Learning on the Web. Case 9: a mother's heartache.

A 35 year old white woman presented with chest pain and breathlessness 10 days following an elective caesarean section. This was her second pregnancy, which had proceeded to term without complications. Up until then, she had been completely fit and well. Her ECGs were found to be abnormal, and the ultrasound study of her heart gave serious cause for concern. This interactive case report charts the evolution of the patient's clinical course and provides concise and up-to-date literature reviews on two cardiac conditions that share a predilection for women in the peripartum period.

Normal radiographic values for cartilage thickness and physeal angle in the pediatric hip.

Ninety-three standing anteroposterior (AP) pelvis roentgenograms in 87 patients were measured for a total of 186 normal hips in children aged 1-17 years. For each hip, the physeal angle relative to the floor, the physeal angle relative to the pelvis, the cartilage thickness perpendicular to the floor, and the cartilage thickness perpendicular to the physis were measured and recorded. The physeal angle varied from ages 1-7 years, stabilizing at age 8 at a mean of 23 degrees . Physeal angle is best measured relative to the floor because pelvic obliquity introduces significant variability to the measurements. Cartilage thickness ("joint space") declined after age 7 years, with measurements in three statistically distinct groups. There was a statistically significant difference between cartilage-thickness measurements of boys versus girls, with girls showing a slightly smaller cartilage thickness than boys. Cartilage thickness measured perpendicular to the floor was not statistically significantly different from that measured perpendicular to the physis. We describe and recommend standard measurement techniques for physeal angle and cartilage thickness. These established normal values may be helpful in the diagnosis and evaluation of coxa vara and chondrolysis, and in identifying the head at risk for slipped capital femoral epiphysis or Legg-Calvé-Perthes disease.

Segmental spinal dysgenesis: a report of three cases.

Segmental spinal dysgenesis is an uncommon congenital spinal defect characterized by localized segmental agenesis of the upper lumbar or thoracolumbar spine. Bony defects include significant focal canal stenosis, hypoplastic or absent vertebrae, subluxation of the spinal column, and instability. The distal bony architecture is usually normal but may be bifid. There is significant narrowing of the thecal sac and absence of adjacent nerve roots at the level of the lesion. Distal neurologic deficits are variable in severity, the prevalence of neurogenic bladder is high, and associated anomalies are common. Progressive kyphosis is inevitable. The cause is unknown, but an association with maternal diabetes and with various medications and toxins has been noted. Other authors suggested a relation to an aberrant segmental vascular supply. Treatment should be directed at the establishment and maintenance of spinal stability and arrest of the progressive kyphosis. It should consist of early anterior and posterior arthrodesis, with or without anterior decompression of the cord. Accurate visualization of this unusual deformity is difficult with conventional radiographic techniques. Three-dimensional computerized tomographic reconstruction can therefore be invaluable in preoperative planning. We report three cases of segmental spinal dysgenesis, all of which have been uniquely detailed by striking three-dimensional imaging studies.

Skeletal infections in children.

Bacteremia is an almost daily occurrence in childhood. Fortunately, infections in children are usually easily controlled and seldom produce serious sequelae. The prompt diagnosis and treatment of osteomyelitis is especially important to prevent catastrophic complications. Recent articles have pointed out that fine-needle aspiration may be diagnostic in only about 60% of children with acute hematogenous osteomyelitis and have suggested that other diagnostic modalities, such as white-cell scintigraphy, ultrasound, and computed tomography, may be more sensitive. Recent recommendations about treatment of osteomyelitis included a comparison of antibiotic agents, a discussion of follow-up evaluation modalities, and a warning that the clinical effects of osteomyelitis may not be apparent until years after the infection has been successfully treated. Two articles noted the increase in the incidence of septic arthritis in children who are HIV-positive and another described a chlamydial-associated syndrome of arthritis and eye involvement. The increased incidence of HIV infections also was cited by three studies as a factor in the increased incidence of tuberculosis infections in children and in the increased risk of extrapulmonary involvement.

Atypical mycobacterial vertebral osteomyelitis in a steroid-dependent adolescent. A case report.

Atypical mycobacterial infections are uncommon, particularly in the spine. The authors present the case of a patient with vertebral osteomyelitis secondary to Mycobacterium chelonae subspecies abscessus that was successfully treated with surgical debridement and stabilization, followed by chemotherapy.

A double-blind comparison of a beta-blocker and a potassium channel opener in exercise induced angina.

This randomized, double-blind, parallel study compared the anti-anginal effects of nicorandil and atenolol in 37 patients with exercise-induced angina pectoris. At the end of a single-blind placebo period, patients were randomized and received either atenolol 50 mg o.d. or nicorandil 10 mg b.d. for 3 weeks. On the third week, the dosage was increased (nicorandil 20 mg b.d. or atenolol 100 mg o.d.) for the final 3-week period. Treadmill exercise tolerance tests were performed immediately before and 2 h after dosing at the end of the placebo period, and at the end of the third and sixth week of active treatment. Demographic characteristics and exercise performance with placebo were comparable between both treatment groups, and at the end of the treatment periods a significant improvement in exercise time was observed: an increase in the time to peak exercise of 1.33 +/- 0.29 min (mean +/- standard error of the mean) in atenolol-treated patients (P < 0.001), and of 1.47 +/- 0.40 min (P < 0.005) in nicorandil-treated patients. While the anti-anginal activity of the two drugs was comparable, their effects on the rate-pressure product heart rate x systolic blood pressure were clearly different; atenolol induced a decrease at peak exercise, but this parameter was not changed or was slightly increased with nicorandil. One patient with severe three-vessel disease died suddenly after 3 days of treatment with nicorandil 10 mg twice daily. The most frequent adverse effect in both groups was headache, which led to discontinuation of one patient in the atenolol group and of five patients in the nicorandil group.(ABSTRACT TRUNCATED AT 250 WORDS)

Hageman factor and risk of myocardial infarction in middle-aged men.

In order to evaluate whether Hageman factor (XII) is increased in survivors of myocardial infarction and whether this in turn influences factor VII coagulant activity (VIIc), we examined the coagulation and lipoprotein profiles in 82 subjects, 51 of whom had a definite history of myocardial infarction and 31 healthy volunteers invited from a local general practice register for a cardiovascular screen. Both serum cholesterol (P = 0.03) and plasma fibrinogen levels (P = 0.02) were significantly elevated in cases compared with controls. There were no significant differences in coagulant activities, and in particular factor XII concentration was not significantly different between groups. Furthermore, in 47 of the subjects, 28 of whom had a history of myocardial infarction, a more detailed analysis, including measurement of VIIc after overnight incubation of plasma at 4 degrees C, was undertaken. Approximately half the subjects in either group showed some evidence of activation, though history of myocardial infarction was not in itself a significant predictor of this. All measures of XII concentration related positively to VIIc after cold activation, the strongest being the measure of amidolytic activity following activation of factor XII (XIIAm) (r = 0.5, P < 0.01). In addition, XIIa, a measure of activity due to enzymes derived from factor XII, related strongly to many of the measured lipoprotein variables, particularly VLDL cholesterol and triglycerides, supporting the hypothesis that negatively charged molecules such as free fatty acids on larger lipoprotein particles provide the contact surface necessary to activate factor XII. The findings confirm the importance of this alternative pathway in leading to activation of factor VII.

Blood pressure changes during the game of squash.

The extent and pattern of the blood pressure response to the playing of squash was studied in five healthy volunteers using intra-arterial blood pressure recordings. Systolic pressure increased more than diastolic, but by only 18% of basal, peaking 5.2 +/- 2.3 min into the game (mean game duration 49 +/- 4 min). Thereafter there was a progressive decline, with reducing pulse pressure towards basal. There was a marked and significant increase in beat-by-beat blood pressure variability (P less than 0.01) and systolic peaks of up to 200 mmHg were recorded. A peak heart rate of 171 +/- 25 beats min-1 occurred at 20 min. These findings do not support the concept of a disproportionate and prolonged pressor response induced by playing squash. The possibility of high single-beat systolic peaks still justifies some caution in subjects at risk of arterial rupture.

Gemfibrozil reduces plasma prothrombin fragment F1 + 2 concentration, a marker of coagulability, in patients with coronary heart disease.

The effects of gemfibrozil on several indices of haemostatic activity were explored in male patients with coronary heart disease (CHD). Sixty-three of 71 patients completed a crossover study in which gemfibrozil 1,200 mg/day and matching placebo were each taken in randomised order for 2 months in a double-blind manner, separated by a 2-month washout period. Serum cholesterol decreased by an average (95% confidence interval) of 12 (9 to 15)% and non-fasting triglyceride concentration by 43 (34 to 51)% during active treatment. Plasma prothrombin fragment F1 + 2 concentration, a marker of the in vivo rate of generation of thrombin, was 25 (12 to 37)% lower on average while on gemfibrozil than during the placebo phase. Factor VII coagulant activity (VIIc) and antigen concentration, and fibrinopeptide A concentration were not influenced by gemfibrozil in the group overall. However, the VIIc response appeared to be dependent upon the untreated cholesterol level. Hypercholesterolaemic men (cholesterol greater than 6.5 mmol/l) experienced a significant reduction in VIIc averaging 6% of standard during active therapy. Other effects of gemfibrozil were a 5 (2 to 9)% increase in plasma fibrinogen by a gravimetric method, an 11 (8 to 13)% increase in platelet count, and a 6 (2 to 10)% reduction in white cell count. The reduced incidence of CHD following gemfibrozil therapy in hyperlipidaemic patients may arise in part through a reduction in procoagulant activity and thus the risk of an occlusive coronary thrombosis.

Myocardial infarction associated with exercise in young men.

Three male patients age 17, 23 and 27 years developed chest pain during, or in one case, immediately after competitive sport. In all cases myocardial infarction was diagnosed by standard criteria or the diagnosis was made on the basis of indium-111 antimyosin imaging, contrast ventriculogram and thallium scan. Coronary arteriography was normal in two and a blocked right coronary artery was found in one. Exercise-related myocardial infarction can occur in young men and chest pain during exercise in this age-group may not always be innocent.

Comparison of nicorandil and atenolol in stable angina pectoris.

The efficacy of nicorandil was compared with atenolol in 37 patients with chronic stable angina using a randomized, placebo-controlled, parallel study design. After a single-blind placebo phase, patients were randomized to receive nicorandil or atenolol using a double-dummy technique. Patients took nicorandil 10 mg twice daily or atenolol 50 mg once daily for the first 3 weeks, and if no adverse effects were encountered they took nicorandil 20 mg twice daily or atenolol 100 mg once daily, for the final 3-week phase. Treadmill exercise tests were performed at the end of each treatment phase immediately before and 2 hours after the morning dose of medication. Groups were demographically similar. Placebo exercise times were 7.06 (0.60) minutes (mean +/- standard error of the mean) in the nicorandil group and 6.81 (0.47) minutes in the atenolol group. After 6 weeks, improvements in exercise time were before dosing: +1.47 (0.40) minutes with nicorandil (p less than 0.005) and +1.33 (0.29) minutes with atenolol (p less than 0.001). Improvements after therapy was administered were +2.45 (0.41) minutes with nicorandil (p less than 0.001) and +2.37 (0.43) minutes with atenolol (p less than 0.0001). Whereas, the predose peak exercise double product (heart rate X systolic blood pressure mm Hg/100) was reduced with atenolol (-43.6 units; p less than 0.001), an increase (+7.56 units; difference not significant) was noted with nicorandil. One patient taking atenolol and 5 taking nicorandil developed persistent headaches. One subject with severe 3-vessel coronary artery disease had fatal myocardial infarction within 3 days of starting nicorandil, 10 mg twice daily.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between plasma cholesterol and coronary artery disease in Asians.

Cholesterol, high density lipoprotein (HDL) cholesterol and triglyceride concentrations were measured in 150 male survivors of first myocardial infarction and in 115 age and ethnic matched healthy controls. The total cholesterol concentration was higher in whites than in respective Asian groups and higher in patients than in controls (P less than 0.001). The ratio of cholesterol to HDL cholesterol was significantly higher in patients (P less than 0.001) and in both ethnic groups was a powerful independent predictor of cases. In Asians, the extent of coronary atheroma assessed by arteriography 2-12 weeks after infarction correlated independently with the total cholesterol concentration (P = 0.03). Thus, in Asian men, the lower level of total cholesterol compared to whites may be misleading. In Asian men the extent of atheroma correlated with the total cholesterol concentration and the relative risk of infarction increased with the ratio of total to HDL cholesterol. At a given level of cholesterol different ethnic groups may be at differing levels of cardiac risk and the cholesterol ratio may be a more appropriate means of inter-ethnic comparison.

Ranolazine (RS-43285): a preliminary study of a new anti-anginal agent with selective effect on ischaemic myocardium.

Ranolazine (RS-43285) has been shown to possess significant anti-ischaemic properties in a canine model of reversible myocardial ischaemia. The clinical efficacy of this new agent was assessed by a single blind, placebo controlled study of 14 patients with chronic stable angina. A 2 week placebo phase was followed by therapy with 30 mg and 60 mg of ranolazine tid for 2 weeks each. Graded, symptom limited treadmill exercise tests were performed at the end of each phase, 1.5 h (AM) and 7 h (PM) after the morning dose. An additional exercise test 1.5 h after the first dose of 30 mg was included to assess the acute dose response. In the AM study, the mean exercise time increased from 6.9 min (placebo) to 7.8 min after the first dose of 30 mg and to 8.2 min and 8.5 min respectively at the end of 30 mg and 60 mg phases. In the PM study, exercise time improved from 6.5 min (placebo) to 8.2 min and 7.8 min respectively at the end of 30 mg and 60 mg phases. The time to onset of angina showed a similar improvement. No significant changes were observed in the resting and peak exercise heart rates and blood pressure. This preliminary study suggests that ranolazine may significantly prolong exercise time in patients with stable coronary artery disease without altering heart rates and blood pressure.

Haemodynamic advantage of the Valsalva manoeuvre during heavy resistance training.

A nuclear probe was used to assess beat-to-beat changes in relative cardiac output in eight elite athletes during isometric exercise. Three subjects underwent simultaneous intra-arterial blood pressure recording. Stroke volume fell by 68 +/- 4% during Valsalva's manoeuvre alone, but by 42 +/- 9% with simultaneous isometric handgrip. Blood pressure changes during isometric handgrip were significantly modified by simultaneous Valsalva's manoeuvre. In particular no late strain phase fall or post-strain overshoot in blood pressure was seen, hence there was no baroreceptor-mediated fall in heart rate. Maximum Valsalva's manoeuvres in athletes invoked extreme falls in cardiac output and blood pressure which were attenuated by simultaneous isometric handgrip. The mechanism of this may be twofold: increased venous tone maintains stroke volume; and/or increased arteriolar tone maintains blood pressure.

Safety and pharmacokinetics of ioversol in healthy volunteers.

Ioversol 320, a new nonionic iodinated contrast medium, was injected intravenously into 24 healthy male volunteers using saline as a control. Physical examination, vital signs, electrocardiogram, biochemical and hematological data were recorded before and at intervals after injection. No significant changes were observed. Seventeen volunteers reported no side effects; six volunteers had mild transitory symptoms considered to be related to the contrast medium. The authors conclude that broader clinical trials can be safely conducted to determine safety and tolerability of ioversol.

Disturbances of insulin in British Asian and white men surviving myocardial infarction.

OBJECTIVE: To examine the role of insulin as a cardiovascular risk factor in British Asian and white men. DESIGN: Case-controlled study of survivors of first myocardial infarction. SETTING: District general hospital. PATIENTS: Consecutive series of 76 white and 74 Asian men who survived first myocardial infarction compared with 58 white and 61 Asian male controls without coronary artery disease who were randomly sampled from the community. RESULTS: More Asians than white subjects had impaired glucose tolerance or overt diabetes as measured by the two hour glucose tolerance test (23/74 (32%) v 11/76 (15%) (p less than 0.001) among patients; 17/61 (28%) v 3/58 (6%) (p less than 0.001) among controls). Insulin and C peptide concentrations were higher in both patient groups than in respective controls (p less than 0.001) and higher in Asian than in white subjects, irrespective of their glucose tolerance. Triglyceride concentrations were higher in patients than in controls (1.92 (SD 1.05) v 1.43 (0.82) mmol/l among Asian men; 1.65 (0.83) v 1.3 (0.61) mmol/l among white subjects; p less than 0.001). Total cholesterol concentrations were lower in both groups of Asians than in respective white subjects (5.78 (0.99) v 6.22 (1.04) mmol/l (p less than 0.01) among patients; 5.54 (1.01) v 5.65 (1.11) mmol/l (p less than 0.6) among controls). High density lipoprotein cholesterol concentrations were lower in Asian than in white subjects. The ratio of total cholesterol to high density lipoprotein cholesterol was significantly higher (p less than 0.001) in both patient groups (6.69 (1.81) in Asian patients and 6.31 (1.91) in white patients) than in respective controls (5.24 (1.19) and 4.77 (1.43)). Regression analysis identified C peptide concentration and the ratio of total to high density lipoprotein cholesterol as powerful independent predictors of myocardial infarction in Asian and white men. Total cholesterol concentration predicted infarction in white but not in Asian men. CONCLUSIONS: Secretion and hepatic extraction of insulin are high in survivors of myocardial infarction and especially high in British Asians. Tissue resistance to the action of insulin, giving rise to increased pancreatic secretion, may be an important risk factor for coronary artery disease in both ethnic groups and may be partly responsible for the high incidence of diabetes and coronary artery disease in Asian populations.