Surgical treatment of calcinosis cutis in the upper extremity

Recent surgical experience with 11 cases of calcinosis cutis has given the authors an opportunity to define the role of surgery in the management of this condition. In scleroderma associated with dermatomyositis, when complications or disability arise from one or more areas of calcinosis, surgery may give significant palliation. Wound healing, although a potential problem, does not constitute a contraindication to operative treatment. Damage to deep structures usually is avoidable, but in some instances is a reasonable trade-off for the benefits obtained. Follow-up has confirmed that surgery is beneficial to patient comfort and function, even in the few patients in whom some calcinosis recurred.     

Anesthesia and sleep

Although both general anesthesia and naturally occurring sleep depress consciousness, distinct physiological differences exist between the two states. Recent lines of evidence have suggested that sleep and anesthesia may be more similar than previously realized. Localization studies of brain nuclei involved in sleep have indicated that such nuclei are important in anesthetic action. Additional observations that regional brain activity during anesthesia resembles that in the sleeping brain have raised the possibility that anesthesia may exert its effects by activating neuronal networks normally involved in sleep. In animals, behavioral interactions between sleep and anesthesia appear to support these mechanistic similarities. Rat studies demonstrate that sleep debt accrued during prolonged wakefulness dissipate during anesthesia. Moreover, anesthetic potency is subject both to circadian effects and to the degree of prior sleep deprivation. Such interactions may partly explain anesthetic variability among patients. Finally, sleep and anesthesia interact physiologically. Endogenous neuromodulators known to regulate sleep also alter anesthetic action, and anesthetics cause sleep with direct administration into brain nuclei known to regulate sleep. Together, these observations provide new research directions for understanding sleep regulation and generation, and suggest the possibility of new clinical therapies both for patients with sleep disturbances and for sleep deprived patients receiving anesthesia.     

Identification and staging of pancreatic tumours using computed tomography, endoscopic ultrasound and mangafodipir trisodium-enhanced magnetic resonance imaging

Pancreatic malignancy can be staged by a number of different investigations, either alone or in combination. The purpose of the present study was to compare the use of endoscopic ultrasound, CT and mangafodipir trisodium-enhanced MRI for the staging of pancreatic malignancy, particularly with respect to determining resectability prior to surgery. Twenty-seven patients referred for the investigation of a suspected pancreatic malignancy were entered into the trial. All patients had contrast-enhanced CT, gadolinium and mangafodipir trisodium-enhanced MRI, and endoscopic ultrasound (EUS). Images were assessed for nodal staging, tumour staging and resectability for each investigation, and the results compared with findings at surgery. The results for the accuracy of MRI, CT and EUS, in detecting T4 disease versus T3 or lower was 78, 79 and 68%, respectively; nodal involvement was 56, 63 and 69%, respectively; and overall resectability (including the T stage, presence of involved nodes and metastases) was 83, 76 and 63%, respectively. There was no significant difference demonstrated between the three tests. The present study suggests that for patients referred for investigation and staging of pancreatic malignancy, EUS and MRI scanning convey little advantage over contrast-enhanced CT. Furthermore, although mangafodipir trisodium improved the conspicuity of pancreatic tumours, it has little influence on T staging.     

Pharmacokinetics and subjective effects of sublingual buprenorphine, alone or in combination with naloxone: lack of dose proportionality

OBJECTIVE: Buprenorphine and buprenorphine/naloxone combinations are effective pharmacotherapies for opioid dependence, but doses are considerably greater than analgesic doses. Because dose-related buprenorphine opioid agonist effects may plateau at higher doses, we evaluated the pharmacokinetics and pharmacodynamics of expected therapeutic doses. DESIGN: The first experiment examined a range of sublingual buprenorphine solution doses with an ascending dose design (n = 12). The second experiment examined a range of doses of sublingual buprenorphine/naloxone tablets along with one dose of buprenorphine alone tablets with a balanced crossover design (n = 8). PARTICIPANTS: Twenty nondependent, opioid-experienced volunteers. METHODS: Subjects in the solution experiment received sublingual buprenorphine solution in single ascending doses of 4, 8, 16 and 32 mg. Subjects in the tablet experiment received sublingual tablets combining buprenorphine 4, 8 and 16 mg with naloxone at a 4 : 1 ratio or buprenorphine 16 mg alone, given as single doses. Plasma buprenorphine, norbuprenorphine and naloxone concentrations and pharmacodynamic effects were measured for 48-72 hours after administration. RESULTS: Buprenorphine concentrations increased with dose, but not proportionally. Dose-adjusted areas under the concentration-time curve for buprenorphine 32 mg solution, buprenorphine 1 6 mg tablet and buprenorphine/naloxone 16/4 mg tablet were only 54 +/- 16%, 70 +/- 25% and 72 +/- 17%, respectively, of that of the 4 mg dose of sublingual solution or tablet. No differences were found between dose strengths for most subjective and physiological effects. Pupil constriction at 48 hours after administration of solution did, however, increase with dose. Subjects reported greater intoxication with the 32 mg solution dose, even though acceptability of the 4 mg dose was greatest. Naloxone did not change the bioavailability or effects of the buprenorphine 16 mg tablet. CONCLUSION: Less than dose-proportional increases in plasma buprenorphine concentrations may contribute to the observed plateau for most pharmacodynamic effects as the dose is increased.     

Adenovirus infection in pediatric small bowel transplantation recipients

BACKGROUND: The purpose of this study was to determine the prevalence of adenoviral infection in pediatric small bowel transplantation (SBT) recipients, examine risk factors for progression to histologic disease, and examine the impact of adenovirus on outcome. METHODS: Beginning in July 2000, all SBT recipients had viral cultures for adenovirus, cytomegalovirus (CMV), and herpes simplex virus (HSV) obtained routinely during graft biopsies. The medical records were retrospectively reviewed for frequency and site of viral culture, types and doses of immunosuppressive drugs, episodes of rejection, histology of allograft biopsies, and other infections. Adenoviral isolates were typed by polymerase chain reaction and type-specific neutralization assays. RESULTS: All 14 SBT recipients who met enrollment criteria had evidence of adenoviral infection (intestinal graft, 13; liver graft, 1). Eight of 14 developed histologic disease with identifiable adenoviral intranuclear inclusions. In contrast, CMV enteritis was identified in only one patient, who subsequently also developed adenoviral disease. No other viruses were detected. Adenoviral cultures were first positive within 30 days of transplant in nine. Patients with histologic disease were more likely than those without to have received intensive corticosteroid therapy (P<0.007), had virus isolated from more than one site (P=0.03), and had persistent positive cultures (P<0.01). CONCLUSIONS: Adenovirus was commonly isolated from children undergoing intestinal transplantation. Progression to disease may be associated with more intensive immunosuppressive therapy and inability to clear virus.     

The pharmacology of cocaethylene in humans following cocaine and ethanol administration

BACKGROUND: Concurrent use of cocaine and alcohol results in formation of a cocaine homolog and metabolite-cocaethylene. METHODS: To characterize cocaethylene pharmacology, ten paid volunteer subjects were given deuterium-labeled (d(5)) cocaine (0.3, 0.6, and 1.2 mg/kg and cocaine placebo) by a 15-min constant rate intravenous injection 1 h after a single oral dose of ethanol (1 g/kg) or ethanol and cocaine placebo using a double-blind, crossover design. Six of the same volunteers subsequently received a 1.2 mg/kg dose of cocaine alone. A small (7.5 mg) nonpharmacologically active dose of deuterium-labeled cocaethylene-d(3) was concurrently administered with the cocaine to enable calculation of absolute cocaethylene formation and clearance. Plasma and urine cocaine, cocaethylene, and benzoylecgonine concentrations, physiologic and subjective effects were measured. RESULTS: When co-administered with ethanol, 17+/-6% (mean+/-S.D.) of the cocaine was converted to cocaethylene. Cocaethylene peak plasma concentrations and AUC increased proportionally to the cocaine dose. Ethanol ingestion prior to cocaine administration decreased urine benzoylecgonine levels by 48% and increased urinary cocaethylene and ecgonine ethyl ester levels. Subjects liked and experienced more total intoxication after the combination of cocaine and ethanol than after either drug alone. CONCLUSIONS: In the presence of ethanol, the altered biotransformation of cocaine resulted in 17% of an intravenous cocaine dose being converted to cocaethylene and relatively lower urinary concentrations of benzoylecgonine.