Resolution of a left ureteral stone using electrohydraulic lithotripsy in a thoroughbred colt

A 3-year-old Thoroughbred colt was presented for evaluation of azotemia and anorexia. Physical examination revealed a ureterolith in the left ureter, approximately 10 cm from the bladder, which was thought to obstruct urine flow by approximately 90% when viewed cystoscopically. Ultrasonographic examination of both kidneys revealed indistinct corticomedullary junctions, and the right kidney was more hyperechoic. A percutaneous biopsy of the right kidney revealed chronic interstitial nephritis with marked interstitial medullary fibrosis. Medical therapy consisting of IV fluids, sodium chloride PO, and ammonium chloride PO was initiated. Ureteroscopic electrohydraulic lithotripsy via a perineal urethrostomy was used to successfully remove the stone. Klebsiella oxytoca, which responded to oral enrofloxacin therapy, was cultured from the urine after surgery. Azotemia resolved and the horse resumed training.     

Population dynamics of the deer mouse (Peromyscus maniculatus) and Sin Nombre virus, California Channel Islands

Alteration of the wild-type (wt) p53 gene by mutation, deletion or re-arrangement is a major factor in the development of human colon cancer. Recent studies have demonstrated that p53 might be an essential component of the apoptotic pathway triggered by DNA-damaging stimuli such as chemotherapeutic agents and ionizing radiation. We examined the anti-tumor effects of adenovirus-mediated wt-p53 gene transfer in combination with a chemotherapeutic drug on the human colon cancer cell line WiDr, which is homozygous for a mutation in the p53 gene. Treatment with the chemotherapeutic drug cisplatin following infection with a replication-deficient, recombinant adenoviral vector expressing wt-p53 (termed AdCMVp53) significantly suppressed the growth of WiDr cells compared to single treatments alone. To evaluate the in vivo efficacy of AdCMVp53 and cisplatin given sequentially, WiDr cells were inoculated s.c. in nu/nu mice. After 3 days, AdCMVp53 was injected s.c. into the area where tumor cells were implanted, followed by i.p. administration of cisplatin. Analysis of initial growth inhibition at 21 days demonstrated a profound therapeutic cooperativity, though administration of either AdCMVp53 or cisplatin alone was followed only by a slowing of growth. Our results suggest that gene therapy using wt-p53-expressing adenovirus in combination with a chemotherapeutic DNA-damaging drug could be a useful strategy for treating human colon cancer.     

Locus heterogeneity for Waardenburg syndrome is predictive of clinical subtypes

Waardenburg syndrome (WS) is a dominantly inherited and clinically variable syndrome of deafness, pigmentary changes, and distinctive facial features. Clinically, WS type I (WS1) is differentiated from WS type II (WS2) by the high frequency of dystopia canthorum in the family. In some families, WS is caused by mutations in the PAX3 gene on chromosome 2q. We have typed microsatellite markers within and flanking PAX3 in 41 WS1 kindreds and 26 WS2 kindreds in order to estimate the proportion of families with probable mutations in PAX3 and to study the relationship between phenotypic and genotypic heterogeneity. Evaluation of heterogeneity in location scores obtained by multilocus analysis indicated that WS is linked to PAX3 in 60% of all WS families and in 100% of WS1 families. None of the WS2 families were linked. In those families in which equivocal lod scores (between -2 and +1) were found, PAX3 mutations have been identified in 5 of the 15 WS1 families but in none of the 4 WS2 families. Although preliminary studies do not suggest any association between the phenotype and the molecular pathology in 20 families with known PAX3 mutations and in four patients with chromosomal abnormalities in the vicinity of PAX3, the presence of dystopia in multiple family members is a reliable indicator for identifying families likely to have a defect in PAX3.     

Effect of a neoprene sleeve on knee joint position sense during sitting open kinetic chain and supine closed kinetic chain tests

The primary objective of the present study was to compare the effect of a neoprene sleeve on knee joint position sense during a sitting open kinetic chain test and a supine closed kinetic chain test. Young (24 +/- 2 years old), healthy subjects (18 men and 18 women) performed knee joint angle replication tests during open kinetic chain knee extension (sitting) and closed kinetic chain leg press (supine with an axial load of 15% body weight) before and after application of a neoprene sleeve over the dominant knee. The improvement in ability to replicate joint angles after application of the sleeve (sleeve effect) was significantly less during the supine closed kinetic chain test (0.3 degree +/- 1.4 degrees) than during the sitting open kinetic chain test (1.2 degrees +/- 1.1 degrees). The sleeve effect was inversely related to subjects' performance without the sleeve during both the sitting open kinetic chain and supine closed kinetic chain tests, suggesting that some people may derive greater benefit from the sleeve than others. Although the sleeve effects were small, particularly during the supine closed kinetic chain test, 72% of subjects felt that the sleeve improved their overall test performance. Future research is needed to establish the functional relevance of the small sleeve effects observed and to identify the characteristics of people who might derive greatest benefit from sleeve use.     

High levels of spontaneous and parasite antigen-driven interleukin-10 production are associated with antigen-specific hyporesponsiveness in human lymphatic filariasis

To determine whether counterregulation by interleukin (IL)-10 plays a role in the generation or maintenance of the antigen-specific hyporesponsiveness seen in asymptomatic microfilaremic (MF) patients, parasite antigen (PAg)- and nonparasite antigen (NPAg)-driven IL-10 production by peripheral blood mononuclear cells (PBMC) was studied in 10 MF patients and in ll patients with chronic lymphatic pathology (CP). PBMC from MF patients spontaneously secreted 10-fold more IL-10 than did PBMC from patients with CP. PAg also induced significantly more IL-10 production by PBMC from CP patients. There was a negative correlation between PAg driven IL-10 production by PBMC and PAg-specific T cell proliferation in the MF group. IL-10 secretion by plastic adherent cells from MF persons was higher in response to PAg than NPAg, whereas IL-6 and tumor necrosis factor-alpha secretion were equivalent for PAg and NPAg, suggesting that PAg preferentially induces IL-10 secretion in these cells. Thus, PAg-induced IL-10 likely plays an important role in down-regulating antigen-specific proliferative responses in MF patients.     

A method for radiologic-assisted gastrostomy when percutaneous endoscopic gastrostomy is contraindicated

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) has been established as a faster and safer procedure than open surgical gastrostomy. It cannot be done, however, for many patients with partially obstructing pharyngeal or esophageal carcinoma, previous gastrectomy, upper abdominal surgery, or bowel distension from distal obstruction. PATIENTS AND METHODS: We attempted percutaneous radiologic-assisted gastrostomy (RAG) in 231 patients referred for gastrostomy, 38 of whom had a relative contraindication for PEG. The procedure involves passing, under radiologic guidance, an orogastric inflation tube that contains a snare. We used a 5-inch long, 18-gauge needle to transabdominally insert a wire into the stomach, avoiding loops of bowel visualized by air contrast. Retrieving the transabdominal wire by snare allowed retrograde passage of the gastrostomy tube as done in standard PEG. RESULTS: The procedure was successful in 230 of 231 cases, including 37 of the 38 patients with contraindications. We could not gain gastric access in 1 patient with a 75% gastrectomy. Overall, 6 patients developed complications and 1 died. There was no procedure-related morbidity or mortality in the patients with contraindications to PEG who underwent successful RAG. Subsequent laparotomy indicated tube passage through the liver in 2 of these cases and small bowel mesentery in 1 case without clinical problems. We performed a percutaneous jejunostomy in the efferent limb of the gastrojejunostomy in 1 patient with a previous gastrectomy. CONCLUSION: The snare technique is simpler and faster than the usual radiologic gastropexy technique, and safer than an endoscopic procedure. It has become our procedure of choice for gaining gastric access.     

Inactivation of O6-alkylguanine-DNA alkyltransferase. 1. Novel O6-(hetarylmethyl)guanines having basic rings in the side chain

A number of novel guanine derivatives containing heterocyclic moieties at the O6-position have been synthesized using a purine quaternary salt which reacts with alkoxides under mild conditions. Initially O6-substituents were investigated in which the benzene ring of the known agent, O6-benzylguanine, was replaced by unsubstituted heterocyclic rings. The ability of these agents to inactivate the DNA repair protein O6-alkylguanine-DNA alkyltransferase (ATase), both as pure recombinant protein and in the human lymphoblastoid cell line Raji, has been compared with that of O6-benzylguanine. The present paper focuses on O6-substituents with basic rings, and under standard conditions several of them proved more effective than benzyl for inactivation of both recombinant and Raji ATase. Among the pyridine derivatives, the 2-picolyl compound 7 is not very active in contrast to the 3- and 4-picolyl compounds, and this influenced our choice of isomers of other basic ring systems for study. Since halogen substitution in the thiophene ring considerably increased the activity (17 versus 6), similar modifications in the pyridine series were examined. The more polar O6-substituents in this study are on the whole compatible with the stereochemical requirements of the ATase protein, and their pharmacological properties may be valuable in subsequent in vivo investigations, particularly the thenyl (6), 5-thiazolylmethyl (12), 5-bromothenyl (17), and 2-chloro-4-picolyl (21) derivatives.     

Wall effects observed in tissue-equivalent proportional counters from 1.05 GeV/nucleon iron-56 particles

A strong overlap between P-glycoprotein (Pgp) and cytochrome P450 3A (CYP3A) substrates and modulators has been reported. To test the hypothesis that CYP3A and Pgp are coordinately regulated, we examined the effects of known inducers of CYP3A (triacetyloleandomycin, rifampicin, dexamethasone, pregnenolone 16alpha-carbonitrile) on Pgp expression in rat liver. We also investigated the gender-specific expression of Pgp and compared its response to dexamethasone between male and female rats. In male rats, western blot analyses showed that rifampicin and dexamethasone caused 50% and 5-fold increases in Pgp levels, respectively. RNase protection assays using gene-specific probes for the three Pgp isoforms revealed a 3-fold increase in mdr2 mRNA levels after dexamethasone administration and a 2-fold increase following rifampicin treatment. Triacetyloleandomycin and pregnenolone 16alpha-carbonitrile had no effect on Pgp expression and mRNA levels. We also observed that the basal level of Pgp was 40% lower in male rats than in females and that mdr2 mRNA levels in male rats were one-half those in females. As opposed to the results in male rats, dexamethasone reduced Pgp expression by approximately 60% and caused a 30% decrease in mdr2 mRNA levels in female rats. Mdr1a was not affected and mdr1b was not detected in female or male rats. We conclude that, at the dosage regimen used, CYP3A and Pgp responses to CYP3A inducers are regulated independently in rat liver. In addition, this study shows that Pgp expression and regulation are gender specific.     

Prophylactic effect of Korean mistletoe (Viscum album coloratum) extract on tumor metastasis is mediated by enhancement of NK cell activity

We here demonstrated the prophylactic effect of an extract (KM-110) from Viscum album coloratum, a Korean mistletoe, on tumor metastasis produced by highly metastatic tumor cells, colon 26-M3.1 carcinoma, B16-BL6 melanoma and L5178Y-ML25 lymphoma cells, using experimental models in mice. Intravenous (i.v.) administration of KM-110 (100 microg/mouse) 2 days before tumor inoculation significantly inhibited lung metastasis of B16-BL6 and colon 26-M3.1 cells, and liver and spleen metastasis of L5178Y-ML25 cells. The prophylactic effect of KM-110 on tumor metastasis was evident with various administration routes, i.e. subcutaneous, oral, intranasal as well as i.v., and was dependent upon the dose of KM-110 administered. Furthermore, mice given KM-110 (100 microg) 2 days before tumor inoculation showed significantly prolonged survival rates compared with the untreated mice. In a time course analysis of NK activity, i.v. administration of KM-110 (100 microg) significantly augmented NK cytotoxicity to Yac-a tumor cells from 1 to 3 days after KM-110 treatment. Furthermore, depletion NK cells by injection of rabbit anti-asialo GM1 serum completely abolished the inhibitory effect of KM-110 on lung metastasis of colon 26-M3.1 cells. These results suggest that KM-110 possesses immunopotentiating activity which enhances the host defense system against tumors, and that its prophylactic effect on tumor metastasis is mediated by NK cell activation.