1. Atenolol (ICI 66.082, Tenormin) is a new beta-adrenoreceptor-blocking agent, devoid of intrinsic sympathomimetic and membrane-stabilizing properties. It does not cross the blood-brain barrier. 2. Atenolol given to hypertensive patients in initial open trials reduced arterial blood pressure significantly. 3. A double-blind comparison between atenolol and placebo in forty-five patients with essential hypertension demonstrated that atenolol gave a statistically significant reduction of blood pressure (delta 28/15 mmHg, P less than 0-005). 4. The optimum anti-hypertensive dose of atenolol in patients with mild to moderately severe essential hypertension was 200 mg daily. 5. Atenolol was compared with propranolol in thirty patients with essential hypertension. No statistically significant differences of anti-hypertensive effect were observed between the two drugs. 6. Long-term results (up to 2 years) in 117 hypertensive patients indicate that drug tolerance is good. No serious toxic effects were observed. 7. In four of twelve hypertensive patients with obstructive airways disease atenolol had to be withdrawn owing to deterioration of ventilatory function.

Antihypertensive Agents↗

PubMed1976

Long-term hypotensive effect of atenolol (ICI 66.082), a new beta-adrenergic blocking agent.

A report is given from an on-going multicenter trial in Sweden, in which 117 hypertensive patients have been treated with a new cardioselective beta-adrenergic blocking agent, atenolol (ICI 66.082, Tenormin) for an average of six months (range 2-21). Statistically significant reductions of BP were observed, recumbent by 29/19 mmHg (p less than 0.0001) and standing by 28/18 mmHg (p less than 0.0001). Few and comparatively mild side-effects were seen.

Adrenergic beta-Antagonists↗

PubMed1976

Zinc and copper in pregnancy, correlations to fetal and maternal complications.

Serum zinc and serum copper concentrations during early pregnancy in 84 consecutive primigravidae were correlated to other haematological factors and were also correlated to complications of labour and/or complications affecting the infant. In women with complications such as abnormal labour or atonic bleeding, serum zinc concentrations were significantly reduced (p less than 0.001) during early pregnancy. Women who gave birth to immature infants also showed significantly lower serum zinc in early pregnancy (p less than 0.01). Women delivered in the 37th week or earlier or in the 43rd week or later showed significantly lower serum zinc during early pregnancy (p less than 0.005) compared to women delivered in the 40th week. One infant showed a congenital heart defect (ventricular septum defect and preductal coarctation of aorta). Her mother showed the lowest serum zinc concentration recorded in the 13th week, but no other abnormal findings. Compared to women with abnormal labours and/or immature infants, mothers with normal deliveries and normal deliveries and normal infants showed significantly higher serum zinc values (p less than 0.001) and significantly lower serum copper concentrations (p less than 0.025) during early pregnancy. A notably high incidence of complications affecting mothers and infants has been recorded among women with low serum zinc. Similarities to effects of experimental zinc deficiency in animals are striking. If a low serum zinc reflects a state of deficiency, and this seems to be the case, zinc deficiency is probably common.

Abortion, Spontaneous↗

PubMed1976

Variations in maternal serum zinc during pregnancy and correlation to congenital malformations, dysmaturity, and abnormal parturition.

Serum zinc concentrations in 234 gravidae showed a gradual fall during the first and second trimesters. From the 25th week of gestation until delivery there is a levelling out of mean zinc values. No correlations between serum zinc, serum HCS, or urinary excretion of oestriol were found. Women with mature infants born by normal delivery showed significantly higher serum zinc during pregnancy than women with abnormal deliveries and/or abnormally developed infants (p less than 0.001). Eight infants showed congenital malformations. Five of the 8 mothers showed the lowest serum zinc concentrations recorded during respective week of pregnancy. A diabetic woman gave birth to an immature infant with multiple skeletal malformations. She showed the lowest serum zinc in the 21st week, and at the same time a very low alkaline phosphatase activity. Her serum proteins and serum HCS were normal. Women with dysmature infants showed significantly lower zinc values during pregnancy (p less than 0.02) than women with mature infants born by normal delivery. Data from studies on zinc metabolism show that there is a requirement of at least 375 mg of zinc during pregnancy in order to meet the demands of normal weight gain. Teenagers, women with multiple pregnancies, women with impaired intestinal absorption due to disease or drugs and in particular women with a low-protein, high-phytate diet seem to risk developing zinc deficiency during pregnancy.

Adolescent↗

PubMed1976

Zinc deficiency in malabsorption states: a cause of infertility?

Thirteen patients with malabsorption, 7 women and 5 men, were investigated extensively. All showed low serum zinc concentrations irrespective of the duration of illness and degree of malabsorption. Eleven of the 13 had active coeliac disease. It was suspected that the low serum zinc concentrations reflected a state of zinc deficiency, and this theory was borne out by the fact that no inflammatory reaction, no clear-cut albumin deficiency, and no oestrogen or corticosteroid influence could be demonstrated. All 7 women suffered from infertility, in most of them of long standing. Two showed secondary infertility after pregnancy and abnormal labour resulting in infants with congenital malformations (one case of bilateral congenital dislocation of the hip and one of multiple cardiac anomalies). I have reported similar complications in pregnancies in which the serum zinc was low. One of the infertile women conceived after the institution of gluten-free diet and zinc therapy, but later aborted spontaneously. Investigations on zinc metabolism and intestinal absorption might well prove valuable in otherwise unexplained infertility and could open up a new therapeutic approach.

Abortion, Spontaneous↗

PubMed1976

Low serum zinc concentrations in pregnancy, results of investigations and treatment.

Twenty gravidae in whom the serum zinc concentration was less than 11.5 mumol/1 were investigated. Haemoglobin, serum vitamin B-12, serum folate, serum copper, and bone marrow smears were assessed. Thirteen showed haemoglobin concentrations below 110 g/1 and in 7 of them the cause of this anaemia was not found. Histological investigations indicated increased intramedullary cell destruction. Eight women selected at random were referred for further investigation including tests of renal and hepatic function, serum protein analyses, tests of haemolysis, and estimation of zinc and oestriol excretion in urine. The low serum zinc concentrations received no probable explanation other than zinc deficiency. Seven gravidae were treated with 90 mg Zn2+ daily as zinc sulphate by mouth during the latter part of pregnancy. Zinc excretion in urine was low and increased significantly (p less than 0.005) after one week's therapy. The serum zinc also increased (p less than 0.05). Zinc therapy gave no reticulocytosis within 8-12 days. Three women reported spontaneously an improvement in sense of taste. Five of 20 gravidae had dysmature infants. Heavy bleeding occurred at delivery in 6 cases, possibly secondary to impaired uterine contractility. Seven women who received zinc therapy had all normal deliveries, but labour was prolonged in one. No side effects of zinc therapy were noted except for nausea in one case. Further trials of zinc supplementation in larger series of women with low serum zinc concentrations during pregnancy seem to be justified.

Adolescent↗

PubMed1976

Refractory anaemia of pregnancy as an expression of zinc deficiency.

Thirty-three gravidae with anemia in spite of iron and vitamin supplementation were examined, and 31 were found to have low or very low serum zinc concentrations with regard to the week of gestation. Twenty-three of the 33 showed no bone marrow haemosiderin or only traces. Thirty showed moderate or great increase in intracellular cell debris in the bone marrow macrophages, indicating an increase in intramedullary cell destruction. Two women showed low serum vitamin B-12 or folate concentrations and they also showed lowest zinc concentrations recorded in the series. Twelve of the 33 women gave birth to mature infants by normal delivery; 21 developed complications during labour or gave birth to immature, dysmature, or, in one case, malformed infants and/or were not delivered at normal term. Low serum zinc in pregnant women increases maternal morbidity and involves a higher risk to the fetus. It is suggested that an aetiological relationship exists between low serum zinc concentrations and refractory anaemia of pregnancy resulting in increased intramedullary cell destruction. This effect might be aggravated by iron deficiency.

Adult↗

PubMed1976

Effects of zinc deficiency in human reproduction.

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Adolescent↗

PubMed1976

Oxymetholone treatment in aregenerative anaemia. II. Remission and survival--a prospective study.

This is a prospective multi-center study in which patients with aregenerative anaemia were treated with a standardized high dosage regime of an anabolic steroid (oxymetholone, Anasteron). 53 patients were included and divided into two groups according to bone marrow cellularity. Furthermore the hypocellular group was subdivided in order to make comparison with earlier studies possible. In the hypocellular group, the frequency of remission was 56% and the 2-year-survival from the onset of symptoms was 75%. This is longer than in some earlier studies, perhaps because of possible differences in etiology and/or because of the effect of systematic high dosage, long term androgen therapy. Patient selection was minimized and was not considered to be of major importance. Patients with hypercellular marrows, on the other hand, responded poorly to androgens. In this group 63% died of acute leukaemia, which confirms earlier suggestions that this form of aregenerative anaemia, frequently is of a preleukaemic nature.

Adolescent↗

PubMed1975

L-asparaginase and prednisolone pretreatment followed by rubidomycin and cytosine arabinoside for induction of remission in adult patients with acute myeloblastic leukaemia.

77 unselected adult patients with acute myeloblastic leukaemia (AML), including practically all AML patients from an area with 1.9 million inhabitants, were randomized for either (1) 5 days pretreatment with 1-asparaginase and prednisolone followed by a combination of rubidomycin and cytosine arabinoside (ARAP), or (2) treatment with a combination of rubidomycin, cytosine arabinoside and prednisolone without 1-asparaginase pretreatment (RAP). Complete remission was induced with ARAP in 12 patients (31%) and with RAP in 13 patients (34%). Thus pretreatment with 1-asparaginase did not improve the therapeutic response. The overall remission frequency was significantly higher below the age of 60; 50% compared to 13% above this age. Side-effects such as liver dysfunction, nausea and vomiting were more common in patients pretreated with 1-asparaginase. Sterilization of the gut did not improve the remission frequency with either regime.

Adolescent↗

PubMed1974