Needs assessment for persons with severe mental illness: What services are needed for successful community living?

The development and implementation of effective community support systems are goals of many public mental health authorities who are attempting to shift the focus and dollars for mental health services from inpatient to community care. This article presents the results of a survey which asked 90 community mental health agency case managers to assess the community support and residential needs of over 1400 of their clients. Medication monitoring and therapy were rated high priority needs. Psychosocial treatment, day and vocational activities also ranked high. Survey responses regarding residential services indicated a need for more supported and supervised options.The study reported was a collaborative effort by county and agency staff.     

Choice of starting dose and escalation for phase I studies of antitumor agents

Summary The standard approaches to initial dose selection and dose escalation in phase I trials may be inappropriately conservative. These approaches mandate accrual of large numbers of patients, most of whom are treated at low and potentially ineffective doses. We compared the clinically determined maximum tolerable dose (MTD) with the starting dose of 45 drugs that had undergone phase I studies during the period 1977–1989. We also examined the number of dose-escalation steps required to achieve the MTD in relation to nonhematologic and hematologic dose-limiting toxicity. The median ratio of MTD to starting dose for all drugs was 20 (range, <1–433) and the median number of dose levels studied to reach the MTD was 8 (range, 0–23). For drugs with nonhematologic dose-limiting toxicity, the median ratio of MTD to starting dose was 30 (range, 3–385) as compared with 12.8 (range, <1–433) for those with hematologic dose-limiting toxicity (P=0.023). The median number of dose-escalation steps required to reach the MTD was 9 (range, 2–18) for drugs with nonhematologic dose-limiting toxicity as compared with 5.5 (range, 0–23) for those with hematologic dose-limiting toxicity (P=0.038). We also examined the response rate for 1,110 patients treated with 21 phase-I-study drugs for which response information was available. Responses were reported for 29 patients (2.6%). Among the 476 patients treated at the 3 highest dose steps, 17 responded (3.6%), which is double the response rate obtained at the lower doses (P=0.08). It is suggested that although the usual methods for choosing starting doses and dose-escalation schemes for phase I studies are safe, they are overly conservative and delay opportunities for therapeutic benefit in phase I and subsequent phase II trials.This research was supported in part by NCI grant 2P30-CA-14236-16     

Xp Microdeletion Syndrome Characterized by Pathognomonic Linear Skin Defects on the Head and Neck

Abstract: We describe a new case of a rare syndrome characterized by ocular abnormalities and pathognomonic linear skin defects. This syndrome is the result of an unbalanced translocation resulting in a deletion of the distal end of the short arm of the X chromosome. We report the thirteenth case and review the clinical and cytogenetic aspects of this disorder. In addition we discuss new findings pertaining to the histopathology of the skin lesions.     

Optical Pretargeting of Tumor with Fluorescent MORF Oligomers

Objective Pretargeting with radioactivity has significantly improved tumor to normal tissue radioactivity ratios over conventional antibody imaging in both animal studies and clinical trials. This laboratory is investigating DNA analogues such as phosphorodiamidate morpholinos (MORFs) for pretargeting using technetium-99m (^99mTc) for detection. However, the unique properties of fluorescence activation and quenching combined with oligomers with their unique properties of hybridization may be particularly useful when used together for pretargeting with optical detection. The use of linear fluorophore-conjugated oligomer duplexes have been little used in animals, and to our knowledge, have not previously been considered for pretargeting applications. Methods A MORF/cDNA pair was selected such that when hybridized, the fluorescence of the Cy5.5-conjugated 25 mer MORF (Cy5.5–MORF25) is inhibited with a BHQ3-conjugated 18 mer complementary DNA (BHQ3–cDNA18). The short BHQ3–cDNA18 was selected to dissociate in the presence of a long cMORF25 in the pretargeted tumor, thus releasing the inhibitor from the Cy5.5 emitter. In this manner, the Cy5.5 fluorescence will be inhibited everywhere but in the target. The dissociation was first examined in vitro by adding the duplex to the cMORF25 both in solution and immobilized on polystyrene microspheres and by surface plasmon resonance (SPR). Thereafter, biotinylated cMORF25 immobilized on streptavidin polystyrene microspheres were administered intramuscularly in one thigh of hairless SKH-1 mice as target while an identical weight of the identical microspheres but without the cMORF25 was administered in the contralateral thigh as control. The animals then received IV the Cy5.5–MORF25/BHQ3–cDNA18 duplex or equal molar dosage of single-chain Cy5.5–MORF25 and were imaged. Results The SPR studies showed that the immobilized cDNA18 rapidly captured the flowing MORF25 to provide a duplex with a slow dissociation rate constant. Furthermore, when cMORF25 was next allowed to flow over the now immobilized duplex, the cDNA18 was unable to prevent dissociation of the heteroduplex and the formation and release of the cMORF25-MORF25 homoduplex. Images of animals obtained soon after receiving the Cy5.5–MORF25 singlet showed intense whole body fluorescence obscuring the target thigh. However, only 5 minutes after receiving the Cy5.5–MORF25/BHQ3–cDNA18 duplex, the target thigh was clearly visible along with only the kidneys. Conclusions This first study of optical pretargeting provides a proof of concept that oligomer pretargeting found to be useful with radioactivity detection is applicable with fluorescent detection as well. In addition, our results demonstrate that by using linear oligomers for optical pretargeting, chain lengths (and base sequences) may be manipulated to provide duplexes with stabilities and fluorescence inhibition optimized for pretargeting and other in vivo applications of optical imaging.     

Baseline heart rate may predict hypotension after spinal anesthesia in prehydrated obstetrical patients

PURPOSE: Hypotension is the most frequent complication of spinal anesthesia in pregnant patients. This study was designed to identify patients at risk for postspinal hypotension based on preoperative vital signs before and after an orthostatic challenge. METHODS: Forty healthy women scheduled for elective Cesarean section were enrolled in this prospective trial. Blood pressure (BP) and heart rate (HR) were recorded with the patient in the lateral supine position and after standing up. After a bupivacaine spinal anesthetic, BP was obtained every two minutes for 30 min. Ephedrine treatment was administered based on the degree of hypotension observed. Hemodynamic parameters were correlated to ephedrine requirements (Spearman's rank order correlation). RESULTS: There was a significant correlation in baseline maternal HR and ephedrine requirements (P=0.005). The degree of orthostatic changes in mean arterial BP and HR did not correlate with postspinal hypotension. CONCLUSIONS: Baseline HR may be predictive of obstetric spinal hypotension. Higher baseline HR, possibly reflecting a higher sympathetic tone, may be a useful parameter to predict postspinal hypotension.