Surgical technique. Intracorporeal laparoscopic-guided feeding jejunostomy.

Laparoscopic feeding jejunostomy is a safe and reproducible method of establishing enteral feeding in patients in whom percutaneous endoscopic gastrostomy is contraindicated. Current technology enables the jejunostomy to be achieved within the peritoneal cavity, without retrieval of the small bowel through the abdominal wall. This quick and simple technique is described.     

An assessment of clinical guidelines for the management of acute pancreatitis.

BACKGROUND: Recent guidelines have been issued for the management of acute pancreatitis. The aim of this study was to audit the management of acute pancreatitis in one district general hospital, to determine the problems and benefits associated with the implementation of such guidelines. METHODS: Data were collected over the period 1991-1995 for all patients diagnosed as having acute pancreatitis who were admitted to one district general hospital. Data regarding severity grading, determination of aetiology and treatment of mild and severe pancreatitis were analysed in conjunction with the recommendations issued by the British Society of Gastroenterology Working Party on the management of acute pancreatitis in 1995. RESULTS: A total of 210 patients were admitted on 263 occasions; 16% of cases were severe but severity prediction was inaccurate. 56.1% had gallstone pancreatitis and 20.9% had idiopathic pancreatitis. Definitive treatment of gallstones was within the recommended time limit in only 70.1%. 27 patients experienced recurrent attacks of pancreatitis before definitive treatment of their gallstones, due either to inadequate investigation for gallstones after suboptimal ultrasound examination (n = 12) or to inappropriate delay before definitive treatment of gallstones (n = 15). Recommendations for the management of severe cases with early ITU/HDU admissions and CT scanning were not followed. 28 day mortality was 6.3%, median age of those dying was 80.5 years. CONCLUSIONS: Acceptable mortality can be achieved for acute pancreatitis despite failure to implement BSG guidelines for the management of severe acute pancreatitis. Inadequate investigation and treatment of gallstone disease leads to an unacceptable incidence of recurrent acute pancreatitis.     

Consequences of prolonged wait before gallbladder surgery

The aim of this study was to document the morbidity associated with long waiting times for laparoscopic cholecystectomy and to relate this to the nature of initial presentation either routine out-patient consultation or emergency admission with acute symptoms. This study was performed over a 50-month period in a DGH (serving a population of 320,000) which lacked sufficient operating capacity to allow routine early cholecystectomy after emergency admission. A total of 387 patients underwent cholecystectomy but 22 of these had an early operation after initial emergency admission with signs of peritonitis and were excluded from the study. The median waiting time for cholecystectomy in this study population of 365 patients was 170 days (range, 6-484) days. Of these 365 patients, 246 (67.4%) were listed for surgery after initial out-patient assessment (out-patient cohort) and 119 (32.6%) were diagnosed after an index emergency admission with symptomatic gallstone disease (emergency cohort). Of the 365 patients, 42 (11.5%) had one or more emergency admissions (57 admissions) with gallstone-related complications whilst on the waiting list for surgery. Complications were acute cholecystitis/biliary colic (n = 40), jaundice/cholangitis (n = 8), acute pancreatitis (n = 6) and perforated gallbladder (n = 3). Re-admissions with gallstone-related complications were much more common in patients whose initial presentation had been as an emergency. Thus, 34 of the 119 emergency cohort (28.5%) required re-admission with complications whilst only 8 of 246 (2.8%) elective cohort were re-admitted. Of the 34 re-admissions in the emergency cohort, 22 occurred within 6 weeks of their discharge from hospital. Median total and postoperative stay were significantly shorter (P < 0.001) in the elective cohort (3 and 2 days, respectively) than the emergency cohort (10 and 3 days, respectively). These results document the high incidence of complications experienced by patients waiting for an elective laparoscopic cholecystectomy. Morbidity is highest in patients with an initial emergency admission. These results suggest that cholecystectomy should be offered to all patients presenting as an emergency with symptomatic gallstones on admission.     

Oral cancer screening: Practices, knowledge, and opinions of dentists working in Ohio nursing homes

The state of oral health of nursing homes residents is less than satisfactory. The oral health care in nursing homes is also deficient, therefore it is likely that oral cancer (OC) screening of residents will be inadequate. The purpose of this cross-sectional study was to determine OC screening practices, knowledge, and opinions of dentists working in nursing homes throughout Ohio. A 28-item pretested questionnaire was mailed to 75 dentists who were serving 606 nursing homes.
The response rate was 49%. The main outcome measures of interest included: OC screening practices of the Ohio dentists, their knowledge of OC detection, and their opinions regarding OC screening competency. Age was found to be a significant factor, with younger dentists being more likely to have higher knowledge scores after adjusting for all other covariates.     

The in vitro pharmacology of the peripherally restricted opioid receptor antagonists,alvimopan, ADL 08-0011 and methylnaltrexone

This study characterized the pharmacology of the peripherally restricted opioid receptor antagonists, alvimopan, its metabolite, ADL 08-0011, and methylnaltrexone. The activities of the compounds were investigated with respect to human or guinea pig opioid receptor binding and function in recombinant cell lines and mechanical responsiveness of the guinea pig ileum. Alvimopan and ADL 08-0011 had higher binding affinity than methylnaltrexone at human μ opioid receptors (pK _i values of 9.6, 9.6, and 8.0, respectively). The compounds had different selectivities for the μ receptor over human δ and guinea pig κ opioid receptors. ADL 08-0011 had the highest μ receptor selectivity. With respect to their μ opioid receptor functional activity ([³⁵S]GTPγS incorporation), methylnaltrexone had a positive intrinsic activity, consistent with partial agonism, unlike alvimopan and ADL 08-0011, which had negative intrinsic activities. Alvimopan, ADL 08-0011, and methylnaltrexone antagonized inhibitory responses mediated by the μ opioid agonist, endomorphin-1 (pA ₂ values of 9.6, 9.4, and 7.6, respectively) and by U69593, a κ opioid agonist (pA ₂ values of 8.4, 7.2, and 6.7, respectively). In morphine-naive guinea pig ileum, methylnaltrexone reduced, while alvimopan and ADL 08-0011 increased, the amplitude of electrically evoked contractions and spontaneous mechanical activity. In tissue from morphine-dependent animals, alvimopan and ADL 08-0011 increased spontaneous activity to a greater degree than methylnaltrexone. The data suggested that alvimopan-induced contractions resulted predominantly from an interaction with κ opioid receptors. It is concluded that alvimopan, ADL 08-0011, and methylnaltrexone differ in their in vitro pharmacological properties, particularly with respect to opioid receptor subtype selectivity and intrinsic activity. The clinical significance of the data from this study remains to be determined.     

Plasma inflammatory biomarkers in cerebral small vessel disease: A review

Cerebral small vessel disease (CSVD) is a group of pathological processes affecting small arteries, arterioles, capillaries, and small veins of the brain. It is one of the most common subtypes of cerebrovascular diseases, especially highly prevalent in elderly populations, and is associated with stroke occurrence and recurrence, cognitive impairment, gait disorders, psychological disturbance, and dysuria. Its diagnosis mainly depends on MRI, characterized by recent small subcortical infarcts, lacunes, white matter hyperintensities (WMHs), enlarged perivascular spaces (EPVS), cerebral microbleeds (CMBs), and brain atrophy. While the pathophysiological processes of CSVD are not fully understood at present, inflammation is noticed as playing an important role. Herein, we aimed to review the relationship between plasma inflammatory biomarkers and the MRI features of CSVD, to provide background for further research.     

Effect of eye pigmentation on transscleral drug delivery

PURPOSE: To determine the influence of eye pigmentation on transscleral retinal delivery of celecoxib. METHODS: Melanin content in ocular tissues of both the strains was determined by sodium hydroxide solubilization METHOD: The affinity of celecoxib to synthetic and natural melanin was estimated by co-incubating celecoxib and melanin in isotonic phosphate-buffered saline. The binding affinity (k) and the maximum binding (r(max)) for celecoxib to both natural and synthetic melanin were estimated. Suspension of celecoxib (3 mg/rat) was injected periocularly into one eye of Sprague-Dawley (SD, albino) and Brown Norway (BN, pigmented) rats. The animals were euthanatized at the end of 0.25, 0.5, 1, 2, 3, 4, 8, or 12 hours after the drug was administered, and celecoxib levels in ocular tissues (sclera, choroid-RPE, retina, vitreous, lens, and cornea) were estimated with an HPLC assay. In addition, celecoxib-poly(lactide) microparticles (750 microg drug/rat) were administered periocularly in SD and BN rats, and celecoxib levels in these eye tissues were assessed on day 8, to determine the effectiveness of the sustained release system. RESULTS: The r(max) and k for celecoxib's binding to natural melanin were (3.92 +/- 0.06) x 10(-7) moles/mg of melanin and (0.08 +/- 0.01) x 10(6) M(-1), respectively. The affinity and the extent of celecoxib's binding to natural melanin were not significantly different from those observed with synthetic melanin. The concentrations of melanin in choroid-RPE, sclera, and retina of BN rats were 200 +/- 30, 12 +/- 4, and 3 +/- 0.2 mug/mg tissue, respectively. Melanin was not detectable in the vitreous, lens, and cornea of BN rats. In SD rats, melanin was not detected in all tissues assessed except in the choroid-RPE, wherein melanin-like activity was 100-fold less than in BN rats. The area under the curve (AUC) for tissue concentration versus time profiles for animals administered with celecoxib suspension was not significantly different between the two strains for sclera, cornea, and lens. However, the retinal (P = 0.001) and vitreal (P = 0.001) AUCs of celecoxib in the treated eyes were approximately 1.5-fold higher in SD rats than in BN rats. Further, the choroid-RPE AUC in the treated and untreated eyes, respectively, were 1.5-fold (P = 0.001) and 2-fold (P = 0.0001) higher in BN rats than in SD rats. With celecoxib-poly(lactide) microparticles, choroid-RPE, retina, and vitreous concentrations on day 8 exhibited similar trends in differences between the two strains, with the differences being greater than those recorded for the celecoxib suspension. CONCLUSIONS: Transscleral retinal and vitreal drug delivery of lipophilic celecoxib is significantly lower in pigmented rats than in albino rats. This difference may be attributable to significant binding of celecoxib to melanin and its accumulation/retention in the melanin-rich choroid-RPE of pigmented rats. The hindrance of retinal and vitreal drug delivery by the choroid-RPE in pigmented rats is also true of sustained-release microparticle systems.