Interferon alfa-2b, colchicine, and benzathine penicillin versus colchicine and benzathine penicillin in Behçet's disease: a randomised trial.

BACKGROUND: Sight-threatening eye involvement is a serious complication of Behçet's disease. Extraocular complications such as arthritis, vascular occlusive disorders, mucocutaneous lesions, and central-nervous-system disease may lead to morbidity and even death. We designed a prospective study in newly diagnosed patients without previous eye disease to assess whether prevention of eye involvement and extraocular manifestations, and preservation of visual acuity are possible with combination treatments with and without interferon alfa-2b. METHODS: Patients were randomly assigned 3 million units interferon alfa-2b subcutaneously every other day for the first 6 months plus 1.5 mg colchicine orally daily and 1.2 million units benzathine penicillin intramuscularly every 3 weeks (n=67), or colchicine and benzathine penicillin alone (n=68). The primary endpoint was visual-acuity loss. Analysis was by intention to treat. FINDINGS: Significantly fewer patients who were treated with interferon had eye involvement than did patients who did not receive interferon (eight vs 27, relative risk 0.21 [95% CI 0.09-0.50], p<0.001). Ocular attack rate was 0.2 (SD 0.62) per year with interferon therapy and 1.02 (1.13) without interferon therapy (p=0.0001). Visual-acuity loss was significantly lower among patients treated with interferon than in those without interferon (two vs 13, relative risk 0.13 [95% CI 0.03-0.60], p=0.003). Arthritis episodes, vascular events, and mucocutaneous lesions were also less frequent in patients treated with interferon than in those not receiving interferon. No serious side-effects were reported. INTERPRETATION: Therapy with interferon alfa-2b, colchicine, and benzathine penicillin seems to be an effective regimen in Behçet's disease for the prevention of recurrent eye attacks and extraocular complications, and for the protection of vision.

Enhanced erythrocyte aggregation in type 2 diabetes with late complications.

We investigated whether erythrocyte aggregation (EA) is enhanced in type 2 diabetic patients who have developed microvascular or macrovascular complications. EA rates at high and low shear rates were analysed in 141 patients with type 2 diabetes who were further divided into 4 subgroups according to the status of diabetic complications and degree of metabolic control. Groups 1 (n = 43) and 2 (n = 23) consisted of well-controlled patients without and with clinically evident late complications, while groups 3 (n = 33) and 4 (n = 42) represented poorly controlled patients without and with these complications, respectively. 124 healthy subjects served as the control group. Mean EA rate was comparable between control subjects and group 1 both at high (2.05 +/- 0.03 vs. 2.14 +/- 0.07, respectively) and low (6.96 +/- 0.02 vs. 7.04 +/- 0.06, respectively) shear rates. Mean EA rate was also comparable between groups 2 and 4 at high (2.76 +/- 0.09 vs. 2.94 +/- 0.07, respectively) and low (8.18 +/- 0.13 vs. 8.41 +/- 0.1, respectively) shear rates. However, EA at both shear rates in groups 2 and 4 were significantly higher than control subjects, group 1 (p < 0.0001) and group 3 (high shear rate EA: 2.76 +/- 0.09 and low shear rate EA: 7.48 +/- 0.07 (p < 0.01). In group 3, EA rates were significantly higher than control subjects and group 1 (p < 0.05) at both shear rates. No significant correlation was found between EA at high and low shear rates and fibrinogen levels in diabetic subgroups and control subjects. The data suggest that patients with type 2 diabetes who had developed clinically evident late complications have enhanced EA regardless of the degree of metabolic control. Whether enhanced EA is a primary phenomenon contributing to the development of these complications or it occurs secondary to their development remains to be clarified.

Acalculous acute cholecystitis in leukemia.

Acalculous acute cholecystitis (AAC) is a well-known complication in critically ill patients. However, there is no satisfactory data regarding this complication in leukemic patients. We reviewed the medical records of 426 patients with acute or chronic leukemia retrospectively to investigate the incidence, possible pathogenetic mechanisms, and clinical course of AAC in leukemia. Six cases of AAC were identified. The incidence was 1.65% (5/302) for acute leukemias. Three out of 6 patients underwent cholecystectomy, and two recovered completely. Percutaneous cholecystostomy was performed in another patient successfully. Careful histological examinations of the surgical specimens did not reveal any specific etiopathogenetic finding. However, clinical data suggested that infectious agents and visceral ischemia may contribute to the pathogenesis of AAC in leukemia.

Fever, hepatosplenomegaly and pancytopenia in a patient living in the Mediterranean region.

A 24 year old woman living in the Mediterranean region of Turkey present with a three-month history of weight loss and irregular fever that was peaking at 40 degrees C with shivering. No definite aetiology could be identified in a local hospital. A bacterial infection had been suspected, but antibiotic therapy, at first with sulbactam-ampicillin and later with azithromycin, had no influence on the fever. Physical examination revealed an emaciated patient with fever (39 degrees C), pallor, and hepatosplenomegaly (spleen 9 cm and liver 5 cm palpable below the costal margin). No peripheral lymphadenopathy was present. The laboratory examinations are summarised in the table. Notably, a prominent increase of macrophages containing intracellular micro-organisms (figures 1 and 2) was seen in the bone marrow smears. The same micro-organisms were also identified within the Kupffer cells in liver biopsy.

Increased erythrocyte aggregation as an indicator for an aggressive clinical course in Behçet's disease: a prospective study.

OBJECTIVE: Changes in blood rheology, especially increased erythrocyte aggregation (EA) might play an important part in the development of arterial and venous thrombotic lesions. A prospective study was designed to evaluate EA in patients with Behçet's disease (BD) and to see if this parameter is predictive for the future development of vascular complications, such as deep vein thrombosis of various organ systems and uveitis. METHODS: EA was measured by a photometric Myrenne aggregometer in 38 patients with BD at the time of initial diagnosis and in 40 age and sex matched healthy controls (HC). RESULTS: During a median follow up period of 13.5 months, 13 patients developed vascular-ocular complications (eight deep vein thrombosis, nine uveitis, and four both deep vein thrombosis and uveitis). Patients were further divided into two groups: BD-a with mucocutaneous symptoms and arthritis only; BD-b with associated vascular-ocular complications. EA values at high shear rate (M) and at low shear rate (M1) were compared among the groups. CONCLUSION: EA values at M and M1 were significantly higher in BD-b than BD-a and HC (p < 0.001). These results suggest that determination of EA rates might be useful to identify subgroups who are likely candidates for developing vascular-ocular complications in BD and management of factors known to affect blood rheology might be beneficial.

Is prevention of cancer possible with tumor-specific vaccines?

Cancer is one of the leading causes of death today, and new therapeutic approaches are continuously being explored. In recent years, cancer vaccines have been tried with the aim of induction of an active specific immune response against the tumor. Although some successful results are obtained, cure rates are still disappointing. The main reason for failure is that vaccines are applied to patients diagnosed with cancer; in these patients, tumor cell burden is so high that it is almost impossible to overcome the disease by increasing the immune response with vaccines at this stage. This hypothesis is based on the following idea: since therapy for cancer is unsuccessful in the majority of patients, methods of prevention should be improved. Immunization against microorganisms has largely prevented morbidity and mortality from infectious disease. In a similar way, if we immunize people before the development of malignant disease with tumor-specific vaccines, then prevention of cancer may be possible.

Hyperkalaemia in acute leukaemia: a sign of adrenocortical insufficiency.

OBJECTIVES: To evaluate adrenal cortical reserve function in hyperkalaemic patients with acute leukaemia (AL). DESIGN: In hyperkalaemic AL patients, after basal blood collection for cortisol, rapid adrenocorticotropic hormone (ACTH) stimulation test was performed with human a1-24-ACTH 0.25 mg, intravenously. Sixty minutes following injection, additional plasma was obtained for cortisol. Normal response was a peak cortisol level greater than 15 micrograms dL-1 with an increment greater than 5 micrograms dL-1. SETTING: Hacettepe University Hospital, Ankara, Turkey. SUBJECTS: Newly diagnosed AL patients with plasma K+ values exceeding 4.5 mmol L-1, who had never received antileukaemia therapy were eligible for entry into the trial. Thirteen patients fulfilled these criteria. Twenty AL patients with normal serum K+ levels were studied as controls. RESULTS: In six patients with hyperkalaemia, adrenal cortical response to rapid ACTH test was inadequate. One patient died during induction chemotherapy due to sepsis. Five of the remaining patients entered remission. Repeat ACTH tests during remission revealed normalization of the adrenocortical function in these patients. However, in only one patient with normal serum K+ level, adrenocortical reserve was decreased. CONCLUSIONS: We suggest that in any AL patient with hyperkalaemia, adrenal reserve function should be evaluated with rapid ACTH stimulation test. In states of resistant hypotension and hyperkalaemia, steroids may be life saving.