent ovarian cancer diagnostic potential. Seventy-seven biomarkers were dysregulated in the ovarian cancer samples, although cancer antigen 125, C-reactive protein, epidermal growth factor receptor, interleukin 10, interleukin 8, connective tissue growth factor, haptoglobin, and tissue inhibitor of metalloproteinase 1 stood out as the most informative. When analyzed by cancer subtype and stage, there were differences in the relative value of biomarkers. In this study, using a large sample cohort, we show that some of the reported ovarian cancer biomarkers are more robust than others, and we identify additional informative candidates. These findings may guide the development of multivariate diagnostic models, which should be tested on additional, prospectively collected samples.     

Spearmint induced hypothalamic oxidative stress and testicular anti-androgenicity in male rats – altered levels of gene expression, enzymes and hormones

Mentha spicata Labiatae, commonly known as spearmint, can be used for various kinds of illnesses in herbal medicines and food industries. One of the prominent functions of this plant extract is its anti-androgenic activity. The present study investigated the probable correlation between oxidative stress in hypothalamic region and anti-androgenic action of this plant’s aqueous extract on rats. Decreased activities of enzymes like superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in hypothalamus of treated rats indicated spearmint induced oxidative stress. Further RT-PCR and immunoblot analysis demonstrated the decreased expression of some of the steroidogenic enzymes, cytochrome P450scc, cytochrome P450C17, 3β-Hydroxysteroid dehydrogenase (3β-HSD), 17β-Hydroxysteroid dehydrogenase (17β-HSD) and other related proteins like, steroidogenic acute regulatory protein, androgen receptor and scavenger receptor class B-1. Further, in vitro enzyme assays demonstrated depressed activities of testicular 3β-HSD and 17β-HSD enzymes. Histopathology indicated a decreased sperm density in cauda epididymis and degeneration of ductus deference. Our study suggested that spearmint probably induced oxidative stress in hypothalamus resulting in decreased synthesis of LH and FSH which in turn down-regulated the production of testicular testosterone through the disruption of a number of intermediate cascades.     

Dopamine increases the efficacy of anticancer drugs in breast and colon cancer preclinical models.

PURPOSE: Because neurotransmitter dopamine inhibits vascular permeability factor/vascular endothelial growth factor (VEGF)-induced angiogenesis and as anti-VEGF agents act synergistically with anticancer drugs, we therefore investigated whether dopamine can increase the efficacies of these drugs. EXPERIMENTAL DESIGN: The effect of dopamine was investigated in human breast cancer-(MCF-7) and colon (HT29) cancer-bearing mice. Experimental groups received either dopamine or doxorubicin or dopamine plus doxorubicin in MCF-7 tumor-bearing mice, and either dopamine or 5-fluorouracil or dopamine plus 5-fluorouracil in HT29-bearing mice. Thereafter, tumor growth, angiogenesis, tumor cell apoptosis, life span, and the effect of dopamine on the growth and survival of tumor cells in vitro were determined. Finally, the effects of dopamine on tumor vascular permeability; on VEGF receptor-2, mitogen-activated protein kinase, and focal adhesion kinase phosphorylation; and also on the proliferation and migration of tumor endothelial cells were investigated. RESULTS: Dopamine, in combination with anticancer drugs, significantly inhibited tumor growth and increased the life span when compared with treatment with dopamine or anticancer drugs alone. Dopamine had no direct effects on the growth and survival of tumor cells. The antiangiogenic action of dopamine was mediated by inhibiting proliferation and migration of tumor endothelial cells through suppression of VEGF receptor-2, mitogen-activated protein kinase, and focal adhesion kinase phosphorylation. CONCLUSION: Our study shows that dopamine significantly enhances the efficacies of commonly used anticancer drugs and also indicates that an inexpensive drug like dopamine, which is being extensively used in the clinics, might have a role as an antiangiogenic agent for the treatment of breast and colon cancer.     

Risk factors for development of dehydration in young children with acute watery diarrhoea: a case-control study

In a case-control study to understand the risk factors for development of life-threatening dehydration, a total of 379 children comprising 243 cases (moderate or severe dehydration) and 136 controls (non or mild dehydration) up to 2 years of age suffering from acute watery diarrhoea were studied. By univariate analysis, the presence of vibrios in stool, withdrawal of breast feeding during diarrhoea, not giving fluids, including oral rehydration solution (ORS), during diarrhoea, frequent purging (> 8/ day), vomiting (> 2/day) and undernutrition were identified as risk factors. However, by multivariate analysis after controlling for confounders, withdrawal of breast feeding during diarrhoea (odds ratio (OR) = 6.8, p < 0.00001) and not giving ORS during diarrhoea (OR = 2.1, p < 0.006) were identified as significant risk factors. The confounding variables which also contributed significantly to increasing the risk were age (≤ 12 months; OR = 2.7, p = 0.001), frequent purging (> 8/day; OR = 4.1, p < 0.00001), vomiting (> 2/day; OR = 2.4, p = 0.001) and severe undernutrition (%median <60 weight-for-age of Indian Academy of Paediatrics classification; OR = 3.1, p = 0.001). We feel that these findings will be useful for Global and National Diarrhoeal Diseases Control Programmes for formulating intervention strategies for preventing death due to diarrhoeal dehydration.     

Septicemia in neonates and early infancy

A detailed clinico-pathological study of 82 bacteriologically confirmed cases of septicemia was performed—55 cases were in neonates (A1) and 27 cases were in early infancy (A2). Male babies with low birth weight predominated (64·9%). The bacteriological study of the blood culture revealed pure gram negative bacilli were the causative agent in 86·6 per cent of the cases. Of these P. aeruginosa was most common followed by Klebsiella and E. coli. The clinical features were statistically analysed in the two age groups (A 1 and A 2) and with the causative agents. This showed tachypnoea (p<0·05) and fever (p<0·01) were mostly seen in A2 group and in septicemia due to organisms other than P. aeruginosa. “Noma” was exclusively found in neonates (A1) (p<0·01). Diarrhea was significant feature of neonatal pseudomonas septicemia whereas fever was present in the early infancy age-group suffering from septicemia with organisms other than P. aeruginosa. The associated findings, blood count, CSF changes and radiology are discussed and highlighed.     

Transesophageal echocardiographic identification of right vertebral artery

We describe a transesophageal technique for identifying the origin and precervical course of the right vertebral artery with the probe positioned in the upper esophagus. The technique was successful in 9 of 11 patients in whom it was attempted.     

Blood-aqueous barrier in prostaglandin EP2 receptor knockout mice

The role of prostaglandin EP(2) receptors in the disruption of the blood-aqueous barrier was examined using EP(2) receptor-deficient mice. Eyes were topically treated with EP receptor agonists or subjected to paracentesis. Fluorescein angiography was performed after topical treatment with 2.0 icrog butaprost. The results show that EP receptor agonists, PGE( 2) and the EP(2) receptor-selective agonist butaprost, increased aqueous humor protein in EP(2) +/+ wild-type mice to 18.0 mg/ml and 12.0 mg/ml, respectively, from the control value of 2.7 mg/ml. The increase in aqueous humor protein concentration in response to these EP receptor agonists was reduced significantly in EP(2) receptor-deficient mice. Fluorescein leakage into the anterior chamber, two minutes after its injection, was significantly greater in butaprost-treated wild-type mice than in butaprost-treated knockout mice. Protein concentration, 15 min after paracentesis, increased from 2.2 mg/ml to 25.0 mg/ml in the aqueous humor of the eyes of wild-type mice, while the increase in knockout mice was 10.6 mg/ml. These results suggest that EP( 2) and EP(4) receptors mediate the disruption of the blood-aqueous barrier induced by EP receptor agonists and paracentesis.     

The critical care pharmacist: an essential intensive care practitioner

Clinical pharmacy services in the critical care setting have expanded dramatically and include assisting physicians in pharmacotherapy decision making, providing pharmacokinetic consultations, monitoring patients for drug efficacy and safety, providing drug information, and offering medical education to physicians, nurses, and patients. Measurable clinical effects of these services include reduced drug errors and adverse drug events, decreased morbidity and mortality rates, and a positive pharmacoeconomic impact by decreasing overall health care costs.