Biomedical subjects

David Mitchell

Publications and source records attributed to David Mitchell.

23 records · Page 2Linked to original sources

PubMed2003

Utilizing capillary gas chromatography mass spectrometry to determine 4-benzotrifluoride t-butyl ether as a reaction by-product in fluoxetine synthesized using potassium t-butoxide as base.

Fluoxetine hydrochloride has been prepared using two similar synthetic routes, both of which rely upon an ether formation reaction mediated by a base. The base used can affect the impurity profile of this reaction. It was proposed that the synthesis of fluoxetine carried out using potassium t-butoxide as base and 4-chlorobenzotrifluoride (or 4-fluorobenzotrifluoride) in the ether formation step may result in the formation of 4-benzotrifluoride t-butyl ether as a reaction by-product. To test this hypothesis, capillary gas chromatography-mass spectrometry (GC/MS) was utilized to evaluate samples of free base fluoxetine synthesized using sodium hydride (NaH) or potassium t-butoxide as the base. Assay conditions using selected ion monitoring (SIM) were developed, which allowed detection of trace levels (parts per million, ppm) of 4-benzotrifluoride t-butyl ether in fluoxetine free base sample matrix. Response linearity, precision, and standard spike recovery were examined during development, and were found to be suitable. Comparisons of fluoxetine samples generated from both NaH and potassium t-butoxide processes were performed using the GC/MS assay.

Butanols↗

PubMed2003

Imaging of the pituitary and parasellar region.

The pituitary is part of a chain of enormous biologic amplification, which is regulated by a small amount of releasing factors in the portal blood from the hypothalamus. The pituitary is a master gland that regulates a number of hormones. A subtle abnormality in the pituitary can cause significant changes in body metabolism. Because the pituitary glands are small structures, high-resolution imaging techniques are required to satisfactorily evaluate the gland. It is imperative for the radiologist to be familiar with the anatomy, physiology, and pathology of the pituitary gland, which provides a solid foundation for accurate interpretation of the imaging studies of the pituitary gland.

Adenoma↗

PubMed2003

Antimicrobial resistance in Staphylococcus aureus in Australian teaching hospitals, 1989-1999.

An annual survey of antimicrobial resistance in clinical isolates of Staphylococcus aureus was conducted in 21 Australian teaching hospital microbiology laboratories in eight major cities from 1989 to 1999. A total of 19,000 isolates were tested for susceptibility to 18 antimicrobials, with 3795 being methicillin-resistant (MRSA). Resistance to ciprofloxacin in MRSA increased from 4.9% to 75.9%. The proportion of MRSA resistant to erythromycin decreased significantly (99.0%-88.9%), as did that to trimethoprim (98.4%-82.4%) and to tetracycline (96.5%-80.1%). The proportion of MRSA isolated increased in Sydney, Melbourne, Canberra, Adelaide, Perth, and Darwin, but not in Brisbane. The proportion in Hobart peaked in 1994. MRSA in Perth were predominantly non-multiresistant (nmMRSA) throughout the survey (i.e., resistant to less than three of eight indicator antibiotics) due mainly to local strains that originated in the community. The proportion of nmMRSA increased to modest levels in the other cities. In eastern cities, this was due to the appearance of strains closely related to nmMRSA seen in other countries of the southwestern Pacific.

Anti-Infective Agents↗

PubMed2003

Synthetic applications of palladium-catalyzed hydroarylation and related systems.

Synthetic organic chemists have recognized the hydroarylation of alkynes and alkenes as a versatile methodology. In the first part of this review, the regio- and stereochemistry of the hydroarylation of alkynes and the synthetic applications of this reaction in the synthesis of antiviral agents and steroid derivatives will be discussed. In the second part, applications of the hydroarylation of alkenes in the syntheses of epibatidine analogs, argemonine, retinoid X receptor (RXR), retinoic acid receptor (RAR) modulators and neurokinin (NK) receptor NK1 antagonists will be discussed. Emphasis will be placed on the application of Pd-catalyzed hydroarylation to the synthesis of biologically active compounds.

Alkenes↗

PubMedDate not supplied

Canadian multicenter pilot trial of haploidentical donor transplantation.

BACKGROUND: Canadian multicenter pilot study of haploidentical donor. AIMS: To assess (1) ability to collect suitable graft (CD34+ > or = 5 x 10(6)/kg and CD3 < 1 x 10(5)/kg recipient body weight), (2) toxicity, (3) survival to day +100. ELIGIBILITY: All hematological malignancies and ages; accrual to end after 20 transplants of patients with AML in remission and age less than 55 years. METHODS: Preparation: Modified Perugia regimen, chemotherapy alone; melphalan 140 mg/m2 day -9, thiotepa 10 mg/kg day -7, fludarabine 40 mg/m2 days -7 to -3, and ATG (Thymoglobulin, Sangstat) days -6 to -2 (total 10.5 mg/kg). Infection prophylaxis: Ganciclovir (GC) 5 mg/kg days 5-20 then x5/week until day +100 then x3/week until 210 (subjects 1-3), foscarnet (FC) 90 mg/kg days 4-21 then short course pre-emptive GC or FC (subjects 4-11); fluconazole; cotrimoxazole. Donors: G-CSF 16 microg/kg daily x5 until second pheresis day. T-cell depletion: CliniMACS (MiltenyiBiotec). RESULTS: Eleven patients with AML have been transplanted from four centers, eight female, three male, median age 34 (range 19-60). Disease status, first CR 1/11, second CR 4/11, third CR1/11, relapse 5/11. Graft CD34+ > or = 5 x 10(6)/kg was achieved in all cases, median 13.72 x 10(6)/kg (Q1, Q3: 8.26, 17.72; min 5.59, max 22.22), and CD3+ was < 1 x 10(5)/kg in all cases, median of 0.49 x 10(4)/kg (Q1, Q3: 0.30, 2.20; min 0.22, max 4.10). Ten of the 11 patients have died, median survival 103.5 days (Q1, Q3: 61.0, 151.0; min 0, max 290.0). Survival to day +100 6/11 (55%). Four patients died of leukemic relapse, six of infection. Of six patients dying of infection, CMV was a definite cause in four. Of four dying with relapse, CMV was significant in one. Engraftment was assessed in 10 patients who survived >0 days. Granulocyte engraftment (> 0.5 x 10(9)/l) was achieved in all patients, median 11.5 days (Q1, Q3: 10, 17; min 8, max 70). Platelet engraftment (> 20 x 10(9)/l) was achieved in 8 of 10 patients, median 15 days (Q1, Q3: 9, 16; min 9, max 97). The two platelet non-engrafters died on days +45 and +61. Toxicity was low, with one toxic death (day 0), and the Bearman organ toxicity gradings were < or = grade 2 in all other patients. There were no instances of graft-vs.-host disease or graft rejection. CONCLUSIONS: The problems of graft-vs.-host disease and graft rejection have been removed as barriers to haploidentical transplantation but the slow immune reconstitution limits its general application. Late referrals contribute to a high relapse rate and have delayed an optimal evaluation of the procedure.

Adult↗