Nitrates in the elderly. Pharmacological considerations.

Although a significant proportion of patients receiving nitrates are elderly, surprisingly little published work is available describing the pharmacokinetics and pharmacodynamics of these agents in elderly patients. The lack of pharmacokinetic data is related to the difficulty in assaying nitrates and there are at present no definitive data describing the effect of aging on their bioavailability or elimination. A common finding in old age is of decreased hepatic first-pass metabolism. This would affect isosorbide-2-mononitrate and isosorbide-5-mononitrate less than isosorbide dinitrate and nitroglycerin (glyceryl trinitrate). Venous responsiveness to nitrates does not appear to alter with age, so that pharmacodynamic properties would not be expected to alter. However, decreased baroreflex function causes an increased tendency for posturally related side effects to occur. Mechanisms of tolerance are likely to be unaltered but any possible alteration in quantitative aspects of tolerance has not been studied. Nitrate therapy in the elderly would benefit from systematic investigation. At the moment, therapy needs to be titrated to the individual patient, with care taken to avoid age-related side effects by careful initiation of therapy and appropriate reviews of each patient.     

Reversal of fulminant hepatic failure using an extracorporeal liver assist device.

Liver transplantation is currently the only effective therapy for patients with fulminant hepatic failure. The availability of an artificial liver could bridge these patients through the relatively brief crisis period and allow their own livers to regenerate, providing a more favorable outcome and sparing the trauma and expense of transplant. We have developed a device consisting of a highly differentiated human liver cell line cultured in a hollow fiber cartridge. This device is capable of supporting dogs with acetaminophen-induced fulminant hepatic failure for a period long enough for their own livers to resume function. Even though liver function tests such as albumin and prothrombin time became extremely abnormal during the course of the experiment, the dogs did not become encephalopathic. Two of the three treated animals recovered sufficient liver function after 42 to 48 hr of treatment that they could be disconnected from the device, and they survived the experiment. Histological results and serum ALT levels suggest that the device affected the course of the disease in two animals, allowing recovery of hepatocytes that would otherwise have lysed. In the third animal, regenerative nodules demonstrated that, even in the presence of severe liver injury, the device was capable of supporting total liver function.     

Volumetric stereotactic surgical resection of intra-axial brain mass lesions

From August 1984 to August 1987 at the Mayo Clinic, 226 computer-assisted stereotactic resections based on computed tomography or magnetic resonance imaging (or both) were performed on 203 supratentorial and 23 infratentorial lesions in various deep-seated or essential brain locations. Histologic examination revealed 112 glial neoplasms, 70 nonglial tumors, and 44 nonneoplastic lesions. The overall morbidity was 9.3% (21 of 226 patients were worse after the procedure), and the 30-day operative mortality was 1% (2 patients). The procedure provides maximal cytoreduction in high-grade glial neoplasms but is most beneficial to patients who have histologically circumscribed tumors, such as pilocytic astrocytomas, metastatic neoplasms, and miscellaneous nonglial and nonneoplastic lesions.     

An assessment of factors which influence the effectiveness of the modified in vivo technetium-99m-erythrocyte labeling technique in clinical use.

This study assessed factors which may contribute to suboptimal image quality when the modified in vivo erythrocyte labeling technique is used with standard clinical 99mTc activities. For each assessment duplicate or triplicate blood specimens were withdrawn from > or = 10 patients, into syringes containing 700-900 MBq 99mTc as pertechnetate. After incubation the percent of 99mTc which was not bound to erythrocytes at blood re-injection time (%Unbound 99mTc), was measured and compared when one of four factors was varied. The most significant results, in descending order of measured effect were: [table: see text] Our data suggest that the requirements for optimal erythrocyte labeling with standard clinical 99mTc activities are: (A) Erythrocyte tinning time between 10 and 30 min; (B) blood volume > or = 3 ml; (C) blood incubation time > or = 20 min; and (D) Generator ingrowth time < or = 24 hr.     

Venous hemangioma of the gallbladder

An 11-year-old girl presenting with right upper quadrant abdominal pain was found to have a venous hemangioma of the posterior wall of the gallbladder. Radiographic, ultrasonographic, and angiographic findings of this entity, along with a review of the literature, are presented.     

An animal model of chronic tympanic membrane perforation.

Previous investigations into the healing and reconstruction of tympanic membrane (TM) perforations have involved animal models with acute TM perforations. A problem with the acute TM perforation model is that most acute TM perforations will heal spontaneously, both in animals and human beings. A second inadequacy of acute perforation models is that they are not analogous to the salient problem in human beings: long-standing TM perforation. The ideal animal model must have a TM perforation that is permanent, well-epithelialized, and free from infection. The perforation must also be subtotal to preserve a rim of membrane for experimental manipulations. In the chinchilla, we have identified a hardy animal with a short, wide ear canal and relatively large tympanic membranes. Thermal myringectomy, followed by medial infolding of TM microflaps, has resulted in permanent, subtotal chronic TM perforations in the chinchilla animal model. Of the 19 chinchillas (38 TMs) perforated, chronic subtotal perforations were created in 32 ears, 6 to 8 weeks after the initial procedure (84% success). Persistent infection or TM regeneration despite reperforation was recorded in 6 ears (16%) failure). This model is currently being used to assess various biomembrane scaffolds impregnated with growth-promoting substances in the regeneration of a physiologically sound TM, initially in our animal model and then in human beings. We envision the development of a biomembrane disc impregnated with biorecombinant growth factors that may provide a simple office technique for the repair of chronic, non-infected TM perforations.     

Update on the Interaction of Rifampin and Warfarin

A 79-year-old man with a history of deep vein thrombosis and pulmonary embolism received anticoagulation therapy with warfarin 5 mg daily for 8 months. He was diagnosed with osteomyelitis and underwent partial metatarsal resection of his right foot. After surgery, antibiotics were initiated including ertapenem sodium 1 g intravenously every 24 hours, vancomycin 1400 mg intravenously every 24 hours, and rifampin 300 mg by mouth twice daily. Achieving a therapeutic level of anticoagulation was difficult despite escalating doses of warfarin, because of the interaction with rifampin. A 5- to 6-fold increase in warfarin dose was prescribed to reach therapeutic international normalized ratios (INRs), but even these increases were insufficient to maintain his INR in the therapeutic range. After rifampin was discontinued, warfarin doses were gradually reduced over the next 2 months. When concurrent warfarin-rifampin therapy is necessary, vigilant monitoring is imperative and significant increases in warfarin doses are likely.