Effect of the immunomodulant ximedone on the pharmacokinetics of isonicotinic acid hydrazide in the human organism

The pharmacokinetics of isonicotinic acid hydrazide upon joint administration with the immunomodulant ximedone has been investigated. Ximedone influences the genetically determined parameters of the isonicotinic acid hydrazide pharmacokinetics. The dose-dependent and temporal schedules of ximedone administration in humans are established, which favor the induction of acetylation processes in patients. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 3, pp. 3–6, March, 2006.     

Transdermal permeation-enhancing activities of some inorganic anions

Effects of sodium salts of various monovalent inorganic anions on transdermal permeation of salicylic acid were investigated. In in-vitro experiment using a Franz-type diffusion cell and excised mouse skin, the permeation-enhancing activities of the sodium salts of inorganic anions were roughly proportional to lyotropic Hofmeister swelling abilities of the anions; F^?<SO₄ ^2?<Cl^? <ClO₄ ^?<NO₃ <SCN^? <Br <I^?, i.e. l, Br and SCN increased the flux of drugs through the mouse skin, while F^?, SO₄ ^2?, Cl^?, ClO₄ ^? and NO₃ ^? decreased or did not affect the flux. In invivo experiment using the rabbit as the test animal, the plasma concentration of salicylic acid of the rabbit to which 10%-salicylic acid ointment containing 5%-Nal or NaBr was applied was significantly higher than that of the rabbit to which the ointment without the electrolytes was applied. The amounts of sterol leached out of stratum corneum sheet when the sheet was immersed in aqueous solutions of Nal, NaBr, or NaSCN were much more than that of stratum corneum immersed in aqueous solutions of the other inorganic anions. The FTIR/ATR spectroscopy showed that the peaks at 2853 cm^?1 and 2924 cm^?1 in the IR absorption spectrum of the stratum corneum sheet of the mouse were shifted to higher frequencies by the anions which enhanced the transdermal drug permeation, while not shifted by the anions which did not have any permeation-enhancing activities or have permeation-reducing activities. These results suggest that sodium salts of some anions such as iodide, bromide and thiocyanate enhance transdermal permeation of salicylic acid through swelling and perturbation of the skin structure by these anions.     

Infection in limb salvage surgery for bone tumors

The authors present a retrospective study of 66 infected cases in their series of limb salvage surgery performed from January 84 to August 92. Special emphasis was given to the alternative techniques of treatment in infection. In 85% of the cases healing was achieved, however removal of the implant and amputation are still frequent occurrences. Time to recovery is very demanding.     

“Lytic” lesions in autologous bone grafts: demonstration of medullary air pockets on post mortem computed tomography

Donor bone grafts are an important aspect of orthopaedic surgery. The use of plain film as a pathological screening tool before donor bone dispatch has revealed “lytic” lesions in proximal humeri. Donor demographics did not support the diagnosis of myeloma and subsequent computed tomography (CT) scans of these bones identified the lesions as air, not pathology. In total, 27 long bones were scanned and 100% (27/27 cases) exhibited air within the trabecular bone. Three distinct patterns were found: ovoid, linear/branching, and broad channel. A longitudinal course of CT scans was performed to identify at which stage air appeared within the bone. Pre-retrieval, preprocessing, and postprocessing scans revealed that air originated between the retrieval and preprocessing stages of donor bone preparation. There may be multiple aetiology of this phenomenon, including bone retrieval and natural decomposition.     

Mortality rate after hip hemiarthroplasty: analysis of risk factors in 299 consecutives cases

Abstract The femoral neck fracture is actually the most important traumatic event in the elderly, because of its high rate and terrible complications. We reviwed clinical records of 314 patients treated in our institution with a bipolar implant for femoral neck fracture. At a mean follow-up of 5 years, 15 patients (4.8%) were lost to followup so data for 299 patients was studied to identity factors associated with mortality. Ten predictor variables were examined: age, sex, waiting time for surgery, pulmonary dysfunction, fracture etiology, and comorbidity with ischemic heart disease, and heart failure, hypertension, cerebrovascular disease, and chronic renal failure. Cumulative mortality rate during the first 6 months was 19% (55 of 299 patients) and in the first year it was 25% (76 of 299). At logistic regression analysis, mortality was associated with age, male gender, waiting period for surgery and presence of neoplastic disease or pathological fracture. Waiting for surgery was a significant factor for mortality at 6, 12 and 24 months: patients surgically treated in the first 24 hours had lower mortality than those who waited longer. The risk of mortality in the first 6 months doubled for an age increase of 12 years, while mortality within 2 years doubled for an age increase of 9 years. Although the motality rate after surgery for femoral neck fracture was high in the first year (25%), it dropped off in successive years to levels observed in a healthy population. Thus, we agree with the literature that femoral fracture is a risk factor for survival only in the first year after trauma, above all in the elderly.     

Bromine-76 and carbon-11 labelled NNC 13-8199, metabolically stable benzodiazepine receptor agonists as radioligands for positron emission tomography (PET)

NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241. This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared ⁷⁶Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised by N-alkylation of the nitrogen of the amide group with [¹¹C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake of radioactivity in the occipital, temporal and frontal cortex. In the study with [⁷⁶Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection. The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands for imaging of benzodiazepine receptors in the primate brain. [⁷⁶Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage. Received 19 April and in revised form 10 June 1997     

Registration of myocardial infarction and stroke in the Kilkenny Health Project: Methodology

A myocardial infarction and stroke register was established in January 1987 as part of the evaluation of the Kilkenny Health Project This is a community programme which aims to reduce risk factors for coronary heart disease. The register records acute myocardial infarction and stroke in residents of County Kilkenny and of the reference county. This will provide accurate estimates of the incidence of these diseases and of trends over time. Methods used comply with the protocol in use by the WHO MONICA Project. This will allow comparison of the incidence of coronary heart disease and stroke in this register with that in other MONICA locations, including that in Belfast, Northern Ireland.