Uncontrolled hypertension among black Africans in the city of Brussels: a case-control study.

AIM: The aim of this study is to identify determinants that are associated with uncontrolled hypertension among black Africans in the city of Brussels. DESIGN: A not-matched case-control study. METHODS: Seventy-five black Africans were assigned to a case group with uncontrolled hypertension and a control group with controlled hypertension. Demographic characteristics, lifestyle and compliance were recorded as well as their blood pressure. Compliance in patients was evaluated by means of the Morisky Medication Adherence Scale-4 (MMAS-4). RESULTS: The mean age of the case group was 52 years (SD 7.8) and for the control group 49 years (SD 6.2). Almost 60% were women. Uncontrolled hypertension was associated with obesity (p = 0.01) and sedentary lifestyle (p = 0.034). About 50% of women were obese and 70% of these had uncontrolled hypertension. Patients with type 2 diabetes had a 4.5 times higher risk for uncontrolled hypertension and lower compliance to the medication regimen compared to non-diabetics. Patients were often treated with diuretics (29%), renin-angiotensin inhibitors (25%), and calcium-channel inhibitors (23%). According to the MMAS4-score uncontrolled patients had an intermediate compliance and the controlled patients had a high compliance. CONCLUSIONS: Black obese women and diabetics had the highest risk for uncontrolled hypertension. Compliance was significantly lower among uncontrolled patients.

Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies.

A Phase I dose escalation trial of i.v. administered recombinant human interleukin 12 (rhIL-12) was performed to determine its toxicity, maximum tolerated dose (MTD), pharmacokinetics, and biological and potential antineoplastic effects. Cohorts of four to six patients with advanced cancer, Karnofsky performance >/=70%, and normal organ function received escalating doses (3-1000 ng/kg/day) of rhIL-12 (Genetics Institute, Inc.) by bolus i.v. injection once as an inpatient and then, after a 2-week rest period, once daily for five days every 3 weeks as an outpatient. Therapy was withheld for grade 3 toxicity (grade 4 hyperbilirubinemia or neutropenia), and dose escalation was halted if three of six patients experienced a dose-limiting toxicity (DLT). After establishment of the MTD, eight more patients were enrolled to further assess the safety, pharmacokinetics, and immunobiology of this dose. Forty patients were enrolled, including 20 with renal cancer, 12 with melanoma, and 5 with colon cancer; 25 patients had received prior systemic therapy. Common toxicities included fever/chills, fatigue, nausea, vomiting, and headache. Fever was first observed at the 3 ng/kg dose level, typically occurred 8-12 h after rhIL-12 administration, and was incompletely suppressed with nonsteroidal anti-inflammatory drugs. Routine laboratory changes included anemia, neutropenia, lymphopenia, hyperglycemia, thrombocytopenia, and hypoalbuminemia. DLTs included oral stomatitis and liver function test abnormalities, predominantly elevated transaminases, which occurred in three of four patients at the 1000 ng/kg dose level. The 500 ng/kg dose level was determined to be the MTD. This dose, administered by this schedule, was associated with asymptomatic hepatic function test abnormalities in three patients and an onstudy death due to Clostridia perfringens septicemia but was otherwise well tolerated by the 14 patients treated in the dose escalation and safety phases. The T1/2 elimination of rhIL-12 was calculated to be 5.3-9.6 h. Biological effects included dose-dependent increases in circulating IFN-gamma, which exhibited attenuation with subsequent cycles. Serum neopterin rose in a reproducible fashion regardless of dose or cycle. Tumor necrosis factor alpha was not detected by ELISA. One of 40 patients developed a low titer antibody to rhIL-12. Lymphopenia was observed at all dose levels, with recovery occurring within several days of completing treatment without rebound lymphocytosis. There was one partial response (renal cell cancer) and one transient complete response (melanoma), both in previously untreated patients. Four additional patients received all proposed treatment without disease progression. rhIL-12 administered according to this schedule is biologically and clinically active at doses tolerable by most patients in an outpatient setting. Nonetheless, additional Phase I studies examining different schedules and the mechanisms of the specific DLTs are indicated before proceeding to Phase II testing.