A comparison of different embalming fluids on the quality of histological preservation in human cadavers.

There are significant problems in obtaining normal human material for histology for teaching or research purposes. This study shows that tissue from cadavers embalmed for teaching can be used for routine histology. Twelve cadavers embalmed with four different formalin-containing embalming fluids were used (n = 3 per fluid): (1) formalin mix (10% formalin); (2) Dunedin mix (an alcohol-based fluid containing phenol); (3) Michigan mix (a water-based fluid); and (4) phenoxyethanol mix (an alcohol-based fluid containing phenoxyethanol). Tissue blocks of liver, heart, kidney, skin and skeletal muscle were taken from each cadaver, paraffin embedded, sectioned and stained with haematoxylin and eosin (H & E), Periodic Acid Schiff (PAS), or Mallory trichrome (Malt). Each section was assigned an overall score based on the histological quality of the cellular components of the tissue. Sections were scored from 1 to 3 (1 = poor, 2 = satisfactory, 3 = good). Satisfactory sections were obtained from all cadavers except those embalmed with the Dunedin mix. The Michigan and phenoxyethanol fluids resulted in consistently good quality sections. No significant differences in tissue morphology were observed between the different stains. The clearest morphology was observed in the skin and skeletal muscle sections, and in tissues embalmed with fluids which do not contain phenol.

Clinical experience with oral ketamine.

Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist used recently for analgesia in patients with chronic pain. Twenty one patients with chronic neuropathic pain were treated with oral ketamine starting at a divided dose of 100 mg/day and titrating upwards by 40 mg/day until efficacy was reached, or until side effects became limiting. A retrospective chart review was conducted to evaluate the analgesic efficacy and side effects of the treatment. Nine patients discontinued ketamine because of intolerable side effects, four patients experienced few or no side effects but had no discernible benefit, four others had equivocal responses. Four patients have continued oral ketamine for long periods. One patient has had no significant benefit or side effects but continues to use ketamine 500 mg/day and three people have used doses ranging from 100-240 mg day for over 1 year duration and have reported improvements in pain and decreased use of analgesics. The analgesic benefits of ketamine appeared to be most pronounced in, but not limited to, patients with pain histories of less than 5 years.

Fentanyl transdermal system. Pain management at home.

PROBLEM BEING ADDRESSED: About 65% of patients with advanced malignancies experience cancer pain. Although oral opioids provide effective analgesia for most of these patients, alternate routes of drug delivery are often necessary as the disease progresses. PURPOSE OF PROGRAM: To study use of Duragesic (fentanyl transdermal system), the only transdermal opioid approved in Canada for treating chronic cancer pain in adults. MAIN COMPONENTS: Transdermal fentanyl was prescribed for a heterogeneous group of 44 patients (aged 29 to 82 years) to treat cancer pain (37 patients), chronic non-malignant pain (six patients), and pain associated with terminal AIDS (one patient), for periods of 2 to 384 days. Patients were treated individually and switched to transdermal fentanyl from other opioids when oral delivery was no longer possible. Doses were titrated as necessary and ranged from 25 micrograms/h to 300 micrograms/h. Incidental pain was treated effectively with short-acting opioids. CONCLUSIONS: Eighty percent of patients experienced good analgesia, which led to an overall improvement in their quality of life. Transdermal fentanyl was discontinued for 17% of patients due to intractable nausea, diarrhea, adherence problems, or poor analgesia. Many patients wore the system until they died or until a few days before death when severe increasing pain necessitated parenteral opioids. The side effects of transdermal fentanyl were similar to those of conventional opioids. Patient compliance and acceptance of this noninvasive, continuous system of drug delivery has been excellent; its simplicity of administration allows patients to be cared for at home.

Using gabapentin to treat neuropathic pain.

OBJECTIVE: To review use of gabapentin as an adjuvant agent to treat neuropathic pain. QUALITY OF EVIDENCE: MEDLINE was searched from 1995 to October 1998 for reports. There were approximately 20 citations. Additional articles from Pain and other medical journals were reviewed. No double-blind studies have examined gabapentin and its use as an analgesic adjuvant agent. MAIN MESSAGE: Gabapentin is an anticonvulsant medication used recently as an effective adjuvant agent for treating neuropathic pain. It is a structural analogue of gamma-aminobutyric acid (GABA), but its receptor and biochemical function remain unknown. Gabapentin has desirable pharmacokinetic properties and acceptable side effects, which simplify its use. There are very few interactions between gabapentin and other medications, and gabapentin is well tolerated. CONCLUSION: Gabapentin could be an effective adjuvant agent for many neuropathic pain states.

Kinetic and structural characterization of spinach carbonic anhydrase.

We have carried out kinetics studies of spinach carbonic anhydrase (CA) using stopped-flow spectrophotometry at steady state and 13C-NMR exchange at chemical equilibrium. We found that the rate of CO2<-->HCO3- exchange catalyzed by spinach CA at pH 7.0 to be 3-5 times faster than the maximal kcat for either CO2 hydration or HCO3- dehydration at steady state, suggesting a rate-determining H+ transfer step in the catalytic mechanism. Correspondingly, we measured a pH-independent solvent deuterium isotope effect on kcat of approximately 2.0, and found that the rate of catalysis was significantly decreased at external buffer concentrations below 5 mM. Our results are consistent with a zinc-hydroxide mechanism of action with for spinach CA, similar to that of animal carbonic anhydrases. We have also collected X-ray absorption spectra of spinach CA. Analysis of the extended fine structure (EXAFS) suggests that the coordination sphere of Zn in spinach CA must have one or more sulfur ligands, in contrast to animal CAs which have only nitrogen and oxygen ligands. The models which best fit the data have average Zn-N(O) distances of 1.99-2.06 A, average Zn-S distances of 2.31--2.32 A, and a total coordination number of 4-6. We conclude that animal and spinach CAs are convergently evolved enzymes which are structurally quite different, but functionally equivalent.