Polymeric Microspheres Prepared by Spraying into Compressed Carbon Dioxide

Purpose. The objective was to prepare polymeric microparticles by atomizing organic polymer solutions into a spray chamber containing compressed CO₂ (PCA-process) and to study the influence of various process parameters on their morphological characteristics. Methods. The swelling of various pharmaceutically acceptable polymers [ethyl cellulose, poly(methyl methacrylate), poly(-caprolactone), poly(dl-lactide), poly(l-lactide) and poly(dl-lactide-glycolide) copolymers] in CO₂ was investigated in order to find polymers which did not agglomerate during the spraying process. Poly(l-lactide) (L-PLA) microparticles were prepared by spraying the organic polymer solution into CO₂ in a specially designed spraying apparatus. The effect of various process (pressure and temperature of the CO₂ phase, flow rate) and formulation (polymer concentration) variables on the morphology and particle size of L-PLA-microparticles was investigated. Results. Polymers with low glass transition temperatures agglomerated even at low temperatures. The formation of microparticles was favored at moderate temperatures, low polymer concentrations, high pressures and high flow rates of CO₂. High polymer concentrations and low flow rates resulted in the formation of polymeric fibers. Colloidal L-PLA particles could also be prepared with this technique in a surfactant-free environment. Initial studies on the microencapsulation of drugs resulted in low encapsulation efficiencies. Conclusions. The PCA method is a promising technique for the preparation of drug-containing microparticles. Potential advantages of this method include the flexibility of preparing microparticles of different size and morphology, the elimination of surfactants, the minimization of residual organic solvents, low to moderate processing temperatures and the potential for scale-up.     

Hospital consolidation. Applying stakeholder analysis to merger life-cycle

Nearly three of every five hospitals in the United States have been involved in some form of consolidation during the past 5 years. Within this turbulent hospital merger environment, nurse executives are confronted with organizational, professional, and personal decisions. Stakeholder analysis is offered as one strategy to facilitate effectiveness throughout the hospitals' merger life-cycle.     

Studentschool bonding and adolescent problem behavior

Adolescent problem behavior, including substance use, schoolmisconduct and delinquency, is a national concern. Implicitin the concept of middle school is the recognition that studentswho develop positive social bonds with their school are morelikely to perform well academically, and refrain from misconductand other antisocial behavior. However, little scientific attentionhas been given to the complex interactions between middle schoolstudents and the school environment. Prior to implementing amiddle school problem behavior prevention program we conducteda survey in the seven middle schools in one US school district.Out of 4668 grade 6–8 students enrolled, 4263 (91.3%)completed the survey. Student–school bonding was positivelycorrelated with school adjustment (r = 0.49) and perceived schoolclimate (r = 0.77), but inversely correlated with problem behavior(r = –0.39 to –0.43). Problem behavior was significantlyhigher (P < 0.001) among males than females and among studentsin higher grades. Conversely, school bonding, climate and adjustmentwere significantly higher (P < 0.001) among females thanmales, but declined significantly from one grade to the next.The data support the conclusion that school bonding is associatedwith problem behavior. We describe the development of a multiple-componentintervention in middle schools designed to increase student–schoolbonding and prevent problem behavior.     

Family treatment for schizophrenia : the design and research application of therapist training models

The NIMH Treatment Strategies in Schizophrenia (TSS) collaborative study group investigated the efficacy of antisychotic drug maintenance strategies involving reduced medication exposure in interaction with applied and supportive family management for the long-term treatment of schizophrenia. Therapy was provided at five centers by 25 clinicians who did not participate in the development of the therapies. They were trained by two of the authors, I.R.H.F and C.W.M, in applied family management, a homebased treatment derived from the behavioral family therapy developed by them. Clinicians' characteristics, selection, and training methods, as well as patient rehospitalization rates, are reported for the two family management conditions. The TSS study represents a bridge between the development of a novel therapy and its dissemination in general clinical practice.     

Planned and unplanned postoperative admissions to critical care for mechanical ventilation

Purpose

To determine which factors influence the clinician in choosing critical care admission and postoperative ventilation, we prospectively examined the incidence, timing, causes, and risk factors for admission to critical care for postoperative ventilation within 48 hr of a surgical procedure (excluding cardiac and neurosurgical).

Methods

Patients were categorized as: admission planned preoperatively; admission unplanned and identified in the OR (Operating Room) or PACU (Post Anaesthetic Care Unit); and admission unplanned, identified after PACU discharge. Rates of admission by category for those with specific preoperative and intraoperative characteristics were compared to those without the characteristics to determine risk factors for admission (P < 0.01).

Results

Only 329 of 15,059 cases (2.2%) had a critical care admission. Of these, 288 were planned, 31 identified in the OR or PACU, and 10 after PACU discharge. A respiratory aetiology was the reason for admission in 75% of unplanned cases. Preoperatively, age ≥ 60 yr and common systemic illnesses (cardiac, renal, pulmonary) were markers for planned admission, but only positive HIV status was a risk factor for unplanned admission. The two main physiological features which identified all critical care admissions were haemoglobin oxygen saturation <90% (preoperatively breathing room air and intraoperatively) and tachycardia during the operative period. Six of ten of the unplanned after PACU discharge patients underwent bronchoscopy with a neurolept analgesic technique.

Conclusion

Postoperative admissions to a critical care unit, both planned and unplanned, are uncommon. This study has identified haemoglobin oxygen desaturation during the perioperative period and intraoperative tachycardia as important markers for all admissions to critical care.     

Fucosidosis: four new mutations and a new polymorphism

Fucosidosis is a rare lysosomal storage disease due to a nearlycomplete deficiency of -L-fucosidase (EC 3.2.1.51 [EC] ). In thisstudy, all 8 exons of the -L-fucosidase structural gene (FUCA-1)were amplified by PCR methods, and the amplified products weresubcloned and sequenced. Five patient groups with fucosidosiswere selected according to their ethnic backgrounds and haplotypesfor RFLPs in FUCA-1. Four presumptive disease causing mutationswere detected: 1) A major deletion of DNA containing the lasttwo exons of FUCA-1 in two Algerian siblings. 2) A G to T mutationin exon 6 resulting in an in-frame termination codon (E375X)in eight Hispanic patients from Colorado and New Mexico. 3)A G to A mutation (G60D) in exon 1 in four Italian patientsand in three related French-American (Cajun) patients. ThisG60D mutation creates a unique site for Afl III. 4) A frameshiftmutation resulted from a two-base deletion in exon 2 (K151fs)in an Italian patient. This deletion obliterates a unique BstXIsite and creates a new BpmI site, and was found in only thispatient and in only one allele. The rationale for proposingthese defects as disease causing mutations includes pedigreeanalysis and the predicted consequences of each defect uponthe activity and the concentration of the enzyme. An A to Gtransition (Q281R) in exon 5 was found to be present in homozygousform in affected patients and also in normal subjects; it appearsto be a newly identified polymorphism. It causes a charge changeand may be responsible for the electrophoretic variant phenotypeof fucosidosis. This polymorphism is inherited concordant withthe RFLP PvuII—BglI haplotype 2 – 2, 2 – 2.The 4 new mutations identified here comprise 70% of allelesof the 25 fucosidosis patients in our study.     

Production of 5–15 µm Diameter Alginate-Polylysine Microcapsules by an Air-Atomization Technique

A novel method of preparing small-sized microcapsules using a Turbotak air-atomizer is reported. Alginate-polylysine microcapsules containing Bacillus Calmette Guérin vaccine have been prepared by an adaptation of the method of Lim (1) which allows the manufacture of small-sized microcapsules. A Turbotak is used to spray sodium alginate solution into calcium chloride solution to form temporary calcium alginate microgel capsules. These temporary microgel droplets are subsequently cross-linked with polylysine to form permanent membranes. Microcapules in the size range of 5–15 µm have been produced which can be compared to an average diameter of 300 µm obtained by the method reported by Lim. The microcapsule size is dependent on the conditions of operation of the Turbotak and the concentration of the sodium alginate solution. Particles within the size range 5–15 µm can be reproducibly manufactured using the conditions of operation reported here. Other size ranges below the minimum of 300 µm reported by Lim are also feasible using this technique.     

Long-term functional results and quality of life after ileal pouch-anal anastomosis and cholecystectomy

Among 971 patients with chronic ulcerative colitis who underwent ilealpouch anal anastomosis during an 8-year period from January, 1982 to December 1989, 30 patients were randomly selected from each year (total = 240 patients) for an assessment of their long-term functional results and quality of life as of 1990. Patients undergoing cholecystectomy during each of the same years served as controls (20 patients/year, total = 160 patients). All 400 patients completed a written questionnaire that measured bowel habits, overall quality of life, general health, and performance in sports/recreation, travel, sex life, family relationship, occupational work, social activities, and household activities. Ileo-anal patients had more frequent stools (median, 6 stools/day) and more fecal spotting (68% of patients had episodes) than cholecystectomy patients (median, 1 stool/day, 13% had episodes,p<0.05). In spite of the altered bowel habits, 90% of ileo-anal patients had an excellent overall quality of life, 76% enjoyed good health, and 91% had good performance scores in the areas examined. In fact, quality of life and performance were similar among ileo-anal patients and cholecystectomy patients. Moreover, quality of life and bowel habits remained steady in both groups of patients during the 8-year follow-up. In conclusion, functional results were satisfactory and quality of life was excellent after ileal pouch-anal anastomosis; neither deteriorated as patients aged over an 8-year period after operation.

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Resumen Se conformó al azar un grupo de 240 pacientes, seleccionando anualmente 30 entre un total de 971 pacientes con colitis ulcerativa crónica que fueron sometidos a resección y recostrucción con anastomosis ileo-bolsa anal en un período de ocho años entre enero de 1982 y diciembre de 1983, con el propósito de valorar los resultados a largo plazo y la calidad de vida en el año 1990. Los pacientes sometidos a colecistectomía en el mismo período sirvieron como controles (20 pacientes año, total = 160 pacientes). Todos los 400 pacientes diligenciaron un cuestionario escrito sobre hábito intestinal, la calidad global de la vida, estado general de salud, rendimiento en cuanto a deportes/recreación, viajes, vida sexual, relación familiar, trabajo ocupacional, actividades sociales y actividades domésticas. Los pacientes con la anastomosis ileoanal presentaron mayor número de defecaciones (6 diarias, medio) y más manchado fecal (68% de los pacientes presentaron tales epísodios) que los pacientes colecistectomizados (1 defecación diaria, medio; 13% presentaron tales epísodios,p<0.05). A pesar de la alteración en el hábito intestinal, el 90% de los pacientes manifestó una excelente calidad global de la vida, el 76% gozó de buena salud y el 91% tuvo un buen rendimiento en las áreas investigadas. En efecto, la calidad de la vida y el rendimiento aparecieron similares entre los pacientes ileoanales y los colecistectomizados; por lo demás, la calidad de la vida y los hábitos intestinales se mantuvieron estables en ambos grupos en el curso de los ocho años de seguimiento. En conclusión, los resultados funcionales fueron satisfactorios y la calidad de la vida fue excelente luego de una anastomosis ileo-bolsa anal, y ésto no pareció deteriorarse con el avance de la edad en el período de seguimiento de ocho años.

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Résumé Parmi 971 patients ayant une rectocolite ulcéreuse chronique et ayant eu une anastomose iléo-anale pendant la période de 8 ans compris entre Janvier 1982 et Décembre 1989, 30 patients ont été sélectionés au hasard chaque année (n=240 patients au total) pour évaluer leur résultats fonctionnels à distance et leur qualité de vie en 1990. Des patients ayant eu une cholécystectomie pendant cette même période de temps ont servi de contrôles (n=20 patients/an pour un total de 160 patients). Les 400 patients inclus dans cette étude ont rempli un questionnaire par écrit qui comportait le nombre et le type des selles, la qualité de vie, l'état général, et l'activité (voyages, vie sexuelle, relations familiales, travail, vie sociale, et vie à la maison). Les patients ayant eu anastomose iléoanale avaient plus de selles (mediane = 6 selles/jour) et plus de pertes fécales (68% des patients avaient des taches fécales) que les patients ayant eu une cholécystectomie (médiane = 1 selle/jour et 13% de patients ayant des taches;p<0.05). Malgré des modification dans les habitudes pour aller à selle, 90% des patients ayant une anastomose iléoanale estimaient avoir une qualité de vie excellente, 76% s'estimaient en bonne santé et 91% avaient de bons scores dans les activités énumérées ci-dessus. La qualité de vie et les scores étaient identiques aux patients cholécystectomisés. La qualité de vie et les selles sont restées stables dans les deux groupes de patients. En conclusion, les résultats fonctionnels étaient satisfaisants et la qualité de vie excellente après une anastomsose iléoanale; elles ne se sont pas détérioriées pendant la période de suivi de huit ans.