bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Diabetic Ketoacidosis: Some Observations on and Deductions about the Sources of Acid
Authors: Sestoft Leif , Folke Morten , Gammeltoft Steen , Bartels Paul D. , Kristensen Lars ø.
Published: August 2010

Abstract. The carboxylic acid balance of perfused livers from normal and streptozotocin diabetic rats (in insulin treatment or deprived of insulin for various time intervals) was determined by measurement of FFA, lactate, pyruvate and in ketone bodies in input and output medium. In livers from fed rats of either type of treatment, the carboxylic acid balance was close to zero, and the same was true for livers from 48‐hour fasting rats after 6 hours or more of insulin deprivation. Thus, when livers were perfused with a medium containing 1 mM of lactate and of FFA, the diabetic state did not turn the liver into a state of net acid production. Addition of a high concentration of glucose to the medium inhibited the rate of ketogenesis significantly in livers from fasting diabetic animals perfused for 6 hours after discontinuation of insulin treatment. In this way a high glucose concentration caused an increased net uptake of carboxylic acid in such livers. A decrease in the liver blood flow to one‐third of the normal invariably turned livers into a state of net acid production due to (a) a strongly diminished uptake of lactate in livers perfused with a medium containing no glucose and (b) by a large net lactate production in livers perfused with 20 mM glucose. On the basis of these observations and of data from available literature it is suggested that the pathogenesis of the diabetic ketoacidosis in humans can be divided into two phases: 1) An initial phase (pH 7.4 to 7.1) distinguished by a gradually increasing accumulation of acid equivalents in the body largely caused by accumulation of the keto acids (3‐hydroxybutyrate and acetoacetate) and of non‐carbonic acid equivalents originating from the excretion in the urine of ketone bodies as bases, i.e. with sodium and potassium as the corresponding cations which ensure electroneutrality. 2) A late phase (π <7.1) distinguished by severely impaired capacity for renal excretion of acid equivalents, of an impaired capacity for respiratory compensation of the metabolic acidosis and by a changed hepatic metabolism of lactate: from a net lactate clearing function the liver is turned into a net lactate producing function due to a low perfusion flow and a high glucose concentration. Thus, in the late phase the organism has lost any possibility to eliminate acid. On the basis of pKa values for the second acid group of organic phosphates and inorganic phosphate the estimate is given that net hydrolysis of organic phosphates, which takes place during the development of diabetic ketoacidosis, will rather cause a net removal than a net supply of non‐carbonic acid to the body fluids.
C‐peptide and Proinsulin after Oral Glucose
Authors: Heding Lise G. , Kasperska‐Czyzykowa T.
Published: August 2010

ABSTRACT. Radioimmunoassays (RIA) for C‐peptide and proinsulin have been developed and their sources of error investigated. Immunoreactive insulin (IRI), C‐peptide and proinsulin were determined prior and up to 3 hours after glucose load in 13 non‐diabetics. Fasting proinsulin constituted 35% of the IRI (μU/μU), but the proportion of proinsulin increased at 2 and 3 hours to about 47 % and 70%. Since this percent depends on the reactivity of proinsulin in the insulin RIA an improved method of expressing the relationship between proinsulin and insulin was used. The insulin concentration (IRI μU/ ml—proinsulin μU/ml) was determined and the molar ratio between proinsulin: insulin calculated. It was 0.83±0.45 at fasting and 0.28±0.14 at 15 min. At 1.5 hours the ratio was 1.30±0.78 and continued to rise in most persons. Proinsulin: C‐peptide was 0.051 at fasting, not changing much during the first hour, after which the ratio increased to 0.113 and 0.141 at 2 and 3 hours, respectively. Thus proinsulin may be secreted in increasing quantities as compared to insulin and C‐peptide in the late phase of a heavy oral glucose load. The B‐cell activity in insulin treated diabetics may be evaluated by C‐peptide determinations. In serum with insulin antibodies, bound proinsulin has to be removed prior to C‐peptide determination to avoid falsely high C‐peptide estimates. The most simple method is a PEG precipitation of the antibody complexes. C‐peptide is then estimated in the 12.5% PEG‐containing supernatant. It was found to be important to prepare the standards in 12.5% PEG to obtain correct results.
NONINVASIVE DIAGNOSIS AND ASSESSMENT OF VENTRICULAR SEPTAL DEFECT BY DOPPLER ULTRASOUND
Authors: Hatle L. , Rokseth R.
Published: August 2010

The presence of ventricular septal defect can be diagnosed noninvasively by Doppler ultrasound. Care must be taken to distinguish between VSD and infundibular pulmonary stenosis. VSD was easily differentiated from other cardiac lesions. In 55% of the patients a pressure drop across the VSD, comparable to that present, could be calculated from maximal velocity recorded. In the remaining patients velocity and pressure drop were underestimated, probably due to a too large angle between ultrasound beam and velocity. Pulmonary artery systolic pressure was correctly estimated from Pc‐To interval and heart rate, and RPEP/RVET indicated whether normal or raised diastolic pressure was present in most patients.
CAN ACETYLSALICYLIC ACID ALONE PREVENT ARTERIAL THROMBOEMBOLISM? A PILOT STUDY IN PATIENTS wITH AORTIC BALL VALVE PROSTHESES
Authors: Dale Jon , Myhre Erik
Published: August 2010

Encouraged by the effective prevention of arterial thromboembolism with a combination of ASA and anticoagulants (9), the present study was done in 77 patients with a single Starr‐Edwards aortic ball valve. They received one gm. of ASA daily, then the dose of anticoagulants was reduced gradually and the drug discontinued on average five weeks later. Six arterial embolic episodes occurred in five patients, the incidence being 14.5 complications per 100 patients per year. Five emboli were cerebral, none of them serious, and one was removed from a femoral artery. Four of the embolic episodes occurred in three of the 11 patients with continuous arrhythmia, probably from venous thrombi that developed in the left atrium. The occurence of only two embolic complications in the 66 patients with sinus rhythm suggests some prevention of arterial thrombus formation on the prosthetic valves. The results indicate that ASA is inferior to anticoagulants in patients with arrhythmia, while it may represent an alternative to anticoagulation in individuals with sinus rhythm. we prefer, however, the combined thereapy in patients with aortic valve prostheses because of the strong anti‐thrombotic effect achieved by this treatment.
CORONARY HEART DISEASE IN NORWEGIAN SEA‐PILOTS; PART OF THE OCCUPATIONAL HAZARD?
Authors: Erikssen Jan , Johansen Arne Høiem , Rodahl Kaare
Published: August 2010

A near maximal bicycle exercise test revealed a prevalence of positive exercise ECG's of 8/68 among apparently healthy sea‐pilots and 93/2014 among apparently healthy men of comparable age in Oslo (P<0.01). This difference could not be explained in terms of differences in commonly accepted coronary heart disease risk factors (cholesterol/triglycerides, smoking habits and blood pressure).

Reasons for the difference should be sought in the working environment of the pilots as well as in possible unfavourable life habits adapted during leisure time as indicated by a relative increase in body weight and somewhat lower working capacity in pilots than in age matched counterparts from Oslo.
URINARY FINDINGS AND RENAL FUNCTION IN HYPERTENSIVE AND NORMOTENSIVE WOMEN
Authors: Sigurdsson Johann A. , Bengtsson Calle
Published: August 2010

ABSTRACT As found from a population study of women, those with arterial hypertension reported more often a history of toxaemia in pregnancy and had more often proteinuria, bacteriuria and impaired renal concentrating capacity than normotensive women. Serum potassium was found to be lower in treated as well as in untreated hypertensive women than in normotensive women.

There are many experimental data suggesting that the kidneys play a fundamental role in the pathogenesis of essential hypertension. However, less is known about the role of the kidneys from clinical and epidemiological points of view. This is especially true for women. The aim of this study is to compare renal function and findings from some urinary tests in hypertensive women with those in a normotensive reference group, using epidemiological methods.
The Heart Cell—Electrophysiological Aspects
Authors: Andersson K‐E
Published: August 2010

A short review is given of the ionic fluxes associated with the action potential in Purkinje fibres, and in sinus and AV‐node, and of the influence of variations in the extracellular concentrations of K+, Na+, Ca2+and Mg2+on basic electrophysiological parameters.

Variations in serum potassium concentration often play an important role in the genesis of arrhythmias by changing several electrophysiological parameters, whereas only extreme variations in the serum calcium level produce electrophysiological effects of clinical importance. Hypo‐ and hypernatremia within the ranges observed clinically most probably do not produce significant electrophysiological changes. Variations in extracellular magnesium concentration seem to have effects on electrophysiological parameters particularly when they occur simultaneously with changes in the concentrations of calcium and potassium.
Systemic Alkalosis and Digitalis Related Arrhythmias
Authors: Brater D. Craig , Morrelli Howard F.
Published: August 2010

Reviews of large series of patients with digitalis‐induced arrhythmias create a seeming paradox: Hypokalemia is infrequently associated with digitalis‐induced arrhythmias but the clinical benefit of supplementation of potassium for most digitalis‐induced arrhythmias is obvious. Examination of the electrophysiologic abnormalities induced by digitalis coupled with the electrophysiologic effects dependent on the ratio of intracellular to extracellular concentrations of potassium clarifies the issue. We present evidence that supports additive effects of the toxicity of digitalis and abnormal ratios of concentrations of potassium inside and outside the cardiac cell using metabolic alkalosis as a marker of intracellular potassium depletion. Patients with metabolic alkalosis and normokalemia with “therapeutic” concentrations of digoxin had significantly greater prevalance of arrhythmias than did patients without alkalosis. We presume this effect of alkalosis to be mediated by effects on extra‐to intracellular ratios of potassium.
Malignant Arrhythmias in Relation to Serum Potassium Values in Patients with an Acute Myocardial Infarction
Authors: Nordrehaug Jan Erik
Published: August 2010

The results presented here confirm that patients with A.M.I. who are also hypokalemic have an increased risk of cardiac arrhythmias, in particular, V.F. It is also suggested that for patients with low potassium values the risk is due to the hypokalemia and not the diuretics.
Diuretic Treatment and Magnesium Losses
Authors: Wester Per Ola , Dyckner Thomas
Published: August 2010

Therapy with most kinds of diuretics causes increased urinary excretion of both potassium and magnesium and after long term treatment the skeletal muscle content of these ions is reduced. Magnesium is known activator of Na‐K‐ATP:ase, which provides the energy for the sodium‐potassium pump. Thus, lack of magnesium may impair the pumping of sodium out from the cell and potassium into the cell. Three studies are presented which agree with this theory. In one study the correlation between potassium in serum and potassium in muscle was, among other factors, found to be dependent on the content of muscle magnesium. In another study it was found in hypokalemic patients that muscle potassium could not be corrected by potassium supplementation if there was a concomitant magnesium deficiency. In the third study it was found that muscle potassium increased after magnesium infusion but not after potassium infusion.
EXERCISE INDUCED NON ISCHEMIC ANGINA PECTORIS DUE TO ABNORMAL LEFT VENTRICULAR COMPLIANCE
Authors: Gleichmann U. , Ohlmeier H. , Trieb G. , Mannebach H.
Published: August 2010

ABSTRACT. In 27 patients (pts.) with a history of exercise induced angina pectoris coronary heart disease (CHD), hypertrophic or congestive cardiomyopathy and mitral valve prolapse were excluded by coronary and left ventricular angiography and echocardiography. The pts. were divided into two subgroups: 12 pts. with normal (groups A) and 15 pts. with abnormal exercise ECG (group B). All but two pts. showed a positive reaction on nitroglycerin. The results of a retrospective analysis of clinical and hemodynamic findings are reported. No age differences were detected. There was an over‐representation of females in group B (12:3). In group B ST‐depression (0,1 − 0,3 mV) during exercise and angina occured in 4 pts., in the remainder only ST‐depression between 0,1 and 0,3 mV was observed. At submaximal exercise (mean in group A 75 watt, group B 82 watt) in both groups left ventricular enddiastolic pressure (LVEDP) and\ or mean pulmonary artery pressure (PAP) increased to abnormal values. The main difference between the two groups beyond the ST‐segment reaction with exercise was the difference in enddiastolic volume indices (EDVI): 74±15 in group A and 90±16 ml/m2 in group B. By these findings exercise induced angina in absence of CHD can occur with two different patterns both showing pathologic LVEDP values with exercise: type A with normal exercise ECG and normal LV volumes, type B with abnormal exercise ECG and borderline or abnormal EDVI, increase of end‐systolic volume index during exercise and constant stroke volume index during rest and exercise. The positive effect of nitroglycerin in both groups can be explained by the reduction of elevated LVEDP during exercise. The etiology of this type of left ventricular compliance disorder is unknown. Long term therapy with isosorbiddinitrate should be discussed in spite of absence of coronary heart disease.
THE VALUE OF ANGINAL PAIN IN EXERCISE TESTING AFTER MYOCARDIAL INFARCTION
Authors: Cokkinos Dennis V. , Boutos Christos , Patsouros Kyriakos , Salpeas Demetrius
Published: August 2010

ABSTRACT. The result of treadmill exercise tests were studied in 158 patients (pts) who were exercised submaximally 1 to 3 month after an acute transmural myocardial infarction. A 4 minute test had initially been performed prior to their discharge, 14 to 20 days after the acute event. Eighty pts had an inferior and 65 an anterior infarction; 13 could not be reliably classified and were not further included. In the inferior infarction group, 10/80 had a positive test characterized by ST changes (9 pts), and anginal pain (4 pts). In the anterior infarction group, 11/65 had a positive test: ST‐changes could be reliably assessed in only 2, while 9 had anginal pain; one had ventricular tachycardia. Fourteen pts underwent coronary arteriography; all showed severe triple vessel disease, and in 8 myocardial revascularization was performed. In pts with a previous anterior myocardial infarction, anginal pain can be a very helpful finding, since ST changes are usually hard to interpret.
RELATION BETWEEN ST‐DEPRESSION AND CHEST PAIN IN PATIENTS WITH CORONARY HEART DISEASE RECEIVING NO TREATMENT AND AFTER β‐BLOCKADE AND COMBINED a‐β‐BLOCKADE
Authors: Nyberg G. , Bjurö T. , Hagman M. , Smith U.
Published: August 2010

ABSTRACT. The bicycle exercise tolerance was studied in ten patients with angina pectoris after one week's treatment with an a‐β‐blocker (labetalol 300 mg b.d.), a‐β‐blocker (propranolol 80 mg b.d.) and placebo. The ST‐segment of the ECG was continously evaluated by on‐line computerized averaging of complexes which greatly reduces noise and eliminates artefacts caused by varying baseline. Blood pressure was lowest with labetalol and heart rate lowest with propranolol. The rate of rise of heart rate during exercise was equally well depressed by both drugs. They also attenuated ST‐depression at a given load but enhanced ST‐depression for a given heart rate. At heart rate 100/min ST‐depression was significantly greater with propranolol than with labetalol. It is concluded that provided ST‐depression during treatment with β‐blockers is correlated to myocardial ischemia in the same way as without such treatments used, other factors, e.g. an increase in cardiac size, will contribute more to the ischemia. Labetalol may cause less increase in cardiac size than propranolol.
PRINZMETAL'S VARIANT ANGINA (PVA). CIRCADIAN VARIATION IN RESPONSE TO HYPERVENTILATION
Authors: Mortensen Svend Aage , Vilhelmsen Regitze , Sandøe Erik
Published: August 2010

ABSTRACT. The study reports on the outcome of hyperventilation tests in a 57‐year‐old male with Prinzmetal's variant angina, formerly often complicated by ventricular fibrillation. It was found that hyperventilation for a period of 6 min after a delay of 4 to 6 min was followed by the development of ST‐elevation and pain, but only when the test was performed in the morning, whereas the outcome of tests performed later in the day were negative. Pretreatment with calcium blockers, nifedipine or verapamil proved effective in preventing the anginal response to the test, also when it was performed in the morning. It is concluded that hyperventilation performed in the early morning, but not later in the day, may prove to be an effective and safe procedure for provoking Prinzmetal's variant angina, and that hyperventilation may be useful in the evaluation of the efficacy of drug therapy.
QUANTITATIVE EVALUATION OF CHEST PAIN
Authors: Borg Gunnar , Lindblad Inger , Holmgren Alf
Published: August 2010

ABSTRACT.The perception of pain in three groups of patients with angina pectoris has been studied. All patients went through a bicycle ergometer test with an increase of 10 watt each minute. Heart rates and ratings of pain were collected towards the end of each work load. Reliable results of diagnostic interest were obtained. The rating procedure is discussed and a new category rating scale with ratio properties is also presented.
OESOPHAGEAL DYSFUNCTION AND ISCHAEMIC HEART DISEASE AS ORIGIN OF CHEST PAIN IN NON‐INFARCTION CORONARY CARE UNIT PATIENTS AND PATIENTS WITH MYOCARDIAL INFARCTION
Authors: Areskog Magnus
Published: August 2010

ABSTRACT. Oesophageal dysfunction (OD), ischaemic heart disease (IHD) and their relation to chest pain were studied in two groups of patients. A group of 55 non‐infarction coronary care unit patients were investigated within 6 months and at a three‐year follow‐up, and 52 male patients were studied within 6 months after an acute myocardial infarction. Oesophageal manometry, pH recording, acid perfusion test, ECG at rest and exercise, history by questionnaire and by interview were used as diagnostic tools. Non‐infarction coronary care unit patients with unknown origin of their chest pain at discharge from hospital had a higher frequency of OD (58%) than patients with recent myocardial infarction (33%, p < 0.05). In 7 of 55 (13%) non‐infarction patients OD was regarded as the cause and in 17 (31%) IHD was regarded as the cause of the pain on admission to the coronary care unit. OD was an uncommon cause of angina‐like chest pain in patients with recent myocardial infarction (1 of 38 patients). Patients with OD had a higher frequency of oesophageally related questionnaire symptoms than patients with normal oesophageal function. For the differential diagnosis of chest pain a careful history is essential. Reproduction of the patient's chest pain during oesophageal acid perfusion test or exercise test offers additional valuable information.
ANGINA PECTORIS SYMPTOMS CAUSED BY THORACIC SPINE DISORDERS. CLINICAL EXAMINATION AND TREATMENT
Authors: Hamberg Jern , Lindahl Olov
Published: August 2010

ABSTRACT. Pain identical with angina pectoris can be released from the disks Th4‐5, Th5‐6 and Th6‐7. Most common, cardiac‐like pain is elicited from Th5‐6. Physical stress such as lifting, rotation of the thorax and heavy work is especially symptom provoking. It is not unusual that movements in the bed during the night can provoke a pain attack. The pain can subside after a while but more often it continues for a long time in spite of rest. In all patients with symptoms of angina pectoris the thoracic spine should be examined. Pressing on the spinous process of the Th5 usually elicits an intensive and typical pain. The verification of the diagnosis is made by a »specific« investigation of the spine and ‐ ex juvantibus ‐ by the momentary relief of pain after manipulation of the actual spinal segment.
ENERGY METABOLISM IN THE REVERSIBLE AND IRREVERSIBLE PHASES OF SEVERE MYOCARDIAL ISCHEMIA
Authors: Reimer Keith A. , Jennings Robert B.
Published: August 2010

High energy phosphate (HEP) utilization and depletion as well as the production and distribution of catabolic products of adenine nucleotides were studied in ischemic dog hearts in order to characterize the transition from reversible to irreversible cell injury. Severe ischemia, induced by coronary occlusion in vivo was compared to total ischemia, in vitro. Much of the creatine phosphate (CP) was lost within the first one to three minutes. During severe ischemia in vivo, adenosine triphosphate (ATP) was depleted to only 35% of control by 15 minutes (when myocytes are still reversibly injured) and to less than 10% by 40 minutes (at which time irreversible injury has occurred). HEP production from anaerobic glycolysis was estimated from the rate of accumulation of myocardial lactate. HEP production ceased when the ATP was less than 0.4 μmol/g wet weight (control = 5–6). Prior to this time, 80% of the HEP which had been utilized in ischemia had been derived from anaerobic glycolysis whereas 20% came from pre‐existing stores of CP and ATP.

ATP depletion was paralleled by dephosphorylation of adenine nucleotides. The lost nucleotides were recovered stoichiometrically as adenosine, inosine, hypoxanthine, and xanthine in both models of ischemia. When myocardium was reperfused after 15 minutes of ischemia, these nucleosides and bases were lost to the systemic circulation, and repletion of adenine nucleotides was incomplete for as long as four days, apparently because both de novo and salvage pathways of adenine nucleotide synthesis are slow in myocardium.

Further studies were done to assess the nature of the associations between the decreasing ATP of the ischemic tissue and the onset of defects in high energy phosphate regeneration, cell volume and ion regulation, and/or membrane permeability. Slices of control tissue from tissue injured by various periods of total ischemia were incubated in oxygenated Krebs Ringer's phosphate medium containing 14 C‐inulin. As long as the ATP of the tissue was not depleted below 5 μmoles/g dry weight prior to incubation, no cellular abnormalities were detected. However, lower ATP levels were associated with depressed high energy phosphate resynthesis and failure of cell volume regulation. Overt membrane damage, as measured by an increased inulin diffusible space, was detected after the tissue ATP content decreased to less than 2.0 μmoles/g dry weight. Thus, cellular viability (reversible injury) was retained despite a modest and persistent ATP depletion, but there was a close assocation between marked ATP depletion and the failure of the damaged tissue to regenerate high energy phosphates and to preserve cell volume and ionic regulation (irreversible injury).
PROSTAGLANDINS AND PLATELET AGGREGATION
Authors: Smith J. B.
Published: August 2010

Prostaglandins may induce or inhibit platelet aggregation and constrict or dilate blood vessels. Recent interest has focussed on prostaglandins which are derivatives of arachidonic acid including prostaglandin endoperoxides, thromboxane A2, prostaglandin E2, prostaglandin D2and prostacyclin. Prostacyclin (PGI2) is a potent vasodilator and inhibitor of platelet aggregation whose enhanced production by vessel walls should be beneficial. It now appears that the circulating levels of PGI2in man are extremely low and little is known about the manner in which to increase them. Furthermore, aspirin, in doses of as little as 4 mg/kg inhibits prostacyclin as well as thromboxane formation. Thromboxane A2may be involved in coronary ischemia because it is a potent vasoconstrictor that is biosynthesized during platelet aggregation. Although thromboxane A2is very unstable indirect evidence obtained by using thromboxane A generating systems or a stable analogue called carbocyclic thromboxane A2(CTA2) suggests that it exacerbates ischaemic damage because of a selective increase in vascular resistance due to coronary vasospasm and platelet aggregation which acts to decrease myocardial blood flow.

The stable prostaglandins PGD2and PGE2are also of interest as both are formed during platelet aggregation. Like PGI2, PGD2inhibits platelet aggregation.
ACUTE INTERVENTION WITH METOPROLOL IN MYOCARDIAL INFARCTION
Authors: Hjalmarson Å
Published: August 2010

Studies in experimental and clinical myocardial infarction support the idea that sympathetic activity and myocardial noradrenaline release play a significant role in the development of myocardial ischemic damage.

Betablockade has been shown to limit infarct size and lower the incidence of ventricular fibrillation in experimental models. Betablockade to patients (pts) with acute myocardial infarction (AMI) has been shown to reduce ischemia reflected as reduction of ischemic chest pain, decrease ST‐segment elevation and increase lactate extraction. Whether this treatment in the clinical situation can prevent development of infarction, reduce infarct size and early mortality in man remains to be proven.

In Gøteborg a double‐blind study on metoprolol and placebo was started four and a half years ago. Inclusion of pts. in the study has been terminated and survival data will be available by May 1, 1981.

1395 pts. were included of whom 800 developed AMI. Metoprolol 15 mg was given IV followed by a total daily dose of 200 mg/day. The tolerance for betablockade was generally good.

Analysis of serum enzyme estimations of maximal LD I + II showed a significant reduction by metoprolol when the treatment was given within 12 hours of onset of pain. In a subgroup consisting of 103 pts. with AMI metoprolol had no clearcut effects on the ventricular arrhytmias during the first 24 hours in hospital. The betablockade resulted in a 15% reduction in heart rate.

The main objective of this study, the mortality during three months of blind treatment will be published late in 1981.
ACUTE INTERVENTION STUDIES IN PATIENTS WITH MYOCARDIAL INFARCTION USING ATENOLOL, PROPRANOLOL, OXPRENOLOL AND DISOPYRAMIDE PHOSPHATE
Authors: Wilcox R. G.
Published: August 2010

The value of beta‐blockade and of disopyramide phosphate in the immediate treatment of patients with suspected acute myocardial infarction was assessed in two placebo controlled trials. In the first study 388 patients with suspected acute myocardial infarction were randomly allocated to treatment with propranolol, atenolol, or placebo, and when analysed on an initial intention to treat basis there was no significant difference between the three groups in respect of the mortality at one year. In addition, there was no evidence to suggest that either atenolol, or propanolol reduced the incidence of ‘serious’ ventricular arrhythmias in the coronary care unit.

In the second study 473 patients with suspected acute myocardial infarction were randomly allocated to treatment with oxprenolol, disopyramide phosphate, or placebo. Again no significant differences were seen with respect to the mortality at six weeks. There was, however, a significantly increased incidence of heart failure in the group which received disopyramide phosphate. Patients who received this drug also showed a reduced number of dysrhythmic episodes on 24‐hour ECG recordings, but this trend did not achieve statistical significance.

These results suggest that none of the three beta‐blockers tested nor disopyramide phosphate is likely to reduce the mortality from acute myocardial infarction when given prophylactically, although disopyramide phosphate does reduce the incidence of ‘serious’ ventricular arrhythmias.
THE NORWEGIAN MULTICENTER STUDY ON TIMOLOL AFTER MYOCARDIAL INFARCTION ‐ DESIGN, MANAGEMENT AND RESULTS ON MORTALITY
Authors: Pedersen Terje
Published: August 2010

A cooperative clinical trial involving 20 hospitals in Norway was carried out to establish the effect of timolol (10 mg twice daily) compared with placebo in patients surviving acute myocardial infarction (AMI). The study was conducted in a randomized double‐blind manner.

All patients 20–75 years of age admitted to the centers with suspected AMI were registered and screened for the qualifying diagnosis. If the diagnosis of AMI was confirmed, the patients were evaluated for inclusion into the trial 6–27 days after onset of symptoms when being clinically stable. Of the 3647 patients evaluated, 1763 (48.3 %) had one or more of the criteria for exclusion from entry. These were contraindications to betablockade (18 %), serious disease impeding follow‐up (7 %), need for betablockade (9 %), need for other concomitant treatment not allowed (e.g. anti‐arrhythmics) (4 %) or administrative reasons and unwillingness to participate (10 %). The remaining, 1884 patients (51.7 %) were randomly allocated to treatment with timolol (945) or placebo (939) the morning after the evaluation.

Patients were stratified into 3 risk groups. In Risk Group I were patients with more than one infarction, Risk Group II were patients with a first AMI at high risk of late cardiac death and Risk Group III were patients with a first AMI at low risk. Clinical examination was done after 1, 3 and 6 months, thereafter every 6 months. Follow‐up time ranged from 12 to 33 months. The groups were comparable with respect to important baseline characteristics.

There were 152 deaths in the placebo group and 98 in the timolol group in the entire series. The life table cumulative probability of total death over 33 months was 21.0 % in the placebo and 13.3 % in the timolol group, corresponding to a reduction of 39.4 % (p=0.0003). The number of patients withdrawn from the trial medication was 219 in the placebo and 275 in the timolol group (p<0.01). The number of deaths during the first 28 days after withdrawal was 19 in the placebo group and 12 in the timolol group. When restricting the analysis to death occurring while the patient was taking the test medication or within 28 days of withdrawal («per protocol») there were 117 deaths in the placebo and 67 in the timolol group. The life table cumulative probability of death analysed per protocol was 17.5 % and 10.6 % in the placebo and timolol groups corresponding to a reduction of 39.3 % (p=0.0005).
Prognosis in Cardiac Pacing
Authors: Otterstad Jan Erik , Selmer Randi , Strøm Odd
Published: August 2010

ABSTRACT.The prognosis of 64 patients with atrioventricular (AV) block among 128 consecutive patients, 65 males and 63 females, treated with permanent pacemakers, was compared with that of 56 patients with sick sinus syndrome (SSS) during a mean observation period of 32.5 months. A poor survival rate was found in patients with known coronary heart disease (CHD) compared to those with isolated conduction defect (ICD). Among patients with CHD, a higher mortality was found in patients with AV block than in those with SSS (58 vs. 24%). Likewise, among patients with ICD the mortality in AV block was higher than in SSS (31 vs. 15%). Regression analysis showed a mortality excess in AV block vs. SSS (p=0.05) and a poor prognosis related to advanced age (p=0.02), males vs. females (p=0.04). The mortality excess in patients with CHD vs. ICD was significant (p=0.01). It is concluded that the increased mortality rate in patients with AV block is related to widespread myocardial damage, this being especially pronounced in patients with CHD.
Net Influx and Efflux of 22Na in Erythrocytes from Normotensive Offspring of Patients with Essential Hypertension
Authors: Henningsen Nels Chr. , Nelson Dick
Published: August 2010

ABSTRACT. Fresh erythrocytes from 35 young normotensive individuals (20 males), the offspring of patients with essential hypertension (EH), and from 24 normotensive controls (14 males) were incubated at 37°C in an isotonic buffer with 22Na. After 80 min, the net influx (net accumulation) of 22Na was not significantly different in either group, but after 140 min it was significantly higher (8.2%, p<0.01) in erythrocytes from male offspring as opposed to male controls. After both 80 and 140 min of incubation, the net influx of 22Na was significantly higher in males than in females in the respective groups. During a 60‐minute period the net efflux of 22Na from preincubated (180 min) erythrocytes in 14 males in the offspring group was not significantly different from that found in 10 male controls. These findings could indicate that little differences exists in vitro between offspring and controls in the unidirectional fluxes across the membrane. The difference between the male groups in the net influx after 140 min could indicate a higher Na content in the intracellular space in the offspring group, as assumption subsequently verified in a follow‐up. The net influx of 22Na after 140 min was significantly correlated (R=0.58, p<0.05) to total plasma aldosterone in male controls, but not in the offspring. No differences in the mean concentrations of total aldosterone, plasma and urinary electrolytes or in serum gamma glutamyl transferase were noted between offspring and controls. Abnormal cellular handling of sodium at least in the male offspring of patients with EH for at least two generations may be an important predisposing factor for EH.
HCG‐α and HCG‐β Subunits as Tumour Markers during Therapy in a Case with So‐Called “Non‐Functioning” Islet Cell Tumour
Authors: Öberg K. , Wide L. , Boström H.
Published: August 2010

ABSTRACT. A 61‐year‐old man with a malignant endocrine pancreatic tumour, so‐called “non‐functioning” islet cell tumour, is described. The tumour consisted of enterochromaffin‐like cells with positive immunocytochemistry for gastrin, glucagon and VIP, but neither of these or other peptides were elevated in the circulation. Elevated serum levels of HCG‐α and HCG‐β subunits were found. They seemed to be valuable tumour markers during cytotoxic therapy.
Early Exercise Tests after Uncomplicated Acute Myocardial Infarction before Early Discharge from Hospital
Authors: Lindvall K. , Kaijser L.
Published: August 2010

ABSTRACT. As part of an early mobilization and early discharge scheme, 76 consecutive low‐risk patients were selected from a population of 298 acute myocardial infarction (AMI) patients, to undergo an exercise test. The test was done on the 7th day after an AMI. The patients were 57 men and 19 women of mean age 57 and 68 years, respectively. Twelve patients were unalbe to complete the test, but no serious complications were observed. Average heart rate during the highest exercise load (50 W) was 106 beats/min. The following risk indices (RI) were considered abnormal and were looked for during or after exercise: 1) heart rate>125 (n = 12), 2) major ventricular arrhythmias (n=3), 3) angina pectoris (n = 9), 4) ST deviation of more than 1 mm (n = 11). Two RIs were found in 9 patients during the exercise test which led to prolonged hospitalization. One RI was found in 26 patients (34%). Eighty‐eight per cent (n = 36) of the patients with normal exercise test had an uneventful recovery during the six‐month observation period, in contrast to 35% (n = 9) of patients with one RI (p<0.05). Only two of the patients with heart rate >125 recovered normally, a significantly lower number (p<0.05) than among patients with a normal exercise test. Reinfarction occurred in one patient with normal exercise test and in six (23%) of those with one RI (p<0.01) and two of those with two RIs (N.S.). We conclude that a submaximal bicycle exercise test seven days after an AMI is a safe and useful selection instrument for early discharge from hospital as well as a useful predicting instrument of future complications.
Diurnal Levels of Lipids, Glucose and Insulin in Type IV Hyperlipidemic Patients on High Carbohydrate and High Fat Diet: Comparison with Normals
Authors: Mirani‐Oostdijk C. Pagano , van Gent C. M. , Terpstra J. , Hessel L. W. , Frölich M.
Published: August 2010

ABSTRACT. Diurnal levels of serum triglyceride (TG), cholesterol, free fatty acids (FFA), glucose and insulin were measured in three type IV hyperlipidemic patients on a fixed solid 65% carbohydrate and a 65% fat diet when in steady state conditions in a metabolic unit. The carbohydrate‐rich food was divided into either three or eight equivalent portions, differently spaced over the day and night. The fat‐rich food was given in three equivalent portions only. The diurnal TG profiles on these diets showed the same characteristics as those found in normals, but increments and mean levels were considerably higher. On the carbohydrate‐rich diet, mean TG levels decreased during the study. This was not seen either on the fat‐rich diet or in normals. In contrast to our findings in normals, chylomicrons formed the major contribution to the serum TG pattern. FFA levels were markedly higher on the high‐fat than on the carbohydrate‐rich diet, but not different from those in normals. Postprandial glucose responses did not differ significantly between the diets. Insulin responses were markedly higher on the carbohydrate‐rich than on the fat‐rich food. Glucose levels did not differ from those in normals. Insulin levels were significantly higher in the patients. Cholesterol showed minimal fluctuations, parallel to the TG pattern, which could be attributed to chylomicron cholesterol.
The Clinical Picture of Deep Vein Thrombosis Correlated to the Frequency of Pulmonary Embolism
Authors: Lundh Björn , Fagher Birger
Published: August 2010

ABSTRACT. Pain and swelling of the leg have been studied in 27 patients with deep vein thrombosis (DVT). Twenty‐three of them were also examined for pulmonary embolism (PE) after one week of heparin treatment. Scoring systems were constructed to quantitate pain, size of DVT and PE. A ratio between swelling and pain (S/P ratio) was calculated for each patient. Actual size of the DVT, as estimated with venous phlebography, was correlated to swelling (rs= 0.51, p<0.01), S/P ratio (rs= 0.53, p<0.01) and PE (rs=0.57, p<0.01). DVTs with no pain at all or just tenderness on palpation were more often associated with PE (p <0.05) and elevated blood pressure (p=0.02) than DVTs with pain on walking. A free floating proximal end of DVT proved unreliable for predicting PE. It is concluded that the risk of developing PE depends not only on DVT size, but also on factors related to pain.
Heparin Treatment of Deep Vein Thrombosis
Authors: Fagher Birger , Lundh Bjorn
Published: August 2010

ABSTRACT. Twenty‐eight patients with the diagnosis of deep vein thrombosis (DVT) were subjected to a prospective, randomized study comparing continuous and intermittent heparin treatment, utilizing the same doses and duration of therapy. The effect on pain (estimated with a scoring system) and the antithrombotic effect (assessed by the inhibition of 125I‐fibrinogen accretion), followed for one week, were unrelated. Pulmonary embolism was scored and studied from lung perfusion scans and chest X‐rays. A high frequency was found in both groups. The therapeutic efficacy and side‐effects did not differ between the two treatment groups. Bleeding, preferentially from vein puncture (post‐phlebography), was more common in women, while a heparin‐induced elevation of serum aminotransferases (S‐ALAT and S‐ASAT) (in 2/3 of the patients) was not related to age, sex or bleeding complications.
Human Monocytes and Lymphocytes Differ in the Rate of DNA Repair Synthesis and Viability after Exposure to Nitrogen Mustard
Authors: Lewensohn R. , Ringborg U.
Published: August 2010

ABSTRACT.Unscheduled DNA synthesis was studied in human lymphocytes and monocytes after treatment with nitrogen mustard, methyl‐methane‐sulphonate and ultraviolet irradiation. The unscheduled DNA synthesis was about 4 times higher in monocytes than in lymphocytes after treatment with nitrogen mustard. Treatment with methylmethane‐sulphonate or ultraviolet irradiation confirmed the higher capacity for unscheduled DNA synthesis in the monocytes. When Ficoll‐Isopaque‐isolated mononuclear cells were exposed to various doses of nitrogen mustard and incubated for different periods, a dose‐ and time‐dependent increase in trypan blue uptake was found. Furthermore, a corresponding dose‐ and time‐dependent decrease was noted in3H‐uridine incorporation. Since trypan blue uptake will not enable differentiation between monocytes and lymphocytes appearing as a mixed cell population,3H‐uridine flash labeling index was studied after exposure to nitrogen mustard. There was a dose‐ and time‐dependent decrease in3H‐uridine labeling index, suggesting a correlation between the absence of3H‐uridine incorporation and increase in trypan blue uptake. When compared to monocytes, the lymphocytes were more affected in this respect after exposure to nitrogen mustard. The possibility that differences in cytotoxic effect may be related to DNA repair mechanisms is discussed.
Simple Screening Procedure for the Diagnosis of Primary Aldosteronism
Authors: Lund J. O. , Nielsen Meta Damkjær , Giese J.
Published: August 2010

ABSTRACT. A simple screening protocol for the diagnosis of primary aldosteronism was applied to 149 hypertensive patients. The diagnostic criterion for possible primary aldosteronism was the combination of supine plasma renin concentration <15 mIU/l (normal range 6–54) and plasma aldosterone concentration >11 ng/100 ml (normal range 3–18). None of 63 persistently normokalaemic hypertensive patients fulfilled this criterion. Seventeen (20%) of 86 hypokalaemic patients showed hormonal values consistent with primary aldosteronism. The presence of an adrenal adenoma was verified in eight of these patients. Thus screening for primary aldosteronism can be restricted to hypokalaemic patients. The prevalence of primary aldosteronism in a hypertensive population was calculated to be < 1%.
Cyclofenil versus Placebo in Progressive Systemic Sclerosis
Authors: Blom‐Bölow Berith , Öberg Kjell , Wollheim Frank A. , Persson Bertil , Jonson Björn , Malmberg Per , Boström Harry , Herbai Georg
Published: August 2010

ABSTRACT. Cyclofenil was evaluated versus placebo in the treatment of progressive systemic sclerosis (PSS, scleroderma) in a 2times6‐month double‐blind crossover study. The mean duration of disease was six years. Of 38 patients entering the study, 27 completed both periods. Reasons for drop‐outs were very high liver transaminases in three cases, cardiac death in two, and drug allergy, alcoholic problems, suspected congestive heart failure, reactivation of tuberculosis, arteriosclerotic heart disease, and lethal progression of PSS in one case each. No fatality was attributed to cyclofenil. Liver enzyme abnormalities were seen in 13 of 35 active drug periods and in 5 of 30 placebo periods. Cutaneous and visceral involvement were assessed by a large battery of subjective parameters and objective tests. Overall improvement was seen during 17 drug periods and nine placebo periods (N.S.), but a paired comparison of the status at the end of each treatment period resulted in the following distribution: 15 were improved at the end of the drug period, four at the end of placebo period (p<0.01) and eight were unchanged. In patients with a disease duration of five years or less, joint stiffness and pain were less on drug than on placebo treatment (p<0.05). In the whole group, oesophageal peristalsis improved (p<0.05). Blood folate increased (p<0.01). Working capacity was lower after the drug period than after the placebo period (p<0.05). Several other parameters, however, did not change significantly. Cyclofenil appears to be a promising drug in the treatment of PSS and should be tested further in controlled long‐term studies.
Dissociation between Changes in Immunoreactive Parathormone and Its Biological Indices Induced by Cimetidine in Primary Hyperparathyroidism
Authors: van der Velden P. C. , Fischer H. R. A. , Hackeng W. H. L. , Schopman W. , Koorevaar G. , den Ottolander G. J. H. , Silberbusch J.
Published: August 2010

ABSTRACT. In three out of four patients with primary hyperparathyroidism, 2000 mg of cimetidine daily caused a reduction of immunoreactive parathormone (iPTH) when measured at 8.30 and 11.30 on days 16 and 17 on treatment. Serum Ca, PO4 and maximal tubular reabsorption of PO4 remained unchanged. Excretion of cAMP/100 ml GFR remained elevated to at least the same extent as before treatment. Two patients, in whom cimetidine treatment was continued for an additional 4 weeks, did not show further hormonal or biochemical changes compared with the evaluation on days 16 and 17. We conclude that reduction of iPTH is not accompanied by any change in biological activity of this hormone. The reason for this discrepancy remains unclear.
Is the Coronary Care Unit a Coronary Scare Unit?
Authors: van der Lelie J. , Endert E. , Wieling W. , Dunning A. J.
Published: August 2010

ABSTRACT. In order to evaluate the influence of stress associated with admission to a coronary care unit (CCU), we measured the plasma noradrenaline and adrenaline concentrations during the first CCU hour in 47 patients with suspected acute myocardial infarction (AMI). These values were compared with those in healthy hospital personnel. AMI patients had significantly higher plasma catecholamines than patients with no apparent cardiac disease. The highest values were found in patients with complicated AMI. Although the patients had significantly higher plasma catecholamines than hospital personnel, it is concluded that the circulation rather than the situation determines plasma noradrenaline and adrenaline levels and that stress does not play a major role. This study provides no support for the suggestion that home care is preferable for patients with AMI as a means of avoiding the stress of admission to hospital.
Gemfibrozil in the Treatment of Dyslipidaemias in Middle‐Aged Male Survivors of Myocardial Infarction
Authors: Kaukola Sirkka , Manninen Vesa , Mälkönen Marjatta , Ehnholm Christian
Published: August 2010

ABSTRACT. The effects of gemfibrozil on serum lipids and apolipoproteins were investigated in 60 male survivors of myocardial infarction (MI) (age range 29–48 years, mean 44). Fifteen had normal serum cholesterol (≤ 7.0 mmol/l) and triglyceride (≤ 1.7 mmol/l) levels, but most had low levels of high density lipoprotein (HDL) cholesterol (<1.00 mmol/l). Ten had type II A, 27 type II B and 8 type IV hyperlipidaemia. A double‐blind placebo‐controlled cross‐over design was used with 3‐month treatment periods. Gemfibrozil was given in daily doses of 1200 mg. The drug was well tolerated and there were no drop‐outs attributable to its use. In all subjects, gemfibrozil reduced the mean serum total cholesterol by 17 % and triglycerides by 54 % and increased HDL cholesterol by 16%. The percentage HDL cholesterol of total cholesterol increased from 14 to 19 %. The changes were similar in patients with normal serum cholesterol and triglyceride values and in those with classical hyperlipidaemias. In contrast, the changes during placebo treatment corresponded to those in healthy male untreated controls who were followed simultaneously. Apoprotein A‐I remained unchanged, but A‐II increased by 20 % during gemfibrozil treatment. It is concluded that gemfibrozil corrects effectively dyslipidaemias in male MI patients but further long‐term studies are warranted.