Determination of extent of formaldehyde-induced crosslinking in hard gelatin capsules by near-infrared spectrophotometry

PURPOSE: To predict the degree of crosslinking from formaldehyde-stressed hard gelatin capsules (HGCs) using near-infrared spectrophotometry (NIR). METHODS: HGCs were exposed to a 150 ppb atmosphere of formaldehyde for 2.25, 4.60, 9.42, 16.0 and 24.0 hours. The capsules were filled with fresh amoxicillin, placed in a 90 degrees conical reflector cone, and scanned in a NIR spectrophotometer. Principal component regression (PCR) was employed to analyze the spectra of the intact capsules. Dissolution profiles were then obtained for each experimental group. RESULTS: The dissolution of amoxicillin from the capsules at pH 1.2 was found to decrease with increasing time of exposure to the formaldehyde atmosphere. A set of principal components (PCs) was formed by a linear combination of the absorbance values at each wavelength scanned. A good correlation was established (r2 = 0.963) when PC values from the NIR spectra of the HGCs were regressed against percentage of amoxicillin dissolved at 45 minutes, at pH 1.2. Water content of the capsules was found to be the largest determinant in the variation between HGC spectra at each exposure time. CONCLUSIONS: NIR spectrophotometry, combined with PCR, was successful at not only predicting dissolution of HGCs exposed to formaldehyde, but also at determining which wavelengths contributed most to spectral variation of these stressed HGCs.     

Being a stroke patient: a review of the literature

The purpose of this paper is to review the research literature on the patient's experience of stroke. Four qualitative studies on how patients experience stroke were identified. The findings of these studies show that the stroke patient often has clear goals for himself in relation to functional abilities, against which he measures all success and forward progress in his rehabilitation. Even though the stroke patient accepts a lower level of functional ability, he is not willing to accept the rehabilitation professionals' prediction of his ultimate functional level if it is lower than his own goal. Furthermore, stroke patients see recovery as a return to the existence they had lived before the stroke, which is different from the health care providers' view. To the health care provider, recovery is measured in terms of isolated and discrete return of movement, whereas in the eyes of the patients, recovery is a return to previously valued activities. Further, studies on psychosocial function after stroke were reviewed. Recent studies show that the psychological impact of the stroke experience is immense and that stroke patients experience stress on a variety of levels. Also, depression exists in a large portion of the stroke population. The impact of stroke also influences the patient's social existence, as studies have shown that stroke patients do manifest diminished social function. However, the reviewed studies are not without limitations. Further studies, with a qualitative design, are needed to throw light on the patient's experience of being ill with stroke, and the process of his recovery.     

A new silver sulfadiazine water soluble gel

Silver sulfadiazine is the most commonly used topical antibacterial agent for the treatment of burn wounds. It has many clinical advantages, including a broad spectrum of antimicrobial activity, low toxicity, and minimal pain on application. The current formulation of silver sulfadiazine contains a lipid soluble carrier, polypropylene glycol, that has certain disadvantages, including pseudo-eschar formation and the need for twice daily application. The purpose of this investigation was to describe a new formulation of silver sulfadiazine in a water soluble gel, poloxamer 188. The antibacterial activity of this new gel has been compared to that of the commercially available silver sulfadiazine cream by in vitro and in vivo testing. The results of the in vitro antibacterial testing of these two different agents demonstrated the superiority of the new gel formulation. In experimental wounds, the antibacterial activity of the gel and the commercially available silver sulfadiazine cream were not significantly different when applied once a day. The antibacterial activity of the gel when applied once a day was comparable to that encountered by twice daily applications of the silver sulfadiazine cream by experimental wounds. The major advantage of this gel was its ease of application and removal that is attributed to its water solubility.     

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.