Individual inactivation of the sphincteric component of the gastroesophageal barrier causes reflux esophagitis in piglets

Background/Purpose: The lower esophageal sphincter and the diaphragmatic crural sling form the gastroesophageal barrier. This work shows that division of the sphincteric component alone suffices to induce reflux esophagitis in piglets. Methods: Male piglets underwent either sham operation (n = 7) or extramucosal myotomy of the gastroesophageal junction (n = 8). Before and 1 week after the operation, pull-through manometry was performed under sedation. Pressures taken on the 4 quadrants at 20 1-mm intervals on both time endpoints were compared by pairwise Wilcoxon tests. The distal esophagus was studied histologically after 8 weeks. Results: The pressure profiles did not change after sham operation. In contrast, they were significantly flattened in the distal half of the high-pressure zone after myotomy reflecting disappearance of the sphincteric component of the barrier. Esophagitis was seen in all myotomized piglets but in none from the sham group. Conclusions: Lower esophageal sphincter myotomy alone with preservation of the crural sling induces reflux esophagitis in piglets. This animal, widely available and not too costly, is an excellent model for gastroesophageal research.     

Management of odontoid fractures using anterior screw fixation: analysis of 15 cases

A retrospective analysis of the results of 15 patients with odontoid fractures type II P and II N, according to Roy-Camille's classification is presented. They were operated on by an anterior approach and direct fixation of the odontoid process through a screw. There were 13 men and 2 women, the age ranging from 14 to 74 years. The follow up period was from 6 to 36 months (mean 20 months). There was only one complication related to the surgical technique: one screw was misplaced and it was necessary another surgery to replace it. There were no deaths in this series. There were no screw breakdown and the fusion rate was 94%. We propose, based on this study, that the classification of Roy-Camille for odontoid fractures should be always used, since it proposes one surgical approach for each type of fracture. The results of this series show that this technique is useful and has advantages over another modalities of treatment. The correct diagnosis of the type of fracture and an appropriate selection of patients are the main elements to achieve good results.     

Aldosterone acts on the kidney,not the brain,to cause mineralocorticoid hypertension in sheep

OBJECTIVE : To determine the extent to which mineralocortioid hypertension depends on a direct action of aldosterone on the kidney or on the brain. METHODS : Studies were performed in conscious sheep that were previously uninephrectomized, implanted with silastic cannulae in the renal artery of the remaining kidney, and had guide tubes implanted over the lateral cerebral ventricles. The effect of aldosterone, infused either intrarenally (i.r.; 2 microg/h) or intravenously (i.v.; 2 and 10 microg/h) for 10 days (n = 5), on arterial pressure and fluid and electrolyte balance was determined. The i.r. (2 microg/h) and i.v. (10 microg/h) doses were calculated to give similar intrarenal concentrations of aldosterone. In a further study, the effect of intracerebroventricular (i.c.v.) infusion of aldosterone (2 microg/h for 21 days) on arterial pressure was examined (n = 5). RESULTS : Infusion of aldosterone caused a progressive increase in mean arterial pressure from 83 +/- 3 mmHg to a maximum of 100 +/- 4 mmHg (P < 0.001) with 2 microg/h i.r. and from 84 +/- 3 mmHg to a maximum of 104 +/- 4 mmHg (P < 0.001) with 10 microg/h i.v., both by day 7. With both infusions there were similar increases in plasma [Na+] and decreases in plasma [K+] and total protein concentration (P < 0.05) between days 3 and 5; these were maintained throughout the infusion. There were no significant changes with i.v. aldosterone (2 microg/h). Long-term i.c.v. infusion of aldosterone (2 microg/h for 21 days) caused no change in arterial pressure. CONCLUSIONS : In conscious sheep the hypertensive response to aldosterone resulted from an action on the kidney, with no evidence for a direct action on the brain.     

Safety and usefulness of transesophageal echocardiography in the acute phase of myocardial infarction

INTRODUCTION AND OBJECTIVES: The usefulness and safety of transesophageal echocardiography have been assessed in other studies but there is no report in which these factors have been evaluated in the acute phase of myocardial infarction.Patients and method. Transesophageal echocardiography was performed 56 times in 55 patients in the first week after a myocardial infarction. RESULTS: The study was completed in 54 of 56 patients. The indications were a transthoracic acoustic window that did not provide an accurate diagnosis in 13 (23.2%), diagnosis of mechanical complications and severity assessment of mitral regurgitation in 35 (62.5%), exclusion of aortic dissection in 4 (7.1%), assessment of the severity of aortic stenosis in 1 (1.8%), exclusion of the presence of atrial thrombus in 1 (1.8%), evaluation of the left ventricular outflow tract gradient in 1 (1.8%), and evaluation of the presence of a left ventricular thrombus in 1 patient (1.8%). Two patients (3.6%) died while the study was being made, the first one 10 minutes after finishing the echocardiogram due to progression of a partial rupture of the papillary muscle and the second due to left ventricle free wall rupture. In both patients, the indication for transesophageal echography was the need for proper evaluation of a post-Acute Myocardial Infarction mechanical complication. CONCLUSIONS: Transesophageal echocardiography is a very useful technique for evaluating patients during the acute phase of myocardial infarction but further studies are needed to establish its safety in these patients.     

Design and synthesis of long-chain arylpiperazines with mixed affinity for serotonin transporter (SERT) and 5-HT(1A) receptor

A new generation of antidepressant agents could be represented by compounds with mixed activity as serotonin transporter (SERT) inhibitors and 5-HT(1A) receptor antagonists. We report here on the synthesis and evaluation of SERT and 5-HT(1A) receptor affinity of long-chain arylpiperazines obtained either by modifying 6-nitroquipazine into a long-chain arylpiperazine or by inserting a modified 6-nitroquipazine moiety or other structures endowed with SERT affinity into a long-chain arylpiperazine with 5-HT(1A) affinity. Among the compounds studied, 2-[4-(2-methoxyphenyl)piperazin-1-yl]-N-(6-nitro-2-quinolyl)ethylamine (21) and 1-(5-bromo-1,2,3,4-tetrahydronaphthalen-1-yl)-3-[4-(2-methoxyphenyl)-piperazin-1-yl]-1-propanone (24) showed good affinity values for SERT and 5-HT(1A) receptors (SERT: K(i) (inhibition constant)=71.8 and 62.8 nM; 5-HT(1A)K(i)=14.2 and 0.82 nM, respectively).     

Effects of prenatal vitamins A, E, and C on the hypoplastic hearts of fetal rats with diaphragmatic hernia

Background/Aim

Nitrofen induces heart hypoplasia together with congenital diaphragmatic hernia (CDH) in rats. Intracellular oxidative stress might be one of the mechanisms of action of the teratogen, and vitamin A has been shown to reverse in part these effects when administered simultaneously or shortly after it. This study aims at testing the hypothesis that vitamin A and other antioxidant vitamins, such as E and C, could improve myocardial development even when administered late in gestation, a likely useful period for prenatal medication.

Material and Methods

Time-mated Sprague-Dawley female rats were exposed to either vehicle (control) or 100 mg of nitrofen (experimental) on day 9.5 of gestation. In 3 additional groups, the animals were exposed to vitamin A (total 15 000 IU), vitamin E (total 150 IU), or vitamin C (total 150 IU) on days 16, 17, and 18. The fetuses were recovered on day 21, and randomly selected hearts of those with CDH were processed for histologic studies (hematoxylin-eosin and periodic acid-Schiff stainings), DNA and protein contents, and ki-67 (proliferation) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling (apoptosis) studies. The differences among groups were assessed by analysis of variance with Bonferroni/Dunn post hoc tests and a threshold of significance of P < .05.

Results

Nitrofen induced heart hypoplasia in terms of decreased heart/body weight, cell mass (less DNA and protein), and proportion of proliferating cells with increased apoptosis. Vitamin C alleviated weight hypoplasia and the 3 vitamins were able to restore cell mass and to reestablish near-normal figures of proliferation and apoptosis.

Conclusions

Antioxidant vitamins A, E, and C given late in gestation alleviate heart hypoplasia that accompanies CDH in the rat model. This timing suggests that the beneficial effects are exerted on the maturational phase of development.     

Calf metastasis of colorectal cancer: report of a case

Colorectal cancer metastases rarely develop outside liver, lungs and lymph nodes, and only exceptionally in skeletal muscle. The very low incidence of such metastasis sites may be due either to underestimation of the problem or to their intrinsic rarity. We report a case of metastasis from colorectal cancer that developed in the left calf and manifested itself as a painful non-fluctuating mass. The relevant literature is also reviewed.     

New insights into cystinuria: 40 new mutations, genotype-phenotype correlation, and digenic inheritance causing partial phenotype

Objective: To clarify the genotype–phenotype correlation and elucidate the role of digenic inheritance in cystinuria. Methods: 164 probands from the International Cystinuria Consortium were screened for mutations in SLC3A1 (type A) and SLC7A9 (type B) and classified on the basis of urine excretion of cystine and dibasic amino acids by obligate heterozygotes into 37 type I (silent heterozygotes), 46 type non-I (hyperexcretor heterozygotes), 14 mixed, and 67 untyped probands. Results: Mutations were identified in 97% of the probands, representing 282 alleles (86.8%). Forty new mutations were identified: 24 in SLC3A1 and 16 in SLC7A9. Type A heterozygotes showed phenotype I, but mutation DupE5-E9 showed phenotype non-I in some heterozygotes. Type B heterozygotes showed phenotype non-I, with the exception of 10 type B mutations which showed phenotype I in some heterozygotes. Thus most type I probands carried type A mutations and all type non-I probands carried type B mutations. Types B and A mutations contributed to mixed type, BB being the most representative genotype. Two mixed cystinuria families transmitted mutations in both genes: double compound heterozygotes (type AB) had greater aminoaciduria than single heterozygotes in their family. Conclusions: Digenic inheritance is an exception (two of 164 families), with a limited contribution to the aminoaciduria values (partial phenotype) in cystinuria. Further mutational analysis could focus on one of the two genes (SLC3A1 preferentially for type I and SLC7A9 for type non-I probands), while for mixed probands analysis of both genes might be required, with priority given to SLC7A9.