Birth-cohort phenomenon in the time trends of mortality from ulcerative colitis

It has been suggested that the mortality trends of ulcerative colitis in England and Wales are shaped by an underlying birth-cohort phenomenon. This pattern implies that exposure to an environmental risk factor early in life plays a crucial role in the development of the disease. The authors tested whether the birth-cohort pattern is unique to British mortality statistics or a common feature of ulcerative colitis in western countries by using the vital statistics from England and Wales, Canada, Scotland, Switzerland, The Netherlands, and the United States. Ulcerative colitis death rates from the six countries were plotted against the periods of death or periods of birth. Mortality from ulcerative colitis increased in successive generations born throughout the second half of the 19th century. It peaked in subjects born between 1880 and 1890 and has declined since then. Strikingly similar patterns were found in the six countries and when women and men were analyzed separately. The birth-cohort pattern indicates that development of ulcerative colitis is strongly influenced by one or several environmental risk factors, which act during a short period early in life. In western countries, exposure to this risk has changed in a similar fashion.     

A double-blinded evaluation of propacetamol versus ketorolac in combination with patient-controlled analgesia morphine: analgesic efficacy and tolerability after gynecologic surgery

We assessed the relative morphine consumption in a combined analgesic regimen (on-demand morphine plus the nonopioids propacetamol or ketorolac) after gynecologic surgery. Two hundred women randomly received two i.v. doses of propacetamol 2 g or ketorolac 30 mg in a double-blinded, double-dummy trial. Patients were monitored for 12 h, and the following efficacy variables were assessed: total dose of morphine, pain intensity, and global efficacy. Safety and tolerability were evaluated by the occurrence of adverse events, especially the presence and intensity of gastrointestinal symptoms. Hemostatic variables were measured 30 and 60 min after the first infusion; arterial blood pressure, heart and respiratory rates, sedation scores, and renal and hepatic function were also assessed. Total morphine requirements were not significantly different between the propacetamol (10.6 +/- 4.8 mg) and ketorolac (10.2 +/- 4.4 mg) groups. The evolution of pain intensity and the global efficacy also showed similar patterns in the two groups: 70.2% of patients in the propacetamol group rated the efficacy as "good/ excellent" compared with 68.2% in the ketorolac group. There were no clinically significant changes in vital signs or laboratory values and no observed differences between the two groups, although ketorolac slightly, but not significantly, prolonged the bleeding time. Epigastric pain was present in 9% and 15% of patients receiving propacetamol and ketorolac, respectively. There were two adverse events in the propacetamol group and four in the ketorolac group. Propacetamol demonstrates an efficacy similar to that of ketorolac and has an excellent tolerability after gynecologic surgery. IMPLICATIONS: Propacetamol and ketorolac, combined with patient-controlled analgesia morphine, show similar analgesic efficacy after gynecologic surgery. Morphine consumption and pain scores were comparable in the two studied groups. Propacetamol is as effective as ketorolac and has an excellent tolerability after gynecologic surgery.     

Silent occult choroidal vascular abnormalities

PURPOSE: To describe clinically occult choroidal vascular abnormalities that can be revealed by indocyanine green (ICG) angiography. METHODS: Out of approximately 2,700 patients who underwent ICG angiography, a lesion was incidentally observed in eight eyes of eight patients. In five patients, the ICG study included a second examination taken during artificially induced intraocular hypertension. Examinations were repeated in six patients over a follow-up period ranging from 4 months to 3 years. RESULTS: On ICG angiogram, the choroidal vasculopathy appeared as a round-oval hyperfluorescent area 2-4 disk diameters in size that was located at the temporal vascular arcades in six eyes, at the inferomacular region in one eye, and above the optic disk in one eye. The lesions were not identifiable with funduscopic, fluorescein angiographic, or ultrasonographic examination. The lesions filled at the same time as the choroidal arteries and lost fluorescence in mid-late phase of the ICG angiogram. The ICG series taken during induced intraocular hypertension showed the hyperfluorescent areas originated from choroidal arterial abnormalities giving rise to confluent hyperfluorescent patches. Draining vessels connecting the choroidal vasculopathy with a vortex vein were evidenced in three eyes. A sector of apparent choroidal hypoperfusion downstream from the lesion was present in three eyes. During the follow-up period, the lesions remained occult and with an unchanged ICG angiographic pattern in all patients. CONCLUSION: Some silent occult choroidal vascular abnormalities may be incidentally revealed by ICG angiography. These must be distinguished from ICG imaging of concomitant chorioretinal disorders.     

Use of acetylcysteine as the life-saving antidote in Amanita phalloides (death cap) poisoning. Case report on 11 patients

alpha-Amanitin is an amatoxin known to produce deleterious effects on the liver and the kidneys, when circulating in the blood. It is produced by a particular kind of mushroom called amanita phalloides. Therapeutic options employed to treat mushroom intoxication, such as haemodiaperfusion on activated charcoal, high dosages of penicillin G, oral charcoal, etc., very often failed to act properly and liver transplantation (when a graft is available) appeared to be the only solution. In recent years, as suggest by some authors, it has been postulated that the oxidant effects of alpha-amanitin could be counteracted by the use of antioxidants such as silibinin. High dosages of N-acetyl-cysteine (CAS 616-91-1, NAC), already used as antioxidant in paracetamol poisoning, were successfully used in our Intensive Care Unit (ICU) in the treatment of Amanita phalloides poisoning. In the last two years, 11 patients (mean age of 5-72 = 38.5) were treated for Amanita phalloides poisoning of various degrees, with a protocol (haemodiaperfusion on activated charcoal, high dosages of penicillin G, etc.) further comprehending NAC (fluimucil). All the patients recovered successfully but one (bearing precedent liver disease) needed liver transplantation. Daily monitoring of liver enzymes, creatinine, coagulation, LDH, blood and urinary alpha-amanitin were used to screen the progresses of the patients.     

Nociceptin and the ORL-1 ligand [Phe1psi (CH2-NH)Gly2]nociceptin(1-13)NH2 exert anti-opioid effects in the Freund's adjuvant-induced arthritic rat model of chronic pain

1 Stimulation of the opioid receptor-like1 (ORL-1) receptor by nociceptin (NC) produces hyperalgesia and reverses the antinociceptive effects induced by opioids. Most studies concerning the central effects of NC were conducted using acute pain models. The role NC may play in chronic inflammation remains unelucidated. 2 The present study was undertaken to assess the action of NC in the Freund's adjuvant-induced monoarthritic rat model. The effects of drugs known to act as analgesics in this model were evaluated. The effects of NC, NCNH2, and the ORL-1 ligand, [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 ([F/G]NC(1-13)NH2), were also studied alone or in association with morphine. 3 NC (1 - 30 nmol, i. c.v.) was inactive, whilst NCNH2 (10 nmol, i.c.v.) exerted hyperalgesic effects (-4.5+/-0.9 vs -0.7+/-0.8 s of vehicle-treated animals). [F/G]NC(1-13)NH2 (0.01 - 10 nmol, i.c.v.) induced hyperalgesia in the arthritic paw (-3.3+/-0.6 vs -0.3+/-0.5 s of vehicle-treated animals; 10 nmol). 4 Both NC (0.01 - 10 nmol, i.c.v. ) and [F/G]NC(1-13)NH2 (0.01 - 1 nmol, i.c.v), 30 min after morphine (3 mg kg-1, s.c.) induced an immediate and short-lived reversal of morphine effects (2.6+/-0.3 vs 10.4+/-1.0 and 1.2+/-1.5 vs 9.3+/-1.1 s of morphine alone, respectively), therefore displaying anti-opioid activity. 5 In the Freund's adjuvant-induced rat model of arthritis, both NC and [F/G]NC(1-13)NH2 act as anti-opioid peptides. Furthermore, NCNH2 and [F/G]NC(1-13)NH2 induce hyperalgesia when given alone. Further investigations and the identification of a centrally acting ORL-1 antagonist are necessary to better understand the role of NC in pain mechanisms.     

Clinical pharmacokinetics of tacrolimus in heart transplant recipients

We report pharmacokinetic data on tacrolimus in 14 heart transplant patients (2 women, 12 men). The median age and the median body weight were 55.5 years (range, 23-61 years) and 67.0 kg (55-79 kg), respectively. All patients were maintained on a triple-drug protocol (tacrolimus, azathioprine, and prednisone), with a 7-day antithymocyte globuline induction. The first tacrolimus dose, administered orally 1 to 5 days posttransplant, ranged from 0.03 to 0.4 mg/kg (median = 0.052 mg/kg). The maintenance dose ranged from 0.03 to 0.13 mg/kg/day (administered in two equal doses) to achieve blood levels of 5 of 20 ng/ml, as determined by a microparticle enzyme immunoassay (MEIA). Whole blood samples were drawn just before, at 0.5 hour, and at 1, 2, 3, 4, 6, 8, 10, and 12 hours after the administration of the first dose; trough levels were measured thereafter.The mean oral clearance (CL/F) and apparent volume of distribution (Vd/F) averaged 0.21+/-0.08 L/hour/kg and 2.4+/-0.8 L/kg while the half-life averaged 8.7+/-3.5 hours. Tacrolimus accumulation index during chronic therapy (Rac = Cmin(steady state)/Cmin(first dose) normalized to the same dose) averaged 1.3. Eighty-eight percent of the trough blood levels measured in our patients were within 5 and 20 ng/ml. The incidence of rejection in the study population was extremely low: a prevalence of grade 2 rejection or more, of 0.4+/-0.8 episodes/ patient was observed after a follow-up period of 8.8+/-2.2 months. Only one patient experienced severe renal toxicity, probably because of his preoperative precarious hemodynamic status. Pharmacokinetic data suggest that maintenance tacrolimus daily dose should be equal to 0.1 mg/kg/day to obtain trough blood concentrations of approximately 10 ng/ml. Inter- and intra-patient variability of tacrolimus blood concentration should be expected and justify careful monitoring.     

Vertical subcutaneous pedicle flaps for posterior perineal reconstruction

PURPOSE: Loss of a certain amount of cutaneous tissue of the perineal region may be remedied by first intention with creation of cutaneous flaps, thus preventing second intention healing. METHODS: We present three emblematic cases in which the posterior perineal region was reconstructed by means of vertical subcutaneous pedicle flaps, subsequent to cutaneous tissue loss after surgery for extensive condilomas or neoplastic pathologies. RESULTS: Tissue loss was repaired by means of a V-Y type vertical subcutaneous pedicle flap, constructed laterally of the extirpation zone and advanced in a median direction. In all cases, no ischemia or infection of flaps occurred; sphincteral continence and long-term aesthetic results have proved to be satisfactory. CONCLUSIONS: Vertical pedicle subcutaneous flaps are well vascularized, extremely mobile, and easy to perform and have no serious postoperative complications.     

Lung metastases from follicular thyroid cancer: a report of a clinical case and a review of the literature

The authors report a case of follicular thyroid cancer in "hot nodule" with micronodular synchronous lung metastases. The treatment consisted in TT associated with radioiodine therapy at the dose of 170 mCi with remission of cancer after six months of follow-up. Follicular variant is a prognostic unfavorable factor such as synchronous or metachronous pulmonary metastases. In those patients prognostic unfavorable variants are also age over 40 years, a poor radiofixation capacity, and a lesion of diameter up 1 cm. A strictly instrumental follow-up is mandatory to obtain diagnosis in a subclinical stage. In such cases the radiometabolic therapy agree to a remission of cancer with high survival after many years. TT yet represents a "minimal" surgical treatment for an accurate radioisotopic diagnosis.