Search

A mixed-phase liquid chromatographic column was used to assay fluconazole in plasma, serum, and cerebrospinal fluid. The assay was linear from 0.2 to 20 micrograms/ml, with an average coefficient of variation of less than 5%. The partitioning of the drug between serum and cerebrospinal fluid was determined for 34 patients. The method was demonstrated to be suitable for both pharmacokinetic studies and monitoring of patients receiving treatment with this antifungal agent.

Case summaries and histological analyses of eight cases of limb lengthening by callus distraction are reported. Problems developing after lengthening required excision of some of the lengthened bone. Specimens were harvested and analyzed from 102 days to 4 years after lengthening. The earliest bone laid down was woven bone with high surface cellular activity. This soon became overlaid with lamellar bone, particularly at the cortex. Later Haversian architecture of cortical bone reappeared, and separate medullary bone developed, progressing toward the normal pattern, in contradistinction to the very abnormal bone that appears to be laid down subsequent to the Wagner method of lengthening. Of particular value in this study were the relatively large sizes of the specimens, allowing truly representative information on collagen orientation and bone surface architecture. The near-normal appearance of the new bone formed by callotasis gives confidence to surgeons about to embark on limb lengthening.

Osteoporosis is a common problem in the elderly female population and pathological fractures are a frequent complication, but how should the pathologist assess the severity of the disease at autopsy?In this study we have compared subjective, semi-quantitative assessments of rib fracturability, vertebral compressibility, Singh index and histomorphometric methods against a ‘gold standard’ assessment, namely the force required to fracture the femoral neck.We have shown good correlations between rib fracturability, Singh index and the standard chosen. Poor correlation was shown between histomorphometric techniques and the standard.Our findings suggest that gross rib fracturability is a good indicator of osteoporosis in as far as bone fragility is an indicator of the severity of osteoporosis.However as the population under examination was small, further studies in this area are clearly warranted in order to extend these findings.

Osteoporosis is a common problem for the pathologist in the elderly female population where pathological fractures particularly of the neck of femur are frequent. Yet how should we assess osteoporosis at autopsy? This study reports on autopsy assessment of osteopenia, comparing our subjective findings of rib fracturability and vertebral compressibility with histological and histomorphometric assessment on a bone biopsy. We have shown a poor correlation between gross autopsy and histological techniques. There is good correlation between two gross autopsy techniques and these methods have been shown to be reproducible between observers. We believe that the most useful test of whether a patient's bones are likely to break is to assess the fracturability of the ribs (and possibly the vertebral bodies) at autopsy. This should be supplemented with undecalcified histology sections from the iliac crest where possible. Further studies are clearly warranted in this area.

Pyrroline-5-carboxylate, the intermediate in the interconversion of proline, ornithine, and glutamate, increases 5-phosphoribosyl 1-pyrophosphate (PP-ribose-P) and purine nucleotide formation in intact human erythrocytes. We proposed that: 1) pyrroline-5-carboxylate is converted to proline by pyrroline-5-carboxylate reductase with concomitant oxidation of NADPH, 2) NADP+ augments glucose-6-phosphate dehydrogenase activity, and 3) production of ribose-5-phosphate via the pentose shunt is increased. Since glucose-6-phosphate dehydrogenase plays a central role in this proposed mechanism, we examined the responsiveness of glucose-6-phosphate dehydrogenase-deficient erythrocytes to pyrroline-5-carboxylate. We compared erythrocytes from four Sardinian glucose-6-phosphate dehydrogenase-deficient subjects and four Sardinian normal controls. Without pyrroline-5-carboxylate treatment, the levels of pentose shunt activity, PP-ribose-P, and inosine monophosphate were comparable in the two populations. However, the response to pyrroline-5-carboxylate in erythrocytes from normal and glucose-6-phosphate dehydrogenase-deficient subjects was markedly different. In normal erythrocytes, pyrroline-5-carboxylate treatment increased pentose shunt activity 600%, PP-ribose-P formation 250%, and the incorporation of hypoxanthine into inosine monophosphate 260%. In contrast, pyrroline-5-carboxylate had no effect on glucose-6-phosphate dehydrogenase-deficient erythrocytes. These findings strongly support our proposed mechanism for the pyrroline-5-carboxylate effect on nucleotides. Furthermore, the markedly different capacities for nucleotide synthesis in the two populations with pyrroline-5-carboxylate treatment suggest a role for pyrroline-5-carboxylate-mediated modulation of nucleotide metabolism in normal cells.

1) A new sympathomimetic drug, xylopropamine sulfate (1-(3,4-Dimethylphenyl)-2-Aminopropane), has been found capable of elevating the threshold of human subjects to experimentally induced pain. The method employed was electrical stimulation of the tooth pulp. There were 8 subjects and the experiment was conducted under “double blind” discipline. Five and 10 mg oral doses of xylopropamine were compared with a placebo and a “dry-run.” The average effect of the 10 mg dose was statistically superior (P<.05) to the effects of the other treatments from 90-180 minutes after medication. 2) It is provocative that xylopropamine is analgesic but apparently not analeptic, while amphetamine is both. It suggests that the two effects on the sensorium could be independent.

Astwood has demonstrated that 6 hours after the administration of estrogens to the 21-day-old rat. there is an increase in uterine weight.1This weight increase is largely due to increased hydration (edema) of the uterus. Pincus and Graubard have essentially confirmed these findings.2Zuckerman has stated that androgens also cause increased hydration of the uterus in the monkey.3Astwood in a brief report has stated that androgens will cause a uterine weight increase in rats similar to that caused by estrogens.4The Astwood technic as originally proposed for estrogen assays is a very rapid and convenient one. Reports have appeared in which it has been applied to urinary estrogen assays.5Inasmuch as androgens are known to be present in the urines of normal, pregnant or castrate women, it seems of interest to report our findings as to the uterine weight-increasing effects of various androgens.Findings. All animals were given the androgen subcutaneously in 0.1 cc of peanut oil and were killed 6 hours after the treatment. Peanut oil has previously been tested in this laboratory and found to contain neither estrogen nor androgen. The cervico-vaginal junctions were cut, the uteri carefully removed and immediately weighed on a Roller-Smith balance sensitive to 0.02 mg. The tissues were preserved in Bouin's fluid and representative uteri were examined microscopically. Detailed weight-findings are presented in tabular form (Table I).The animals of Groups 1 and 2 were 21 days old. Group 1 served as controls (A). As can be noted in the table, 0.5 mg testosterone (Group 2) caused a statistically significant increase in uterine weight, 22.8% over that of the controls.

A megabore column gas-liquid chromatographic method which uses nitrogen-phosphorus detection was developed for the analysis of fluconazole in plasma, serum, cerebrospinal fluid, or urine. The assay was linear from 0.2 to 200 micrograms/ml and had an average coefficient of variation of 7%. The suitability of the assay for pharmacokinetic studies was demonstrated.

A case of osteosarcoma of the carpus is reported and the relevant literature reviewed.