Familial hypercholesterolaemia with severe cardiac involvement in a boy: successful management and mid-term follow-up

A 13-year-old boy with double heterozygosity for familial hypercholesterolaemia with a 90% left coronary artery main stem stenosis is reported. The patient's cholesterol levels were effectively controlled with weekly sessions of selective low-density lipoprotein cholesterol removal through immunoadsorption by use of an extracorporeal system. Left main coronary artery stenosis was successfully treated with percutaneous transluminal balloon dilation. At 30 months after the intervention and still under treatment with weekly sessions of low-density lipoprotein apheresis the patient is free of cardiac symptoms. He shows normal exercise capacity and normal myocardial perfusion. It is concluded that aggressive management is justified in such patients and may result in a near-normal quality of life.     

Epithelioid sarcoma

In a 9-year period we treated 11 patients with an epithelioid sarcoma. Most patients were young adults. The tumour affected mainly the distal upper extremity (hand and fingers: four patients; wrist and forearm: three patients); one patient had an epithelioid sarcoma of the knee. Trunk localizations were seen in two patients and one patient presented with a vulva localization. Treatment consisted of surgery, regional isolation perfusion with doxorubicin (Adriamycin) or melphalan, radiation therapy, systemic chemotherapy or a combination of these modalities. Radical surgery in eight patients resulted in only two local recurrences. Locoregional metastases occurred in five patients. In five patients a therapeutic lymph node dissection was performed, in all instances followed by extensive recurrent disease. Distant metastases were seen in seven patients and mainly affected the skeleton (6x) and the lungs (4x); in the majority of cases these metastases occurred within a year after excision of the primary. Remissions following regional or systemic chemotherapy were not observed. At the time of analysis seven patients had died as a result of their epithelioid sarcoma; two patients were still alive with tumour 18 and 27 months after diagnosis. Only two patients remained tumour free for 17 and 65 months respectively following radical surgery, postoperative radiation therapy and (in one case) adjuvant chemotherapy. It is concluded that epithelioid sarcoma is a rare but exceedingly aggressive tumour. Since early diagnosis can only be auspicious, familiarity with the clinical features is of great importance.     

Oral acyclovir suppressive therapy in severe recurrent genital herpes. A double-blind, placebo-controlled cross-over study

A randomised, double-blind, placebo-controlled cross-over study was conducted in 24 patients, nine females and 15 males, with a history of more than eight recurrences of genital herpes in the past year. The patients received a first treatment course with 400 mg acyclovir or matching placebo by mouth, twice daily, for 12 weeks. After cross-over patients received alternative medication for another 12 weeks. The patients were followed without treatment for a further three-month period. During acyclovir therapy, recurrences were completely prevented in 17 patients (71%) and the remaining seven patients had nine recurrences as compared to 18 recurrences while receiving placebo. The placebo treatment did not reduce the recurrence rate. No adverse effects were attributable to the acyclovir treatment period. All virus isolates tested after treatment remained sensitive to acyclovir. Acyclovir prophylaxis of recurrent genital herpes is effective and safe. A continuous suppressive therapy with acyclovir offers a basis for a normal sexual life to those patients severely incapacitated by their disease, but once medication is stopped, patients shed virus as before suppression.     

Metabolism of carcinogenic heterocyclic and aromatic amines by recombinant human cytochrome P450 enzymes

The N-hydroxylation of carcinogenic arylamines represents an initial step in their metabolic activation. Animal studies have shown that this reaction is catalyzed by the cytochrome P450 (P450) enzymes P450 1A1 and P450 1A2. In this study, utilizing enzymes expressed in Escherichia coli (and purified) or in human B-lymphoblastoid cells, the catalytic activities of recombinant human P450 1A1, P450 1A2, and P450 3A4 for N- hydroxylation of several carcinogenic arylamines were determined. P450 1A2 from both expression systems catalyzed the N-hydroxylation of 4- aminobiphenyl and the heterocyclic amines, 2-amino-3-methylimidazo[4,5- f/quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Rates were similar, with values of 1.1-7.8 nmol/min/nmol P450. In contrast, P450 1A1 catalyzed N-hydroxylation of only PhIP, and no activity was observed with P450 3A4. Further kinetic analysis with purified P450 1A2 showed similar Km and Vmax values for N-hydroxylation of the arylamines. Furafylline and fluvoxamine, inhibitors of P450 1A2 activity in human liver microsomes, were found to be inhibitory of the recombinant P450 1A2 N-hydroxylation activity. Results from this study are supportive of a major role for human P450 1A2 in the metabolic activation of arylamines.      

Effect of isoprinosine on HIV antigenaemia.

OBJECTIVE: The objective of this study was to evaluate the effect of isoprinosine on HIV-antigen expression in HIV-positive patients without AIDS. DESIGN: Serum samples from anti-HIV-positive patients without AIDS participating in a double-blind, placebo-controlled trial of isoprinosine in the treatment of HIV infection were analysed for the presence of HIV antigen. SETTING: Data and samples were collected from the 21 medical centres who participated in the Scandinavian multicentre placebo-controlled isoprinosine study. PATIENTS, PARTICIPANTS: Samples were available from 19 of 21 participating centres. Of 866 patients who enrolled, baseline serum samples were available for 642 (74%; 308 isoprinosine- and 334 placebo-treated patients). INTERVENTIONS: Treatment was 1 g isoprinosine administered orally three times a day or matching placebo for 24 weeks. MAIN OUTCOME MEASURES: Comparison of HIV-antigen levels before and during treatment in both the isoprinosine-treated group and the placebo-treated group of patients. RESULTS: During the study, AIDS developed in 19 patients; 17 of whom were receiving placebo treatment and two isoprinosine. The proportion of HIV-antigen-positive patients developing AIDS during treatment was significantly different from the proportion of HIV-antigen-negative patients in whom AIDS developed (6 versus 2%; P = 0.02). No significant changes in HIV-antigen levels were observed between the isoprinosine- and the placebo-treated group of HIV-antigen-positive patients. Median HIV-antigen levels did not change significantly in either the isoprinosine- or the placebo-treated group. CONCLUSION: Our results suggest that isoprinosine does not have antiviral activity against HIV in vivo.