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Biomedical subjects

K R Stewart

Publications and source records attributed to K R Stewart.

At least 37 records · Page 2Linked to original sources

Stability of metronidazole and ten antibiotics when mixed with magnesium sulphate solutions.

The chemical stabilities of metronidazole (in water) and ten antibiotics (ampicillin, carbenicillin, cefamandole, cefazolin, cefoxitin, moxalactam, nafcillin, penicillin G, piperacillin, and ticarcillin) in 5% dextrose injection (except ampicillin which was in 0.9% sodium chloride) with magnesium sulphate were studied at 25 degrees C. The clarity of the solutions did not change in 20 h. The pH values of metronidazole, nafcillin and penicillin G solutions containing magnesium sulphate were lower (at 0 and 20 h) by up to 1.2 units as compared with solutions without magnesium sulphate. The decomposition of nafcillin and penicillin G solutions was hastened significantly by magnesium sulphate due to effect on the pH values of the solutions.

Anti-Bacterial Agents↗

Chemical stabilities of cefamandole nafate and metronidazole when mixed together for intravenous infusion.

The chemical stabilities of cefamandole nafate and metronidazole, when mixed together for intravenous infusion, have been studied using a stability-indicating, high-performance liquid chromatographic method of assay. Cefamandole nafate was stable for 5 days at 25 degrees C and at least 14 days at 5 degrees C. The addition of metronidazole did not affect the stability of cefamandole nafate. In a 2% solution of cefamandole in metronidazole injection (0.5%), metronidazole lost about 9.1% of potency in less than 2 h at 25 degrees C and in less than 6 h at 5 degrees C. The per cent loss was directly related to the initial concentration of cefamandole nafate. Change in the concentration of metronidazole did not affect the per cent of metronidazole lost.

Cefamandole↗

pH-dependent effect of magnesium sulfate on the stability of penicillin G potassium solution.

The effect of magnesium sulfate on the stability of penicillin G potassium solutions (0.5 mg/mL) was investigated using a stability-indicating high-performance liquid chromatography method. The penicillin G potassium powder buffered with and without citrate was used. Twelve aqueous duplicate penicillin solutions with various concentrations of magnesium sulfate and with or without buffers were prepared and stored at room temperature. Data on clarity, pH values, and HPLC assay results were determined at intervals during the 10-day storage period. The results indicated that the presence of high concentrations of magnesium sulfate in unbuffered penicillin solutions can cause large pH changes and the degradation of penicillin. However, the effect of magnesium sulfate on the stability of penicillin G potassium was negligible in the buffered solutions. Solutions with a constant pH value of 5.6 prepared using 0.1 M acetate buffer with and without magnesium sulfate showed similar apparent first-order degradation after the 10-day storage period at 24 degrees C. During decomposition, the pH values of the unbuffered solutions decreased for three days and then started increasing in most solutions. The degradation of penicillin G potassium by magnesium sulfate in aqueous solutions resulted from decreases in pH values of the solutions.

Chemistry, Pharmaceutical↗

Effect of clinical features on the association of estrogens and breast cancer.

In a case-control study using several distinctive control subgroups, no increased risk of breast cancer was found in postmenopausal women who used replacement estrogens. When breast cancer patients and control patients with no breast lesions were assembled from patients who had all received mammography, the overall odds ratio was 0.5, and varied from 0.2 to 1.2 according to the patient's indication for estrogen treatment and the clinical reason for mammography. When a biopsy registry was the source of breast cancer patients and control patients with benign breast disease, the odds ratio was 0.8. In a conventional case-control comparison of breast cancer patients with hospitalized patients having other diagnoses, the odds ratio was 0.9 when specific data about exposure were used to classify patients as estrogen users, but the odds ratio was 3.3 when data about exposure were not recorded equally in the compared groups. These results show that calculations of "risk" depend on important clinical phenomena that have not previously been given suitable attention. The data also provide a possible explanation for the perplexing findings among earlier studies in which the odds ratios varied from "protective" to "causal" values. When the data from the present study are partitioned according to differences in patients' clinical characteristics and reasons for the diagnostic breast procedure, the conflicting results of earlier studies can be reconciled.

Biopsy↗

Stability of cefsulodin in aqueous buffered solutions and some intravenous admixtures.

The stability of cefsulodin in aqueous solutions of various pH values, buffer concentrations, ionic strengths and intravenous admixtures were studied using a stability-indicating high-pressure liquid chromatography method. The pH range of optimum stability was determined to be 3.2-5.7. Cefsulodin was more stable on the acidic and less on the alkaline side as compared with most of the other cephalosporins such as cefoxitin (pH range of optimum stability approximately 4-7). In 5% dextrose and 0.9% sodium chloride injection, cefsulodin was stable (at least 90% potent) for about 1, 17 and at least 60 days at 24 degrees, 5 degrees and -10 degrees C, respectively.

Buffers↗

Stability of dobutamine hydrochloride and verapamil hydrochloride in 0.9% sodium chloride and 5% dextrose injections.

The stability of dobutamine hydrochloride (250 micrograms/ml) and verapamil hydrochloride (160 micrograms/ml) alone and in combination in 0.9% sodium chloride injection or 5% dextrose injection was studied. Solutions were stored both in plastic i.v. bags and in amber-colored glass bottles at 24 degrees C and 5 degrees C for up to seven days. Before storage and at various times during storage, solutions were assayed at least in triplicate by high-performance liquid chromatography, pH was recorded, and visual appearance was noted. All solutions tested under all conditions retained at least 90% potency for seven days. In plastic i.v. bags, dobutamine either alone or in combination with verapamil in both diluents turned a light-pink color in 24 hours at 24 degrees C. The intensity of the pink color increased with time in 0.9% sodium chloride injection; in 5% dextrose injection, solutions, became clear in 48 hours. The pH of solutions prepared in plastic i.v. bags in 5% dextrose injection decreased from 4.0 to 3.1 during the seven-day period at 24 degrees C; results for solutions in amber bottles were similar. At 5 degrees C, the pH and clarity of all solutions in bags and bottles remained stable for seven days. At the concentrations tested, dobutamine hydrochloride combined with verapamil hydrochloride is stable in 0.9% sodium chloride injection and 5% dextrose injection for 48 hours at 24 degrees C and for seven days at 5 degrees C.

Catecholamines↗

Quantitation of amikacin, kanamycin, neomycin, and tobramycin in pharmaceutical dosage forms using the Hantzsch reaction.

A spectrophotometric assay method for the quantitative determination of amikacin, kanamycin, neomycin, and tobramycin in pharmaceutical dosage forms has been developed. The method is based on the Hantzsch reaction, forming dihydrolutidine derivatives which can be measured spectrophotometrically. The excipients EDTA, phenol, sodium bisulfite, and sodium citrate do not interfere, while salts of ammonia do interfere. The relative standard deviations based on seven readings were 1.64, 1.88, 2.10, and 1.93% for amikacin, kanamycin, neomycin, and tobramycin, respectively. Assay results have been compared with microbiological assay results provided by the manufacturers. The assay method appears to be stability indicating.

Amikacin↗

Extracellular slime associated with Proteus mirabilis during swarming.

Light microscopy, transmission electron microscopy, and scanning electron microscopy were used to visualize the extracellular slime of Proteus mirabilis swarm cells. Slime was observed with phase-contrast microscopy after fixation in hot sulfuric acid-sodium borate. Ruthenium red was used to stain slime for transmission electron microscopy. Copious quantities of extracellular slime were observed surrounding swarm cells; the slime appeared to provide a matrix through which the cells could migrate. Swarm cells were always found embedded in slime. These observations support the argument that swarming of P. mirabilis is associated with the production of large quantities of extracellular slime. Examination of nonswarming mutants of P. mirabilis revealed that a number of morphological changes, including cell elongation and increased flagellum synthesis, were required for swarm cell migration. It is still unclear whether extracellular slime production also is required for migration.

Flagella↗

Stability of haloperidol in 5% dextrose injection.

The stability of haloperidol in 5% dextrose injection using a high-pressure liquid chromatographic (HPLC) method is reported. A solution of haloperidol 10 mg/dl in 5% dextrose injection was prepared using commercially available haloperidol injection. The solution was stored at 24 degrees C, half in an amber glass bottle and half in a plastic bag. These were assayed on days 0, 1, 7, 14, and 38. Solutions prepared from commercial dosage forms of haloperidol (injection, oral liquid concentrate, and tablets) were assayed to verify the accuracy of the HPLC assay to quantify haloperidol. There was no loss of haloperidol potency in 38 days when stored 24 degrees C in either the amber glass bottle or plastic bag. There was a substantial loss of methylparaben and propylparaben (present in commercial haloperidol injection) in the solution stored in the plastic bag. Oxidation products of haloperidol did not interfere with the assay, and the HPLC assay accurately measured haloperidol in solutions prepared from commercial dosage forms. The results show that haloperidol 10 mg/dl in 5% dextrose injection was stable for at least 38 days. While the loss of parabens is not of practical importance, the HPLC method developed provided this information while the previously used USP-NF procedure did not. The assay can be used to quantify haloperidol in commercial dosage forms.

Chemistry, Pharmaceutical↗

Endodermal sinus tumor of the ovary with virilization. Light- and electron-microscopic study.

A case of endodermal sinus tumor of the ovary associated with hirsutism and increased testosterone production is described. Electron-microscopic examination revealed accumulation of basement membrane-like material and other ultrastructural features consistent with endodermal sinus tumor. Groups of polyhedral cells associated with the tumor were found to contain abundant lipid material. These luteinized stromal cells were evidently responsible for the endocrine manifestations.

Adult↗

Stability of cefamandole nafate and cefoxitin sodium solutions.

High-pressure liquid chromatographic (HPLC) methods for the quantitative determinations of cefamandole, cefamandole nafate, and cefoxitin sodium were developed and used to study the stabilities of reconstituted solutions of the latter two antibiotics. Results from the HPLC procedures were compared with those from a previously reported colorimetric procedure. Solutions (2%) of cefamandole nafate and cefoxitin sodium in 0.9% sodium chloride injection and in 5% dextrose injection were studied at 24 degrees C and 5 degrees C. The colorimetric method, which is supposed to be specific for compounds with beta-lactam rings, gave misleading results because of the hydrolysis of the antibiotics. The results obtained by HPLC were reproducible and the procedure separated cefamandole, the hydrolyzed compound, from its ester (cefamandole nafate), which was essential for conducting these studies. The cefamandole solutions were stable for approximately five days at 24 degrees C and 44 days at 5 degrees C. The cefoxitin solutions were stable for 24 hours at 24 degrees C and for at least 13 days at 5 degrees C.

Cefamandole↗

Effect of pH, chlorobutanol, cysteine hydrochloride, ethylenediaminetetraacetic acid, propylene glycol, sodium metabisulfite, and sodium sulfite on furosemide stability in aqueous solutions.

A study was conducted to determine the effects of pH, two antioxidants, a chelating agent, a preservative, and propylene glycol on furosemide stability. Aqueous solutions of furosemide containing 10% alcohol (v/v) were prepared in phosphate buffers with various pH values (5, 6, and 9) whose ionic strength was adjusted to 0.1 M with potassium chloride. Some solutions contained chlorobutanol, ethylenediaminetetraacetic acid, or sodium metabisulfite. Another set of aqueous solutions contained phosphate buffer (0.1 M), alcohol (10% v/v), and propylene glycol (40% v/v) with or without cysteine hydrochloride, ethylenediaminetetraacetic acid, and sodium sulfite. The solutions were divided into two parts, stored at 24 and 50 degrees, and assayed frequently using a previously developed high-pressure liquid chromatographic procedure. At the lowest pH value (pH 5), furosemide appeared to be very unstable. Cysteine hydrochloride, ethylenediaminetetraacetic acid, and sodium sulfite failed to improve the stability of furosemide. Chlorobutanol and sodium metabisulfite had an adverse effect on the stability, probably due to the fact that they decreased the pH of the solution. The pH value appears to be the only critical factor for the stability of furosemide. Buffered solutions containing propylene glycol were very stable at both temperatures for 170 days, and they tasted good.

Chemical Phenomena↗

Quantitation of carbenicillin disodium, cefazolin sodium, cephalothin sodium, nafcillin sodium, and ticarcillin disodium by high-pressure liquid chromatography.

High-pressure liquid chromatographic (HPLC) methods for the quantitation of carbenicillin, cefazolin, cephalothin, nafcillin, and ticarcillin were developed. The stability of 2% solutions of the antibiotics in normal saline and in 5% dextrose in water were studied at 24 and 5 degrees. The assays were conducted using a previously reported colorimetric method, and some assays also were performed using HPLC. For discolored solutions of cephalothin, the colorimetric method was not stability indicating. The percent relative standard deviations by HPLC based on six injections were 1.69, 0.94, 1.30, 1.59, and 1.6 for carbenicillin, cefazolin, cephalothin, nafcillin, and ticarcillin, respectively. Both carbenicillin and ticarcillin apparently may be mixtures of two isomers at equilibrium with each other. The shelflives recommended by the manufacturers at 5 degrees may be too conservative.

Carbenicillin↗

Menstrual regulation in Ibadan, Nigeria.

Menstrual regulation (MR) (i.e., vacuum aspiration of the uterus with a small diameter, flexible cannula before pregnancy can be determined by a conventional pregnancy test) has been proven safe and effective in many clinics around the world. The present study, which we believe is the first such study of MR in Subsaharan Africa, shows that, for women in an urban African setting, MR is an acceptable backup for other contraceptive methods. Data on 507 MR patients treated at the University College Hospital in Ibadan, Nigeria, between January 1974 and April 1976, showed that the procedure was both safe and effective for 93.4% of the study subjects: there was an overall complication rate of 3.4% and MR failed in seven cases (3.2%). Data also showed that MR is an effective method of recruiting new contraceptive acceptors, as well as an effective back-up procedure in case of contraceptive failure.

Adult↗