Surgical Treatment of Severe Attacks of Ulcerative Colitis,with Special Reference to the Advantages of Early Operation

The management and outcome of 258 severe attacks of ulcerative colitis from 1952 to 1969 has been reviewed. If remission did not occur during an initial course of intensive medical treatment, including administration of corticosteroids, operation (generally ileostomy with proctocolectomy or subtotal colectomy) was performed. This took place some 12 to 17 days after admission as a rule during the years 1952-63, but usually within five to seven days from 1964 to 1969.Roughly half the attacks underwent spontaneous remission during the two periods, but the medical mortality was 4·8% in the former and 0·7% in the latter, the operative mortality 20·0 and 7·0%, and the overall mortality 11·3 and 4.5% respectively. The lowering of the mortality was particularly striking in severe first attacks and in severe attacks in patients over 60 years of age.Perforation of the colon was found in 21 cases, or nearly 20% of 112 patients coming to operation during attacks, being commoner in the first period (32·5%) than in the second (11·1%). The immediate mortality of all such operations was 11·6%; in cases with perforation it was 28·6%.Acute colonic dilatation was observed in 28 cases. All but one were treated by emergency colectomy, at which the colon was noted to be perforated in 11. The mortality of these operations was 18·5%.Follow-up of the 140 patients who survived without coming to operation during their attacks shows that 52 (37·1%) subsequently underwent surgical treatment either during further attacks or electively.Though all 258 attacks were thought at the time to be due to ordinary ulcerative colitis, subsequent pathological examination of operative specimens derived from 98 patients who came to urgent or subsequent operation during the 1964-9 period revealed that the lesion in the large bowel was Crohn''s disease in 17 instances.     

Epidemiology and Course of Gastrointestinal Haemorrhage in North-east Scotland

A prospective study was made of 817 consecutive episodes of major gastrointestinal haemorrhage in patients admitted to hospital during 1967-8 from the defined population of North-East Scotland. The yearly admission rate was 116 per 100,000 population. Comparison of the data for city and country residents showed no appreciable differences. In the duodenal ulcer group there was an undue incidence of bleeding among foremen and skilled workers and among those who were unmarried or widowed.Both the clinical history and the results of any previous barium meal examinations were unreliable guides to the source of the current haemorrhage. Prognosis was worse for patients who did not have a dyspeptic history and was better for those who had bled on a previous occasion. The simultaneous ingestion of alcohol and aspirin had an adverse effect on the occurrence of bleeding. Forty-seven per cent. of the patients had another major coincidental disease.Mortality was 13·7% in the whole series and 8·6% in those with peptic ulcer (duodenal ulcer 7·1%, gastric ulcer 16·9%). In 28% of the patients further haemorrhage occurred after admission to hospital and caused a 28·8% mortality. Seventy-four patients were already in hospital when they first bled and 44% of them died.     

Emergency geriatric surgical admissions

The emergency surgical work load created by patients aged 80 and over in a district hospital was assessed and the results of treatment examined. Over one year 248 patients aged 80 or over were admitted as emergencies, and the overall mortality rate was 21·8%. When terminal disease was excluded mortality rate was 12·5%. These elderly patients had an average length of stay in the acute surgical ward of 14·7 days compared with a mean of 8·4 days for all patients, and all but seven patients were discharged to their original place of referral.Elderly patients do exacerbate the bed shortage in acute surgical wards because they tend to stay longer than younger patients, but these elderly surgical patients imposed only a small load on the inpatient geriatric services, as 78% were discharged straight to their own homes and a further 17% went home after a period on the surgical convalescent wards.     

Results of Early Mobilization and Discharge after Myocardial Infarction

A total of 342 patients with acute myocardial infarction who were admitted to a coronary care unit are reviewed to assess the results of early mobilization and discharge. The mean duration of admission was 8·4 days and 89% of the survivors were discharged from hospital by the tenth day. The inpatient mortality was 15·5%. An additional 6·7% died during the six weeks'' follow-up period, giving a total mortality of 22·2%. Altogether, 7·6% of patients were readmitted. Venous thromboembolic phenomena occurred in 3·5% during the inpatient period. Of patients who were eligible 62% were back at work five months after their myocardial infarction. We think the results justify a short hospital admission period for acute myocardial infarction.     

Rates of entry and oxidation of acetate,glucose, d(?)-β-hydroxybutyrate,palmitate, oleate and stearate,and rates of production and oxidation of propionate and butyrate in fed and starved sheep

1. Rates of entry and oxidation of a range of metabolites have been measured in tracheostomized sheep (diet, 800g. of lucerne chaff and 100g. of maize/day) by combining isotope-dilution techniques with the continuous measurement of total respiratory gas exchange, and ¹⁴CO₂ production during the intravenous or intraruminal infusion of ¹⁴C-labelled substrates. 2. Mean entry rates in fed and starved (24hr.) sheep respectively, expressed as mg./min./kg. body wt.^0·75, were: glucose, 5·0 (range 4·8–5·1, 2 observations) and 3·8 (3·2–4·2, 4); acetate, 10·8 (9·1–13·5, 4) and 5·8 (1); d(−)-β-hydroxybutyrate, 1·4 (1) and 1·5 (0·8–2·4, 4); palmitate, oleate and stearate (starved sheep only) 1·0 (0·6–1·9, 7), 0·9 (0·2–1·6, 10) and 0·9 (0·5–1·1, 11) respectively. 3. Production rates of propionate and butyrate in continuously feeding sheep were 6·4 (4·7–8·3, 4) and 4·3 (3·4–6·1, 4) mg./min./kg.^0·75 respectively, and in starved (24hr.) sheep were 2·5 (2·2–2·9, 2) and 1·0 (0·8–1·2, 2) mg./min./kg.^0·75 respectively. 4. Calculated terminal values for the specific radioactivity of respiratory ¹⁴CO₂ during measurements of entry rates and production rates were used to calculate the contributions of individual substrates to overall oxidative metabolism. Mean values for fed and starved sheep respectively were: glucose, 9·1 (8·6–9·6, 2) and 11·2 (5·9–15·1, 4)%; acetate, 31·6 (26·8–38·1, 4) and 22·1 (1)%; d(−)-β-hydroxybutyrate, 10·4 (1) and 4·8 (1·9–7·7, 4)%; propionate, 23·0 (13·8–29·9, 4) and 7·1 (6·8–7·4, 2)%; butyrate, 16·5 (13·7–20·5, 4) and 5·3 (5·2–5·3, 2)%; palmitate, oleate and stearate (starved sheep only), 4·7 (2·0–7·7, 7), 4·0 (1·2–6·6, 10) and 4·4 (3·8–5·8, 9)% respectively. The sum of these values for individual substrates in fed and starved sheep, excluding that of β-hydroxybutyrate and after correction of the glucose value for the known interrelations of this substrate with propionate, accounted for 76% and 58% respectively of total production of carbon dioxide. 5. Calculations based on the proportion of substrate entry directly oxidized indicated that the substrates studied accounted for 63% (fed sheep) and 43% (starved sheep) of total energy expenditure measured by oxygen uptake. The contribution of β-hydroxybutyrate was excluded, and corrections were made for glucose–propionate interrelations, and for the different rates of oxidation of the methyl and carboxyl fragments of acetate. 6. The present results have been combined with those obtained earlier in this Laboratory to examine the relationships between rates of substrate entry and oxidation, and concentrations of substrate in blood. Rates of entry of acetate, glucose, d(−)-β-hydroxybutyrate, palmitate and oleate (but not stearate) were well correlated with concentration in blood, and substrate contribution to production of carbon dioxide showed a similar correlation to blood concentration, except with glucose. 7. It was concluded that the general technique is of potential value in providing valid quantitative parameters of animal metabolism.     

Clinical Problems: Hepatitis in Dialysis Units in the United Kingdom

A prospective study of hepatitis in 20 dialysis units in the United Kingdom showed that the number of units with outbreaks increased from one in 1968 to three in 1969 and the overall attack rate rose from 1·7 to 5·3% in patients and from 0·5 to 1·3% in staff.In July 1969 a pilot study of patients'' sera showed that all of the outbreaks were associated with Australia (Au) antigen. Au antigen was not detected in the unaffected units or in one unit in which there were several patients with abnormal liver function.In January 1970 systematic prospective testing for Au antigen was begun. Au antigen was detected in single patients in five more of the 20 units. The transfer of the affected patients to isolation for dialysis seemed to prevent the spread of infection in the units. The incidence of hepatitis in 1970 was 5·6% in patients and 0·4% in staff.     

Streptokinase in Recent Myocardial Infarction: A Controlled Multicentre Trial

In this controlled multicentre trial treatment with either streptokinase or heparin was allocated at random to patients suffering from myocardial infarction of less than 24 hours'' duration. Treatment with either drug was standardized and lasted for 24 hours. A total of 764 patients entered the trial; 34 patient charts were rejected (including all 28 charts from one centre) because of data failure. On retrospective analysis of the 730 remaining patients the two groups were found to have been comparable at the start.The total hospital mortality was 18·5% of 373 patients allotted to streptokinase treatment and 26·3% of 357 given herapin. The mortality after infusion (24 hours) was 10·6% of 340 patients treated with streptokinase and 17·8% of 320 given herapin (P=0·011). Reinfarction in hospital after the 24-hour period of infusion occurred significantly less often in patients treated with streptokinase (P=0·036). Bleeding from puncture sites and pyrexia occurred more frequently during streptokinase treatment.After exclusion of those patients whose diagnosis was unconfirmed on retrospective assessment, the total hospital mortality rate was 19·0% of 357 patients treated with streptokinase and 27·4% of 339 treated with heparin (P=0·011). These results indicate that in recent myocardial infarction streptokinase was superior to heparin in reducing mortality and reinfarction rate during an average period of six weeks in hospital.     

Collaborative systematic review of the randomised trials of organised inpatient (stroke unit) care after stroke. Stroke Unit Trialists' Collaboration.

OBJECTIVES: To define the characteristics and determine the effectiveness of organised inpatient (stroke unit) care compared with conventional care in reducing death, dependency, and the requirement for long term institutional care after stroke. DESIGN: Systematic review of all randomised trials which compared organised inpatient stroke care with the contemporary conventional care. Specialist stroke unit interventions were defined as either a ward or team exclusively managing stroke (dedicated stroke unit) or a ward or team specialising in the management of disabling illnesses, which include stroke (mixed assessment/rehabilitation unit). Conventional care was usually provided in a general medical ward. SETTING: 19 trials (of which three had two treatment arms). 12 trials randomised a total of 2060 patients to a dedicated stroke unit or a general medical ward, six trials (647 patients) compared a mixed assessment/rehabilitation unit with a general medical ward, and four trials (542 patients) compared a dedicated stroke unit with a mixed assessment/rehabilitation unit. MAIN OUTCOME MEASURES: Death, institutionalisation, and dependency. RESULTS: Organised inpatient (stroke unit) care, when compared with conventional care, was best characterised by coordinated multidisciplinary rehabilitation, programmes of education and training in stroke, and specialisation of medical and nursing staff. The stroke unit care was usually housed in a geographically discrete ward. Stroke unit care was associated with a long term (median one year follow up) reduction of death (odds ratio 0.83, 95% confidence interval 0.69 to 0.98; P < 0.05) and of the combined poor outcomes of death or dependency (0.69, 0.59 to 0.82; P < 0.0001) and death or institutionalisation (0.75, 0.65 to 0.87; P < 0.0001). Beneficial effects were independent of patients'' age, sex, or stroke severity and of variations in stroke unit organisation. Length of stay in a hospital or institution was reduced by 8% (95% confidence interval 3% to 13%) compared with conventional care but there was considerable heterogeneity of results. CONCLUSIONS: Organised stroke unit care resulted in long term reductions in death, dependency, and the need for institutional care. The observed benefits were not restricted to any particular subgroup of patients or model of stroke unit care. No systematic increase in the use of resources (in terms of length of stay) was apparent.     

Exchangeable and Total Body Potassium in Patients with Chronic Renal Failure

Total body potassium determined by whole-body monitoring and exchangeable body potassium estimated with ⁴³K were measured simultaneously in 12 patients with stable chronic renal failure. Values for the exchangeable potassium were obtained after equilibration periods of 24, 48, and 64 hours. The exchangeable body potassium, expressed as a percentage of the total body potassium (mean ± S.E. of mean), gave values of 60·7 ± 3·3%, 83·6 ± 2·7%, and 85·9 ± 2·7% at 24, 48, and 64 hours respectively. It seems that the equilibration between radioactive and native potassium is incomplete after 24 hours; and that exchangeable potassium measured at this time is not an accurate index of the status of total body potassium in such patients. Furthermore, the finding that the value at 64 hours is significantly less than found in healthy subjects suggests that the exchangeable potassium is a smaller fraction of the total body potassium in patients with chronic renal failure.     

Use of Learning Media by Undergraduate Medical Students in Pharmacology: A Prospective Cohort Study

The ubiquity of the internet and computer-based technologies has an increasing impact on higher education and the way students access information for learning. Moreover, there is a paucity of information about the quantitative and qualitative use of learning media by the current student generation. In this study we systematically analyzed the use of digital and non-digital learning resources by undergraduate medical students. Daily online surveys and semi-structured interviews were conducted with a cohort of 338 third year medical students enrolled in a general pharmacology course. Our data demonstrate a predominant use of digital over non-digital learning resources (69 ± 7% vs. 31 ± 7%; p < 0.01) by students. Most used media for learning were lecture slides (26.8 ± 3.0%), apps (22.0 ± 3.7%) and personal notes (15.5 ± 2.7%), followed by textbooks (> 300 pages) (10.6 ± 3.3%), internet search (7.9 ± 1.6%) and e-learning cases (7.6 ± 3.0%). When comparing learning media use of teaching vs. pre-exam self-study periods, textbooks were used significantly less during self-study (-55%; p < 0.01), while exam questions (+334%; p < 0.01) and e-learning cases (+176%; p < 0.01) were utilized more. Taken together, our study revealed a high prevalence and acceptance of digital learning resources by undergraduate medical students, in particular mobile applications.     

Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy

Six men aged 26-35 years with proteinuria due to insulindependent juvenile-onset diabetes were treated for moderate hypertension (mean blood pressure 162/103 mm Hg) and studied for a mean of 73 months for the effect on the progression of nephropathy. All patients were of normal weight. During a mean control period of 28 months before treatment the mean glomerular filtration rate (three or four measurements) was 86·1 ml/min and mean 24-hour urinary albumin excretion (also three or four measurements) 3·9 g (range 0·5-8·8 g).During antihypertensive treatment the mean systolic blood pressure fell to 144 mm Hg and mean diastolic pressure to 95 mm Hg. In the control period five patients had shown a mean monthly decline in glomerular filtration rate of 1·23 ml/min; with antihypertensive treatment, however, this decline fell to 0·49 ml/min (2p=0·042). In the remaining patient the glomerular filtration rate was 137 ml/min before treatment and 135 ml/min at the end of the treatment period. In all patients the mean yearly increase in albumin clearance (expressed as a percentage of the glomerular filtration rate) fell from 107% before treatment to 5% during treatment (2p=0·0099).This small study indicates that antihypertensive treatment slows the decline in renal function in diabetic nephropathy. Clinical trials beginning treatment in the incipient phase of diabetic nephropathy will define the optimal modality of treatment in this large patient population.     

One Year's Experience in a Ministry of Health Dialysis Centre

A 10-bed dialysis unit, opened at the London Hospital in 1968, admitted 37 patients during its first year of operation. The aims of the unit were to prepare patients for renal transplantation and to provide instruction for dialysis treatment at home. A total of 2,012 days were spent in hospital, the average intervals between admission, the first dialysis, and discharge being 23·8 and 20 days, respectively. The overall number of readmissions was 1·5 per patient. These figures, together with the increasing number of patients accepted for such treatment, indicate the considerable number of supporting hospital beds, as well as medical and technical staff, required to maintain a dialysis unit.     

Results of Surgery for Inflammatory Bowel Disease: A Further Survey of One Hospital Region

Case records have been studied for the results of surgery in 294 patients operated on for inflammatory bowel disease during 1967-72 at 34 non-teaching hospitals within the North-east Metropolitan Hospital Region. All patients treated surgically for acute colitis and those treated for chronic disease by total colectomy were included.The postoperative mortality of the primary surgery was 23·7%. The mortality was 2·1% in patients treated by elective operation, 37·6% in patients coming to urgent operation, and 60·9% in patients treated by emergency operation. The three most important factors affecting the mortality were considered to be: increasing age of the patient, the presence of established colonic dilatation, and preoperative perforation of the colon.     

A new urethral catheter

A new balloon catheter for women with a flexible urethral portion that conforms to the shape of the closed urethra was tested. In sheep control catheters caused epithelial destruction, which was absent with the conformable catheter. A 12 week crossover trial compared control catheters in 52 long stay geriatric patients. Eighty two out of 91 conformable catheters were rated as comfortable compared with 68 of 87 control (p=0·006). The average length of time in situ was 15·9 days for the conformable catheter compared with 12·9 days for the control (p=0·001). The average number of bypasses a week with the conformable catheter was 1·1 compared with 1·3 for the control; this difference was not significant. Examination of 249 used catheters showed significantly fewer with intraluminal obstruction with struvite among the conformable than control catheters (1 (0·8%) versus 15 (11·5%); p<0·001).This new catheter for women is a substantial improvement over the Foley catheter and (except in urethral stricture) is suitable for all forms of drainage.     

Circulating Mitochondrial DNA in Patients in the ICU as a Marker of Mortality: Derivation and Validation

Background

Mitochondrial DNA (mtDNA) is a critical activator of inflammation and the innate immune system. However, mtDNA level has not been tested for its role as a biomarker in the intensive care unit (ICU). We hypothesized that circulating cell-free mtDNA levels would be associated with mortality and improve risk prediction in ICU patients.

Methods and Findings

Analyses of mtDNA levels were performed on blood samples obtained from two prospective observational cohort studies of ICU patients (the Brigham and Women''s Hospital Registry of Critical Illness [BWH RoCI, n = 200] and Molecular Epidemiology of Acute Respiratory Distress Syndrome [ME ARDS, n = 243]). mtDNA levels in plasma were assessed by measuring the copy number of the NADH dehydrogenase 1 gene using quantitative real-time PCR. Medical ICU patients with an elevated mtDNA level (≥3,200 copies/µl plasma) had increased odds of dying within 28 d of ICU admission in both the BWH RoCI (odds ratio [OR] 7.5, 95% CI 3.6–15.8, p = 1×10⁻⁷) and ME ARDS (OR 8.4, 95% CI 2.9–24.2, p = 9×10⁻⁵) cohorts, while no evidence for association was noted in non-medical ICU patients. The addition of an elevated mtDNA level improved the net reclassification index (NRI) of 28-d mortality among medical ICU patients when added to clinical models in both the BWH RoCI (NRI 79%, standard error 14%, p<1×10⁻⁴) and ME ARDS (NRI 55%, standard error 20%, p = 0.007) cohorts. In the BWH RoCI cohort, those with an elevated mtDNA level had an increased risk of death, even in analyses limited to patients with sepsis or acute respiratory distress syndrome. Study limitations include the lack of data elucidating the concise pathological roles of mtDNA in the patients, and the limited numbers of measurements for some of biomarkers.

Conclusions

Increased mtDNA levels are associated with ICU mortality, and inclusion of mtDNA level improves risk prediction in medical ICU patients. Our data suggest that mtDNA could serve as a viable plasma biomarker in medical ICU patients. Please see later in the article for the Editors'' Summary     

Statin Treatment in Hypercholesterolemic Men Does Not Attenuate Angiotensin II-Induced Venoconstriction

Experimental studies suggested that statins attenuate vascular AT₁ receptor responsiveness. Moreover, the augmented excessive pressor response to systemic angiotensin II infusions in hypercholesterolemic patients was normalized with statin treatment. In 12 hypercholesterolemic patients, we tested the hypothesis that statin treatment attenuates angiotensin II-mediated vasoconstriction in hand veins assessed by a linear variable differential transducer. Subjects ingested daily doses of either atorvastatin (40 mg) or positive control irbesartan (150 mg) for 30 days in a randomized and cross-over fashion. Ang II–induced venoconstriction at minute 4 averaged 59%±10% before and 28%±9% after irbesartan (mean ± SEM; P<0.05) compared to 65%±11% before and 73%±11% after 30 days of atorvastatin treatment. Plasma angiotensin levels increased significantly after irbesartan treatment (Ang II: 17±22 before vs 52±40 pg/mL after [p = 0.048]; Ang-(1–7): 18±10 before vs 37±14 pg/mL after [p = 0.002]) compared to atorvastatin treatment (Ang II: 9±4 vs 11±10 pg/mL [p = 0.40]; Ang-(1–7): 24±9 vs 32±8 pg/mL [p = 0.023]). Our study suggests that statin treatment does not elicit major changes in angiotensin II-mediated venoconstriction or in circulating angiotensin II levels whereas angiotensin-(1–7) levels increased modestly. The discrepancy between local vascular and systemic angiotensin II responses might suggest that statin treatment interferes with blood pressure buffering reflexes.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00154024","term_id":"NCT00154024"}}NCT00154024     

Inference of link among diabetes,obesity, and thyroid dysfunction in data from a clinic at Saudi Arabia

The clinical link among diabetes, obesity, and thyroid dysfunction is of interest. Hence, medical records of 601 patients with diabetes, obesity, and thyroid dysfunctions at the Abha Specialist Center and Military Diabetic Endocrine Center we used in this analysis. Approximately 28% of diabetic patients had thyroid dysfunction, and 12.4% were vitamin D deficient. The patients with thyroid dysfunction had significantly elevated triglyceride levels compared to the patients without thyroid dysfunction (173.6 vs. 128. p=0.009). Vitamin D deficient obese patients were significantly younger (33.99±10.69 vs. 43.68±14.42; p<0.001) and had significantly lower levels of HbA1c (5.73±1.16 vs. 6.83±2.08; p=0.014) and lower systolic BP (120.26±11.75 vs. 124.58±13.63; p=0.049) than non-vitamin D deficient obese patients. Vitamin D deficient thyroid patients had significantly lower diastolic BP (71.4±9.9 vs. 74.9±9.7; p=0.040) and higher HbA1c (8.7±3.6 vs. 6.4±1.7; p=0.003) in comparison to non-vitamin D deficient thyroid patients. Hence, analysis of metabolic disorders in these patients will help combat complications in these cases.     

Long term management of duodenal ulcer in general practice: How best to use cimetidine?

Two hundred and sixty seven patients with duodenal ulceration were entered into a five year study of two strategies of treatment with cimetidine. Two thirds were treated continuously with 400 mg at bedtime supplemented by temporary increases in dosage if they had symptomatic relapses (group 1), and the remaining third were given intermittent “healing” doses for four to eight weeks if a symptomatic recurrence was judged to have occurred (group 2). Life table analysis showed that the probability of remaining free of clinically important symptoms five years after the start of treatment was 24% (95% confidence interval (CI) 15·5% to 32·6%) in group 1 compared with nil in group 2 (p<0·0001). The median values for the longest periods free from relapse for each patient were 108 weeks in group 1 and 32 weeks in group 2, respectively (p<0·0001; 95% CI of the median difference 36 to 76). Over the five years 10 patients suffered major complications, two requiring emergency surgery, while a further nine had elective surgery because of the failure of medical treatment. There were no deaths that could be attributed either to ulceration or to treatment with cimetidine.Medical management was therefore very satisfactory for most patients, though those treated continuously with cimetidine suffered considerably less from their ulcer symptoms. As 80% of patients studied relapsed during the two years after a healing course of cimetidine, continuous treatment will benefit many patients treated in general practice.     

Raised plasma intact parathyroid hormone concentrations in young people with mildly raised blood pressure

To study the role of parathyroid gland activity in early primary hypertension plasma concentrations of intact parathyroid hormone were measured in 90 untreated young subjects, aged 16-29, with stable mildly raised blood pressure and in 40 normotensive control subjects selected from the same population in Zoetermeer, The Netherlands. Intact parathyroid hormone concentration was significantly higher in the hypertensive than the normotensive group (2.34 (SE 0.11) pmol/l v 1·47 (0·13)pmol/l, respectively; difference 0·87 pmol/l; 95% confidence interval 0·55 to 1·21; p<0·0001). Serum total calcium concentration was 2·36 (0·01) mmol/l in the hypertensive group and 2·42 (0·01) mmol/l in the normotensive group (difference 0·06 mmol/l; 95% confidence interval 0·02 to 0·09; p=0·02). Urinary calcium excretion over 24 hours did not differ significantly between the two groups (4·17 (0·28) mmol/24 h in the hypertensive group and 3·89 (0·39) mmol/24 h in the normotensive group; difference 0·28 mmol/24 h; 95% confidence interval -0·66 to 1·22). In the hypertensive group both systolic and diastolic blood pressures increased slightly though significantly with intact parathyroid hormone concentrations. No obvious associations between serum calcium concentration and blood pressure were observed.These findings support the view that enhanced activity of the parathyroid gland may play a part in the early stage of primary hypertension.     

Preliminary Evaluation of Four Oral Contraceptives Containing only Progestogens

One hundred and seventy-five women took part in a comparative clinical trial of four progestogen-only oral contraceptives and were followed for either a year or until treatment was discontinued. Megestrol acetate 0·25 mg. was found to be a very ineffective contraceptive, 21 out of 43 women becoming pregnant. One, three, and four pregnancies occurred during treatment with norethisterone acetate 0·3 mg., norgestrel 0·05 mg., and chlormadinone 0·5 mg., respectively, corresponding to pregnancy rates of 4, 9, and 12 per 100 woman-years of use.All three effective progestogens were very much less acceptable than modern low-dose combined oral contraceptives. Discontinuation of treatment for medical reasons (particularly menstrual disturbances) during the course of only one year affected 24% receiving norethisterone acetate, 38% receiving norgestrel, and 46% receiving chlormadinone.