Effect of chewing a mixture of areca nut and tobacco on periodontal tissues and oral hygiene status

The present study was conducted to clarify the effects of chewing a quid containing areca nut and tobacco on periodontal tissue and oral hygiene status. A total of 365 subjects (168 chewers and 197 non-chewers with a mean age of 32.5 +/- 0.7 and 30.4 +/- 0.8 years, respectively) were enrolled. Clinical data on periodontal tissues, oral hygiene status, as well as information on bleeding from gums, ulcers in the oral cavity, or a burning sensation in the soft tissues, were collected as indicators of the possible presence and extent of periodontal lesions. The results indicated that a significantly higher number of quid-chewers suffered bleeding from the gums, halitosis, difficulty in opening the mouth and swallowing solid food, a burning sensation in the soft tissues, and ulcers in the oral cavity than non-chewers. There was no significant difference between quid-chewers and non-chewers with respect to oral hygiene measures adopted. However, clinical examination using the oral hygiene index score indicated that the oral hygiene status of quid-chewers was significantly deteriorated. The effect of quid-chewing on the periodontium, i.e. the occurrence of periodontal pockets, gingival lesions and gum recession, were significantly higher in quid-chewers than in non-chewers. Age, sex and smoking adjusted odds ratios for quid-chewers against non-chewers using logistic regression analysis indicated that, in general, chewers were at significantly higher risk for various oral complaints and periodontium status. The present data indicate that chewing quid comprising areca nut and tobacco has adverse effects on periodontal tissues, oral hygiene and incidence of oral lesions.     

Decrease in shigellosis-related deaths without Shigella spp.-specific interventions, Asia

In 1999, a review of the literature for 1966-1997 suggested that ≈1.1 million persons die annually of shigellosis, including ≈880,000 in Asia. Our recent review of the literature for 1990-2009 indicates that ≈125 million shigellosis cases occur annually in Asia, of which ≈14,000 are fatal. This estimate for illnesses is similar to the earlier estimate, but the number of deaths is 98% lower; that is, the lower estimate of deaths is associated with markedly reduced case-fatality rates rather than fewer cases. Shigella spp.-related deaths decreased substantially during a period without Shigella spp.-specific interventions. We speculate that nonspecific interventions, e.g., measles vaccination, vitamin A supplementation, and improved nutrition, may have led to the reduced number of shigellosis-related deaths.     

Homocysteine,Alcoholism, and Its Potential Epigenetic Mechanism

Alcohol is the most socially accepted addictive drug. Alcohol consumption is associated with some health problems such as neurological, cognitive, behavioral deficits, cancer, heart, and liver disease. Mechanisms of alcohol‐induced toxicity are presently not yet clear. One of the mechanisms underlying alcohol toxicity has to do with its interaction with amino acid homocysteine (Hcy), which has been linked with brain neurotoxicity. Elevated Hcy impairs with various physiological mechanisms in the body, especially metabolic pathways. Hcy metabolism is predominantly controlled by epigenetic regulation such as DNA methylation, histone modifications, and acetylation. An alteration in these processes leads to epigenetic modification. Therefore, in this review, we summarize the role of Hcy metabolism abnormalities in alcohol‐induced toxicity with epigenetic adaptation and their influences on cerebrovascular pathology.     

Early histopathologic changes in purple glove syndrome

An 86-year-old African-American man presented with tonic-clonic seizures. Intravenous phenytoin was urgently administered into the dorsum of the right hand. The patient developed a raised purple area of discoloration around the intravenous insertion site within 2 h and edema and vesiculobullous lesions of the distal forearm, hands, and fingers within 8 h. Microscopic sections from a biopsy at 12 h revealed epidermal necrosis, superficial ulceration, and a mild superficial and deep perivascular lymphoid infiltrate, associated with numerous thrombi of small vessels throughout the dermis. The findings were judged to be consistent with soft-tissue injury associated with intravenous administration of phenytoin, also termed purple glove syndrome. Purple glove syndrome, named for its distinctive purple discoloration and swelling of the hands in the distribution of a glove, is an uncommon complication of intravenous phenytoin administration through small dorsal veins of the hands. It is comprised by pain, discoloration, and edema in the vicinity of intravenous infusion of phenytoin through dorsal veins of the hand. The histopathologic features of fully developed lesions have been reported; however, early-stage findings have not been previously described, and the histogenesis of this lesion is controversial. The presence of thrombi in this early-stage lesion suggests that thrombosis plays a role in the initial pathogenesis of this condition.     

Predictors of death in under-five children with diarrhoea admitted to a critical care ward in an urban hospital in Bangladesh

Aim : To evaluate the clinical and laboratory predictors of death in hospitalized under‐five children with diarrhoea. Methods : This is a prospective cohort study carried out in the Special Care Ward (SCW) of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh. All admitted diarrhoeal children of both sexes, aged 0–59 months, from September 2007 through December 2007 were enrolled. We compared and analysed factors among diarrhoeal children who died (n = 29) with those who survived (n = 229). Results : In logistic regression analysis, after adjusting for potential confounders (infusion of intravenous fluid and immature PMN), absent peripheral pulse even after complete rehydration (OR 10.9, 95% CI 2.1–56.8; p < 0.01), severe malnutrition (OR 7.9, 95% CI 1.8–34.8; p < 0.01), hypoxaemia (OR 8.5, 95% CI 1.0‐75.0; p = 0.05), radiological lobar pneumonia (OR 17.8, 95% CI 3.7–84.5; p < 0.01) and hypernatraemia (OR 15.8, 95% CI 3.0–81.8; p < 0.01) were independently associated with deaths among diarrhoeal children admitted to SCW. Conclusions:  Thus, the absence of peripheral pulses even after full rehydration, severe malnutrition, hypoxaemia, lobar pneumonia and hypernatraemia are independent predictors of death among the under‐five children with diarrhoea admitted to critical care ward of a resource‐limited setting in Bangladesh.     

Head-up tilt testing in children and young people: a retrospective observational study

Aim: Head‐up tilt testing (HUTT) is the gold standard investigation for adults with transient loss of consciousness (TLOC), but it is controversial in children and young people, because of a lack of systematic investigation and because the test can be uncomfortable. As it was introduced recently for children attending our hospital, we undertook a retrospective registered clinical audit of its usefulness. Methods: The medical records of 100 consecutive patients aged less than 18 years undergoing HUTT from October 2001 to December 2008 were reviewed. Information about their episodes, prodromes, triggers, previous tests, indications for the HUTT, the HUTT and clinical outcomes was extracted. Results: Children were 6–17 years old; 68/100 were female. In 32/100, no trigger was reported. The most reported triggers included standing up (20%) and prolonged standing (18%). Dizziness (64%) and altered vision (39%) were the most experienced prodromal symptoms. Twenty‐eight of 100 had a positive test, with reproduction of symptoms in 24. Seventeen of 100 tests were negative but symptomatic; 55/100 had a negative asymptomatic test. In 17/28 positive HUTTs, the tilt confirmed the suspected diagnosis and elucidated the mechanism. Two of 28 were started on medication. However, in 9/28, neither was the diagnosis clarified nor was therapy instigated. Conclusions: Potentially useful information about the TLOC was obtained in 45/100 cases. The 17/100 with negative but symptomatic results may have had medically unexplained TLOC or emotional attacks, although without concurrent electroencephalogram, some uncertainty remains. Therefore, a new protocol with video–electroencephalogram–polygraphy and beat‐to‐beat finger blood pressure recording, and more explicit clinical reporting is being developed.     

A tipping-point for apoptosis following dual inhibition of HER2 signaling network by T-DM1 plus GDC-0980 maximizes anti-tumor efficacy

HER2 signaling network and its complex relationship with the PI3K-AKT-mTOR pathway explain the acquired resistance to anti-HER2 therapy observed in clinics. Such complexity has been clinically evident from the limited efficacy of data in the BOLERO-1 and BOLERO-3 trials, which tested combinations of trastuzumab (T), everolimus, and chemotherapy in women with HER2+ advanced BC. In the following MARIANNE trial also, a combination of T-DM1 plus pertuzumab delivered a non-inferior but yet not superior PFS compared to trastuzumab plus a taxane. Algorithmic inhibition of PI3K/mTOR along with T or T-DM1 is, therefore, an attractive drug combination, and we tested the combination(s) in HER2+ BC, especially in T-resistant and PIK3CA mutated conditions. GDC-0980, a dual pan-PI3K/mTOR inhibitor alone or in combination with T or T-DM1, was examined in a panel of HER2+ T-sensitive (BT474, SKBR3), HER2+ T-resistant (BT474HerR), HER2+/PIK3CA mutant (HCC1954, MDA-MB453), and HER2+/PTEN mutant (HCC1569) BC cell lines. GDC-0980 re-sensitized trastuzumab-resistant, PIK3CA mutant, or PTEN mutant cells to T and acted additively with T. Importantly, this activity was more when GDC-0980 is combined with T-DM1. The combination (with T or with T-DM1) was then tested in the HER2+/T-sensitive, HER2+/T-resistant, and HER2+/PIK3CA mutated BC xenograft models for the anti-tumor effect. Along with its anti-tumor effect, GDC-0980 effectively decreased tumor angiogenesis (CD31 staining). Maximum anti-tumor (from tumor growth inhibition to tumor regression) efficiency was observed in all three xenograft models when T-DM1 was combined with GDC-0980. The anti-proliferative effects of GDC-0980 as evidenced by a decreased p-AKT (Ser473, The308), p-P70S6K, p-S6RP, and p-4EBP1, along with blockade of clonogenic 3D growth was accompanied by the initiation of apoptotic activity (annexin V, CASPASE3, cleaved PARP1 and mitochondrial depolarization); and was significantly superior when GDC-0980 combined with T-DM1. Interestingly, both trastuzumab and T-DM1 induce PD-L1 expression in HER2 amplified BC cells. Our data provide evidence that an oncogenic mutation of PIK3CA and HER2-amplification may represent biomarkers to identify patients who may benefit most from the use of GDC-0980 and an opportunity to include immunotherapy in the combination of anti-HER2 therapy.     

Eccrine angiomatous naevus revisited

Hamartomatous, circumscribed swellings of the extremities make an interesting study. Presentations are manifold and the naevi are not always present from birth. Excessive growth of hairs leads to remarkable appearance of such swellings. A young woman presented to the dermatology department, complaining of tenderness over 4(th) finger of her left hand. The defect was present for the last couple of years and was typified by visible hyperhidrosis on gentle tapping. Counseling of the affected lady made her agree for a skin biopsy. The histopathology revealed it to be of the nature of eccrine angiomatous hamartoma. Blood vessels were scarce. Eccrine ducts were plentiful without other associated anomalies. The deformity was removed by simple excision with good result.     

Pantoprazole therapy in the long-term management of severe acid peptic disease Clinical efficacy, safety, serum gastrin, gastric histology, and endocrine cell studies

OBJECTIVE: Pantoprazole is the third proton pump inhibitor to become available. When this study was started, there were few data on its long-term use. Our aim was to investigate this aspect and, because powerful inhibitors of acid secretion can cause hypergastrinemia and, in experimental animals, enterochromaffin-like cell hyperplasia, we also monitored serum gastrin and endocrine cell histology. METHODS: One hundred fifty patients refractory to H2-receptor antagonists, running an aggressive course or with complications, were entered into a 5-yr treatment program. We performed serial endoscopy, checked for adverse events, and laboratory values. We also monitored serum gastrin, gastric endocrine cell histology, and antral and corpus gastritis. RESULTS: This report presents results from up to 3 yr of treatment. Cumulative healing on 40-80 mg of pantoprazole was 82% at 4 wk and 92% by 12 wk. Most patients became asymptomatic within 4 wk. Remission on maintenance treatment with 40 mg (n = 111) was 85% at 12 months and 78% at 24 months. Treatment was safe; only four patients had adverse events definitely related to pantoprazole. Elevations in gastrin were modest and there were no significant changes in gastric endocrine cells. The number of enterochromaffin-like cells tended to decrease. CONCLUSION: Pantoprazole is effective, safe, and does not seem to be associated with large increases in serum gastrin or alterations in gastric endocrine cells.