Biomedical subjects
Publications and source records attributed to R Adamson.
Carcinoma of the breast with sarcomatous metaplasia (CSM) is a rare and interesting tumour with a poorer prognosis than the usual breast malignancies. The mammographic appearances of this lesion have only previously been described once in the literature. A case of CSM is presented with mammographic-pathological correlation and review of the literature.
In this study we have analysed 38 squamous cell carcinomas (SCC) two basal cell carcinomas (BCC), a malignant salivary gland carcinoma, a neurosarcoma and a Warthins carcinoma, all isolated from patients with head and neck cancers. These tumour types have been examined by PCR for loss of heterozygosity (LOH) on both arms of chromosome 17 using nine polymorphic microsatellite markers. LOH on 17p in SCCHN was found to be 50% (19/38), and often involved TP53 (42%) but more frequently involved the CHRNB1 locus (56%). Twelve tumours showed loss of heterozygosity on 17q (34%) and ten of these also had loss on 17p. Four SCCHN tumours lost an entire copy of chromosome 17. It was of particular note that 77% (10/13) of the SCCHN at the hypopharyngeal site had LOH at CHRNB1. We propose from our data that the 17p12-p11 region contains a novel predisposing gene for hypopharyngeal SCCHN that may function as a tumour suppressor gene.
OBJECTIVES: The goal of this study was to assess patients with end-stage heart disease after implantation of a left ventricular assist device at rest and during exercise compatible with activities of daily life. BACKGROUND: Mechanical circulatory assistance with a left ventricular assist device is an accepted therapy for bridging patients with end-stage heart disease to heart transplantation and has been proposed for long-term implantation. METHODS: Three patients (aged 37, 42 and 57 years) with end-stage heart failure required implantation of a pneumatically driven, asynchronous Thermedics left ventricular assist device while awaiting heart transplantation. All were assessed 1 month later during graded supine bicycle exercise (maximal work load 100 to 150 W). Detailed central hemodynamics, including continuous pulmonary artery oxygen saturation and oxygen consumption measurements, were obtained. Two of the patients also underwent upright treadmill exercise with oxygen consumption measurements. RESULTS: During supine bicycle exercise, the heart rate increased from 93 +/- 37 beats/min (95% confidence interval: mean +/- t0.025 x SE) at rest to 119 +/- 54 beats/min and left ventricular assist device rate increased from 82 +/- 47 to 109 +/- 55 beats/min. Oxygen consumption increased from 3.0 +/- 0.9 to 8.7 +/- 2.9 ml oxygen/min per kg body weight. Cardiac output increased from 6.0 +/- 4.4 to 9.6 +/- 7.1 liters/min, yielding an average exercise factor of 8.5 +/- 7.7 and an exercise index of 0.83 +/- 0.61. The patients assessed during treadmill exercise achieved a maximal oxygen consumption of 14.3 and 16.7 ml of oxygen/min per kg. No thromboembolic or other complications attributable to left ventricular assist device implantation occurred during the duration of support. All patients survived orthotopic heart transplantation and are doing well. CONCLUSIONS: Significant work loads compatible with activities of daily life and adequate exercise hemodynamics were demonstrated by these patients while awaiting heart transplantation. Definitive conclusions regarding the use of this device must be viewed as preliminary because only three patients were involved in this study and the failure rate may be as high as 71% (95% confidence interval of left ventricular assist device success as a bridge to transplantation 29.3% to 100%). Final conclusions regarding the safety and efficacy of the left ventricular assist device as a possible long-term circulatory support device must await results of larger multicenter trials in progress.
In summary, this brief report documents the cell culture and rAHF purification systems used to produce rFVIII and has focused on the unique characteristics of the cell line, the production process, and purification system used. This review emphasizes the general philosophy used throughout the research and development of this innovative and complex therapeutic agent, in order to provide a safe and efficacious rAHF in the management of individuals with hemophilia A. This review provides a brief description of the in-process system and controls that have been incorporated to meet the high standards and safety objective.
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Fifty-six balloon dilatations in 51 patients with upper-extremity dialysis access fistulas were performed over a 4-year period. Forty-four venous anastomotic lesions in patients with either internal or graft fistulas were dilated. Three arterial anastomotic lesions and nine distant venous stenoses were treated. Thirty-nine of 56 (70%) dilatations were initially successful. Of the initial successes, 28/35 (80%) were patent at 3 months, 19/27 (70%) at 6 months, 12/22 (55%) at 1 year, 7/14 (50%) at 2 years, and 3/9 (33%) at 3 years. Three complications (5%) were encountered. These included two graft thromboses and one pseudoaneurysm at the dilatation site. The procedure may be performed on an outpatient basis.
The synthesis of a tetrapeptide on a base functionalised sporopollenin using sonic agitation for coupling and washing processes is described.
Our experience with the NCGT graft has now encompassed 12 years in experimental animals and 4.5 years clinical experience with 134 grafts in man. It has previously been suggested that vessel wall structure, interface-charge, electric potential, and polarity of the blood intimal interface appear critical in the prevention of intravascular thrombosis in all vascular prosthetic bypass grafts. This concept has now been confirmed using ferritin, colloidal iron and fluorescamine intimal labelling. These provide a quantitative special characterization of the surface charges of several grafts, including the NCGT graft. Study indicates that each step in the production of the NCGT graft results in a cumulative increase in the structured negative charge of the vascular interface. The more dense the structured negative charge of the prosthesis, the more resistant is the graft to short and long-term thrombosis in experimental animals and man. The experience has been confirmed with a comparative analysis of implantation results in 105 patients up to 4.5 years with 65 to 70% patency rate over that time interval. Statistical analysis of parameters confirm again that the polarity and structure of the vascular interface is important in the effective function and patency rate of the grafts.
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The establishment and characterisation of 7 small cell lung cancer cell lines is described. Four cell lines were established from biopsies taken from untreated patients and one of these was from primary tumour taken via the fibreoptic bronchoscope. The other three were from biopsies taken from patients who had relapsed after chemotherapy. All grow as non-adherent aggregates of cell and express a range of neuroendocrine and epithelial features characteristics of small cell lung cancer cell lines. No relationship was observed between the characteristics of the cell line in vitro and the treatment status of the patient from whom the biopsy was taken. Furthermore, none of the cell lines expressed p-glycoprotein even though 3 were derived from relapse biopsies where chemotherapy included drugs associated with the multidrug resistance phenotype.
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Leishmaniasis is on the increase in Venezuela (ca 30,000 new cases per year) due to deterioration in health management, increased risk groups among inmunosuppressed individuals and increased human penetration into the ecological habitats of sandfly vectors. An STD2-funded project (1989-1992) focused on the Andean state of Táchira, which showed the highest annual index of new cases (ca 200-250). The project aimed at contributing to vector/parasite identification through a combination of molecular and well established field techniques: Newly developed molecular methods distinguished among Lu. spinicrassa, Lu. youngi and Lu. townsendi. These three species of the Verrucarum group are sympatric in the Northeast of the state and could be successfully identified by CHA, DNA probes and RAPD. A Le. braziliensis specific KDNA probe used with squash blots indicated that Lu. spinicrassa is the main vector and that Le. braziliensis is the main parasite species in Táchira state, Venezuela. PCR and the Le. brasiliensis specific DNA probe, schizodemes, isoenzymes and polyclonal antibodies agreed as taxonomic criteria for classification of Leishmania isolated from parasitologically confirmed cases in Tachira. Considerable degree of antigen heterogeneity in Venezuelan Le. braziliensis complex and Le. mexicana complex isolates from Tachira suggests multiple candidate antigens for improving the specificity of immunological diagnosis. The methods developed and tested in Táchira state should be valuable in order to help solving other outstanding epidemiological problems such as following of the epidemiological impact of intervention and vector control measures in highly endemic areas. Future work (STD3 funded, 1993-1996) aims to apply these molecular techniques to a vector control pilot study in Lara state, an area showing the highest incidence of new cases in the country.
Studies of patients supported with a left ventricular assist device have considered determinants of acute survival emphasizing the role of right heart function. In patients with refractory heart failure awaiting heart transplantation, chronic left ventricular assist device implantation may provide an opportunity for rehabilitation before surgery if hemodynamics are adequate at rest and during activities of daily life. For the assessment of the efficacy of the left ventricular assist device in this setting, four patients in whom the HeartMate pneumatic left ventricular assist device had been implanted were tested during graded supine bicycle exercise with Doppler echocardiography interrogation and central hemodynamic measurements. Patients with left ventricular assist device increased total left ventricular-left ventricular assist device complex output with exercise as Fick cardiac output increased from 5.7 +/- 1.5 to 8.6 +/- 3.1 L/min (mean +/- standard deviation). In two patients, peak left ventricular assist device rate and output were either present at the start of exercise or reached at mid-exercise and were associated with abrupt increases in left ventricular filling pressures (pulmonary capillary wedge pressure = 9 to 27 mm Hg and 12 to 24 mm Hg, respectively). During exercise, left ventricular end-diastolic size and pressure increased as right ventricular dimensions decreased or remained the same (patients 1, 3, and 4: 1.7 to 1.8 cm, 4.7 to 3.9 cm, and 2.6 to 1.8 cm, respectively) despite increased right atrial filling pressures, implying a decrease in functional right ventricular diastolic compliance. Although the left ventricular assist device functioned as a series pump at rest, Fick cardiac output exceeded left ventricular assist device output during exercise consistent with parallel ejection of the left ventricle through the native aortic valve. During exercise, residual left ventricular function may contribute to the hemodynamic response by (1) active filling of the left ventricular assist device to reduce filling time and to overcome left ventricular assist device inflow cannula impedance, (2) augmentation of total cardiac output with parallel ejection out of the native aortic valve, or (3) reduction of ventricular interaction-related changes in functional right ventricular diastolic compliance. When residual left ventricular function is sufficient, hemodynamics with exercise may be limited by peak left ventricular assist device rate. Although right ventricular function may affect acute postoperative survival, residual left ventricular function and peak left ventricular assist device rate may be important determinants of exercise performance during chronic implantation. A preliminary model of factors affecting the "left ventricular-left ventricular assist device complex" performance at rest and during exercise is presented.