Design of a placebo-controlled clinical trial of long-acting diltiazem and aspirin versus aspirin alone in patients receiving thrombolysis with a first acute myocardial infarction. Incomplete Infarction Trial of European Research Collaborators Evaluating Prognosis Post-Thrombolysis (diltiazem) (INTERCEPT) Research Group.

Several pharmacologic forms of adjunctive therapy, designed to enhance the efficacy of thrombolysis following acute myocardial infarction (AMI), are being explored. However, few studies have assessed the use of standard secondary prevention therapies (beta-blockers, angiotensin-converting enzyme inhibitors, magnesium, calcium antagonists, etc.) for antecedent thrombolysis. Although calcium antagonists have not been shown to alter post-AMI mortality, diltiazem has been shown to reduce recurrent nonfatal infarction and myocardial ischemia following non-Q-wave AMI. Because both non-Q-wave AMI and AMI treated with thrombolytic therapy result in early reperfusion and clinical manifestations of "incomplete infarction" (i.e., aborted transmural infarction), we hypothesize that prophylactic administration of diltiazem to AMI patients who receive thrombolysis before other therapies might decrease ischemic complications. We have initiated a multicenter, randomized, placebo-controlled, double-blind, parallel-group comparison of long-acting diltiazem 300 mg/day and aspirin 160 mg/day versus aspirin 160 mg/day alone in up to 920 patients with an uncomplicated first AMI (no heart failure or left ventricular dysfunction) within 36 to 96 hours of receiving thrombolysis. Active enrollment is under way at 46 centers in the United Kingdom, Belgium, The Netherlands, and Denmark. This trial (known as the Incomplete INfarction Trial of European Research Collaborators Evaluating Prognosis Post-Thrombolysis [diltiazem], or INTERCEPT) represents the first long-term, large-scale, prospective study of a calcium antagonist administered post-thrombolysis as adjunctive therapy to AMI patients in which the primary trial objective is to assess the effect of blinded therapy on the 6-month cumulative occurrence of a combined clinical end point (cardiac death, recurrent nonfatal AMI, and medically refractory ischemia).

A comparative study of long acting diltiazem (Tildiem LA) with sustained release nifedipine (nifedipine SR) and bendrofluazide in the treatment of mild to moderate hypertension.

The therapeutic efficacy of long acting diltiazem 300 mg od (Tildiem LA) was compared with sustained release nifedipine 20 mg bd and bendrofluazide 5 mg od in a multicentre study with 230 patients diagnosed with mild to moderate essential hypertension, with 77, 77 and 76 randomized to the diltiazem, nifedipine SR and bendrofluazide groups respectively. Patients were entered into this randomised, single (investigator) blind, parallel-group multicentre study if the systolic and diastolic blood pressures were > or = 145 mm Hg and/or 95 mm Hg respectively at the admission visit. Twenty-one general practitioners and two hospital physicians monitored patients at baseline and at four and eight weeks of continuous dosing. After eight weeks of therapy, clinically acceptable control of blood pressure was seen in all groups: reductions were 19.2/13.5 mm Hg, 20.4/14 mm Hg and 18.5/10.8 mm Hg for the Tildiem, nifedipine and bendrofluazide groups respectively. Significant differences were shown between bendrofluazide and the other two groups on diastolic pressures (p = 0.01). The non-significant trend was for systolic pressures to mirror these effects. Significantly higher withdrawals caused by adverse events were seen with nifedipine. These were as follows: 14 patients receiving nifedipine (18%), 5 patients receiving diltiazem (6%) and 4 patients receiving bendrofluazide (5%). The difference in this withdrawal rate between treatments was statistically significant (p = 0.01). Post hoc tests revealed that both diltiazem and bendrofluazide had statistically significant lower withdrawals for adverse events than the nifedipine group (p = 0.047). Nifedipine was associated with a marginal increase in standing apex pulse rate and only diltiazem LA significantly maintained serum potassium levels. These results indicate that diltiazem 300 mg is an effective antihypertensive agent and is equivalent in efficacy to nifedipine SR 20 mg and both are superior to bendrofluazide. Nifedipine SR was however the worst tolerated and had the highest withdrawal rate (p = 0.013).

Factors influencing the development of area health education centers with Texas-Mexico border populations.

Area Health Education Centers (AHECs) have been viewed as an appropriate vehicle for implementing new initiatives for training health professionals who will work along the U.S.-Mexico border. Perceptions about this program in Texas were evaluated from July 1988 to June 1989 to identify problems and formulate suggestions that might be of use to academic health science centers (HSCs)--and in particular medical schools--working with Hispanic populations. Interviews were conducted with 116 people: the presidents and/or deans of all eight Texas HSCs and/or medical schools, other deans and faculty, community leaders in five border counties, and state officials. The school and community perspectives about past and present AHEC activities were compared. Some of the barriers were: insufficient components of the health care delivery system to support medical education in severely underserved areas; differing school and community priorities; cultural differences between the school faculty and the community; and feeling among community physicians and dentists that AHECs were a source of competition. The school and community respondents agreed that the AHEC program needs more cooperative planning and training that emphasizes public health education for future AHEC-like activities with border populations.

Urinary excretion of HMMA in children.

In two centres urinary excretion of HMMA was measured in a total of 359 children, aged from birth to 17 years, who were suspected of having a neuroblastoma; the diagnosis was subsequently confirmed in 39. Measurements were made on 24 h urine samples in 246 children, and on random samples in a further 113. The urinary excretion of HMMA relative to creatinine declined progressively with increasing age. After the age of four years the rate of decline was such that some age groups could be combined for statistical analysis. The range of values for each group was similar whether 24 h or random urine collections were used. It is concluded that the latter are adequate for the initial assessment of HMMA excretion.

Hypoglycaemia due to an insulin-receptor antibody in Hodgkin's disease.

Severe fasting hypoglycaemia developed in a patient with Hodgkin's disease after many courses of chemotherapy. Her serum contained a factor which stimulated glucose uptake by rat adipocytes, and this factor was found in the immunoglobulin fraction. The serum also displaced insulin bound to human erythrocytes and both precipitated and phosphorylated insulin receptors extracted from human placenta. The insulin-like substance is probably an antibody to the insulin receptor.

Plasma alkaline phosphatase activity and its relation to rickets in pre-term infants.

Sequential measurements of plasma alkaline phosphatase activity were made in 84 pre-term infants delivered before 38 weeks gestation. In 67% of infants, without evidence of rickets but in whom three or more measurements were made and the peak activity was less than 10 times the adult reference range, the activity rose to a peak and declined to previous levels, or lower. The time taken for these changes varied greatly. The range of values was inspected at each week of age, and in all but six cases the level did not exceed 10 times the upper limit of the adult reference range. Three infants had radiological evidence of rickets, and of the six cases in whom higher levels were found, only one had radiological evidence of rickets; the remainder did not. It is recommended that in the latter, the high plasma alkaline phosphatase activity should be regarded as evidence of subclinical bone disease.

Plasma pyruvate kinase and creatine kinase activity in Becker muscular dystrophy.

Plasma creatine kinase (CK) and pyruvate kinase (PK) were measured in 31 obligate carriers of Becker muscular dystrophy (BMD), 36 BMD patients and appropriate controls. Mean plasma CK was 108 U/l in obligate carriers and 62 U/l in 43 age- and sex-matched controls (P less than 0.001 carriers vs controls). Control CK reference range was 31-125 U/l (mean +/- 2 SD of log transformed values). Mean plasma PK was 40 U/l in obligate carriers and 34 U/l in 56 controls (P less than 0.02 carriers vs controls). Control PK reference range was 18-61 U/l. Values of CK above the reference range upper limit were found in 13 of 31 BMD obligate carriers but only 2 showed elevated PK values. The sensitivity of CK in determining BMD carrier status, although only 42%, was markedly better than PK at 6.5%. Mean plasma CK in BMD patients was 2366 U/l, a 19-fold increase over the control value of 127 U/l (P less than 0.001 patients vs controls). Control CK reference range was 40-316 U/l. In contrast, mean plasma PK in BMD patients was 353 U/l, only 7-fold higher than the mean control value of 57 U/l (P less than 0.001 patients vs controls). Control PK reference range was 22-126 U/l. Clearly, the estimation of plasma PK as a means of determining BMD carrier status is markedly inferior to CK. Previous reports of increased sensitivity of PK compared with CK may have been due to artefactually elevated PK levels produced during sample preparation.

Hyponatraemia in diabetes without ketoacidosis.

At diagnosis six of 18 diabetic children had hyponatraemia with hyperglycaemia but no signs of dehydration or lipaemia. With insulin treatment alone plasma sodium concentrations in two children returned to normal. These children do not require specific treatment to correct the hyponatraemia.