The quest for value in health care

Purchasers and consumers of health care will increasingly refine their definitions of "quality" and the "cost" associated with treatment. The beneficial relationship of these concepts is "value." In the new era of managed care, those providers who offer the best value will succeed. Low-value producers will fail. Understanding buyer perceptions and expectations of value will become increasingly important as markets mature and integrated systems vie for dominance.     

Patient maintained alfentanil target-controlled infusion for analgesia during extracorporeal shock wave lithotripsy

PURPOSE: The purpose of this study was to determine whether alfentanil given by a pharmacokinetic-based target controlled infusion (TCI) system under patient control is a suitable analgesic technique for extracorporeal shock wave lithotripsy (ESWL). METHODS: The design was an open, unblinded, noncomparative, prospective study. Forty outpatients undergoing ESWL were given patient maintained alfentanil TCI. Pain, nausea and sedation were assessed every 300 shocks. Vital signs were recorded every three minutes, pulse oximetry and electrocardiography being monitored continuously. Blood alfentanil concentration was measured for comparison with the predicted value. RESULTS: Alfentanil consumption (median 1.34 mg, range 0.8-3.6) and measured levels following treatment (median 60 ng.ml-1, range 15.6-134.3) varied widely. The precision of the TCI system and the median prediction error (bias) were both 49%. The median of pain scores recorded during treatment was 4 (range 0-8). The median respiration rate was 15 bpm (range 10-23), three patients required oxygen (SaO2 < 92%) cardiovascular measurements were stable and there was no excessive sedation. The incidence of nausea was 15%. All patients were ready for hospital discharge within one hour following treatment. CONCLUSIONS: Patient maintained alfentanil TCI provides good analgesia for ESWL in the majority of patients with little sedation. Respiratory depression is uncommon but supplementary oxygen should be given prophylactically. There is considerable interindividual variation in demand for alfentanil indicating the usefulness of the patient control method. The TCI system underestimated alfentanil blood concentrations but this did not affect its clinical usefulness.     

Biosafety in the clinical mycobacteriology laboratory

This article presents an expanded agent summary statement for laboratorians working with Mycobacterium tuberculosis. It focuses on reducing the serious risk of infection in clinical laboratories that process specimens from tuberculosis patients or that work with purified cultures of tubercle bacilli. Administrative and engineering controls, practices and procedures, and personal protective equipment are discussed. Guidelines for packaging specimens for transfer to another laboratory also are presented.     

Brefeldin A inhibits the constitutive-like secretion of a sulfated protein in pancreatic acinar cells

Sulfation is a common posttranslational modification of secretory proteins and serves as a valuable marker of constitutive and regulated secretory pathways. We investigated the cellular localization and the secretory behavior of sulfated macromolecules in the mouse pancreatic acinar cell. The major sulfated proteins of the cell were present in isolated zymogen granules, as determined by metabolic labeling with [35S]sulfate and subcellular fractionation. The sulfated proteins fell into three groups: gp300 is not secreted and is a component of the zymogen granule membrane; pancreatic lipase (56 kDa) and a 40 kDa protein are soluble and exhibit regulated secretion kinetics; and p82 is initially granule membrane associated, but is released from the cell with constitutive-like kinetics as a 75 kDa protein (p75). Secretion of p75 could be stimulated for up to 4 h after pulse labeling, presumably from immature secretory granules, but not after 6 h of chase. Treatment of cells with brefeldin A (BFA) at the start of the [35S]sulfate pulse resulted in almost total inhibition of sulfation. Addition of BFA during the chase (0-2 h) allowed normal basal and stimulated secretion of regulated secretory proteins, but reversibly inhibited the constitutive-like secretion of p75. In this case, the behavior of p75 was maintained as that of a regulated secretory protein for up to 6 h of chase. In untreated cells, immunofluorescence of p82/p75 was along the acinar lumen, and in small punctate structures in the apical cytoplasm. In BFA-treated cells, immunolabeling of p82/p75 was lost from the acinar lumen, and cytoplasmic labeling was finer and appeared to be associated with the secretory granule membranes. These data suggest a role for brefeldin A-sensitive coat formation in maturation of secretory granules after they bud from the TGN.     

Cerebral palsy: a comprehensive review

Cerebral palsy is a broad range of static, nonprogressive motor disabilities that present from birth or early childhood as a result of injury to neuromotor components of the central nervous system. Motor performance is normally coordinated via communication between the cerebral cortex, thalamus, basal ganglia, brain stem, cerebellum, spinal cord, and communicating sensori-motor pathways. This complex network lends itself to injury at many different levels. Etiologies are numerous and can occur during the prenatal, perinatal, and postnatal periods. The severity of the neurologic deficit and the clinical manifestations are varied depending on the time, location and nature of the original injury. In order to approach cerebral palsy systematically, the primary health care practitioner must be prepared to recognize neuromotor deficits, diagnose and classify the type of disorder, and implement a methodical treatment plan. The purpose of this article is to review the etiology, pathophysiology, diagnostic classification (Swedish system), clinical manifestations, and therapeutic management of cerebral palsy and prepare the advanced practice nurse to care for the individual and family.     

Evidence that the Wiskott-Aldrich syndrome protein may be involved in lymphoid cell signaling pathways

Wiskott-Aldrich syndrome is an X-linked combined immunodeficiency affecting cells of several different hemopoietic lineages. The Wiskott-Aldrich syndrome protein (WASP), which has no homology with any other known protein families, is rich in proline motifs known to contribute to Src homology 3 binding sites. However, its function has not been determined. The Tec family of cytoplasmic tyrosine kinases, which include Btk (the X-linked agammaglobulinemia gene), Itk, and Tec, is thought to be involved in lymphoid cell signaling pathways. In this work, we show binding of WASP to the Src homology 3 domains of Btk, Itk, Tec, Grb2, and phospholipase C-gamma, which suggests a function for WASP in lymphoid cell signaling.     

Development of monoclonal gammopathy precedes the development of Epstein-Barr virus-induced posttransplant lymphoproliferative disorder

Epstein-Barr virus (EBV)-induced posttransplant lymphoproliferative disorder (PTLD) develops in 3% to 10% of solid organ transplant recipients with a resultant mortality of up to 70%. Unfortunately, there is no current marker which identifies patients who will develop this disease. We therefore conducted a risk factor analysis of variables that might predict the development of PTLD. Specifically, since EBV may cause both PTLD and the development of monoclonal proteins (M protein), we sought to determine if the development of an M protein preceded and therefore might serve as a predictive marker of subsequent PTLD. Before and after liver transplantation, 201 patients were evaluated for the presence of urine and serum M proteins. Patients were followed to monitor the development of PTLD for a mean of 1,733 days. PTLD developed in seven patients (3.5%), three (43%) of whom died from disseminated PTLD. PTLD was classified as polymorphous in six patients and monomorphous in one patient. Fifty-seven patients (28%) developed an M protein after transplantation: five of seven patients (71%) with PTLD and 52/194 (27%) of patients without PTLD. Multivariate risk factor analysis for the development of an M protein after transplantation identified cytomegalovirus (CMV) donor seropositivity (P = 0.0002) and postoperative symptomatic CMV infection (P = 0.019) as risk factors. Whereas EBV serostatus of either the donor or recipient was not found to be a risk factor for the occurrence of either an M protein or PTLD, the development of a serum immunoglobulin M (IgM) M protein (P = 0.04) and of any urine M protein (P = 0.01) was identified by univariate analysis as being associated with the development of PTLD. Further studies are needed to determine the predictive value of M proteins as a marker for PTLD. Until such time, the development of serum or urine M protein should heighten the suspicion of developing PTLD.     

Dysautonomia in dogs: a retrospective study

Dysautonomia was diagnosed in 11 young (median age, 14-months), predominantly medium- to large-breed dogs from 1988 to 1995. Clinical signs caused by autonomic dysfunction of the urinary, alimentary, and ocular systems were most common. Dysuria, mydriasis, absence of pupillary light reflexes, decreased tear production, dry mucous membranes, weight loss, and decreased anal tone were present in over 75% of affected dogs. Ocular pharmacological testing with a dilute (0.1%) solution of pilocarpine was used to demonstrate iris sphincter receptor function in all dogs. A low-dose (0.0375 mg/kg s.c.) bethanechol test and pharmacological testing with phenylephrine and epinephrine also demonstrated cholinergic and adrenergic receptor function in 4 dogs. All dogs died or were euthanized as a results of autonomic dysfunction. Neuronal depletion, with associated gliosis and minimal inflammation were noted histologically in the autonomic ganglia of each dog. The pelvic, ciliary, celiac, cranial cervical, and cranial and caudal mesenteric ganglia were affected in all dogs. The cause of autonomic failure in these dogs was not determined.