Multiple sclerosis. Recent concepts of etiology.
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Biomedical subjects
Publications and source records attributed to T E Davis.
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To develop safe and rapid methods for identification of Staphylococcus aureus and Streptococcus pneumoniae directly from positive blood culture bottles (BCB) (BACTEC, Johnston Laboratories), several commercial biochemical and immunological tests as well as modified conventional tests were evaluated. Preliminary studies demonstrated that both S. aureus and St. pneumoniae could be identified directly using only a small aliquot (100 microliters) of the blood culture broth obtained via vent without need for centrifugation or other separation steps. A simple tube coagulase exhibited 98% sensitivity and 100% specificity for 32 S. aureus isolates and 157 blood cultures positive for coagulase-negative staphylococci when read at 2 hr. All systems employed for direct identification of St. pneumoniae exhibited excellent sensitivity and specificity using aliquots from blood culture broths, but Pneumoslide (BBL Microbiology Systems, Cockeysville, MD) was easiest to perform and interpret. The results of this study show that S. aureus and St. pneumoniae can be identified directly from blood culture broth aliquots using rapid methods that eliminate the need for centrifugation or use of needles and syringes.
Arbitrary criteria can give unreliable diagnoses. Conditions that occupy the same marginal diagnostic space, such as interstitial cell hyperplasia and interstitial cell adenoma, sometimes will be mistaken for one another. When the true prevalence is low, the risk of false positives, as a percentage of all positives, is high. The preceding analysis predicts that, with currently recommended diagnostic criteria, any compound that causes nonneoplastic interstitial cell hyperplasia will be interpreted to cause interstitial cell neoplasia if SD rats are used and only microscopic diagnoses are considered. Conversely, the analysis predicts that no compound that actually causes neoplasia in interstitial cells will be identified as an interstitial cell tumorigen if F-344 rats are used and only microscopic diagnoses are considered. These predictions are consistent with experience.
Giardia lamblia is a flagellated protozoan that inhabits the upper portions of the small intestine; trophozoites are the usual stage seen in duodenal aspirates, biopsies of the duodenum and jejunum and, infrequently, in stools, in which cysts are more likely to be found. A unique occurrence of G lamblia cysts and trophozoites within the peritoneal fluid of a patient with a blunt abdominal trauma is reported. Cytotechnologists and pathologists should be aware that trophozoites and cysts of G lamblia may appear in peritoneal lavage fluid from patients with blunt abdominal trauma and duodenal injury, indicating a need for exploratory laparotomy.
Overcoming resistance to chemotherapy is an important goal in cancer treatment. In many systems, resistance to anthracyclines and vinca alkaloids correlates with a diminished intracellular content of drug. In P388 leukemia and Ehrlich ascites tumor, an active outward transport of anthracyclines and vinca alkaloids occurs. Calcium channel blockers, such as verapamil, inhibit this active outward transport and increase intracellular content of vinblastine and anthracyclines in cells resistant to vinca alkaloids and anthracyclines, respectively. We report a phase I trial of vinblastine (1.5 mg/m2 daily as iv continuous infusion X 5 days) in 17 patients and concurrent verapamil in escalating doses. Verapamil was administered as a loading dose (0.02-0.1 mg/kg) followed by a maintenance infusion (0.036-0.18 mg/kg/hour) for 5 1/2 days with continuous cardiac monitoring. There was no apparent augmentation of vinblastine toxicity when vinblastine and verapamil were given concurrently. ECG change was the dose-limiting toxicity. At 0.12 mg/kg/hour, five of nine patients developed first-degree heart block (mean P-R interval, 0.32 seconds; range, 0.23-0.52 seconds). Junctional rhythms were noted in two of 17 patients. Reversible nonspecific T-wave changes were seen in four of 17 patients. Blood pressure and left ventricular ejection fractions (ultrasonic) were not altered. Five of 17 patients had wbc count nadirs less than 2000/mm3, and two of 17 patients had platelet count nadirs less than 100,000/mm3. Four patients experienced neurotoxicity. A mean vinblastine concentration of 2.2 ng/ml (0.55 nM) and a mean verapamil concentration of 290 ng/ml (0.45 microM) were achieved with the concurrent 5-day infusion. The tolerable levels of verapamil obtained appear to be less than those which were reported to inhibit vinblastine efflux in vitro. Additional in vitro experiments at the tolerable doses of vinblastine and verapamil are recommended.
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Acivicin, an L-glutamine antagonist, was administered to 37 evaluable patients with refractory advanced solid tumors in a phase I trial. A total of 67 evaluable 72-hr iv infusions were given at 3- to 4-week intervals. Doses ranged from 3.0 to 90 mg/m2/course. Reversible CNS toxicity was dose-limiting and included lethargy, somnolence, anxiety, hallucinations, and paranoid psychoses. Four of five patients experienced unacceptable CNS toxicity at 90 mg/m2. Three of eight patients experienced reversible diaphoresis and chills without fever at 75 mg/m2, and two had dizziness and ataxia. Hematopoietic toxicity, nausea, emesis, and diarrhea were mild and dose-related. One patient developed a blue-green discoloration of the infusion arm. Serial plasma and urine specimens from 13 patients were assayed for acivicin using a microbiologic method. Peak plasma levels at the end of the 72-hr infusions correlated with dose and ranged from 0.09 to 1.10 microgram/ml. When data from six patients were fitted to a two-compartment open model, alpha-half-life ranged from 1.1 to 63 mins, while beta-half-life ranged fro 338 to 629 mins. Renal clearance ranged from 6 to 24 mL/min, and nonrenal clearance accounted for 58%-83% of the total drug clearance. CNS toxicity correlated with plasma acivicin levels which exceeded 0.9 microgram/ml for greater than 16 hrs, but not with peak plasma levels or with the integrals of the concentration x time curves. Minor responses were seen in one patient with melanoma, in one with epidermoid pulmonary carcinoma, and in two with colon carcinoma. A starting dose of 60 mg/m2/course was recommended for phase II trials, with possible escalation to 75 mg/m2 in the second course if the drug was well-tolerated.