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Biomedical subjects

A Newland

Publications and source records attributed to A Newland.

16 recordsLinked to original sources

The evaluation of a humidifying device for vitreoretinal surgery.

AIM: To study the feasibility of humidifying air during vitreoretinal surgery and measure the water content of air before and after intraocular transit. METHODS: The absolute water content of air was measured in a series of six eyes undergoing fluid-air exchange during macular hole surgery. Infrared absorption spectroscopy was used to determine the water content of the air infusing and exiting each eye. After baseline measurements for each eye were recorded, a second fluid-air exchange was performed and the effect of humidifying the air infusion was documented. The humidifying device used in this study was a prototype adapted from a commercially available respiratory humidifier and enables humidified air to be delivered at a controlled temperature. RESULTS: The water content of air increased following intraocular transit, implying dehydration occurs from the intraocular surfaces. For a standard airline infusion the mean increase in water content of air egressing from an eye was 13.4 mg/l. Humidifying the air reduced the rate of water loss by nearly 90%. CONCLUSIONS: Significant water losses can occur from eyes undergoing fluid-air exchange. Humidifying the infused air can substantially reduce the dehydrating effect during an air exchange. This outcome may have a beneficial effect in reducing cataract formation and visual field defects associated with macular hole surgery.

Air↗

A phase II protection study of BB-10010 in patients with high grade non-Hodgkin's lymphoma undergoing intensive chemotherapy.

The aim of this study was to determine whether administration of BB-10010, a synthetic stem cell inhibitor, would allow more intensive chemotherapy to be administered to patients with newly diagnosed high grade NHL. Thirteen patients were randomised to receive BB-10010 concurrently with dose-intensified BEMOP/CA chemotherapy (7 patients) or chemotherapy alone (6 patients). Although the mean neutrophil count of BB-10010 treated patients was higher following cycles 1, 2 and 3 of chemotherapy compared with those receiving chemotherapy alone, there was no difference in the mean number of cycles tolerated, blood component usage and hospital admissions due to infections. No specific toxicity of BB-10010 was identified. Whilst BB-10010 can be administered safely, it does not improve the ability of patients to tolerate intensive chemotherapy for high grade NHL.

Adult↗

Humidity devices in vitreoretinal surgery.

PURPOSE: To assess a humidity device used in vitreoretinal surgery. METHODS: Infrared absorption spectroscopy analysis of absolute water content (absolute humidity) was determined for a typical vitreoretinal air infusion line with and without the humidifying device. A variety of experimental laboratory conditions were utilized and designed to mimic those found in the operating room. The effect on physical parameters, such as flow rates and resistance to flow, were also determined. RESULTS: While large bore infusion (LBI) lines had a negligible effect on flow rate and resistance to flow (reduction in infusion pressure), the standard 20 G infusion line (SI) reduced flow rate and infusion pressure by approximately 25%. When used together, the humidifying device and SI reduced flow rate and infusion pressure by one third. The humidifying device was found to add 6.5 mg/L water content to the air infusion line system. Typical operating room (OR) air contains 9.5 mg/L water content, and 43.876 mg/L water content is required to saturate air at body temperature. CONCLUSION: To eliminate dehydration as a cause of intraocular morbidity, one must first saturate the infused air. If the visual field defects and other complications are eliminated, this would be good evidence for saturating infused air. As infusion pressure (flow rate) influences dehydration rate, unless saturated air is used, infusion pressure cannot be considered an independent variable in the analysis of field defects.

Body Temperature↗

Amphotericin B lipid complex (ABLC) for the treatment of confirmed or presumed fungal infections in immunocompromised patients with hematologic malignancies.

Sixty-four adult patients (median age 43) with hematologic malignancies who were immunocompromised after allogeneic (n = 23) or autologous (n = 9) blood/marrow transplantation, or chemotherapy (n = 32) received 68 courses of amphotericin B lipid complex (ABLC, Abelcet) at the daily dose of 5 mg/kg for presumed (n = 52) or proven (n = 16) fungal infection. The major indications for ABLC were failure of previous antifungal therapy and/or renal dysfunction. Fifty-three treatment courses in 49 patients comprising 4-58 doses (median 10) were considered evaluable. Fourteen courses administered for confirmed infections resulted in nine complete and one partial responses, and four failures (71% response). Thirty-nine empiric courses resulted in 18 complete and six partial responses, and 14 failures (64% response). The overall response rate was 66%. Five of seven evaluable patients with aspergillus pneumonia responded. Response rates were comparable for chemotherapy, autograft and allograft recipients. The change in serum creatinine from the beginning to the end of therapy was -284 to +277 mumol/l (median +24). The creatinine doubled during seven evaluable courses of therapy, five of which were associated with concomitant nephrotoxic therapy. Nephrotoxicity was comparable for transplant and chemotherapy patients. Renal dysfunction necessitated discontinuation of ABLC in only four patients. These data suggest that ABLC is effective in presumed or confirmed fungal infections in immunocompromised patients after transplantation or chemotherapy.

Adolescent↗

Factor VIIa and other haemostatic variables following bone marrow transplantation.

Hepatic venocclusive disease causes considerable morbidity and mortality following bone marrow transplantation. There are two hypotheses regarding the aetiology of this syndrome; firstly that changes in plasma coagulation factors and natural anticoagulants lead to a prothrombotic state and secondly that endothelial cell activation stimulates intravascular deposition of fibrin. We have investigated these mechanisms by measuring the changes in proteins C and S and factors VII and X in the post transplant period and by using the plasma concentration of factor VIIa as an in vivo marker of potential endothelial cell tissue factor expression. Protein C fell in both allograft and autograft patients but more so in the allografts. Similar results were found for factors VII and X. These changes were predominantly due to hepatic dysfunction induced by the chemo-radiotherapy. Factor VIIa levels were unchanged in both the allograft and autograft patients. We conclude that there is no convincing evidence for a procoagulant state following BMT as there are both anticoagulant and procoagulant changes. The absence of any changes in factor VIIa levels suggests that tissue factor was not exposed to the general circulation following BMT but does not exclude focal expression at the sites of thrombosis.

Bone Marrow Transplantation↗

Cyclosporine and cremaphor modulate von Willebrand factor release from cultured human endothelial cells.

Cyclosporine has been associated with microangiopathic hemolysis (MAHA) and other thrombotic complications of bone marrow and renal transplantation. MAHA is characterized by intravascular platelet aggregation, which, in some situations, is thought to be mediated by hyperactive high molecular weight von Willebrand factor (vWF). We have hypothesized that transplant-related MAHA may be caused by CsA-mediated release of von Willebrand factor from endothelial cells. This hypothesis was tested by studying vWF release from human umbilical vein endothelial cells primed with either CsA or cremophor EL. CsA and cremophor alone did not increase vWF release until toxic concentrations were reached (50-100 micrograms/ml). However, at therapeutic concentrations (0.1-5 micrograms/ml) vWF release by cells stimulated with thrombin, histamine, PMA, and the calcium ionophore A23187 was enhanced by both CsA and cremophor in a concentration-dependent manner. In single isolated endothelial cells, the thrombin-induced increase in cytosolic free calcium was enhanced by both CsA and cremophor. Preincubation for 24 hr with CsA but not cremophor suppressed vWF release after thrombin stimulation. These observations were mirrored by a concentration-dependent suppression of [3H]thymidine uptake by CsA. We conclude that CsA vehicle, cremophor, enhances stimulated vWF release in vitro, probably by processes dependent upon increased cytosolic free calcium. This suggests a possible mechanism for thrombotic transplant complications.

Calcium↗

Different forms of chronic childhood thrombocytopenic purpura defined by antiplatelet autoantibodies.

To determine whether detection of antiplatelet autoantibodies (AAb) to glycoproteins IIb/IIIa and Ib/IX may be useful in defining different forms of chronic thrombocytopenic purpura (TP) in children, we analyzed for AAb the platelet and plasma samples from 36 children with chronic TP (mean duration 4.4 years), from 31 children with normal platelet counts at the time of blood sampling but with chronic TP in the past (mean duration 2.9 years), and from 23 adults with chronic TP; the results were correlated with the clinical data. Antiplatelet autoantibodies were detected in 26 (72.2%) of 36 children with ongoing TP, 15 (48.4%) of 31 children with TP in the past, and 12 (66.7%) of 18 adults with TP. All children with high AAb ratios (greater than 5 times the control mean + 3 SD) were more than 8 years of age at diagnosis (mean age 12.4 years compared with 7.1 years in children with moderate or negative AAb levels; p = 0.003). The results suggest that the outcome for adolescents with high platelet-associated AAb levels may be similar to that of adults, whereas younger children may have a greater chance of spontaneous remission. The children with chronic TP in the past and elevated platelet-associated AAb levels may have a "compensated" TP and therefore may be at risk for relapses. Future studies aimed at serial AAb determination throughout the patients' courses may further define TP subgroups.

Adolescent↗

Infusion of vincristine and doxorubicin with oral dexamethasone as first-line therapy for multiple myeloma.

32 previously untreated patients with multiple myeloma received vincristine, doxorubicin ('Adriamycin'), and dexamethasone (VAD) as first-line therapy. The overall response rate was 84%, with 28% of all patients entering complete remission. Response was rapid, with near-maximum response occurring after two courses of treatment and rapid improvement in bone-marrow function. Median response duration was 18 months and this seemed to be unaffected by initial prognostic criteria or by degree of remission achieved. The projected median survival was 44 months, with 75% of all patients and 83% of responders being alive at 2 years. Side-effects due to steroids were common, but there was only 1 treatment-related death. The high response rate and lack of toxicity offer an advantage over other forms of initial treatment, although other strategies will be necessary to prolong the duration of response.

Administration, Oral↗

One-shot high-dose pamidronate disodium (APD): effective, simple treatment for hypercalcaemia in haematological malignancy.

Fifteen patients with haematological malignancy and hypercalcaemia (mean +/- SEM calcium 3.44 +/- 0.14 mmol/l) received pamidronate (1 mg/kg) by infusion on 17 occasions (two patients were retreated 2 and 6 months after the first dose). After 4 days the plasma calcium had fallen to 2.84 +/- 0.14 mmol/l (P less than 0.001; n = 17), and in 10/17 episodes was less than 2.6 mmol/l. The mean fall was 0.61 mmol/l (95% confidence intervals 0.49-0.72 mmol/l). By 7 days a further decrease to 2.53 +/- 0.10 mmol/l had occurred, continuing to 2.38 +/- 0.11 mmol/l after 14 days. Plasma phosphate fell from 1.18 +/- 0.16 to 0.74 +/- 0.07 mmol/l at 7 days (P less than 0.001; n = 12). In 9 of the 17 episodes plasma creatinine initially exceeded 120 mumol/l (four of these greater than 300 mumol/l). This did not impair the response to pamidronate and there was no significant change in plasma creatinine following treatment. A single large dose of pamidronate was a simple, well-tolerated and very reliable treatment for hypercalcaemia complicating haematological malignancy, irrespective of renal function.

Adult↗