Dror Harats, MD, Offer Yodfat, MD, Ram Doolman, MSc, Slava Gavendo, MSc, Daniella Marko, BSc, Aviv Shaish, PhD and Ben-Ami Sela, PhD
Background: Case-control and prospective studies indicate that an elevated plasma homocysteine level is a powerful risk factor for atherosclerotic vascular diseases. Certain medications can induce hyperhomocystinemia, such as methotrexate, trimethoprim and anti-epileptic drugs. There are few reports indicating an interaction between lipid-lowering drugs (cholestyramine and niacin) and homocysteine. Recently, an interaction was shown between fenofibrate and benzafibrates (a fibric acid derivative) and homocysteine plasma levels.
Objectives: To evaluate the effects of different fibrates on plasma homocysteine levels and to measure the reversibility of this effect.
Methods and Results: We investigated the effects of ciprofibrate and bezafibrate on homocysteine levels in patients with type IV hyperlipidemia and/or low high density lipoprotein levels. While a 57% increase in homocysteine was detected in the ciprofibrate-treated group (n=26), a 17% reduction n homocysteine was detected in the group treated with bezafibrate (n=12). The increase in homocysteine in the ciprofibrate-treated group was sustained for the 12 weeks of treatment and was partially reversible after 6 weeks of discontinuing the ciprofibrate therapy.
Conclusions: These results indicate that an increase In plasma homocysteine levels following administration of flbrates is not a class effect, at least in its magnitude. Moreover, it is reversible upon discontinuation of the treatment.
Arie Regev, MD, Rafit Drori, MD, Gerald M. Fraser, MD and Yaron Niv, MD
Background: Alkaline tide is the transient increase in blood and urine pH following stimulation of gastric acid secretion. It is attributed to HC03 release from parietal cells in parallel with H+ secretion. The enzyme carbonic anhydrase is thought to be responsible for HC03 production from CO2 and 0H in the parietal cell.
Objective: To examine the effect of pretreatment with the carbonic anhydrase inhibitor, acetazolamide, on the alkaline tide phenomenon.
Methods: Ten patients with dyspepsia and demonstrable alkaline tide were tested on three separate days. The pH and base excess were determined in arterialized venous blood before and 45 minutes after an intramuscular injection of pentagastrin. The pH of the urine was measured before and 120 mm after pentagastrin injection. Measurements were performed after pentagastrin alone on day 1 following pretreatment with acetazolamide 60 mm before pentagastrin on day 2, and after the administration of acetazolamide alone on day 3.
Results: Following the administration of pentagastrin alone, the blood base excess increased by 1.61 +0.2 mEq/L (mean + standard deviation) and the calculated alkaline tide at 45 mm was 33.99 ±4.49 mEq. On day 2 with prior administration of acetazolamide, base excess decreased by 0.21 + 0.39 mEq/L, and the calculated alkaline tide was -3.28±7.57 mEq, which was significantly lower than on day 1 (P=0 0001). On day 3, following acetazolamide alone, the base excess values decreased by 0.53~0.2 mEq/L and the alkaline tide was -10.05 +3.33 mEq there was no significant difference compared with day 2 (P= 0.44).
Conclusion: Pretreatment with acetazolamide abolished the alkaline tide induced by pentagastrin. This finding supports the view that carbonic anhydrase has a major role in the alkaline tide phenomenon.
Jamal Zidan, MD, Wolf Robenstein, MD, Amira Abzah, RN and Sigalit Tamam, RN
Background: Classic Kaposi's sarcoma is a rare tumor with an indolent behavior. Local therapy is not applicable in disseminated cutaneous disease. Patients with advanced disease are usually treated with systemic chemotherapy.
Objectives: To assess the effectiveness and toxicity of single-agent vinblastine in the treatment of disseminated and recurrent Kaposi's sarcoma.
Methods: Ten patients with wide cutaneous spread of classic Kaposis sarcoma were treated with single-agent vinblastine, 6 mg/m2 intravenously once every 2 weeks. Vinblastine was continued for 2 months after achieving a maximal response.
Results: The male:female ratio was 2.3:1, and median age 64 years (range 50-79 years). The median number of involved nodules in the skin was 34. The overall response rate was 90%, 5 with complete response (50%) and 4 with partial response (40%). Complete responders had a longer duration of response than partial responders: 41.2 vs. 14.8 months. The median survival of all patients was 33 months. Side effects were minimal and tolerable.
Conclusions: Vinblastine is very effective in the treatment of extensive classic Kaposi's sarcoma, and results in a high response rate, long survival and disease-free survival with tolerable toxicity.
Ausim Azizi, MD, PhD, Perry Black, MD, Curtis Miyamoto, MD and Sidney E. Croul, MD
Background: The impact of repeated surgical resection on the survivorship of patients with malignant astrocytomas is an issue of some controversy in the medical literature.
Objectives: To clarify this issue through a retrospective analysis of treatment outcomes in a brain tumor clinic.
Methods: The patient records from the Brain Tumor Clinic at Hahnemann University Hospital for the period 1988 to 2000 were reviewed. From these, 112 cases of glioblastoma multiforme and 50 cases of anaplastic astrocytoma were chosen for analysis.
Results: The group of patients with glioblastomas showed a median survival of 415 days. When analyzed as subgroups based on the number of surgical resections, the median survival was 393 days in the group with biopsy only, 380 days in the group with one surgical resection, and 548 days in the group with two or three resections. Using the Kaplan-Meier method to generate survival plots and the log rank test to compare groups, repeat debulking was found to be a significant predictor of survival (P= 0.1 73). The group of patients with anaplastic astrocytomas showed a median survival of 1,311 days. When analyzed by subgroups, the patients with biopsy only had a median survival of 544 days, those with one debulking 1,589 days and those with two or three debulkings 1,421 days. There was a trend toward increased survival with debulking and the log rank test again showed statistical significance (P 0.1998).
Conclusions: This study indicates that repeated surgical resections offer increased survival for both glioblastomas and anaplastic astrocytomas.
Dror Kraus Bmed, Sc, Igor Kaiserman, MD, Joseph Frucht-Pery, MD and Rami Rahamimoff, MD
Allan Wilk
Anti-neutrophil cytoplasm antibodies are important markers of certain small vessel necrotizing vasculitides, but the optimal use of laboratory results in daily clinical practice necessitates collaboration between clinicians and laboratory specialists. Physicians must familiarize themselves with ANCA tests in ANCA-related vasculitides as well as in differential diagnostic patient populations in order to define cutoff values. Indirect immunofluorescence with a consensus-agreed technique combined with standardized enzyme immunoassays is the modality for detecting the main SSV-associated ANCA specificities using cutoff values that can sufficiently distinguish SVV from non-SVV patients. The combined use of IF and direct EIA to demonstrate proteinase 3-ANCA and myeloperoxidase-ANCA at significant levels leads to a very high diagnostic specificity towards SVV conditions such as Wegener’s granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and limited forms of these such as renal-limited focal necrotizing glomerulonephritis. A strong reactivity of ANCA against several azurophil granule components indicates a drug-induced syndrome. ANCA-related SVV and druginduced vasculitis or lupus syndromes have characteristic ANCA profiles that can help distinguish these conditions from other inflammatory diseases.