Tumorigenic effect of 4-methylphenylhydrazine hydrochloride in Swiss mice

Summary 4-Methylphenylhydrazine hydrochloride was administered as 10 weekly subcutaneous injections of 140 g/g body weight and as 7 weekly intragastric instillations of 250 g/g body weight in physiological saline to randomly bred Swiss mice. Treatments given subcutaneously resulted in induction of lung tumors in incidences of 36% in females and 44% in males, while intragastric treatment caused a 40% incidence in females. In addition, it gave rise to blood vessel tumors by intragastric route in incidences of 32% in females and 18% in males. In the two physiological saline-treated control groups, the lung tumor incidence (combined) was 20% in females and 21% in males, while the blood vessel tumor incidence (combined) was 7% in females and 6% in males. Histopathologically, the lesions were classified as adenomas and adenocarcinomas of the lungs, and angiomas and angiosarcomas of blood vessels.4-Methylphenylhydrazine was postulated to be a metabolite of 4-hydroxymethylphenylhydrazine, an ingredient of the commonly eaten mushroom Agaricus bisporus. The implications are discussed with respect to the tumorigenesis data.This study was supported by Public Health Service Contract NOl CP33278 from the National Cancer Institute, NIH, USA     

Repeated Valsalva maneuvers promote symptomatic manifestations of cerebral microhemorrhages: implications for the pathogenesis of vascular cognitive impairment in older adults

Multifocal cerebral microhemorrhages (CMHs, also known as “cerebral microbleeds”), which are associated with rupture of small intracerebral vessels, have been recognized as an important cause for cognitive decline in older adults. Although recent studies demonstrate that CMHs are highly prevalent in patients 65 and older, many aspects of the pathogenesis and clinical significance of CMHs remain obscure. In this longitudinal observational study, a case of a 77-year-old man with multifocal CMHs is described, in whom the rupture of intracerebral vessels could be linked to repeatedly performing extended Valsalva maneuvers. This patient was initially seen with acute aphasia after performing a prolonged Valsalva maneuver during underwater swimming. T2-weighted magnetic resonance imaging revealed a left acute frontal intracerebral hemorrhage (ICH) with multiple CMHs. The aphasia was resolved and no cognitive impairment was present. Two years later, he developed unsteadiness and confusion after performing two prolonged Valsalva maneuvers during underwater swimming separated by about 12 days. Repeat brain imaging revealed an acute right and a subacute left ICH, with a marked interval increase in the number of CMHs. The patient also exhibited manifest memory loss after the second admission and was diagnosed with dementia. These observations suggest that prolonged Valsalva maneuver is potentially a common precipitating cause of both CMHs and symptomatic ICHs. The Valsalva maneuver both increases the systolic arterial pressure and gives rise to a venous pressure wave transmitted to the brain in the absence of the competent antireflux jugular vein valves. This pressure increase is superimposed on existing hypertension and/or increases in blood pressure due to exercise and increased venous return due to immersion of the body in water. We advocate that further studies are needed to distinguish between CMHs with arterial and venous origins and their potential to lead to ICH induced by Valsalva maneuver as well as to determine whether these lesions have a predilection for a particular location.     

Non-Epstein–Barr virus associated lymphoepithelioma-like carcinoma of the esophagogastric junction with microsatellite instability,K-ras wild type

A 60-year-old male was admitted to our hospital for gastric cancer. Considering his general condition, total gastrectomy and dissection of regional lymph nodes were performed. Macroscopically, a 45 mm × 20 mm × 10 mm-sized, ulcero-infiltrative tumor located in the esophagogastric junction was described. Microscopically, the tumor consisted of a poorly differentiated adenocarcinoma intermingled with dense lymphoid infiltration predominantly composed of T-cell lymphocytes. The tumor cells infiltrated the submucosa, muscularis and subserosal layers of the stomach, respectively the esophageal adventitia. No metastases were noticed in the 58 regional lymph nodes. Based on the histopathological features, the diagnosis was lymphoepithelioma-like carcinoma, pT3N0 stage. In situ hybridization for Epstein–Barr virus showed no nuclear signal in tumor cells. The p53 expression was observed in fewer than 10% of the tumor cells. Real-time PCR analysis showed microsatellite instability without K-ras mutation in codon 12. No recurrences or metastases were reported 6 months after surgical intervention. No adjuvant therapy was performed.     

FISSURE SEALANT IN A NUTSHELL. EVIDENCE-BASED META-EVALUATION OF SEALANTS’ EFFECTIVENESS IN CARIES PREVENTION AND ARREST

ObjectiveThis meta-evaluation aimed to summarize all available evidence regarding different fissure sealants on occlusal caries prevention, arrest, retention rate, adverse effect, and cost-effectiveness; when compared with no intervention, other preventive or minimally-invasive procedures.Materials and MethodsThe systematic reviews and meta-analyses were identified via four electronic databases and manual searching. Two independent reviewers performed study selection, data extraction, quality assessment with AMSTAR-2.ResultsAmong the 366 records yielded, 38 systematic reviews were identified as eligible 24 of them included meta-analyses. Moderate evidence has supported the efficacies of resin-based sealants (RBS) in occlusal caries prevention, arrest and cost-effectiveness compared to no interventions. Low to very low certainty of evidence suggested similar effectiveness of glass-ionomer cements in caries prevention with RBS and more superior performance of resin infiltration in arresting non-cavitated occlusal lesions.ConclusionThis meta-evaluation supports the use of RBS on permanent molars to reduce occlusal caries occurrence, arrest lesion progression and alleviate oral health inequalities between individuals of different socioeconomic status. This meta-evaluation also advocates further research on glass-ionomer cements and resin infiltration with respect to their efficacies in caries prevention and arrest.     

Narrative representations of caregivers and self in maltreated pre-schoolers

This study examined narrative representations of parents and of self, as well as child behavior during the assessment, in maltreated (N = 56) and demographically comparable non-maltreated (N = 37) pre-school-aged children in a one-year longitudinal study. Maltreated children evidenced more negative representations of parents and of self at Time 2, including the juxtaposition of both a negative and a grandiose self. Over time there was a marginal interaction such that maltreated children portrayed fewer disciplining parent representations and nonmaltreated children portrayed more. Also over time, maltreated children portrayed marginally more grandiose self-representations and nonmaltreated children fewer. Furthermore, maltreated children demonstrated less responsivity to the examiner over time and nonmaltreated children demonstrated more. The deleterious effects of maltreatment on representations of self and of others, especially as development proceeds, are discussed, and the importance of providing attachment-informed intervention prior to the consolidation of these negative representations is highlighted.     

Pilot study of Sandostatin (octreotide) therapy of refractory HIV-associated diarrhea

Seventeen AIDS patients were enrolled in a prospective open-label dose-finding study of octreotide (Sandostatin) therapy for refractory diarrhea. Five were nonevaluable due to progression of AIDS symptomatology, and one was excluded because of lack of confirmation of HIV infection. Five of 11 evaluable patients responded to therapy (45%); two each at 50 g and 100 g, and one at 250 g thrice daily doses. A sixth patient demonstrated a moderate reduction in stool volume at 250 g thrice daily, which, although deemed clinically relevant, did not meet the criteria for response. On discontinuation of therapy, diarrhea recurred in all patients within 1–12 days, and responded to reinitiation of octreotide in those five patients who resumed treatment. Only one of the three patients with concurrent cryptosporidial infection responded to treatment. The drug was well tolerated, with mild symptomatology in three patients. Long-term treatment at a stable dose was effective in three of five treated patients for periods for seven months in one (moderate responder) and one year in two. One patient required dose increases to control symptoms, but after one year of treatment developed severe nausea following injections, which required dose cessation. One patient had partial control of his diarrhea for only three months despite two dose increases. These data suggest that octreotide may be of useful therapeutic value in HIV-associated diarrhea and that further studies are indicated.This study was supported by Sandoz Canada Inc.     

Dental caries status of Dai preschool children in Yunnan Province,China

Background

The Dai people, one of the ethnic minorities in China, have a population of 1,260,000. They have the same origin as one of the main ethnic groups of Laos and Thailand. Most of the Dai live in Yunnan province, which is located in the less-developed southwestern part of China. This study aimed to describe the oral health status of Dai preschool children in China and the factors that influence their oral health status.

Methods

An oral health survey was performed between 2011 and 2012 to select Dai five-year-old children using multi-stage stratified sampling in Yunnan. Their dental caries experience was measured using the “dmft” index, and severe caries was assessed using the “pa” index, which is modified from the “pufa” index. Oral hygiene status was assessed using the visual plaque index (VPI). A questionnaire to study the children’s socio-demographic background and oral health-related behaviours was completed by the children’s parents.

Results

A total of 833 children were examined. Their caries prevalence was 89% and 49% of the children had carious tooth with pulp involvement. The mean (SD) dmft score was 7.0 (5.3). Higher dmft scores were found among children who were girls, were currently bottle-fed, took daily sweet snacks, had higher VPI scores, and had visited a dentist within the last year.

Conclusions

The caries prevalence and experience of the five-year-old Dai children in Yunnan, China was high, and almost half had severe caries. The caries experience was associated with gender, snack habits, dental visit habits, and oral hygiene status.