Clinical Relevance of Acute Pancreatitis in Allogeneic Hemopoietic Stem Cell (Bone Marrow or Peripheral Blood) Transplants

This study investigated the clinical relevanceof acute pancreatitis in allogeneic hemopoietic stemcell (bone marrow or peripheral blood) transplants(BMT). We studied 26 patients undergoing BMT. Thepreparative regimen was busulfan and cyclophosphamide in 17patients and total body irradiation and cyclophosphamidein 9 patients. Graft-versus-host disease (GVHD)prophylaxis consisted of cyclosporin A and short-term methotrexate in all 26 patients. The pancreaswas studied using amylase and lipase serum levels,abdominal contrast-enhanced tomography, and/orultrasound. Clinical and laboratory signs of acutepancreatitis were found in two patients with acutehepatointestinal GVHD, and in one patient with acutehepatic GVHD and cytomegalovirus infection. This patientdied of multiorgan failure, with interstitial acutepancreatitis at autopsy; the other two patients recoveredwith general supportive care and GVHD therapy. Wesuggest that in the patients with complications afterBMT, particularly acute hepatic/hepatointestinal GVHD, and cytomegalovirus infection, the possibilityof acute pancreatitis should be considered.     

Hepatitis C virus infection is associated with a higher incidence of cholestasis of pregnancy

To investigate a possible relationship between hepatitis C virus infection and cholestasis of pregnancy, we identified all cases of cholestasis of pregnancy (145/16,271) and hepatitis C virus infection (63/16,27 1) between January 1992 and December 1997. Serologic screening was performed universally. The rate of cholestasis of pregnancy was greater in women whose hepatitis C virus antibodies were positive rather than negative [15.9% (10/63) vs 0.8% (135/16,208),   P < 0.0011  . Among women with cholestasis of pregnancy, mean (standard deviation) gestational age at onset of symptoms and at delivery was significantly lower among women whose hepatitis C virus antibodies were positive compared with negative women: 28.9 (3.2) vs 34.3 (3–5) weeks,   P < 0.001  and 36–3 (0.9) vs 37.0 (1–6) weeks,   P = 0.03  , respectively. These findings suggest that early Occurrence of cholestasis of pregnancy may be an indication for serologic testing for hepatitis C virus.     

Action-potential-like depolarizations relieve opioid inhibition of N-type Ca2+ channels in NG108–15 cells

 The ability of action-potential-like waveforms (APWs) to attenuate opioid-induced inhibition of N-type Ca²⁺ channels was investigated in the neuroblastoma × glioma cell line NG108–15 using whole-cell voltage clamp methods. In in vitro differentiated NG108–15 cells, the opioid agonist [d-ala²]-methionine-enkephalin (DAME) reversibly decreased ω-conotoxin-GVIA-sensitive Ba²⁺ currents (N-type currents). Agonist-mediated inhibition of N-type currents could be transiently relieved by strong unphysiological depolarizing prepulses to +80 mV (facilitation). Significant facilitation was also achieved by conditioning the cell with a train of 15 APWs, which roughly mimicked physiological action potentials (1- to 6-ms-long depolarizations to +30 mV from a holding potential of –40 mV). The APW-induced facilitation depended on both conditioning pulse frequency and duration. Summation of the disinhibition produced by each APW was possible because reinhibition following repolarization to –40 mV was a much slower process (τ=88 ms) than the onset of facilitation at +80 mV (τ=7 ms). These results provide evidence that N-type Ca²⁺ channel facilitation may be a physiologically relevant process, and suggest that neuronal firing may relieve agonist-induced inhibition of N-type currents to an extent depending on both the shape of action potentials and the frequency of firing. Received: 14 September 1998 / Accepted: 29 September 1998     

Linguistic impairment after right cerebellar stroke: a case report

Increasing evidence suggests the involvement of the cerebellum in non-motor functions. We describe a patient who presented speech deficits after a right cerebellar infarction without other cognitive impairments. 99mTc-HMPAO single-photon emission computed tomography showed a marked hypoperfusion in the right cerebellar hemisphere, but did not show crossed cerebellar- cerebral diaschisis. The absence of neuroradiological evidence of structural supratentorial lesions supports the cerebellar role in modulating not only the motor system, but also higher order functions.     

DEXA analysis of Antega total hip prosthesis

Periprosthetic bone remodeling can be studied using dual-energy absorptiometry X-ray analysis (DEXA), the most precise and effective method for analyzing bone mineral density (BMD). However, in order to show significant differences in BMD using DEXA, it is necessary to use high resolution equipment, to demonstrate reproducibility of the examination, and to adopt statistical rigor in data analysis. We performed a longitudinal study using DEXA on a consecutive and homogeneous series of 40 patients (20 males and 20 females) who underwent total hip replacement. The patients received a cementless Antega prosthesis, of titanium alloy with a plasma spray covering. DEXA exams were performed 1, 4, 7, 12 and 24 months after surgery, and the images were analyzed in the areas of Gruen. Globally, BMD was significantly reduced at month 4 in reference to baseline (exam at month 1). At subsequent exams, BMD did not further decrease but was followed by a progressive recovery over the 2-year study. The recovery at 2 years (with respect to the 4-month exam) was statistically significant for female patients but not for males. No statistical differences in BMD were found between patients (60 years and > 60 years, nor for patients with different sized stems. For the individual zones of Gruen, the mineralometric behaviors for zones 2, 3, 5 and 6 were similar while that for zones 1 and 7 showed a particular behavior. The trend in variations of periprosthetic BMD observed in our population differs from that in the majority of studies published in the literature. Our longitudinal densitometric study has all the requisites to be considered reliable; a longer follow-up will strengthen our results which, already in the short term, are valid and support the use of the Antega stem in hip replacement surgery. Received: 14 January 2000/Accepted: 18 February 2000     

The influence of lipophilicity on the pharmacokinetic behavior of drugs: Concepts and examples

In this review, we first examine the contextual background of structure–pharmacokinetic relationships. Some concepts in drug disposition are briefly recalled, and inherent difficulties instructure–pharmacokinetic relationships are outlined. Lipophilicity is then investigated in the light of the intermolecular and intramolecular interactions it encodes. In the main body of the review, a number of pharmacokinetic processes are examined for their relations with lipophilicity. These processes are taken in a logical sequence of permeation, absorption (intestine, skin, cornea, brain), plasma protein binding, tissue distribution, volume of distribution and renal clearance. Relations between metabolism and lipophilicity are more complex, since biotransformation involves both low-energy (enzyme binding) and high-energy (catalysis) processes. Only the former may be related to lipophilicity. The conclusion argues against faulty statistics and over-interpretation. This revised version was published online in August 2006 with corrections to the Cover Date.     

Management of Dietary Habits and Diarrhea in Fap Individuals: A Mediterranean Low-Inflammatory Dietary Intervention

Background: A total colectomy and a frequent life-long endoscopic surveillance are guaranteed to patients with Familial Adenomatous Polyposis (FAP) to reduce their risk of duodenal and rectal stump cancers. However, after surgery, individuals with FAP suffer from an increased number of diarrheal discharges that force them to dietary restrictions. A non-randomized pilot study was conducted to assess whether a three-month low-inflammatory Mediterranean dietary intervention reduces gastro-intestinal markers of inflammation in FAP individuals. The aim of the present work is to evaluate the participant’s adherence to the proposed dietary recommendations and the change in their number of diarrheal discharges. Methods: 26 FAP individuals aged >18 years, who underwent a total colectomy with ileo-rectal anastomosis and were involved in the surveillance program at the Fondazione IRCCS Istituto Nazionale Tumori of Milan, were included in the present analysis. Results: FAP individuals significantly reduced the Not recommended foods (p-value: 0.002) and increased the consumption of the Recommended ones (p-value: 0.075). The adherence to the proposed dietary recommendations was accompanied by a significant decrease in the number of diarrheal discharges (p-value: 0.008). Conclusions: This study suggests that adhering to a low-inflammatory Mediterranean diet has a potential protective effect on the number of diarrheal discharges in FAP individuals.