Post-natal erythromycin exposure and risk of infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis.

PURPOSE: Macrolide antibiotics, erythromycin, in particular, have been linked to the development of infantile hypertrophic pyloric stenosis (IHPS). Our aim was to conduct a systematic review of the evidence of whether post-natal erythromycin exposure is associated with subsequent development of IHPS. METHODS: A systematic review of postnatal erythromycin administration and IHPS was performed. Papers were included if data were available on development (yes/no) of IHPS in infants exposed/unexposed to erythromycin. Data were meta-analysed using Review Manager 5.3. A random effects model was decided on a priori due to heterogeneity of study design; data are odds ratio (OR) with 95 % CI. RESULTS: Nine papers reported data suitable for analysis; two randomised controlled trials and seven retrospective studies. Overall, erythromycin exposure was significantly associated with development of IHPS [OR 2.45 (1.12-5.35), p = 0.02]. However, significant heterogeneity existed between the studies (I 2 = 84 %, p < 0.0001). Data on erythromycin exposure in the first 14 days of life was extracted from 4/9 studies and identified a strong association between erythromycin exposure and subsequent development IHPS [OR 12.89 (7.67-2167), p < 0.00001]. CONCLUSION: This study demonstrates a significant association between post-natal erythromycin exposure and development of IHPS, which seems stronger when exposure occurs in the first 2 weeks of life.

Metformin and contrast media--a dangerous combination?

Metformin is a biguanide used to treat type II diabetes mellitus. Since the recent introduction of this drug into the United States there has been considerable interest in metformin associated lactic acidosis (MALA) following intravenous contrast media. The Royal College of Radiologists published advice in November, 1996 (Advice to Members and Fellows with regard to metformin-induced lactic acidosis and X-ray contrast medium agents, RCR Publication) supporting the manufacturers' advice that metformin should not be used in the 48 h before or after intravenous (i.v.) contrast medium. We performed a systematic review of the literature and this has shown that almost all reported cases of MALA following i.v. contrast medium occurred where there was either pre-existing poor renal function or another contraindication to metformin usage. There has been only one reported case of lactic acidosis following the use of intravenous contrast medium in a patient with normal renal function. We suggest that the Royal College of Radiologists' advice should be modified and that it is safe to give i.v. contrast medium to patients on metformin with normal renal function.

Aggressive limb salvage using tibio-pedal bypass grafting with free tissue transfer in a diabetic patient.

A 63-year-old man presented with intermittent claudication, diabetes, and an ischaemic heel ulcer. After control of infection, the os calcis was left exposed. An aggressive combined infra-inguinal revascularization and reconstruction procedure involving free-tissue transfer resulted in rapid wound healing with independent walking by day 26. Recent improvements in surgical techniques mean that this approach should be considered in selected patients.

Bone mineral density and metabolism in premenopausal women taking L-thyroxine replacement therapy.

BACKGROUND AND OBJECTIVE: Excess endogenous thyroxine causes bone loss, but the effects of exogenous thyroxine are disputed. We report on bone mass and metabolism in women taking L-thyroxine therapy. DESIGN: Cross-sectional and longitudinal studies. PATIENTS: Cross-sectional study: 40 healthy premenopausal women with autoimmune thyroiditis taking either physiological (serum TSH usually normal, 0.35-3.3 mU/l) or suppressive (serum TSH usually < 0.35 mU/l) doses of L-thyroxine; patients were also compared with previously acquired age and weight matched premenopausal volunteers with no history of thyroid dysfunction. Longitudinal study: 28 patients were followed-up > or = 1 year later. MEASUREMENTS: In all subjects bone mineral density (BMD) was measured at the anteroposterior lumbar spine and left hip (femoral neck, greater trochanter and Ward's area) using dual-energy X-ray absorptiometry, and physical activity assessed using the Framingham physical activity index. Serum osteocalcin (OC), PTH and vitamin D, and urinary pyridinoline and deoxypyridinoline excretion were measured in patients. RESULTS: Cross-sectional study: The patient groups were well matched for disease duration and physical activity although the suppressed group were slightly younger (mean 38.1 (SD 7.5) vs 43.3 (3.9) years, P < 0.05). BMD, serum OC, PTH and vitamin D, and urinary cross-link excretion did not differ significantly between the two groups. Multivariate analysis of the whole group suggested that BMD at the femoral neck and greater trochanter was related positively to weight and physical activity and negatively to thyroxine dose (microgram/kg/day) and patient age. At the lumbar spine BMD was reduced non-specifically in the presence of thyroid disease and treatment, but this effect appeared to decline with increasing duration of therapy. A similar analysis of the patient group suggested that urinary cross-link excretion correlated positively with thyroxine dose, and negatively with duration of treatment. Longitudinal study: Annualized changes in BMD were inversely related to thyroxine dose (microgram/kg/day) at all sites but achieved statistical significance only at the femoral neck and Ward's area. CONCLUSION: We did not find any effect of persistent historical TSH suppression on current bone mass, and this might relate to the relative insensitivity of older TSH assays. However, the cross-sectional and longitudinal data suggest that high daily doses of thyroxine in relation to patient body weight might adversely affect bone mass, particularly at the hip. These findings support the contention that excess exogenous thyroxine might predominantly deplete skeletal sites, such as the femoral neck, rich in cortical bone.

Mortality in diabetes mellitus: experience of a geographically defined population.

A population-based cohort study identified 915 deaths in 4186 patients with diabetes mellitus over a 5-year period. Ischaemic heart disease, cerebrovascular disease and malignant neoplasms were the major causes of death and accounted for 40%, 16%, and 14% of deaths, respectively, compared with 27%, 14%, and 25% of deaths in the non-diabetic population. Diabetic patients had a standardized mortality ratio (SMR) of 1.15 (95% Cl 1.08-1.22) (p less than 0.001). This excess risk of death was largely due to the excess death from ischaemic heart disease (SMR 1.55 (1.40-1.71); p less than 0.001) and the impact was greatest in middle-aged female patients. Stroke mortality was not significantly increased (SMR 1.09 (0.92-1.29)) while cancer mortality was reduced (SMR 0.75 (0.63-0.89); p less than 0.01). Death rates in diabetic male patients (SMR 1.04 (0.96-1.13)) did not differ significantly from those in non-diabetic male patients because the increased risk of ischaemic heart disease deaths (SMR 1.41 (1.22-1.62); p less than 0.001) was offset by the reduced risk of deaths from malignant neoplasms (SMR 0.65 (0.51-0.82); p less than 0.001). The reduction in cancer mortality did not reach statistical significance in diabetic women (SMR 0.82 (0.64-1.05)). Diabetic nephropathy and metabolic disasters were uncommon as causes of death.

Hypercarbic periodic breathing during sleep in a child with a central nervous system tumor.

A 4-yr-old girl with a ganglioglioma involving the cerebellum and pons presented with CO2 retention and arterial O2 desaturation during wakefulness and sleep. Despite the presence of a regular respiratory pattern during wakefulness, NREM sleep was associated with the appearance of a sustained periodic respiratory pattern characterized by clusters of usually two breaths separated by an 8 to 10-s expiratory pause. At sleep onset, this Biot's respiratory pattern appeared immediately after a sigh. Breathing frequency during NREM sleep became regular with administration of supplemental O2 and an attendant increase in end-tidal CO2. Shortly after withdrawal of supplemental O2 during NREM sleep, the periodic pattern resumed and was again immediately preceded by a sigh. The observations during NREM sleep in this patient with a central nervous system abnormality indicate that Biot's type respiratory pattern may be reversed by administration of supplemental oxygen. The results in this patient suggest: (1) the presence of a very elevated CO2 apnea threshold, and (2) that the pons may play a role in determining the effect of hypercapnic hypoxia on respiratory pattern during sleep.

Measuring outcome of diabetes: a retrospective survey.

The feasibility of using hospital discharge data to monitor six outcome indicators for diabetes care was assessed by reviewing retrospectively the occurrence of these events recorded in hospital records. The population studied was that of the Orkney Islands (19,500) over a 10-year period (1976-1985). During that time, 230 Orkney diabetic patients were treated in Orkney and/or Aberdeen hospitals. The six outcome indicators were: hospital admission rates for diabetic patients (609 in 230 patients), hospital admission rates specifically for diabetic ketoacidosis (29 in 20 patients), rates of diabetes-related lower limb amputations (36 in 23 patients), perinatal mortality rates related to maternal diabetes (nil), visual loss or blindness (13 eyes in 9 patients) and end-stage renal failure (one patient). Scottish Morbidity Returns (which collect data similar to that in the Hospital In-patient Enquiry in England) were shown by case note review to underestimate these outcomes by 41%. Cardiovascular disease, cerebrovascular disease, and peripheral vascular disease accounted for half of all in-patient bed use by diabetic patients (6077 of 13,951 days). The routinely available Scottish hospital discharge data, which are collected for a different purpose, are not sufficiently accurate or complete to reflect variations in actual diabetic events.

Angiotensin converting enzyme inhibitors may cause renal impairment in diabetes mellitus.

Angiotensin converting enzyme (ACE) inhibitors have been recommended for the treatment of diabetic nephropathy. However, it should be remembered that diabetic patients may also develop atheromatous renal artery stenosis. In such patients ACE inhibitors may have adverse effects on renal function. Careful investigation and monitoring is essential when ACE inhibitors are used in diabetes.

Comparison of propranolol and metoprolol in the management of hyperthyroidism.

1 Propranolol and metoprolol were both effective in controlling the symptoms and signs of hyperthyroidism. 2 Propranolol caused a highly significant increase in serum reverse T3 concentrations with lesser changes in other serum thyroid hormone levels, whereas metoprolol did not have this effect. 3 Steady-state plasma propranolol and metoprolol levels showed marked inter-individual variation. Metoprolol concentrations showed relatively little intra-individual variability, and could be related to the clinical efficacy of the drug, whereas no such relationship was demonstrated for propranolol.

Coagulation and fibrinolysis in thyroid disease.

The levels of components of the coagulation mechanism and fibrinolytic system in 20 hyperthyroid patients and 9 hypothyroid patients were compared with those of 20 euthyroid control subjects. The mean levels of fibrinolytic activity and plasminogen were significantly reduced in the hyperthyroid patients while mean levels of alpha1-antitrypsin and C1 inactivator were increased. Patients with hypothyroidism had significantly increased levels of fibrinolytic activity and alpha2-macroglobulin, a prolonged partial thromboplastin time, and reduced levels of factor XII and antithrombin III.

Metabolic effects of salbutamol: comparison of aerosol and intravenous administration.

The effects of intravenous salbutamol (4 mug/kg) were compared with those of aerosol salbutamol (200 mug) in 10 asthmatic patients in a double-blind placebo-controlled study. Both methods of administration produced equal bronchodilatation. Intravenous salbutamol caused significant increases in plasma insulin and glucose levels and a fall in serum potassium concentration in addition to tachycardia and tremor, whereas aerosol salbutamol produced only a small transient increase in the plasma glucose level. The initially raised non-esterified fatty acid levels decreased significantly after aerosol and placebo but not after intravenous salbutamol.

Comparison of propranolol and practolol in the management of hyperthyroidism.

Twenty-one hyperthyroid patients participated in an 8-week double-blind crossover trial of propranolol and practolol, and the effecte of these drugs on the clinical and metabolic features of the disease were studied. Propranolol was marginally more effective than practolol, as measured by the hyperthyroid diagnostic index and anxiety scale. Propranolol produced a significant reduction in the serum concentration ratio of tri-iodothyronine to thyroxine, compatible with partial inhibition of peripheral deiodination of thyroxine. Adverse reactions occurred more frequently with propranolol than with practolol. In veiw of the efficacy of practoloo, further trials in hyperthyroid patients of newer beta1-adrenoceptor antagonists, preferably without partial agonist activity, are indicated.

Lack of effect of bumetanide on body potassium content in hypertension.

1 Twelve patients with mild hypertension were treated with bumetanide for a six-month period. No evidence was found of hypokalaemia or decreased total exchangeable potassium in subjects with or without additional potassium supplements. 2 Bumetanide was well tolerated by all patients. It caused hyperuricaemia but no episodes of gout occurred. Minor abnormalities of liver function were noted. 3 Bumetanide did not have a sustained antihypertensive action.