Efficacy of cryotherapy as first line therapy in patients with Barrett's neoplasia: a systematic review and pooled analysis.

Cryotherapy has been used as salvage therapy; however, its efficacy as first line treatment in patients with Barrett's esophagus (BE) neoplasia has not been well studied. The aim of this paper was to perform a systematic review to look at the efficacy of cryotherapy as the primary treatment of BE. An electronic database search was performed (PubMed, Embase, Cochrane, and Google Scholar) to search for studies with cryotherapy as the initial primary modality of ablation in patients with BE neoplasia. Studies that included patients with other prior forms of therapy were excluded. The primary outcomes were the pooled rates of complete eradication of intestinal metaplasia (CE-IM) and CE of neoplasia (CE-N). Secondary outcomes were recurrence rates of neoplasia and intestinal metaplasia (IM) and adverse events. The statistical software OpenMetaAnalyst was used for analysis with pooled estimates reported as proportions (%) with 95% confidence intervals (CI) with heterogeneity (I2) among studies. The search revealed 6 eligible studies with a total of 282 patients (91.5% male, average age 65.3 years) with 459 person years of follow-up. 69.35% [95% CI (52.1%-86.5%)] of patients achieved CE-IM and 97.9% (95% CI: 95.5%-100%) had CE-N. 7.3% of patients had persistent dysplasia with 4% progressing to cancer. The recurrence rate of neoplasia was 10.4 and that of IM was 19.1 per 100 patient years of follow-up. The overall rate of stricture formation was 4.9%. There are scarce data on the use of cryotherapy as the primary modality for the treatment of BE dysplasia. The published data demonstrate efficacy rates of 69% and 98% for complete eradication of metaplasia and neoplasia, respectively. These results need to be assessed in prospective, comparative trials with other forms of therapy.

Energy restriction suppresses microsomal Ca(2+)-ATPase activities in various organs in C57BL/6 female mice in both euthermic and torpor states.

C57BL/6 female mice were fed a daily control diet (n = 5, 3.9 g/day, 95 kcal/week) or ER diet (n = 5, 2.3 g/day, 48 kcal/week) at 1800 h from 6 weeks of age. Telemetry, conducted at 6 months of age, confirmed that all ER mice entered daily torpor (core body temperature less than 31 degrees C) for 6.63 +/- 2.34 h/day while control mice were euthermic (> 35 degrees C). In vitro activities of microsomal Ca(2+)-ATPase were determined in the brain, liver, salivary gland and kidney from these mice at 6 months of age. Assays were performed at three incubation temperatures of 37 degrees C, 31 degrees C and 25 degrees C. In assays at 37 degrees C, the activities of Ca(2+)-ATPase in the brain and salivary gland from ER mice were lower than those in corresponding organs from control mice. The suppression became profound as the incubation temperature decreased. On the other hand, at 37 degrees C Ca(2+)-ATPase activities in the liver and kidney from ER mice were not lower than those in corresponding organs from control mice, but decreased significantly at low temperatures. Microsomal Ca(2+)-ATPase activities thus appeared to be reduced in ER mice, although it remains unknown whether the present results represent reduced in vivo capacities to regulate cytosolic Ca2+ concentrations.

alpha-Hydroperoxy diethyl peroxide, an unusual natural compound isolated from an ascidian (Phallusia mammillata): acute toxicity in DDY mice.

alpha-Hydroperoxy diethyl peroxide, a novel compound found in the tunic of ascidians, has two peroxide moieties per molecule. Since ascidians are a widely served food item in Japan, human exposure to this compound potentially exists in the seafood preparation industries. No toxicological data have so far been published on this compound, and so we determined the intraperitoneal 6-day LD50 in mice and conducted histopathological examinations. The 6-day LD50 was found to be 199 mg/kg with 95% confidence limits of 126-314 mg/kg. Histopathological examination revealed necrosis induced in a variety of cells that had been directly exposed to the compound. These cells included hepatocytes, parenchymal pancreatic cells and fat cells. It is concluded that direct contact with this compound is likely to elicit cellular necrosis of various organs. The specific toxicological effects are probably dependent on the route of exposure.

[Basic knowledge on concussion in the German Ice Hockey League (DEL)]. / Wissensgrundlagen zur Gehirnerschütterung in der Deutschen Eishockey Liga (DEL).

OBJECTIVE: In professional ice hockey there is a high incidence of concussion. In order to implement preventative measures as well as to introduce a treatment concept it is necessary to analyse the basic knowledge about concussion of all participants and to identify aspects requiring additional educational measures. METHOD: By means of an internet-based questionnaire comprising 18 questions, trainers and co-trainers, sport directors, team physicians and team captains of all teams in the German ice hockey league were interviewed about their knowledge and impressions with regard to general knowledge, game-stop, protection, and training as well as their opinions about changing the penalty system. RESULTS: The response rate amounted to 57.8 %. Not only team physicians but also players, trainers and sport directors exhibited a good basic knowledge on concussion, duration of treatment and rehabilitation as well as possible long-term sequelae. There were only slight differences in knowledge between team physicians and not-medically trained personnel. This survey also revealed a broad support for educational measures about concussion and the possibility for rule changes to further protect the players. CONCLUSION: There appears to be an acceptable basic knowledge about concussion and its symptoms and no major underestimation of the problems. All participants were in favour of the provision of further information as well as the implementation of preventative measures.

O,O,S-Trimethyl phosphorothioate induces hypothermia in Fischer 344 rats in a manner dependent on both doses and housing temperatures.

We explored the effects of O,O,S-trimethyl phosphorothioate (OOS-TMP) on body temperatures in Fischer 344 female rats. The 7-day LD50 p.o. for Fischer 344 female rats was found to be 11.8 mg/kg. OOS-TMP induced long-lasting (more than 48 h) and extensive hypothermia at doses > or = 14 mg/kg at a typical laboratory temperature (22 degrees C) while it produced typical symptoms at 10 mg/kg without hypothermia. In contrast, pair-fed (to 20 mg/kg rats) rats (n = 4) did not become hypothermic, negating any role of hypophagia in OOS-TMP associated hypothermia. We next investigated the effects of housing temperatures on toxicities at a LD50 dose (12 mg/kg). At 30 degrees C (n = 11) and 22 degrees C (n = 13), rats did not have hypothermic bouts but at 15 degrees C, eight out of ten rats had. Evidence that changes of housing temperatures neither modified clinical symptoms nor changed mortality rates discards a possibility of hypothermia being involved in delayed toxicity. A novel result of the present study suggests that thermoregulation may be heavily impaired by a special class of organophosphorus compounds.

O,O,S-trimethyl phosphorothioate increases Ca2+ independent nitric oxide synthase activity in the lung but decreases Ca2+/calmodulin dependent type in the cerebellum in Fischer 344 rats.

In the present study, we investigated the possible role of nitric oxide synthase in lung injury using female Fischer 344 rats as a model animal and O,O,S-trimethyl phosphorothioate as an example of lung toxicants. One form of nitric oxide synthase, Ca2+/calmodulin dependent type, decreased monotonously in a dose-dependent manner in the cerebellum. In contrast, O,O,S-trimethyl phosphorothioate increased activities of Ca2+ independent nitric oxide synthase in the lung in a dose-associated manner from 5 mg/kg to 15 mg/kg, but decreased at 30 mg/kg. Lung toxicity of O,O,S-trimethyl phosphorothioate, however, as judged both by functional impairments (PaCO2 and [HCO3-]) and histopathological changes, increased sharply at 30 mg/kg. We thus tested the hypothesis that a potent nitric oxide synthase inhibitor, NG-nitro-L-arginine-methyl ester, may modify lung injury induced by O,O,S-trimethyl phosphorothioate. Treatment with NG-nitro-L-arginine-methyl ester at 20 mg/kg/day aggravated lung injury induced by O,O,S-trimethyl phosphorothioate: Pulmonary oedema and bleeding occurred, leading to an increase in mortalities at 15 mg/kg of O,O,S-trimethyl phosphorothioate, at which level it did not induce such changes as when dosed alone. These findings indicate that nitric oxide synthase in the lung might play a protective role in lung injury.

Electrophoresis of phosphoglycerate kinase-2 to determine testicular damage induced by ethylene glycol monomethyl ether and sterility associated with chromosomal abnormality.

Phosphoglycerate kinase (PGK, EC 2.7.2.3), which is expressed specifically in sperm and spermatids, is an enzyme in the Embden-Meyerhof pathway that converts glucose to pyruvate. We developed an electrophoresis method to determine relative PGK-2 quantity and applied it to evaluate spermatogenesis activity. In the ethylene glycol monomethyl ether (EGME)-induced testicular toxicity, relative PGK-2 quantity had not decreased until 4 weeks of exposure. Mean relative PGK-2 quantities, defined as PGK-2 quantity over PGK-1 quantity in a pooled spleen sample (+/- SD) were: 1.43 +/- 0.32 for control animals (N = 10); 1.67 +/- 0.24 for the group exposed at 500 mg/kg for 5 days (N = 6); 1.85 +/- 0.58 for the group exposed at 500 mg/kg for 2 weeks (N = 6); 0.09 +/- 0.06 for the group exposed at 500 mg/kg for 4 weeks (N = 6); not detectable in animals exposed at 500 mg/kg for 5 weeks (N = 7); 0.208 +/- 0.103 for the group exposed at 250 mg/kg for 5 weeks (N = 6); and 1.35 +/- 0.38 for the group exposed at 125 mg/kg for 5 weeks (N = 6). These relative quantities showed a good correlation with sperm/spermatid counts (r = 0.823, p less than 0.01) and histological findings. These findings suggest that EGME has toxicity on primary spermatocytes and spermatogonia. In the case of sterility associated with a chromosomal abnormality (chromosomal translocation between chromosome X and 16), relative PGK-2 quantity was not detected in any of the seven adult (12 weeks of age) mice, although many primary spermatocytes were detected by histological examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Stable Lyonization of X-linked pgk-1 gene during aging in normal tissues and tumors of mice carrying Searle's translocation.

We investigated whether age-dependent reactivation of a repressed X-linked gene occurs. Subjects were female mice, carrying the X-autosomal translocation, T(X;16)16H (Searle's translocation). The mice were also heterozygous, for the X-linked gene coding for phosphoglycerate kinase (T16H pgk-1b/+ pgk-1a and pgk-1a was selectively repressed in these mice (McMahon and Monk, 1983). An electrophoretic method was applied to determine the PGK-1 allozyme patterns in blood, bone marrow, brain, gastrointestinal tract, liver, heart, spleen, and uterus (including tumor tissues when found). Samples were collected from mice of three different ages: 2 months (n = 4), 11 to 12 months (n = 10), or 18 to 21 months (n = 15). The lowest detection limit of the relative cellular population expressing the PGK-1A allozyme was found to be 2%, which was sensitive enough to detect the reported reactivation ratio (more than 10% of cells in a lower power microscopic field). We could not detect PGK-1A activity in any organ, including tumors in any age group, leading to the conclusion that reactivation of the repressed pgk-1a gene did not occur during aging.

A direct involvement of the central nervous system in hypophagia and inhibition of respiratory rate in rats after treatment with O,O,S-trimethyl phosphorothioate.

O,O,S-Trimethyl phosphorothioate (OOS-TMP) is known to induce unique symptoms, which are characterized by hypophagia, progressive weight loss, and hypothermia. To determine whether there is the possibility of a causal relationship between these toxic symptoms and a direct action of OOS-TMP on the central nervous system, we investigated the development of these symptoms in Fischer 344 female rats after oral or intracerebral treatment with OOS-TMP. Oral administration of OOS-TMP at 20 mg/kg induced marked hypophagia, progressive weight loss and hypothermia. Moreover, inhibition of respiratory rate was observed immediately after treatment. It lasts during the entire experimental period. Profound hypothermia below 34 degrees C was observed more frequently in the rats, which became hypercapnic (PaCO2 > or = 50 mmHg). In contrast, administration of OOS-TMP at 20 mg/kg (as much as the oral dose) into the cerebral lateral ventricle succeeded in inducing hypophagia, progressive weight loss and lowered respiratory rates. On the other hand, by this route of administration, OOS-TMP at 20 mg/kg failed to induce hypothermia, hypercapnia and lung injury. The present results suggest that hypophagia and inhibitions of respiratory rate are attributable to the direct action of OOS-TMP on the central nervous system, while other symptoms are associated with lung injury.

Peutz-Jeghers syndrome. Association of duodenal and bilateral breast cancers in the same patient.

A female patient with Peutz-Jeghers syndrome successively developed bilateral breast carcinoma and malignant transformation of a duodenal hamartomatous polyp, from which she died.