FT-IR breath test in the diagnosis and control of treatment of methanol intoxications.

A portable Fourier transform infrared (FT-IR) multicomponent point-of-care analyzer was tested for the diagnosis of methanol intoxications. Breath analysis with FT-IR was fast and easy, and no sample preparation was needed. The analyzer was adequately sensitive and accurate in detecting and quantitating clinically relevant amounts of ethanol and methanol in the breath of seriously ill patients. FT-IR spectrometry was also suitable for nearly on-line monitoring of the exhaled ethanol and methanol during hemodialysis. The breath analysis results correlated well with blood samples. The FT-IR method used also has a traceable calibration to physical properties of the analyte, and the measured spectra can be saved for later analysis.

Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial.

BACKGROUND: Angiotensin-converting-enzyme (ACE) inhibitors have been used for more than a decade to treat high blood pressure, despite the lack of data from randomised intervention trials to show that such treatment affects cardiovascular morbidity and mortality. The Captopril Prevention Project (CAPPP) is a randomised intervention trial to compare the effects of ACE inhibition and conventional therapy on cardiovascular morbidity and mortality in patients with hypertension. METHODS: CAPPP was a prospective, randomised, open trial with blinded endpoint evaluation. 10,985 patients were enrolled at 536 health centres in Sweden and Finland. Patients aged 25-66 years with a measured diastolic blood pressure of 100 mm Hg or more on two occasions were randomly assigned captopril or conventional antihypertensive treatment (diuretics, beta-blockers). Analysis was by intention-to-treat. The primary endpoint was a composite of fatal and non-fatal myocardial infarction, stroke, and other cardiovascular deaths. FINDINGS: Of 5492 patients assigned captopril and 5493 assigned conventional therapy, 14 and 13, respectively, were lost to follow-up. Primary endpoint events occurred in 363 patients in the captopril group (11.1 per 1000 patient-years) and 335 in the conventional-treatment group (10.2 per 1000 patient-years; relative risk 1.05 [95% CI 0.90-1.22], p=0-52). Cardiovascular mortality was lower with captopril than with conventional treatment (76 vs 95 events; relative risk 0.77 [0.57-1-04], p=0.092), the rate of fatal and non-fatal myocardial infarction was similar (162 vs 161), but fatal and non-fatal stroke was more common with captopril (189 vs 148; 1.25 [1-01-1-55]. p=0.044). INTERPRETATION: Captopril and conventional treatment did not differ in efficacy in preventing cardiovascular morbidity and mortality. The difference in stroke risk is probably due to the lower levels of blood pressure obtained initially in previously treated patients randomised to conventional therapy.

A prospective study of acute poisonings in Finnish hospital patients.

1. We have carried out a prospective study of all adult patients presenting with acute poisoning during one month to the Helsinki University Central Hospital (Meilahti Hospital). 2. Two hundred and twenty-six cases of acute poisoning (113 males and 113 females) presented to the emergency department. Most cases in both men (66%) and women (67%) involved alcohol. As to drugs, psychotropic agents predominated in both men and women. The frequency of patient presentation peaked between 7 p.m. and 9 p.m. and was lowest between 8 a.m. and 10 a.m. In most cases, the delay from ingestion of the poison to presentation was longer than 4 h. 3. The clinical status of the patients on arrival was generally good; more than half (55%) of them were fully awake. Serious symptoms (e.g. unconsciousness, insufficient respiration necessitating intubation, aspiration, convulsions or hypotension) occurred in 15% of the presentations. There were no fatalities. 4. One hundred and thirty-five patients (60%) received at least one 50-g dose of activated charcoal. However, charcoal was given in 86% of the cases of drug poisoning. Gastric lavage was performed in 112 cases (50%), and 106 cases (47%) involved both gastric lavage and administration of charcoal. Twenty-one patients received antidotes (flumazenil, calcium gluconate or naloxone) and three patients were hemodialysed. 5. Of the 226 cases, 142 (63%) were managed solely in the emergency department. Of the 84 cases admitted to the hospital, eight had to be managed in the intensive care unit. Almost all patients (94%) were discharged within 24 h. 6. In this survey on 226 consecutive cases of acute poisoning, about two-thirds of the cases involved alcohol, while the most common drugs taken were psychotropic agents. The poisoning was mild in the great majority of the cases. Activated charcoal was generally administered in all but trivial cases of drug poisoning.

Family history as a risk factor of coronary heart disease in patients under 60 years of age.

The role of family history as a risk factor of coronary heart disease was explored in the first-degree relatives of 121 female and 586 male survivors of a recent acute myocardial infarction and in those of 130 control women. It was significantly more common for female patients than male patients to have first-degree relatives with coronary artery disease before the age of 65 (76% vs 62%, P = 0.0026). For the sisters of the female patients the cumulative risk of coronary heart disease by the age of 65 years was almost twice that of the sisters of the male patients (25.9% vs 15.8%, P = 0.0123). The risk for the brothers of the females did not significantly differ from that of the brothers of the male patients, but it was 3.5 times that of the brothers of the controls. Thus, while a history of coronary heart disease in first-degree relatives is a risk factor for the disease, the risk is greater in women than in men.

Pharmacokinetics of diltiazem in massive overdose.

Several cases of poisoning with diltiazem have been described in the literature, but information about the pharmacokinetics of diltiazem in overdose is sparse. The authors report pharmacokinetic and clinical observations in a patient who ingested 7.2 g of slow-release dilitiazem. Grave, persistent hypotension was the overriding clinical manifestation, but the patient eventually survived with aggressive cardiovascular support. No serious conduction abnormalities were seen. Blood samples were taken repeatedly for 2-3 days for analysis of serum diltiazem and desacetyldiltiazem and desacetyldiltiazem concentrations. The serum diltiazem concentration measured in the first sample taken (16.5 h postingestion), 3,171 ng/ml, is one of the highest concentrations reported in a patient who survived. The half-life was 13.3 h for diltiazem and 10.5 h for desacetyldiltiazem. Charcoal hemoperfusion had no apparent effect on the elimination of either compound. The relatively long half-life of diltiazem may have resulted from rate-limiting absorption and probably does not indicate saturation of diltiazem metabolism. The patient was discharged with no apparent neurological or cardiological deficits.

The Captopril Prevention Project (CAPPP) in hypertension--baseline data and current status.

The Captopril Prevention Project (CAPPP) is an ongoing intervention study conducted in 11,019 hypertensive patients in Sweden and Finland. Patients have been randomized to receive either conventional antihypertensive therapy (diuretics and/or beta-blockers) or captopril-based treatment. A prospective, randomized, open, blinded-endpoint evaluation (PROBE) study design is used to compare these two therapeutic regimens as regards cardiovascular morbidity and mortality. The rationale for the CAPPP Study are the many observations of beneficial effects of ACE inhibition, as compared to diuretics and beta-blockers, on intermediary endpoints such as insulin sensitivity, serum lipoproteins, left ventricular hypertrophy and renal function. Captopril has also been shown to be markedly effective in the treatment of left ventricular dysfunction as well as congestive heart failure. The hypothesis is that these differences might result in improved risk reduction when ACE inhibitors are used in the treatment of hypertension. The present paper describes the baseline data and the changes in blood pressure during the first year in the total cohort. During the first year the average blood pressure was reduced by 11/8 mm Hg. A number of substudies have been conducted in the CAPPP Study. In one of these insulin sensitivity was compared in a subgroup of the patients using the euglycemic insulin clamp technique. In another substudy the ACE gene was sequenced and some new polymorphisms were discovered. Several other substudies are in progress or in the planning phase. The main results of the CAPPP Study should be available by mid-1998. Some of the intended anayses of the final results as well as other planned substudies are briefly described here.

A multicentre comparison of once-daily subcutaneous dalteparin (low molecular weight heparin) and continuous intravenous heparin in the treatment of deep vein thrombosis.

OBJECTIVES: To compare the efficacy and safety of the low molecular weight heparin (LMWH) dalteparin with unfractionated heparin (UFH) in the acute treatment of DVT patients who had not previously received UFH. DESIGN: An open randomized multicentre trial with blinded analysis of venograms. SETTING: Seven hospitals in Sweden, Finland and the USA. SUBJECTS: A total of 330 patients, of 20 years or older, with suspected DVT, verified using venography. INTERVENTIONS: Fixed-dose dalteparin (200 IU kg-1) given as a once-daily subcutaneous injection, or aPTT adjusted i.v. UFH infusion for 6 to 10 days. MAIN OUTCOME MEASURES: Change in Marder score in patients with confirmed DVT and two evaluable venograms; PE, bleeding events and follow-up. RESULTS: Marder scores improved in 51% (95% CI 42-60%) of 92 patients treated with dalteparin and in 62% (95% CI 53-70%) of 98 patients treated with UFH (P = 0.152). One dalteparin-treated patient had a PE confirmed by V/Q scan; another had progressive thrombosis with swelling in the affected limb. Bleeding complications occurred in six patients in each group. One patient treated with dalteparin and five treated with UFH died during the 6-month follow-up period as a result of underlying malignancy or heart disease. The 6-month recurrence rate was low with both treatments (dalteparin, 3/97; UFH, 2/103). CONCLUSIONS: Fixed-dose subcutaneous dalteparin given once daily from the start of treatment is of equivalent efficacy and safety to conventional UFH therapy in the routine management of DVT.

Mechanisms of hypocalcemia and markers of bone turnover in alcohol-intoxicated drinkers.

Studies of hypocalcemia and osteoporosis frequently encountered in heavy users of alcohol have previously been performed on alcoholic people who have already recovered from alcohol intoxication. Bone and mineral metabolism during and after the intoxication may be different. We measured serum parameters of bone and mineral metabolism in 26 alcohol-intoxicated men and in 19 healthy control men. Although serum ionized calcium was 12% (P < 0.0001) lower in the patients than in the controls, serum intact parathyroid hormone was similar in the study groups. As reflected by decreased serum levels of osteocalcin (-43%; P < 0.001), bone formation was depressed in the patients. Serum cross-linked carboxyterminal telopeptide of human type I collagen (ICTP), a novel parameter of bone matrix degradation, was 9% higher in the patients (P = 0.03) than controls. The positive correlation between serum osteocalcin and ICTP in the controls (r = 0.59, P < 0.01) was absent in the patients (r = 0.05, P = 0.8). We conclude that in alcohol-intoxicated alcohol users, the parathyroid glands do not respond normally to a hypocalcemic stimulus, and that depressed bone formation is uncoupled from accelerated bone resorption.

Efficacy and tolerability of isradipine and metoprolol in treatment of hypertension: the Finnish Isradipine Study in Hypertension (FISH).

Eight hundred seventy-six men and women with diastolic blood pressure (DBP) of 95-115 mm Hg during a 4-week placebo period were included in a multicenter trial; 479 patients had previously been treated for hypertension. The patients were randomized to receive isradipine or metoprolol; both groups were comparable for age, weight, height, smoking habits, and duration of hypertension. By the end of the placebo period, 79 patients did not fulfill the final entry criteria and were withdrawn. The isradipine group consisted of 398 patients (164 women and 234 men), and the metoprolol group consisted of 399 patients (173 women and 226 men). The initial dose of isradipine was 1.25 mg twice daily (b.i.d.), and the initial dose of metoprolol was 50 mg b.i.d.; the doses were doubled after 4 weeks if DBP had not decreased to less than or equal to 90 mm Hg. After 8 weeks, the isradipine group began combination therapy with metoprolol 50 mg b.i.d. and the metoprolol group began combination therapy with isradipine 1.25 mg b.i.d. if DBP was not less than or equal to 90 mm Hg. After 8 weeks monotherapy, mean BP (MBP) was reduced by 13/11 mm Hg (161/104 to 148/93) in the isradipine group and by 15/12 mm Hg (160/103 to 145/91) in the metoprolol group. Monotherapy with isradipine normalized DBP to less than or equal to 90 mm Hg in 52% with a mean dose of 4.26 mg daily, and monotherapy with metoprolol normalized DBP in 58% with a mean dose of 155 mg daily.1+

Cardiac glycosides in the treatment of experimental overdose with calcium-blocking agents.

The ability of digitalis compounds to counteract calcium antagonist overdose was studied in anesthetized dogs (n = 6, 13.5 +/- 0.7 kg) and isolated trabeculae from human hearts (n = 7). Digitalis caused by increasing intracellular cytosolic Ca2+ concentration through Na+/Ca(2+)-exchange across the cell membrane, was postulated to overcome the detrimental effects of excessive slow calcium-channel blockade. In anesthetized dogs, an infusion of verapamil (40 mg/30 min, i.v.) decreased mean arterial pressure from 88 +/- 6 to 66 +/- 6 mm Hg (P < 0.05), reduced systemic vascular resistance (SVR) from 3838 +/- 916 to 2200 +/- 669 dyne.s/cm5 (P < 0.05), and induced total atrio-ventricular (A-V) block in three animals. Stroke volume (SV) remained unchanged. Administration (i.v.) of NaCl (0.9%, 200 ml) and calcium gluconate (100 mg)--to increase the availability of Na+ and Ca(2+)--together with atropine (0.2 mg)--to block the parasympathetic effects of digoxin on A-V conduction--increased left ventricular contractility (15%) but had no significant effects on blood pressure, SV, or A-V block. Digoxin (0.125 mg) returned sinus rhythm in all dogs and, by increasing SVR (P < 0.05) and left ventricular contractility (P < 0.05), returned arterial pressures to baseline. Because of increased afterload, SV decreased slightly (15%) despite increased cardiac contractility. In experiments with isolated trabeculae from diseased human hearts, TA 3090 (Clentiazem) depressed contractile force and ouabain, another glycoside, restored contractile force within 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol and new onset atrial fibrillation: a case-control study of a current series.

The aetiological role of alcohol in new onset atrial fibrillation was evaluated in a case-control study of 100 consecutive patients aged 21-64 years. Clinical examination, routine diagnostic tests, and echocardiography revealed an underlying disease or other identifiable factor for atrial fibrillation in 65 patients (group 1); 35 patients had idiopathic atrial fibrillation (group 2). The most common diseases associated with atrial fibrillation were ischaemic heart disease (21%), hypertension (13%), and cardiomyopathy (8%). Data on alcohol consumption were obtained by interviewing the patients and their age and sex matched controls on admission. The mean daily alcohol intake of group 2 patients during the week preceding atrial fibrillation was significantly larger than that of either controls or group 1 patients. Compared with controls significantly more patients in both groups with atrial fibrillation had consumed alcohol within two days of the onset of the arrhythmia. Significantly more patients had onset of arrhythmia on Wednesday, Thursday, or Friday than on any other weekday, including patients with high alcohol intake. This study establishes alcohol as an important precipitating factor for new onset atrial fibrillation.