Intestinalization of pancreatic fragments in dogs: improvement in survival rate after acute segmental pancreatitis

Intestinalization, a new method of pancreatic preservation in which vascularized pancreatic fragments are placed inside a jejunal pouch, has been tested for its effectiveness in the prevention of shock and death due to segmental pancreatitis. Intestinalization of the fragment resulted in the survival of eight of nine animals (89 percent) in which recovery was uneventful, whereas animals with pancreatitis in situ or in a mobilized fragment without intestinalization had a mortality rate of 100 percent within 2 days. We conclude that intestinalization ameliorates the outcome of hemorrhagic pancreatitis in the pancreatic fragment by effectively draining toxic products. The procedure may also be useful in pancreatic transplantation since no reintervention is necessary if graft failure or rejection occurs because the pancreas is accessible by endoscopy.     

Antiviral Activities of Selected Medicinal Plants II: Effect of Extracts of Diospyros barteri,Diospyros monbutensis and Sphenocentrum jollyanum on Cowpea Mosaic Viruses

The hexane and methanol extracts of various morphological parts of Diospyros barteri Hiern, Diospyros monbutensis Gurke and Sphenocentrum jollyanum Pierre were screened for their effectiveness in the control of four mosaic viruses affecting cowpea (CMeV, CYMV, BICMV, and CABMVa). The methanol leaf extract of D. barteri at 1mgml –i concentration level was found to be more effective in the control of Cowpea Aphid-Borne Mosaic Virus (CABMVa - Onne strain) than all the other viruses investigated. Further investigation to prove the effectiveness of the D. barteri methanol leaf extract was carried out serologically by using the ELISA technique. The ELISA results confirmed the effectiveness of the D. barteri methanol leaf extract in the control of CABMVa (Onne strain) at 1mgml –i concentration level.     

Evaluation of Occlusal Splint Therapy

Occlusal splints have been widely used in dentistry for treating craniomandibular disorders, yet the precise effect that splints have on symptoms is still undetermined. When the available research evidence is closely scrutinized it is found to be weak and generally unsupported. Most studies are lacking in sound research design and often draw conclusions that are unsubstantiated. Recognizing these weaknesses, this article proposes a research design that will effectively evaluate treatment effects through rigid, well-controlled, and accurately documented experimentation. Using this research design clinically may be a difficult task. However, incorporation of one or more of the suggested parameters will help to strengthen any research proposal.     

Dyspnea assessment and management in hospice patients with pulmonary disorders

Accurate assessments and appropriate management of dyspnea are essential to provide improved quality of life for hospice patients. This study describes methods of assessing dyspnea and interventions used to manage dyspnea in 72 hospice patients with end-stage lung disease or lung cancer. The mean age of the sample was 72.46 years old and the majority was white (80 percent) and male (62 percent). Paired t-tests were used to compare mean scores on admission and near death for dyspnea severity, Karnofsky functional status, pain, and Mini-Mental Status scores. Results showed significant decline in functional and cognitive status, but no significant changes in dyspnea severity and pain. Dyspnea was often assessed subjectively with observational methods only. Use of inhalants, oxygen, positioning, steroids, and oral opioids were the most frequent therapies for dyspnea. Relaxation, guided imagery, and other complementary therapies were rarely used (five percent or less). Measurement of dyspnea needs to be done frequently by using standardized instruments to assess severity and degree of symptom distress as well as the effects of treatment. Clinical trials are needed to determine which dyspnea interventions are most effective in terminally ill patients. Guidelines such as those developed for pain management are needed for effectively managing dyspnea.     

Epidemiology of smoking among Kuwaiti adults: prevalence, characteristics, and attitudes

INTRODUCTION: In 1996 we conducted a cross-sectional survey to study the epidemiology of smoking among Kuwaiti adults. METHODS: The 4000 participants were selected using a three-stage stratified cluster sampling design. Altogether 3859 participants (1798 males, 2061 females) returned a completed self-administered questionnaire. RESULTS: The prevalence of smoking was 34.4% (95% confidence interval (CI) = 32.2-36.6) among men and 1.9% (95% CI = 1.3-2.5) among women. Among men, the highest prevalence (56.5%; 95% CI = 36.2-76.8) was observed in the youngest age group (< or = 20 years). Among women the highest prevalence was observed in one of the older age groups (46-50 years) (7.1%; 95% CI = 3.1-11.1). Multiple logistic regression analysis showed that the following factors were independently associated with smoking: lower levels of education (odds ratio (OR) 3.5; 95% CI = 1.5-8.4), lower employment grade (OR = 4.1; 2.5-6.7), and being a separated, divorced, or widowed woman (OR = 4.9; 95% CI = 2.0-11.8). The majority of smokers (68%) began smoking when younger than 20 years; significantly more men (70%) than women (33%) began smoking at these ages (P < 0.0001). On average, men began smoking at an earlier age (18 years vs 21 years; P < 0.001) and therefore had smoked for a longer period (15 years vs 12 years; P < 0.05); men also consumed a higher number of cigarettes each day (26 vs 17; P < 0.05). A large proportion of smokers were ignorant about the health consequences of passive smoking: about 77% of those with children reported that they smoked in the presence of their children. Almost half (47%) of all smokers stated that they wanted to stop smoking, and about 56% had attempted to quit. The biggest perceived barrier to quitting was uncertainty about "how to quit". A total of 338 respondents (8.8%; 95% CI = 5.8-11.9) were classified as former smokers. About half of the former smokers had quit between the ages of 20 and 29 years; the average age of quitting was 28 years. Former smokers were more likely to have smoked fewer cigarettes per day and to have smoked for significantly less time than current smokers. DISCUSSION: Given the fact that free education is provided at all levels by the government, anti-tobacco education and awareness should be included as an integral part of the curriculum in schools and colleges.     

Modifying rates of reductive elimination of leaving groups from indolequinone prodrugs: a key factor in controlling hypoxia-selective drug release

3-(4-Methylcoumarin-7-yloxy)methylindole-4,7-diones were synthesised as model prodrugs in order to investigate the correlation between rates of reductive elimination from the (indolyl-3-yl)methyl position with reductive metabolism by hypoxic tumor cells and NADPH: cytochrome P450. Rates of elimination of the chromophore/fluorophore (7-hydroxy-4-methylcoumarin) following one-electron reduction of indolequinones to their semiquinone radicals (Q*-) was measured by pulse radiolysis utilising spectrophotometric and fluorometric detection. Incorporation of a thienyl or methyl substituent at the (indol-3-yl)CHR-position (where R=thienyl or methyl adjacent to the phenolic ether linking bond) significantly shortened the half-life of reductive elimination from 87 to 6 and 2 ms, respectively. Elimination from the methyl substituted analogue can thus compete effectively with the reaction of the semiquinone radical with oxygen at levels typically present in tumours (half-life approximately 1.8 ms at 0.5% O2). Chemical kinetic predictions were confirmed by metabolism in breast tumour MCF-7 cells between 0-2.1% O2. Rates of reductive release of the fluorophore from the non-fluorescent parent indolequinones (R=H, Me, thienyl) were similar under anoxia ( approximately 1.7 nmol coumarinmin(-1)mg protein(-1)) reflecting the similarity in one-electron reduction potential. Whereas coumarin release from the indolequinone (R=H) was completely inhibited above 0.5% O2, the enhanced rate of reductive elimination when R=thienyl or Me increased the metabolic rate of release to approximately 0.35 and 0.7 nmol coumarinmin(-1)mg protein(-1), respectively at 0.5% O2; complete inhibition occurring by 2.1% O2. Similar 'oxygen profiles' of release were observed with NADPH: cytochrome P450 reductase. In conclusion, it is possible to modify rates of reductive elimination from indolequinones to control the release of drugs over a range of tumour hypoxia.     

Quantitative analysis of selegiline and three metabolites (N-desmethylselegiline,methamphetamine, and amphetamine) in human plasma by high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry

This report describes a sensitive and specific high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry method for the detection of subnanogram concentrations of selegiline and its three principle metabolites, N-desmethylselegiline, methamphetamine, and amphetamine, in human plasma. The assay has a dynamic range of 0.1-20 ng/mL for selegiline and N-desmethylselegiline (norselegiline) and 0.2-20 ng/mL for methamphetamine and amphetamine. The inter- and intra-assay precision and accuracy varied by less than 11% for all analytes at 0.3, 2.5, and 15 ng/mL and less than 16% at the lower limit of quantitation (0.1 ng/mL for selegiline and norselegiline; and 0.2 ng/mL for methamphetamine and amphetamine). Selegiline and its metabolites showed no significant loss in quantitative accuracy after three freeze/thaw cycles or after up to 6 h at room temperature prior to extraction. Extracted plasma samples retained quantitative accuracy after storage for at least 7 days at -20 degrees C or up to 70 h at room temperature. Methanolic stock solutions were stable for at least 6 h when kept at room temperature or at least 90 days when kept at -20 degrees C.     

Neurotensin causes tyrosine phosphorylation of focal adhesion kinase in lung cancer cells

The effects of neurotensin on focal adhesion kinase were investigated using lung cancer cells. Neurotensin bound with high affinity to large cell carcinoma cell line NCI-H1299 as did neurotensin-(8-13), but not neurotensin-(1-7) or levocabastine. Addition of 100 nM neurotensin to NCI-H1299 cells caused transient tyrosine phosphorylation of focal adhesion kinase which was maximal after 1-2.5 min. Also, neurotensin-(8-13), but not neurotensin-(1-8) or levocabastine, caused tyrosine phosphorylation of focal adhesion kinase after addition to NCI-H1299 cells. Focal adhesion kinase tyrosine phosphorylation caused by neurotensin was inhibited by the nonpeptide neurotensin receptor antagonist (2-(1-(7-chloroquinolin-4-yl)-5-(2,6-dimethoxyphenyl)-1H-pyrazole-3-carbonyl)amino)-adamantane-2-carboxylic acid) (SR48692). SR48692 inhibited the clonal growth of NCI-H1299 cells, whereas neurotensin-stimulated proliferation and levocabastine had no effect. These results indicate that lung cancer cells have functional neurotensin receptors which regulate focal adhesion kinase tyrosine phosphorylation. It remains to be determined if neurotensin receptors and focal adhesion kinase plays a role in lung cancer cellular adhesion and migration.     

Developmental toxicity of levo-alpha-acetylmethadol (LAAM) in tolerant rats

Mated Crl:CD VAF/Plus female rats, in a range-finding study (n = 5-6 per dose) and a subsequent definitive study (n = 30 per dose) were used to determine the developmental toxicity, including the teratogenic potential of levo-alpha-acetylmethadol (LAAM) hydrochloride, in tolerant rats. Tolerance was induced by initially administering the drug by gavage (10 ml/kg) at 2 mg/kg/day and increasing the dose every 2 weeks for 12 weeks until the doses of 2, 6, 9, 12, and 15, or 2, 6, and 12 mg/kg/day were achieved in the range-finding or definitive study, respectively. Females were then mated to stock males and treated throughout mating and gestation. Controls received distilled water on a similar regimen. The range-finding experiment was used for initial clinical evaluations and to determine tissue concentrations of LAAM and metabolites. In plasma, liver, and brain collected from dams and fetuses pooled by litter on gestation day 20, LAAM and its two N-demethylated metabolites, norLAAM and dinorLAAM, showed dose-dependent increases in concentration and in tissue to plasma ratios. Tissue to dam plasma ratios were highest in dam liver (17-60), intermediate in fetal liver (3-16), and fetal brain (3-14), and lowest in dam brain (0.8-5.6) and fetal plasma (0.3-2.1). In the definitive study, caesarean section examinations were performed following euthanization on gestation day 20 on all surviving females followed by teratologic examination of the fetuses. Drug-related outcomes, including increased activity, secondary hair loss, scabbing, focal swelling, and material around the nose, were exhibited by all groups receiving LAAM. Maternal toxicity was evident as decreased body weights, with maximum reduction at the 6-mg/kg/day dose, and reduction in feed consumption. There was also evidence of developmental toxicity in the form of postimplantation losses at all doses of LAAM. There were no deaths attributable to LAAM. No grossly observable visceral or skeletal anomalies related to LAAM were observed in the fetuses. In conclusion, the no-observable-effect level when administered to tolerant rats was less than 2 mg/kg/day with regard to clinical signs, body weight, body weight gain, and feed consumption, and with regard to developmental toxicity as reflected by postimplantation losses. Despite maternal and developmental toxicity, there was no evidence of selective fetal toxicity or teratogenic activity attributable to LAAM.