Enantioselective synthesis of the antiinflammatory agent (-)-acanthoic acid.

An enantioselective synthesis of the potent antiinflammatory agent (-)-acanthoic acid (1) is described. The successful strategy departs from (-)-Wieland-Miescher ketone (10), which is readily available in both enantiomeric forms and constitutes the starting point toward a fully functionalized AB ring system of 1. Conditions were developed for a regioselective double alkylation at the C4 center of the A ring, which produced compound 32 as a single stereoisomer. Construction of the C ring of 1 was accomplished via a Diels-Alder reaction between sulfur-containing diene 43 and methacrolein (36), which after desulfurization and further functionalization yielded synthetic acanthoic acid. The described synthesis confirms the proposed stereochemistry of the natural product and represents a fully stereocontrolled entry into an underexplored class of biologically active diterpenes.

Stereoselective synthesis of (-)-acanthoic acid.

[reaction: see text] The first stereoselective synthesis of (-)-acanthoic acid (1) has been designed and accomplished. Our synthetic plan departs from (-) Wieland-Miesher ketone (7) and calls upon a Diels-Alder cycloaddition reaction for the construction of the C ring of 1. The described synthesis confirms the proposed stereochemistry of 1 and represents an efficient entry into an unexplored class of biologically active diterpenes.

Use of ECT in California, revisited: 1984-1994.

The use of ECT in California was examined from 1984 to 1994 and compared with a previous study examining use from 1977 to 1983. Data were collected from legally required reports submitted to the state for all ECT performed. A total of 28,437 patients (mean = 2585.18 per year) received a total of 160,847 treatments with a mean rate of 0.90 patients/10,000 population. The rate in 1984 (1.15) was similar to the mean rate for 1977-1983 (1.12). The rate dropped in 1986 (0.92) and again in 1991 (0.74). There were 821 patients (2.89% of total) judged to be incapable of giving informed consent who received ECT after a court review. This is similar to the rate of 3% for 1977 to 1983. The number of counties where ECT was available increased from 15 in 1983 to 19 in 1991 and returned to 15 in 1994. The number of facilities providing ECT increased from 62 in 1983 to 83 in 1990 and decreased to 69 in 1994. White patients comprised 91.5% of ECT recipients. Three deaths were reported for a rate of 0.19 deaths/10,000 treatments. Despite its safety and efficacy, the availability of ECT in California continues to remain limited geographically and socioeconomically. The rate of its use has declined. Access to ECT is most limited for public patients. While some of the decline may be related to the introduction of new antidepressants and the rapid expansion of managed care, complex legal regulation bears much of the responsibility.

A naturalistic review of maintenance ECT at a university setting.

This is a naturalistic review of maintenance electroconvulsive therapy (MECT) during the first 4 1/2 years of a university ECT service. A total of 56 patients, ages 30-84, received MECT. Patients could be classified under five different clinical groups: major depression; bipolar disorder; combined depression and axis 2 disorder; Parkinson's disease plus depression; and schizophrenia. Effectiveness in the different groups and issues related to partial improvement or treatment failure are discussed.

Cosmetic outcome in patients receiving an interstitial implant as part of breast-conservation therapy.

PURPOSE: To study factors related to breast cosmetic outcome in patients treated with an interstitial implant as part of breast-conservation therapy. MATERIALS AND METHODS: One hundred fifty-six patients with stage I or II breast carcinoma who received 50 Gy of external-beam irradiation followed by a 20-Gy interstitial boost were examined. The dose homogeneity index (DHI) was calculated for each evaluable implant and was examined in light of other patient-, treatment-, and tumor-related variables previously demonstrated to affect cosmesis. RESULTS: Of the variables examined, both the DHI (P = .021) and the total excision volume (P = .019) were significantly related to cosmetic outcome (excellent vs less than excellent) in a univariate model. In the multivariate analysis, only the total excision volume remained significant (P = .032). The mean total excision volume +/- SD in patients with excellent cosmetic outcome (81.8 cm3 +/- 84.0) was significantly less than that in patients with less than excellent cosmetic outcome (120 cm3 +/- 84). The probability of excellent cosmetic outcome linearly increased with an increase in DHI. The mean DHI was 0.74 +/- 0.12 for the cases with excellent cosmetic outcome and 0.68 +/- 0.10 for those with less than excellent cosmetic outcome. CONCLUSION: To achieve optimal cosmesis, DHI should be maximized. The volume of tissue removed, however, remains the most significant determinant.

A teaching guide for electroconvulsive therapy.

Concern has been raised regarding the erratic and sometimes less than adequate teaching of electroconvulsive therapy (ECT) to health professionals. The development of standardized curricula will ultimately improve the quality of care for patients receiving ECT and help to minimize the myths and misinformation clinicians have regarding ECT. An outline for teaching ECT is presented that covers the following areas: preconceptions, history, patient selection, conditions of increased risk, medical and neurological side effects, memory issues, technical aspects, electrode placement, clinical problems, management of the post-ECT course, legal and ethical issues, mechanisms of action, and educational issues. This outline can be expanded to encompass up to a 6-hour course for psychiatric residents, or compressed to provide the basics to nursing, medical, or pharmacy students.

A seasonal schedule for maintenance ECT.

The case of a patient with bipolar disorder is presented to illustrate that past clinical course may suggest flexible scheduling strategies for maintenance ECT (MECT), which will allow some patients to be successfully treated with the fewest number of ECT. For 7 years prior to MECT, manic episodes regularly occurred during early summer and late autumn/early winter. ECT rapidly aborted the mania in the two episodes prior to referral for MECT. Given the rhythmicity of his manic episodes, MECT was begun by giving four outpatient ECT during the two at-risk periods each year to both abort and prevent affective episodes and to stop cycling. No breakthrough hypomania occurred by the third such period, and the ECT was reduced to three ECT for the following period and two for the next. The patient had no significant affective episodes or hospitalizations during the 3 years of MECT. He continued maintenance lithium carbonate between ECT. This treatment strategy has allowed the patient to maintain stability in his employment and personal life.

A naturalistic comparison of adverse effects between slow titration and loading of divalproex sodium in psychiatric inpatients.

BACKGROUND: This study compares the incidence, severity and onset of treatment-emergent adverse effects between slow titration and loading of divalproex sodium in psychiatric inpatients. METHOD: Forty-seven patients were prescribed either loading or slow titration of divalproex sodium. Under single-blind conditions, adverse effects were assessed using a valproate adverse effects rating scale. Except for a statistically significant greater incidence of somnolence in the slow titration group, no statistically or clinically significant differences in incidence, severity or onset of treatment-emergent adverse effects were found between groups. RESULTS/CONCLUSION: Overall, adverse effects were well tolerated by both groups.

ECT in elderly patients with schizophrenia.

Five female patients with chronic schizophrenia and schizoaffective disorder received electroconvulsive therapy (ECT). Patients were 58 to 74 years old when ECT began. Three patients followed the acute course of ECT with a course of maintenance ECT. Four patients were considered treatment-resistant to medication. One patient objected to any use of medication and opted for ECT when she became psychotic. Four patients received concurrent antipsychotic medication during and after the course of ECT. All five patients experienced improvement in their psychosis.

Dosimetric comparison of stereotactic radiosurgery to intensity modulated radiotherapy.

To compare the dosimetry achievable with an intensity modulated radiotherapy (IMR) system to that of stereotactic radiosurgery (SRS) for an irregularly shaped moderate size target. A treatment plan was selected from 109 single fraction SRS cases having had multiple non-coplanar arc therapy using a 6 MV linear accelerator fitted with circular tertiary collimators 1.00 to 4.00 cm in diameter at isocenter. The CT scan with delineated regions of interest was then entered into an IMR treatment planning system and optimized dose distributions, using a back projection technique for dynamic multileaf collimator delivery, were generated with a stimulated annealing algorithm. Dose volume histograms (DVH), homogeneity indices (HI), conformity indices (CI), minimum and maximum doses to surrounding highly sensitive intracranial structures, as well as the volume of tissue treated to > 80, 50, and 20% of the prescription dose from the IMR plan were then compared to those from the single isocenter SRS plan used and a hypothetical three isocenter SRS plan. For an irregularly shaped target, the IMR plan produced a HI of 1.08 and CI of 1.50 compared to 1.75 and 4.41, respectively, for the single isocenter SRS plan (SRS1) and 3.33 and 3.43 for the triple isocenter SRS plan (SRS3). The maximum and minimum doses to surrounding critical structures were less with the IMR plan in comparison to both SRS plans. However, the volume of non-target tissue treated to > 80, 50, and 20% of the prescription dose with the IMR plan was 137, 170, and 163%, respectively, of that treated with the SRS1 plan and 85, 100, and 123% of the volume when compared to SRS3 plan. The IMR system provided more conformal target doses than were provided by the single isocenter or three isocenter SRS plans. IMR delivered less dose to critical normal tissues and provided increased homogeneity within the target volume for a moderate size irregularly shaped target, at the cost of a larger penumbra.

Intravenous versus intramuscular atropine in ECT.

Twelve patients receiving ECT consented to random assignment to either intravenous or intramuscular administration of atropine for a total of 48 ECTs. There were no statistically significant differences between routes of administration in heart rate, blood pressures, or sialorrhea, but intravenous administration eliminated one injection per treatment and the development of dry mouth and tachycardia between the intramuscular injection and ECT. The authors recommend that atropine for ECT be administered intravenously.

ECT use in the public sector: California.

Availability of ECT in the United States often has been greater in the private sector than in the public sector. This is especially true in California, where ECT is heavily regulated. In 1986, ECT was available at 29.6% of the public hospitals and 42.9% of the private hospitals with psychiatric units in California. Public hospital patients accounted for 8.5% of all ECT in the state, while private hospital patients accounted for 91.5%. Of the 88 patients unable to give informed consent, 34.1% came from public hospitals vs. 65.9% from private hospitals. Two university-affiliated county hospitals accounted for 43 of 52 patients (82.7%) treated in the 6 county hospitals with psychiatric units. White patients accounted for 92.4% of ECT, leaving minorities undertreated. Private patients have a greater degree of choice regarding changing physician or hospital if ECT is needed but unavailable. The choices for public patients are limited. Possible causes and potential solutions to this problem are discussed.