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Biomedical subjects

K Bowyer

Publications and source records attributed to K Bowyer.

8 recordsLinked to original sources

Role of plasminogen activator inhibitor-1 (PAI-1) levels in the diagnosis of BMT-associated hepatic veno-occlusive disease and monitoring of subsequent therapy with defibrotide (DF).

UNLABELLED: Hepatic veno-occlusive disease (VOD) is a common and potentially fatal complication of high dose chemotherapy with allogeneic/autologous stem cell transplant (SCT). The diagnosis and treatment of hepatic VOD is controversial. Clinical features are non-specific and may be mimicked by a number of other conditions causing hyperbilirubinaemia post-transplantation. Plasminogen activator inhibitor-1 (PAI-1) has been proposed as a specific marker of VOD [1]. Defibrotide (DF) is a polydeoxyribonucleotide, which has been found to have anti-thrombotic, anti-ischaemic and thrombolytic properties without causing significant anti-coagulation. Recent evidence [2,3] suggests that use of DF in patients with severe VOD results in a promising response rate without attributable significant toxicity. Between January 1998 and July 1999, PAI-1 levels were measured serially in 16 patients undergoing SCT who had subsequently developed hyperbilirubinaemia. Diagnosis of VOD was made by established clinical criteria [4,5]. At the time of diagnosis, PAI-1 levels (mean+/-SD) were significantly elevated in patients with VOD (90.7+/-47 ng/ml, n=7) when compared with patients with jaundice from other causes post transplantation (12.1+/-6.4 ng/ml, n=9). Five of the patients with VOD received treatment with DF. Four out of five patients showed an initial response to DF (significant fall in bilirubin and improvement in other signs/symptoms) with one of these patients having a complete response (bilirubin < 2.0 mg/dl and full resolution of signs/symptoms and end-organ toxicity). Following treatment with DF, a corresponding fall in PAI-1 levels was noted in those responding, with non-responders maintaining raised levels. CONCLUSION: Raised PAI-1 levels post stem cell transplant are specific for VOD and a subsequent decrease in levels following treatment with DF may be associated with response to treatment.

Adolescent↗

Unexplained groin pain: safety and reliability of herniography for the diagnosis of occult hernias.

A retrospective study of our initial experience of herniography in a district general hospital is presented. A total of 43 herniograms were performed in 41 patients (median age 57, range 16-77, 27 males, 14 females) over a two year period. Four herniograms were unsuccessful due to failed intraperitoneal contrast injection, of which two were repeated (success rate 90.5%). A total of 25 groin hernias were identified radiologically (two on the asymptomatic side). Twenty one patients underwent surgery and a hernia was confirmed in 19 (true positive rate 90.5%). Sixteen herniograms were considered negative and after a median follow up of 28 months (range 16-42 months), none of these patients have developed a hernia. There were no major complications. It is concluded that herniography is a safe and reliable method of determining or excluding the presence of an occult groin hernia.

Adolescent↗

Defibrotide for the treatment of hepatic veno-occlusive disease: results of the European compassionate-use study.

Severe hepatic veno-occlusive disease (VOD) is a recognized complication of autologous and allogeneic stem cell transplantation (SCT) that is often fatal. Defibrotide (DF) is a polydeoxyribonucleotide that has been found to have anti-thrombotic, anti-ischaemic and thrombolytic properties without causing significant anticoagulation. Preliminary studies have demonstrated activity for DF in the treatment of VOD, with minimal associated toxicity. In the present study, 40 patients who fulfilled established criteria for VOD were treated with DF on compassionate grounds in 19 European centres; 28 patients met risk criteria predicting progression of VOD and fatality or had evidence of multiorgan failure (MOF), and were defined as 'poor-risk'. DF was commenced intravenously at a median of 14 d (range, -2 d to 53 d) post SCT at doses ranging from 10 to 40 mg/kg. The median duration of therapy was 18 d (range, 2--71 d). Twenty-two patients showed a complete response (CR) (bilirubin < 34.2 micromol/l and resolution of signs/symptoms of VOD and end-organ dysfunction) [CR = 55%, confidence interval (CI) 40--70%] and 17 patients (43%) are alive beyond d +100. Ten poor-risk patients showed a complete response (CR = 36%, CI 21--51%). These results demonstrate that DF is an active treatment for VOD following SCT and a randomized trial is now underway in order to further evaluate its role.

Acute Disease↗

Radionuclide analysis of right and left ventricular response to exercise in patients with atrial and ventricular septal defects.

In patients with ventricular or atrial septal defect, the ventricle which is chronically volume overloaded might not appropriately respond to increased demand for an augmentation in output and thereby might limit total cardiac function. In this study we simultaneously measured right and left ventricular response to exercise in 10 normal individuals, 10 patients with ventricular septal defect (VSD), and 10 patients with atrial septal defect (ASD). The normal subjects increased both right and left ventricular ejection fraction, end-diastolic volume, and stroke volume to achieve a higher cardiac output during exercise. Patients with VSD failed to increase right ventricular ejection fraction, but increased right ventricular end-diastolic volume and stroke volume. Left ventricular end-diastolic volume did not increase in these patients but ejection fraction, stroke volume, and forward left ventricular output achieved during exercise were comparable to the response observed in healthy subjects. In the patients with ASD, no rest-to-exercise change occurred in either right ventricular ejection fraction, end-diastolic volume, or stroke volume. In addition, left ventricular end-diastolic volume failed to increase, and despite an increase in ejection fraction, left ventricular stroke volume remained unchanged from rest to exercise. Therefore, cardiac output was augmented only by the heart rate increase in these patients. Right ventricular function appeared to be the major determinant of total cardiac output during exercise in patients with cardiac septal defects and left-to-right shunt.

Adolescent↗

Chloral hydrate overdose and cardiac arrhythmias.

Two cases of chloral hydrate overdosage were associated with multiform ventricular tachycardia. Both were refractory to a number of antiarrhythmics, but responded to propranolol administration. Two of nine other cases reported in the literature also responded to beta-blocking agents. Mechanisms for the arrhythmia and its apparent response to beta blockade are discussed.

Adolescent↗

CT-guided stereotaxis using a modified conventional stereotaxic frame.

Computed tomographic (CT)-guided stereotaxic procedure have become established in a few major centers but a single optimal system has not yet emerged. At Duke University Medical Center, availability of a stereotaxic frame with design features that lend themselves to CT adaptation made modification of this unit, rather than construction of a new dedicated frame, cost-effective. As other centers may seek to modify available stereotaxic equipment in a similar way, this report documents the modifications ans the early clinical experience in four patients in whom CT-guided stereotaxic biopsy procedures were performed.

Adolescent↗