The effect of adherence to therapy on sustained response in daily or three times a week interferon alpha-2b plus ribavirin treatment of naive and nonresponder chronic hepatitis C patients

The aim was to demonstrate adherence to treatment has been suggested to enhance rates of sustained response in patients with hepatitis C. In this study, we evaluated the effect of drug dosage reduction or the duration of the expected therapy in patients treated with interferon (IFN)-alpha2b plus ribavirin. Virologic response rates were re-analysed according to compliance to therapy in (i) 301 naive and (ii) 142 nonresponders to previous IFN therapy treated with either IFN 5 MU TIW for 8 weeks followed by IFN 3 MU TIW for 40 weeks plus ribavirin or IFN 3 MU QD for 16 weeks followed by IFN 3 MU TIW for 24 weeks plus ribavirin. Patients were separated into those who adhered to > or =80% of their intended treatment schedule (dose of both drugs and duration) and those who did not. Compliance to treatment resulted in significantly higher response rates in both groups of patients: 43.93% compared with 6.90% of noncompliant naive patients and 30.77% compared with 10.53% of nonresponder patients. Compliance to treatment was found to have a similar effect when the results were analysed according to HCV genotype. Our findings suggest that compliance to treatment for > or =80% of the intended treatment schedule results in significantly higher sustained response rates in both naive and nonresponder patients. Consequently, every effort should be made to improve patient adherence to therapy.     

Acute promyelocytic leukaemia (M3): Relapse with acute myeloblastic leukaemia (M2) and dic(5;17) (q11; p11)

Secondary leukaemia following treatment of M3 acute promyelocytic leukaemia (APL) is a rare event. We describe a patient in remission following chemotherapy for APL who relapsed with M2 acute non-lymphoblastic leukaemia (ANLL). The original t(15;17) (q22; q21) chromosome translocation was lost and replaced by a clone containing a dic(5;17) (q11; p11) abnormality. Southern genomic analysis demonstrated re-arrangements of the retinoic acid receptor α (RARα) and PML genes in the APL blasts at presentation but not in the M2 ANLL marrow at relapse. The significance of unbalanced 5;17 translocations as markers for therapy-related secondary leukaemia is discussed. ©1995 Wiley-Liss, Inc.     

Homozygous protein C deficiency in a newborn. Clinicopathologic correlation

A rare case of homozygous protein C deficiency occurred in a newborn. The patient presented with purpura fulminans in the first few hours after birth and showed multiple hemorrhagic lesions on computed tomography of the brain at 5 days of age. Neurologic symptoms developed at two weeks and the patient died at 37 weeks. His protein C level was less than 5%. Autopsy revealed thrombosis of the dural sinuses, multiple cortical infarcts, intraparenchymal hemorrhages, and hydrocephalus. The pathologic findings are correlated with the neurologic deficits and previously documented cases are reviewed.     

Morphologic alterations in rat brain following systemic and intraventricular methotrexate injection: light and electron microscopic studies

To determine the morphological substrate of acute methotrexate (MTX) encephalopathy, light and electron microscopic studies were performed on rat brains after short-term intraperitoneal (IP) and intraventricular (IV) injections of MTX. In both models, Alzheimer type II astrocytosis was the initial and major pathologic alteration seen by light microscopy. The neurons, oligodendrocytes, myelin and endothelial cells were relatively spared. Ultrastructural studies showed pleomorphism and condensation of mitochondria, membrane-bound vacuoles, prominent stacks of sparsely granular, rough endoplasmic reticulum and progressive hydropic swelling of astrocytic perikarya and their processes. The astroglial alterations were reversible after cessation of the drug but persisted for a longer time with repeated IP administration. Gastrointestinal complications and overall mortality were also greater with higher doses and increasing frequency of IP MTX injection. White matter necrosis was noted only after IV injection of high-dose MTX. The neuropathologic changes of MTX leukoencephalopathy can be replicated in an animal model by IV injection of the drug. The reversibility of the changes that were seen following IP administration correlates with the transient neurologic deficits observed in some patients after high-dose systemic MTX therapy. The initially selective astroglial effect suggests that astrocytes might be a target for MTX toxicity, although other central nervous system components may also be adversely affected by the drug.     

Emergency liver resection for combined biliary and vascular injury following laparoscopic cholecystectomy: case report and review of the literature

A 75-year-old woman suffering from symptomatic cholelithiasis was admitted to our hospital for elective laparoscopic cholecystectomy (LC). Intraoperatively, because of severe inflammation and dense adhesions in the region of the Calot triangle and bleeding arising from the porta hepatis which obscured the operating field, the method was converted to a conventional open approach. Copious hemostasis was achieved using sutures, clips and diathermy, and no bile duct or vascular injuries were recognized intraoperatively. Because of severe right upper quadrant abdominal pain and significant deterioration of the liver function tests (LFTs) on the first postoperative day, the patient underwent a Doppler ultrasound scan which showed absence of blood flow at the level of porta hepatis. Urgent relaparotomy revealed an ischemic liver on the right, a transected common bile duct at the level of its confluence, a divided and ligated right hepatic artery and thrombosed portal vein down to its confluence. Thrombectomy and reconstruction of the portal vein were performed to salvage the left hemiliver, and after restoration of blood flow to the left hemiliver, a right hemihepatectomy and a Roux-en-Y hepaticojejunostomy on the left were performed. Liver resection serves an important role in the case of parenchymal necrosis due to combined biliary, hepatic artery and portal vein injury following laparoscopic cholecystectomy and moreover, the operation can be safely performed in the acute setting.     

Nuchal nevus flammeus as a skin marker of prognosis in alopecia areata

In this work, the incidence of nuchal nevus flammeus was studied in 205 patients suffering from various forms of alopecia areata, as well as in a group of 555 volunteers without alopecia areata examined in our outpatient clinic. The incidence of nuchal nevus flammeus in the totalis-universalis form of alopecia areata was 58.2% (examined patients, n = 79), in ophiasis-extensive forms 22.8% (examined patients, n = 70) and in simple forms of alopecia areata 3.6% (examined patients, n = 56). In the group of 555 volunteers without alopecia areata the incidence of nuchal nevus flammeus was 4.5%. Our results show that nuchal nevus flammeus could be a valuable skin marker indicating a more severe course of alopecia areata.