Rapid and non-radioactive prenatal diagnosis of β thalassaemia and sickle cell disease: application of the polymerase chain reaction (PCR)

The standard method for the prenatal diagnosis of the haemoglobinopathies is by restriction enzyme mapping of chorionic villus DNA using Southern blotting and radioactively labelled gene probes. An improvement of the procedure which involves the selective amplification of DNA fragments by the polymerase chain reaction allows one to visualize restriction fragments directly without the use of radioactivity and within 2 d after obtaining the sample. We report here the prenatal diagnosis of two pregnancies at risk for homozygous beta thalassaemia and homozygous sickle cell disease using this novel approach.     

Metoclopramide-Induced Normalization of Impaired Gastric Emptying in Spinal Cord Injury

In a partial, two-way crossover study of gastric emptying (GE) in spinal cord injury (SCI), fasted, healthy, unmedicated male volunteers were given a 99mTc-labeled liquid meal on two occasions. Metoclopramide (10 mg) was administered intravenously to each subject before the second evaluation of GE. We used single and multiexponential models with linear and nonlinear least-squares regression techniques to study the time-course of the disappearance of 99mTc from the stomach. The GE pattern in all subjects was most accurately characterized by nonlinear analysis (NONLIN) and consisted of two components, an initial adynamic phase and a phase of rapid emptying. The GE t1/2 of a liquid meal decreased from 106.6 +/- 58.3 min (mean +/- SD) in all SCI subjects (quadriplegic plus paraplegic) prior to treatment to 21.6 +/- 8.2 min after the intravenous administration of metoclopramide (p less than 0.006). Significant correlations between GE t1/2 and injury duration (yr) or level of spinal injury were observed. Impaired gastric emptying in SCI can be pharmacologically modified by metoclopramide to resemble a normal gastric emptying profile. Metoclopramide-altered gastric emptying in SCI may be expected to result in changes in the therapeutic efficacy of orally administered drugs when drug absorption is dependent on gastric motility or emptying efficiency.     

Increased serum pigment epithelium-derived factor is associated with microvascular complications, vascular stiffness and inflammation in Type 1 diabetes.

AIMS: To determine in Type 1 diabetes patients if levels of pigment epithelium-derived factor (PEDF), an anti-angiogenic, anti-inflammatory and antioxidant factor, are increased in individuals with complications and positively related to vascular and renal dysfunction, body mass index, glycated haemoglobin, lipids, inflammation and oxidative stress. METHODS: Serum PEDF levels were measured by ELISA in a cross-sectional study of 123 Type 1 diabetic patients (71 without and 52 with microvascular complications) and 31 non-diabetic control subjects. PEDF associations with complication status, pulse-wave analysis and biochemical results were explored. RESULTS: PEDF levels [geometric mean (95% CI)] were increased in patients with complications 8.2 (7.0-9.6) microg/ml, vs. complication-free patients [5.3 (4.7-6.0) microg/ml, P < 0.001] and control subjects [5.3 (4.6-6.1) microg/ml, P < 0.001; anova between three groups, P < 0.001], but did not differ significantly between control subjects and complication-free patients (P > 0.05). In diabetes, PEDF levels correlated (all P < 0.001) with systolic blood pressure (r = 0.317), pulse pressure (r = 0.337), small artery elasticity (r = -0.269), glycated haemoglobin (r = 0.245), body mass index (r = 0.362), renal dysfunction [including serum creatinine (r = 0.491), cystatin C (r = 0.500)], triglycerides (r = 0.367), and inflammation [including log(e)C-reactive protein (CRP; r = 0.329), and soluble vascular cell adhesion molecule-1 (r = 0.363)]. Age, blood urea nitrogen, systolic blood pressure, pulse pressure and log(e)CRP correlated with PEDF levels in control subjects (all P < 0.04). PEDF levels were not significantly correlated with measures of oxidative stress: isoprostanes, oxidized low-density lipoprotein or paraoxonase-1 activity. On stepwise linear regression analysis (all subjects), independent determinants of PEDF levels were renal function, triglycerides, inflammation, small artery elasticity and age (r(2) = 0.427). CONCLUSIONS: In Type 1 diabetes, serum PEDF levels are associated with microvascular complications, poor vascular health, hyperglycaemia, adiposity and inflammation.     

Assessment of left ventricular performance during percutaneous transluminal coronary angioplasty: a study by intravenous digital subtraction ventriculography.

Left ventricular performance during percutaneous transluminal coronary angioplasty was assessed in 52 patients by intravenous digital subtraction ventriculography. After injection of contrast into the right atrium ventriculograms were obtained before and during balloon inflation. In 37 patients they were also obtained after the procedure. A 12 lead electrocardiogram was monitored throughout. During balloon inflation the left ventricular ejection fraction fell (from 73% to 57%) in all but one patient; the decreases in patients with single vessel or multivessel disease were similar. The fall in left ventricular ejection fraction during percutaneous transluminal coronary angioplasty of the left anterior descending artery (19%) was significantly greater than that during balloon inflation in the right coronary (10%) or circumflex (8%) coronary arteries. It also reduced anterobasal, anterior, and apical segmental shortening while right coronary percutaneous transluminal coronary angioplasty affected inferior and apical segments. In 33 (63%) patients the ST segment was altered during balloon inflation. The fall in left ventricular ejection fraction correlated significantly with the magnitude of both ST segment elevation (r = 0.637) and ST depression (r = 0.396). Left ventricular ejection fraction and regional wall motion returned to baseline values after the procedure. Balloon inflation during percutaneous transluminal coronary angioplasty produces considerable abnormalities of global and regional left ventricular performance and this indicates the presence of myocardial ischaemia, which may not be apparent on electrocardiographic monitoring. Intravenous digital subtraction ventriculography is useful for monitoring left ventricular performance during controlled episodes of coronary occlusion produced by balloon inflation.     

Effect of exercise level on the ability of thallium-201 tomographic imaging in detecting coronary artery disease: analysis of 461 patients

This study examined the effect of the level of exercise on the ability of thallium-201 imaging with single photon emission computed tomography (SPECT) to detect coronary artery disease. Patients in group 1 (n = 164) achieved adequate exercise end points, defined as positive exercise electrocardiograms or greater than or equal to 85% of maximal predicted heart rate. Patients in group 2 (n = 108) had submaximal exercise. The SPECT thallium-201 images showed perfusion defects in 74%, 88%, and 98%, respectively, of patients with one, two and three vessel coronary artery disease in group 1, compared with 52%, 84% and 79%, respectively, of such patients in group 2 (p less than 0.05). Perfusion defects showed partial or complete redistribution consistent with ischemia in 56%, 80% and 88%, respectively, of patients with one, two and three vessel coronary artery disease in group 1 compared with 35%, 58% and 56%, respectively, of such patients in group 2 (p = 0.08, less than 0.03 and less than 0.001, respectively). Of 58 patients with normal coronary angiograms or less than 50% diameter stenosis, 36 (62%) had normal SPECT images. In a separate group of 131 patients with less than 5% pretest probability of coronary artery disease, the specificity was 93%. The sensitivity of exercise SPECT imaging in group 1 was higher than that of ST segment depression (p less than 0.001). Thus, the level of exercise affects the results of SPECT thallium imaging in the localization and evaluation of the extent of coronary artery disease and the detection of ischemia.     

Accelerometers in rehabilitation medicine for older adults

Recent technological developments have led to the production of inexpensive, miniature accelerometer sensors with potential for use in a clinical setting. These sensors can provide reliable information on mobility and objective measurement of gait. They are currently used mainly in a research setting; however, with recent advances, incorporation into clinical practice is possible. For illustrative purposes this paper describes some current applications of accelerometers in gait and balance evaluation, falls risk assessment and mobility monitoring. Accelerometers provide quantitative measures of gait, they are capable of identifying specific gait changes in older adults and in fallers and can be used to objectively quantify ambulatory activity levels. Accelerometers have many potential uses in monitoring of patients in rehabilitation. They provide an added objective and quantitative dimension to gait analysis when combined with clinical assessment. They have the potential in the future to stratify falls risk facilitating early initiation of appropriate therapeutic intervention, thus reducing further falls. The challenge facing clinicians and biomedical engineers is to further harness this technology making it part of everyday clinical practice.     

Bodily Maps of Emotion in Major Depressive Disorder

Cognitive Therapy and Research - Emotions play a central role in mental disorder and especially in depression. They are sensed in the body, and it has recently been shown in healthy participants...     

Extra-Aortic Mycotic Aneurysm Due to Group A Streptococcus after Pharyngitis

Mycotic aneurysms, especially outside the aorta, are uncommon, with group A Streptococcus a particularly rare cause. We report a case of extra-aortic mycotic aneurysm following a sore throat without demonstrable bacteremia where identification of the pathological organism was made by molecular diagnostic techniques after a standard laboratory culture was negative.     

Vitamin D receptor gene polymorphisms and susceptibility to Mycobacterium malmoense pulmonary disease

Polymerase chain reaction using sequence-specific primers was utilized to ascertain the prevalence of 3 polymorphisms of the vitamin D receptor (VDR) gene (FokI F/f, ApaI A/a, and TaqI T/t) in 56 patients with Mycobacterium malmoense pulmonary disease. When compared with 101 controls, M. malmoense patients displayed an increased prevalence of Apa1 A (P=.03; Fisher's exact test), TaqI t (P=.04), and the At VDR haplotype (P=.04), and they displayed a decreased prevalence of FokI f (P=.04). Only 4 (7%) of 56 patients (vs. 29 [28%] of 101 controls) were both positive for FokI f and negative for At (P=.001). This indicates that polymorphisms in the VDR (or in closely linked genes) modulate the susceptibility to M. malmoense and that susceptibility involves multiple genetic and environmental factors.