Evolution of white matter lesions in neurofibromatosis type 1: MR findings.

To characterize further the evolution of white matter lesions in neurofibromatosis type 1, we reviewed 68 MR images in 43 patients (age, 1-31 years), including 25 follow-up studies (mean interval, 27 months). Lesion number, location, morphology, signal characteristics, and contrast enhancement were assessed. Lesion characteristics and changes thereof were correlated with the patients' ages. Thirty-four patients (79%) had white matter lesions. These lesions were hyperintense on T2-weighted images, were isointense on T1-weighted images, and showed no mass effect or contrast enhancement in 31 patients; in three patients, T1-prolongation was observed (one with significant mass effect). None of the lesions evolved into a glioma. The most common locations were the cerebellum (49%), brainstem (22%), and internal capsule (19%). Nineteen patients had white matter lesions and follow-up studies. Lesions decreased in size or number in seven patients (average age, 13 years), showed no change in three (average age, 12 years), increased in size or number in four (average age, 5 years), and showed a mixed pattern (increased/decreased size/number) in four (average age, 7 years). White matter lesions in neurofibromatosis type 1 frequently increase in size or number early in childhood; this did not indicate neoplasia in our study. The lesions tend to resolve with increasing age. Lesion progression in a child more than 10 years old warrants close follow-up to rule out a neoplasm.     

In vitro stability of a novel compliant poly(carbonate-urea)urethane to oxidative and hydrolytic stress.

Poly(ester)urethane and poly(ether)urethane vascular grafts fail in vivo because of hydrolytic and oxidative degradative mechanisms. Studies have shown that poly(carbonate)urethanes have enhanced resistance. There is still a need for a viable, nonrigid, small-diameter, synthetic vascular graft. In this study, we sought to confirm this by exposing a novel formulation of compliant poly(carbonate-urea)urethane (CPU) manufactured by an innovative process, resulting in a stress-free. Small-diameter prosthesis, and a conventional poly(ether)urethane Pulse-Tec graft known to readily undergo oxidation in a variety of degradative solutions, and we assessed them for the development of oxidative and hydrolytic degradation, changes in elastic properties, and chemical stability. To simulate the in vivo environment, we used buffered solutions of phospholipase A(2) and cholesterol esterase; solutions of H(2)O(2)/CoCl(2), t-butyl peroxide/CoCl(2) (t-but/CoCl(2)), and glutathione/t-butyl peroxide/CoCl(2) (Glut/t-but/CoCl(2)); and plasma fractions I-IV, which were derived from fresh human plasma centrifuged in poly(ethylene glycol). To act as a negative control, both graft types were incubated in distilled water. Samples of both graft types (100 mm with a 5.0-mm inner diameter) were incubated in these solutions at 37 degrees C for 70 days before environmental scanning electron microscopy, radial tensile strength and quality control, gel permeation chromatography, and in vitro compliance assessments were performed. Oxidative degradation was ascertained from significant changes in molecular weight with respect to a control on all Pulse-Tec grafts treated with t-but/CoCl(2), Glut/t-but/CoCl(2), and plasma fractions I-III. Pulse-Tec grafts exposed to the H(2)O(2)/CoCl(2) mixture had significantly greater compliance than controls incubated in distilled water (p < 0.001 at 50 mmHg). No changes in molecular weight with respect to the control were observed for the CPU samples; only those immersed in t-but/CoCl(2) and Glut/t-but/CoCl(2) showed an 11% increase in molecular weight to 108,000. Only CPU grafts treated with the Glut/t-but/CoCl(2) mixture exhibited significantly greater compliance (p < 0.05 at 50 mmHg). Overall, results from this study indicate that CPU presents a far greater chemical stability than poly(ether)-urethane grafts do.     

Epidural pethidine and bupivacaine in labour

A double-blind randomised study was performed to assess the value of the addition of pethidine 50 mg to the initial dose of bupivacaine given for epidural analgesia in labour. Forty-nine patients received either 1 ml of saline (n = 24), or 50 mg of pethidine (n = 25), added to 9 ml of 0.25% bupivacaine as an initial injection for intrapartum epidural analgesia. There was a significant increase in the mean duration of analgesia in the pethidine group. However, pethidine did not increase the speed of onset of analgesia, or improve the quality of analgesia.     

Comparison of FK-506 and cyclosporine regimens in pediatric renal transplantation

Clinical aspects of FK-506 or cyclosporine immunosuppression regimens were evaluated in 48 consecutive pediatric renal transplant recipients. Tapering and discontinuation of prednisone was employed only in children receiving FK-506 who experienced minor or no rejection episodes during the 1st posttransplant month. At 1 year follow-up, 17 of 22 (77%) of all children with functioning allografts were receiving no prednisone (n=13) or a mean dosage of 0.07 mg/kg per day (n=4). During the 1st month, acute cellular rejection was more common in the FK-506 group (0.58 vs. 0.21 rejections per patient,P<0.05) but allograft survival (92%) and renal function at 1 year posttransplant were identical in both groups. Compared with the cyclosporine regimen, FK-506 immunosuppression may be associated with a higher incidence of cytomegalovirus or reversible Epstein-Barr virus-induced lymphoproliferative disease. However, the FK-506 group had less hirsutism and gingival hypertrophy and required fewer antihypertensive medications independent of steroid use. Height standard deviation scores and weight-for-height index improved only in preadolescents receiving FK-506 but no prednisone (P<0.02 andP<0.05, respectively), but did not differ between children on FK-506 plus prednisone and those in the cyclosporine group. We conclude that the major advantages of FK-506 over cyclosporine immunosuppression are a reduced severity of hypertension and an improved cosmetic appearance which may improve long-term medical compliance. When used as monotherapy, FK-506 also shows promise in relieving the growth retardation associated with cyclosporine regimens that include prednisone.     

Pretransplant Exposure to Donor HLA-DR Antigen in Random Transfusion Units and the Development of Donor Antigen-Specific Hyporeactivity

Our previous studies have shown that the in vitro assay of donor antigen-specific hyporeactivity is a useful marker for identifying solid organ transplant recipients (kidney, lung and heart) at low risk for immunologic complications (i.e., late acute rejection episodes and chronic rejection). Donor antigen-specific hyporeactivity is defined as a significantly decreased post- vs. pretransplant proliferative response to donor antigens while response to third-party controls remains unchanged. We analyzed whether exposure to the same HLA-DR antigen pretransplant via random blood transfusion and posttransplant via the transplanted organ influenced the development of hyporeactivity. Thirty previously nontransfused recipients, each receiving two 150 ml pretransplant random blood transfusions, were assessed for hyporeactivity at 1 year posttransplant. Of the 12 recipients with pretransplant exposure to kidney HLA-DR via transfusions, 6 (50%) developed hyporesponsiveness; in contrast, of the 18 recipients who were not preexposed, only 3 (15%) exhibited this form of immunomodulation. Of interest, 2 of the 3 hyporesponsive recipients who were not preexposed, received units containing HLA-DR antigens previously shown to share crossreactive epitopes with the kidney HLA-DR. In conclusion, these results suggest a increased incidence in the development of hyporeactivity in patients receiving pretransplant transfusions which share an HLA-DR antigen with the transplanted kidney.     

The effect of pirenzepine on gastric emptying and salivary flow rate: constraints on the use of saliva paracetamol concentrations for the determination of paracetamol pharmacokinetics.

1. The effects of pirenzepine on gastric emptying, salivary flow and saliva paracetamol concentrations were investigated in healthy volunteers. 2. Pirenzepine significantly reduced the area under the saliva flow-time curves (7.29 +/- 3.30 g min-1 h without pirenzepine; 4.19 +/- 2.59 g min-1 h with pirenzepine, P less than 0.01). Pirenzepine had no significant effect on plasma paracetamol Cmax (17.5 +/- 7.8 micrograms ml-1 without pirenzepine; 12.6 +/- 7.7 micrograms ml-1 with pirenzepine), plasma tmax (0.2 h (0.2-0.8 h) without pirenzepine; (0.2 h 0.2-0.8 h) with pirenzepine) and plasma AUC(0.6 h) (32.3 +/- 7.2 micrograms ml-1 h without pirenzepine; 30.3 +/- 6.5 micrograms ml-1 h with pirenzepine). 3. Mean ratios of saliva:plasma paracetamol AUC (1.06 +/- 0.24 without pirenzepine; 1.84 +/- 0.48 with pirenzepine, P less than 0.001) and saliva:plasma paracetamol Cmax (1.7 +/- 1.0 without pirenzepine; 6.5 +/- 2.7 with pirenzepine, P less than 0.01) were significantly increased by pirenzepine pretreatment, but there was a poor correlation between the percentage change in the area under the saliva flow-time curve and the percentage change in saliva paracetamol AUC (r = 0.47, P = 0.21). 4. The findings suggest that a) pirenzepine is a more selective antagonist of the muscarinic receptors in salivary glands than those in gastric smooth muscle and b) caution is required when using saliva paracetamol concentrations to determine the pharmacokinetics of the drug in the presence of other agents which may influence salivary flow rate.     

Current practice in the pre-operative assessment of patients for elective repair of abdominal aortic aneurysmA survey of UK hospitals

A postal survey of 100 hospitals throughout the United Kingdom and Ireland was conducted to assess current practice in the pre-operative assessment and use of pulmonary artery catheters in patients undergoing elective abdominal aortic aneurysm repair. Seventy-four completed questionnaires were received. The survey revealed that 53% of respondents hold designated pre-operative assessment clinics, attended by anaesthetists in 54% and cardiologists in 26%. However, only 4% of respondents have a written protocol for stratifying patients and assessing peri-operative risk. By far the commonest investigation of choice for further cardiological assessment is transthoracic echocardiography (67%). Other investigations of choice are multiple update gated acquisition (MUGA) scan (13%), dipyridamole thallium imaging (9%), exercise ECG (6%), stress echocardiography (1%) and stress MUGA (1%). Two units (3%) never undertook further investigation. Pulmonary artery flotation catheters are used as a routine by 9% of respondents, dependent upon left ventricular ejection fraction by 65%, dependent on other factors by 7% and not used at all by 19%. The survey reveals widespread variation in pre-operative assessment of patients undergoing elective repair of abdominal aortic aneurysm.     

Subclavian revascularization. A quarter century experience.

OBJECTIVE: Twenty-five years of experience with subclavian revascularizations were reviewed to determine the long-term patency rates of different extrathoracic approaches. SUMMARY BACKGROUND DATA: Although it is generally agreed that proximal subclavian stenosis should be treated by an extrathoracic route whenever possible, the optimum procedure is debated. Alternatives include subclavian carotid bypass, subclavian-to-subclavian or axillo-axillary bypasses, and the authors' preferred technique of subclavian carotid transposition (SCT). METHODS: Records were researched for the past 25 years in a single specialty surgical clinic for extrathoracic subclavian revascularizations. One hundred ninety such procedures were identified, and hospital charts and office medical records were reviewed for procedure, preoperative symptoms, blood pressure differentials, and postoperative complications. Patency was determined by physical examination, differential blood pressures, Doppler spectral analysis, duplex examinations, and arteriography. RESULTS: Bypass procedures were used infrequently, and although the results are reported, they are excluded from any analysis. Subclavian carotid transposition was used in 178 procedures. All anastomoses were found to be patient at follow-up, except for one, which failed at 26 months. Mean follow-up was 46 months, with five patients lost to follow-up. Overall mortality rate was 2.2%, with the mortality falling to 1.1% if only subclavian carotid transposition patients are included. CONCLUSIONS: Subclavian carotid transposition should be the treatment of choice for routine subclavian carotid occlusive disease because of its exceptional long-term patency and low morbidity.