Monoclonal antibodies directed characterization of epidermal and hepatic cytochrome P-450 isozymes induced by skin application of therapeutic crude coal tar

A single application of crude coal tar (CCT) solution (USP) to the skin of neonatal rats was shown to induce epidermal and hepatic cytochrome P-450(P-450)-dependent monooxygenase activities. To further characterize the induction response, in this study we have utilized highly specific monoclonal antibodies (MoAb) 1-7-1, 2-66-3, and 1-98-1 directed against highly purified rat liver P-450s induced by 3-methyl-cholanthrene, phenobarbital and ethanol, respectively. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of hepatic microsomes prepared from CCT-treated animals showed a significant increase in the coomassie blue stainable proteins in the P-450 region; however, this was not evident in epidermal microsomes. Immunoblot analysis of epidermal and hepatic microsomes with MoAb 1-7-1 revealed strong immunoprecipitin bands in both tissues. MoAb 2-66-3 showed significant immunoreactivity only with hepatic microsomes. Interestingly, CCT treatment resulted in suppression of immunoreactivity with MoAb 1-98-1 in hepatic microsomes. MoAb 1-7-1 and 2-66-3 exhibited concentration-dependent inhibitory effects in aryl hydrocarbon hydroxylase and 7-ethoxycoumarin-O-deethylase activities induced by CCT application. MoAb 1-7-1 was substantially more effective in this respect. Epidermal and hepatic microsomes prepared from CCT-treated rats showed significantly greater metabolism of benzo(a)pyrene (BP). MoAb 1-7-1 and MoAb 2-66-3 inhibited BP metabolism in both the tissues. However, MoAb 1-7-1 was more inhibitory in this regard as compared to MoAb 2-66-3. These studies indicate that topical application of therapeutic CCT to the skin of neonatal rats results in induction of P-450 isozyme c in epidermis and isozymes b and c in liver, and that this induction is associated with the suppression of P-450 isozyme j in liver.     

Effect of meal on the physiological and physicochemical actions of potassium citrate

The effect of meals on the physiological and physicochemical actions of potassium citrate was examined in 8 patients with nephrolithiasis maintained on a constant metabolic dietary regimen. Potassium citrate (20 mEq. 3 times per day), whether given with food or on an empty stomach, significantly increased urinary pH, citrate and potassium, and decreased urinary calcium and ammonium. Moreover, potassium citrate decreased urinary saturation of calcium oxalate and uric acid, although it slightly increased that of brushite. However, there was no significant difference in these measures when the drug was given with meals from the time when it was given on an empty stomach. Thus, the effect of potassium citrate on urinary risk factors is unaffected by food.     

Multiple medication: problems of the elderly patient.

Elderly persons are apt to receive multiple drugs for many diseases. Prescribers should take extra care in persons aged over 65-70 years, and especially the very old. The main problem of the elderly is the unpredictability of their response to drugs. Self-medication with both prescribed and over-the-counter drugs worsens this problem. Drug actions may be altered by impairment of the liver, kidneys and brain, or acute illness, or both. Unwanted (adverse) drug reactions often produce rapid and unduly severe illness in the old. Some antibacterial antibiotics like the sulphonamides are best avoided. Taking many drugs together promotes adverse interactions between the drugs. Drugs with a narrow therapeutic ratio, such as warfarin, digoxin, the aminoglycosides, and many antiarrhythmic drugs, cause clinical problems. Old persons respond more abruptly to drugs like benzodiazepines, opioid analgesics, and antiparkinsonian drugs. Anaesthesia given on top of psychotropic drugs may damage the central nervous system. The elderly brain is more sensitive to induction agents and short-acting intravenous anaesthetics, like alfentanil and midazolam; the elderly liver is more easily damaged by inhalational anaesthetics like halothane. The overall benefit:risk ratio should be judged for every drug in each patient. Wherever possible, drug treatment should be avoided. If drugs are given, safe drugs with broad therapeutic ratios and tissue- or receptor-specific actions are preferable. Drug doses are usually, but not always, reduced. Benefit from a drug should be assessed early. Severe unpredictable adverse reactions need immediate cessation of the drug and prompt patient support. The practitioner should frequently review the patient's continuing need for drugs.     

Molecular and mechanical property changes during aging of bone cement in vitro and in vivo

The changes in mechanical properties and free radical concentration of curing Simplex P Radiopaque Bone Cement in vivo and in vitro conditions were studied. Samples were prepared so that each in vivo sample that cured and aged in the canine femoral intramedullary cavities had an in vitro counterpart that was cured and aged in a constant-temperature saline bath at 37 degrees C. An electron paramagnetic resonance (EPR) spectrometer was used to measure the growth and decay (curing) of polymerization radicals. The results of EPR measurements showed that the curing (disappearance of free radicals) of in vivo samples takes a much longer time (more than 4 weeks) than in vitro curing (less than 2 weeks). The mechanical tests indicate that, whether aged in vivo or in vitro, the strength increased rapidly for the first 1-2 weeks and then slight increases were seen for up to 6 months.     

Ceftriaxone-associated gallbladder sludge. Identification of calcium-ceftriaxone salt as a major component of gallbladder precipitate

Ceftriaxone, a third-generation cephalosporin, is partially excreted into bile. With its clinical use, the formation of gallbladder sludge detected by ultrasonography has been reported. Four surgical specimens were examined and no gallstones were found. Instead, fine precipitates of 20-250 microns were present. Microscopically, there was a small number of cholesterol monohydrate crystals and bilirubin granules among an abundant amount of granular-crystalline material that was not morphologically cholesterol monohydrate crystals. The chemical composition of the precipitates (n = 4) was determined. There was a small amount of cholesterol (1.7% +/- 0.8%) and bilirubin (13.9% +/- 0.74%). The major component of the precipitate was a residue. On further analysis using thin-layer chromatography, high-performance liquid chromatography, and electron microprobe analysis, the residue was identified as a calcium salt of ceftriaxone. The residue also had identical crystal morphology and chromatographic elution profile as authentic calcium-ceftriaxone standards. It is concluded that ceftriaxone, after excretion and being concentrated in the gallbladder bile, can form a precipitate. The major constituent has been identified as a ceftriaxone-calcium salt.     

Immunoscintigraphy in the detection of tuberculosis with radiolabelled antibody fragment against Mycobacterium bovis bacillus Calmette-Guérin: a preliminary study in a rabbit model.

Immunoscintigraphy with radiolabelled monoclonal antibodies is widely used to detect solid tumours, but only a few trials have been carried out concerning the specific in vivo localization of an inflammatory process. The purpose of this study was to investigate the detectability of tuberculous foci utilizing this method with radiolabelled bacillus Calmette-Guérin (BCG)-specific F(ab')2 in rabbits. All of the tuberculous lesions (n = 8) were clearly visualized on serial scintigraphy for up to 48 h after injection of the antibody. Immunohistochemical and Ziel-Neelson staining of the tuberculous lesions confirmed the presence of the tuberculous antigens and bacilli. It failed to demonstrate any sustained retention of the BCG-specific antibody fragment in the control group with syphilitic orchitis (n = 2). Therefore, the specific in vivo localization of tuberculosis is feasible by immunoscintigraphy.     

Partial mastectomy with axillary lymph node dissection and radiotherapy as a new treatment modality of breast cancer (I).

This is the first preliminary report among two consecutive papers. Partial mastectomy(PM), axillary lymph node dissection(AD) and radiotherapy (RT) were performed on seventeen operable breast cancer patients who had been admitted from April 1991 to March 1992 to the department of surgery, Yongdong Severance Hospital for improved cosmetic appearance and better survival rate. Of seventeen patients, 47% were T1 lesion and 76% were stage I and II. Extensive intraductal component(EIC) within or around the tumor was also analyzed. Twenty nine per cent of the patients were EIC positive. The mean number of axillary lymph nodes was 21.5 after PM with AD and 20.5 after mastectomy. For radiotherapy, 4,500 rad was delivered to the breast parenchyma and 1,600 rad of boost to the primary tumor site using the electron beam method after surgery. All patients have since been living well without any local recurrence and were satisfied with breast preservation for the one-year follow-up period. We concluded that the PM, AD and RT can be another surgical treatment modality of breast cancer. A longer follow-up data will be followed on the second paper.