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Biomedical subjects

R John

Publications and source records attributed to R John.

At least 109 records · Page 6Linked to original sources
PubMed1993

A comparison of total and free beta-HCG assays in Down syndrome screening.

Free beta-HCG is a new analyte that has been suggested to be superior to total HCG when used in combination with alpha-fetoprotein (AFP) for Down syndrome risk screening in early pregnancy. We have evaluated this claim on 21 samples collected from Down syndrome pregnancies and 180 samples from unaffected pregnancies. The detection rates for the combination of AFP with free beta-HCG or the combination of AFP with total HCG were identical (71 per cent) but the initial screen positive rate (equivalent to the false-positive rate) was 7.5 per cent for AFP + free beta-HCG screening compared with 3.5 per cent for AFP + total HCG screening. We conclude that the case for free beta-HCG is unproven and suggest that further data be collected before free beta-HCG becomes acceptable.

Biomarkers↗
PubMed1993

Serum tumor necrosis factor-alpha profile in trauma patients.

Tumor necrosis factor-alpha (TNF-alpha) has been implicated in several late consequences of trauma such as sepsis, multiple organ failure, and ischemia-reperfusion injury. However, no data are available to indicate whether TNF-alpha is involved in the initial pathophysiologic response to trauma. To address this issue, serum TNF-alpha was determined (by ELISA) longitudinally (first blood sample on admission) in 100 randomly selected trauma patients admitted to the emergency department and trauma division at Jefferson Medical Center, Philadelphia. The TNF-alpha levels were detectable at one or more time points in 35 patients. Mean values tended to be elevated (50.3 +/- 11.5 pg/mL) during the first 5 days, but this trend did not differ statistically from that in healthy controls (n = 12) and did not correlate with the severity of injury (Injury Severity Score and Glasgow Coma Scale score). The TNF-alpha response was not dependent on the mechanism and site of injury, the presence of shock (systolic blood pressure < 90 mm Hg), and the need for emergent surgery. Also, serum TNF-alpha levels were not significantly elevated in patients who subsequently developed multiple organ failure (n = 4), septic shock (n = 5), or both (n = 3). Taken together, these data do not support a role for circulating TNF-alpha in the initial acute inflammatory response to trauma.

Adult↗
PubMed1993

Secundum atrial septal defect repair: long-term surgical outcome and the problem of late mitral regurgitation.

This study examines the clinical and surgical outcome of a group of 55 patients (mean age 33 years) with secundum atrial septal defect who underwent surgical repair of this defect between 1981 and 1990. A group of 25 of these patients underwent late echocardiographic follow-up. Fifty-two patients underwent repair by direct suturing and three by patch closure. Surgical mortality was nil. There was one late death of a 58 year old who died from cardiac failure 4 years after surgery. Late postoperative morbidity consisted of two patients; one, age 63 at the time of surgery, required mitral and tricuspid valve replacement 6 years later and one, age 77 at surgery, developed cardiac failure 3 years later. Atrial fibrillation persisted in the six patients who had the rhythm before surgery and developed postoperatively in two patients aged 54 and 58. Two patients aged 49 and 57 developed immediate postoperative sinus node dysfunction requiring permanent pacing. The mean age at surgery of those six patients who suffered cardiac morbidity was 60 years. The patients with preoperative angiographic evidence of mitral valve prolapse were significantly older (P < 0.001) and had higher mean pulmonary artery pressures (P < 0.001) than patients with normal valves. There was no significant relationship between shunt size and mitral valve prolapse. Echocardiographic follow-up showed persistent mitral valve prolapse in all nine patients who developed the condition preoperatively. Five patients developed mitral valve prolapse with mitral regurgitation postoperatively, one of whom needed subsequent mitral and tricuspid valve replacement. These five patient were on average older (mean age 54) but the group was too small to prove significance. The follow-up data illustrate the current low mortality and morbidity associated with surgical closure of atrial septal defects. Late postoperative echocardiography had revealed not only that mitral valve prolapse persists in those patients who developed the condition pre-operatively but that new cases of mitral valve prolapse with mitral regurgitation can occur after atrial septal defect closure.

Adult↗
PubMed1992

High-resolution localization of 69 potential human zinc finger protein genes: a number are clustered.

In this study, we describe the identification and partial characterization of 101 potential human zinc finger protein genes (ZnFPs). These sequences were isolated by hybridization of cosmids, obtained from mouse-human cell lines enriched for chromosome 11p, with an oligonucleotide specific for the "link" sequence between contiguous zinc fingers. Sixty-nine of these cosmids were regionally localized to human prometaphase chromosomes by in situ hybridization. The localization of these cosmids suggests that a number of finger protein genes occur in linked clusters. Their assignment to chromosomes 3p, 11p, 19p, 19qter, 20p, and 21q makes them valuable as markers or "candidate" genes for diseases associated with these chromosome regions.

Amino Acid Sequence↗
PubMed1992

Monophasic action potential recordings during acute changes in ventricular loading induced by the Valsalva manoeuvre.

OBJECTIVE: The strong association between ventricular arrhythmia and ventricular dysfunction is unexplained. This study was designed to investigate a mechanism by which a change in ventricular loading could alter the time course of repolarisation and hence refractoriness. A possible mechanism may be a direct effect of an altered pattern of contraction on ventricular repolarisation and hence refractoriness. This relation has been termed contraction-excitation feedback or mechano-electric feedback. METHODS: Monophasic action potentials were recorded from the left ventricular endocardium as a measure of the time course of local repolarisation. The Valsalva manoeuvre was used to change ventricular loading by increasing the intrathoracic pressure and impeding venous return, and hence reducing ventricular pressure and volume (ventricular unloading). PATIENTS: 23 patients undergoing routine cardiac catheterisation procedures: seven with no angiographic evidence of abnormal wall motion or history of myocardial infarction (normal), five with a history of myocardial infarction but with normal wall motion, and 10 with angiographic evidence of abnormal wall motion--with or without previous infarction. One patient was a transplant recipient and was analysed separately. SETTING: Tertiary referral centre for cardiology. RESULTS: In patients with normal ventricles during the unloading phase of the Valsalva manoeuvre (mean (SD)) monophasic action potential duration shortened from 311 (47) ms to 295 (47) ms (p less than 0.001). After release of the forced expiration as venous return was restored the monophasic action potential duration lengthened from 285 (44) ms to 304 (44) ms (p less than 0.0001). In the group with evidence of abnormal wall motion the direction of change of action potential duration during the strain phase was normal in 7/21 observations, abnormal in 6/21, and showed no clear change in 8/21. During the release phase 11/20 observations were normal, five abnormal, and four showed no clear change. In those with myocardial infarction four out of five patients had changes that resembled those with normal ventricles but the changes were less pronounced. There were no differences in any of the three groups between the changes in monophasic action potential duration in patients taking beta blockers and those who were not. The changes in monophasic action potential duration in the transplanted heart resembled those in the group with normal ventricles. Inflections on the repolarisation phase of the monophasic action potential consistent with early afterdepolarisations were seen in three of the patients with abnormal wall motion and in none of those with normal wall motion. CONCLUSIONS: These results are further evidence that changes in ventricular loading influence repolarisation. When wall motion was abnormal the effects on regional endocardial repolarisation were often opposite in direction to those when it was normal. Thus regional differences in wall motion could generate local electrophysiological inhomogeneity which may be relevant to the association of arrhythmia with impaired left ventricular function.

Action Potentials↗
PubMed1992

Endemic goitre in Senegal--thyroid function etiological factors and treatment with oral iodized oil.

Endemic goitre and its response to orally administered iodized oil has been studied in seven villages 25-30 km south of Velingara, Eastern Casamance, Senegal. In 502 adults aged greater than 15 years goitre prevalence was 62% with 18.2% having goitre grade 2 or 3. Mean free T4 (FT4) was 11.9 +/- 3.5 (SD) pmol/l and iodine deficiency was confirmed by noting median urinary I of 0.079 mumol/l (14.9 mumol I/mol creatinine) with elevated free T3 (FT3)/FT4 ratios. Serum selenium concentrations were normal. The response to 480 mg of oral iodized oil assessed at 6 and 12 months was characterized by a 35.8% increase in FT4, a 25% decrease in FT3 and a 50% decrease in TSH (all p less than 0.01) at 12 months associated with a significant decrease in goitre size measured in 70 persons when compared to 65 controls not receiving iodine. Urinary iodine rose from 0.071 mumol/l to 0.189 mumol/l (p less than 0.01) during this time and no adverse effects on thyroid antibodies (anti-thyroid peroxidase and anti-thyroglobulin) were observed. A variation in goitre prevalence between villages was noted which, in such a small geographical area, suggests that etiological factors in addition to iodine deficiency may be important in goitre pathogenesis. Oral iodized oil administration is an effective treatment for iodine deficiency goitre in the short term.

Adolescent↗
PubMed1992

Comparison of assay kits for unconjugated estriol shows that expressing results as multiples of the median causes unacceptable variation in calculated risk factors for Down syndrome.

We compared the performance of two methods for assaying unconjugated estriol in serum: the modified Amerlex third-trimester RIA kit, as used in seminal papers on unconjugated estriol in Down syndrome screening, and the new optimized Amerlex-M second-trimester kit. The significant difference between the results of each assay could cause unacceptable changes in the detection rate and false-positive rate of Down syndrome screening programs, especially if previously published values for estriol are used in the risk calculation. It is not possible to define new calculation parameters for every assay kit because new parameters will need to be defined every time kit changes occur, which would require a large collection of samples from Down syndrome pregnancies for standardization. Possible solutions to this problem are discussed.

Down Syndrome↗
PubMed1991

The effect of weight correction on risk calculations for Down's syndrome screening.

Recent advances in prenatal screening have led to the possibility that the risk of Down's syndrome associated pregnancy may be assessed by blood tests for maternal serum alphafetoprotein, human chorionic gonadotrophin (and possibly unconjugated oestriol) taken at 15-18 weeks of gestation. In neural tube defect screening correction of maternal serum alphafetoprotein for maternal weight has been recommended, although the precise method for weight correction is still under debate. We report an assessment of weight correction for maternal serum alphafetoprotein and human chorionic gonadotrophin based on 1408 singleton pregnancies and for unconjugated oestriol based on 197 singleton pregnancies. We demonstrate that weight correction of maternal serum alphafetoprotein and human chorionic gonadotrophin is statistically valid but that correction of unconjugated oestriol is not.

Body Weight↗
PubMed1991

Interference in thyroid-function tests in postpartum thyroiditis.

Three women are described from a study of patients with postpartum thyroiditis whose sera gave spuriously increased concentrations of free thyroid hormone because of antibody binding of radiolabeled thyroxin (T4) and triiodothyronine (T3) analogs. All of the women showed increased serum concentrations of thyroid autoantibodies. The antibody binding of radiolabeled analogs and its effect on free T4 and free T3 assays disappeared by 48 weeks postpartum. Postpartum women who develop thyroid autoantibodies have approximately 2% prevalence of increased binding of radiolabeled analogs, which can result in an interference in thyroid hormone assays involving T4 and T3 analogs.

Autoantibodies↗
PubMed1990

A long-term follow-up of postpartum thyroiditis.

To investigate the long-term outcome of postpartum thyroiditis (PPT), 43 patients with PPT and 171 control women were evaluated 3.5 (range 2-4) years postpartum. Ten (23%) PPT patients were hypothyroid compared to none of the controls (P less than 0.001). Factors associated with the development of hypothyroidism were high antimicrosomal antibody titre measured at 16 weeks gestation (P less than 0.01), severity of hypothyroid phase of PPT, multiparity, and a previous history of spontaneous abortion. The presence of microsomal antibody but no PPT in one pregnancy did not prevent the occurrence of PPT in the next pregnancy in two patients and a further five patients had PPT in two successive pregnancies. There was no association between HLA haplotype, family history of thyroid disease, smoking or frequency of oral contraception, and the development of long-term hypothyroidism after PPT. It is concluded that permanent hypothyroidism is an important sequel to PPT and patients with PPT should be followed up appropriately.

Adult↗
PubMed1990

Rate of cerebral embolic events in relation to antibiotic and anticoagulant therapy in patients with bacterial endocarditis.

To quantitate embolic risk we studied a retrospective series of 61 patients with strictly defined bacterial endocarditis. Eighteen patients had neurological complications attributable to cerebral embolism. Seventeen embolic episodes occurred prior to antibiotic treatment and 8 episodes after its commencement. The rate of embolism per patient-week during a 20-week observation period showed a highly significant almost 4-fold reduction to a low level soon after antibiotics were started. Patients already on anticoagulation for prosthetic valves had the same embolic risk as those not so treated. The evidence suggests that anticoagulation at the time of diagnosis of bacterial endocarditis is not warranted.

Adult↗