Correction: Mitochondrial oxodicarboxylate carrier deficiency is associated with mitochondrial DNA depletion and spinal muscular atrophy-like disease.

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Polymyxin B infusion leading to cardiac arrest: a case report and literature review.

We describe a 52-year-old female patient who developed cardiopulmonary arrest due to neuromuscular paralysis after initiation of polymyxin B for septicemia caused by extended spectrum ß-lactamase-producing Klebsiella pneumoniae. Due to emerging antibiotic resistance patterns, use of polymyxins is increasing and an understanding of their toxicity is critical.

The impact of hemolysis on Ortho-Clinical Diagnostic's ECi and Roche's elecsys immunoassay systems.

BACKGROUND: Hemolysis is regularly encountered in clinical specimens and often interferes with a variety of laboratory test methods. Although not widely recognized, immunoassays based on nonisotopic detection systems can also be affected by hemolysis. For this reason, we investigated the effect of differing amounts of hemolysis across a range of values for several immunoassays on the Ortho-Clinical Diagnostics ECi and Roche Elecsys platforms. METHODS: Hemolysate was prepared from whole blood and spiked at varying concentrations into pooled patient serum samples for different analytes. RESULTS: Out of the 21 analytes tested, six (28.6%) exhibited significant increases or decreases in measured concentrations with increasing amounts of hemolysis. CONCLUSIONS: Although immunoassays are generally thought to be impervious to hemolysis interference, hemolysis can interfere in immunoassay testing platforms. For these reasons, we recommend that laboratories conduct hemolysis interference studies for all laboratory test protocols.

Identification of genotypic changes in human immunodeficiency virus protease that correlate with reduced susceptibility to the protease inhibitor lopinavir among viral isolates from protease inhibitor-experienced patients.

The association of genotypic changes in human immunodeficiency virus (HIV) protease with reduced in vitro susceptibility to the new protease inhibitor lopinavir (previously ABT-378) was explored using a panel of viral isolates from subjects failing therapy with other protease inhibitors. Two statistical tests showed that specific mutations at 11 amino acid positions in protease (L10F/I/R/V, K20M/R, L24I, M46I/L, F53L, I54L/T/V, L63P, A71I/L/T/V, V82A/F/T, I84V, and L90M) were associated with reduced susceptibility. Mutations at positions 82, 54, 10, 63, 71, and 84 were most closely associated with relatively modest (4- and 10-fold) changes in phenotype, while the K20M/R and F53L mutations, in conjunction with multiple other mutations, were associated with >20- and >40-fold-reduced susceptibility, respectively. The median 50% inhibitory concentrations (IC(50)) of lopinavir against isolates with 0 to 3, 4 or 5, 6 or 7, and 8 to 10 of the above 11 mutations were 0.8-, 2.7-, 13.5-, and 44.0-fold higher, respectively, than the IC(50) against wild-type HIV. On average, the IC(50) of lopinavir increased by 1.74-fold per mutation in isolates containing three or more mutations. Each of the 16 viruses that displayed a >20-fold change in susceptibility contained mutations at residues 10, 54, 63, and 82 and/or 84, along with a median of three mutations at residues 20, 24, 46, 53, 71, and 90. The number of protease mutations from the 11 identified in these analyses (the lopinavir mutation score) may be useful for the interpretation of HIV genotypic resistance testing with respect to lopinavir-ritonavir (Kaletra) regimens and may provide insight into the genetic barrier to resistance to lopinavir-ritonavir in both antiretroviral therapy-naive and protease inhibitor-experienced patients.

Accuracy of CPT evaluation and management coding by family physicians.

BACKGROUND: Limited data are available on physicians' accuracy in coding for their services. The purpose of this study was to determine the current procedural terminology (CPT) evaluation and management coding accuracy of family physicians and define demographic variables associated with coding accuracy. METHODS: Six hundred randomly selected active members of the Illinois Academy of Family Physicians were sent six hypothetical progress notes of office visits along with a demographic survey. The study group assigned CPT evaluation and management codes to each of the progress notes and completed the demographic survey. Five expert coders also assigned codes to each of the cases. The accuracy of family physicians in determining CPT E/M codes was determined relative to that of expert coders. RESULTS: Family physicians agreed with the experts' CPT evaluation and management codes for 52% of established patient progress notes, the most common error being undercoding. In contrast, for new patient progress notes, family physicians agreed with the experts only 17% of the time, the predominant error being overcoding. No surveyed demographic variable was associated with coding accuracy. CONCLUSIONS: The error rate for physician CPT coding is substantial and occurs more commonly with new patients. The complexity of the CPT coding guidelines, along with limited physician training in CPT coding, likely account for these results.

Preoperative evaluation.

A history and physical examination, focusing on risk factors for cardiac, pulmonary and infectious complications, and a determination of a patient's functional capacity, are essential to any preoperative evaluation. In addition, the type of surgery influences the overall perioperative risk and the need for further cardiac evaluation. Routine laboratory studies are rarely helpful except to monitor known disease states. Patients with good functional capacity do not require preoperative cardiac stress testing in most surgical cases. Unstable angina, myocardial infarction within six weeks and aortic or peripheral vascular surgery place a patient into a high-risk category for perioperative cardiac complications. Patients with respiratory disease may benefit from perioperative use of bronchodilators or steroids. Patients at increased risk of pulmonary complications should receive instruction in deep-breathing exercises or incentive spirometry. Assessment of nutritional status should be performed. An albumin level of less than 3.2 mg per dL (32 g per L) suggests an increased risk of complications. Patients deemed at risk because of compromised nutritional status may benefit from pre- and postoperative nutritional supplementation.

Biophysical properties and responses to glutamate receptor agonists of identified subpopulations of rat geniculate ganglion neurons.

The goal of the current study was to evaluate the electrophysiological properties and responses to glutamate receptor agonists of rat geniculate ganglion (GG) neurons innervating the tongue. Subpopulations of GG neurons were labeled by injecting Fluoro-Gold (FG) or True Blue chloride into the anterior tongue and soft palate (AT and SP neurons) and applying FG crystals to the posterior auricular branch of the facial nerve (PA neurons). Three to 12 days later, the GG neurons were acutely isolated and patch clamped. Although many biophysical properties of the AT, SP and PA neurons were similar, significant differences were found among these groups in properties related to cell excitability. For example, the average amount of current necessary to elicit an action potential was 61 pA in AT neurons (n=55), 90 pA in SP neurons (n=41) and 189 pA in PA neurons (n=35, P<0.001). In addition, AT neurons tended to fire significantly more action potentials during depolarization as well as following hyperpolarizing pulses than SP or PA neuron types. Most GG neurons responded to application of glutamate receptor agonists. The neurons responded with a depolarization accompanied by a reduction in input resistance. These results suggest that subpopulations of neurons in the geniculate ganglion have distinct biophysical properties and express functional glutamate receptors. The differing biophysical properties of GG neurons is possibly related to their functional heterogeneity and glutaminergic neurotransmission may function in the processing of gustatory, and other sensory information, within the geniculate ganglion and its projections.

Evaluation of nursing home patients. A systematic approach can improve care.

As the US population ages, the proportion of patients receiving long-term care is increasing. To meet the challenge of providing quality care for these patients, physicians need to be prepared to efficiently evaluate their needs and formulate individualized care plans. In this article, Drs King and Lipsky discuss the unique aspects of caring for nursing home patients, including the role of patients' families in the overall plan. They present a practical, structured approach to evaluation and follow-up care, which they have encapsulated into two handy assessment forms.

Adrenal insufficiency: an uncommon cause of fatigue.

BACKGROUND: Adrenal insufficiency is a rare condition that can cause common and nonspecific symptoms. One such symptom, reported by all patients with adrenal insufficiency, is fatigue. On the other hand, up to 20% of patients seeking care from primary care physicians will have fatigue as a complaint. Only a small percentage of patients are found to have underlying medical disease. METHODS: A MEDLINE literature search was performed from 1966 to the present using the key words "fatigue," "adrenal insufficiency," and "polyglandular autoimmune endocrinopathy." Major endocrinology textbooks were also referenced. In addition, references were obtained from bibliographies of available articles. RESULTS AND CONCLUSIONS: This article describes a patient with adrenal insufficiency and fatigue as the primary complaint. A brief discussion of fatigue and clues to organic causes follows, along with a more detailed discussion of adrenal insufficiency. Important medical history or signs and symptoms of organic disease suggest the need for screening tests and more detailed evaluation to uncover the uncommon medical causes of fatigue.

A subpopulation of neurons in the rat rostral nucleus of the solitary tract that project to the parabrachial nucleus express glutamate-like immunoreactivity.

In rodents, gustatory information is transmitted from second order neurons in the rostral nucleus of the solitary tract (rNST) to the parabrachial nucleus (PBN) in the pons. The chemical nature of this projection is unknown. Therefore, the goal of the current study was to determine if rNST neurons that project to the PBN express glutamate-like immunoreactivity. Projection neurons were retrogradely labeled following stereotaxic injection of rhodamine-filled latex microspheres into the right PBN of seven rats while glutamate-immunoreactive (GLU-IR) structures were visualized in the same tissue using an immunoperoxidase procedure. The number of single- and double-labeled neurons located in the right (ipsilateral) and left rNST, in each of the nuclear subdivisions as well as their position along the rostral-caudal axis of the rNST was determined. GLU-IR cell bodies were located throughout the rNST. Although the rostral central subdivision contained the highest percentage (33.8%) of GLU-IR perikarya, immunolabeled neurons were most concentrated (number/area of subdivision) within the medial subnucleus. The rostral third of the rNST contained the fewest (20. 5%) and lowest density of GLU-IR cell bodies. The highest percentage of rNST neurons retrogradely labeled from the PBN were located ipsilateral (85.4%) to the pontine injection site, in the middle third of the nucleus (44.2%) and within the rostral central subdivision (52.4%). Overall, 18% of the labeled rNST projection neurons were GLU-IR. The distribution of double-labeled neurons mirrored that of the projection neurons with the largest number located in the ipsilateral rNST (84.5%), middle third of the nucleus (40.5%) and rostral central subdivision (64.7%). These results indicate that glutamate may be a main component of the ascending pathway from the rNST to the PBN. In addition, since GLU-IR neurons were located throughout the rNST and most were not retrogradely-labeled, the current results suggest that glutamate may be an important neurotrans-mitter within the medulla.

The influence of the full blood count on medical inpatient management.

AIM: This investigation studied the use of the full blood count (FBC) in a general medical inpatient ward at Groote Schuur Hospital. OBJECTIVES: To determine the relative frequency of the reasons for which FBCs were requested (clinically indicated v. routine) and how they influenced patient management. PATIENTS: One hundred and sixty-five consecutive general medical inpatients admitted to the ward between September and December 1993 were included. Each patient underwent an FBC and differential white cell count prior to entering the ward. DESIGN: After taking a history and examining the patient, the physician responsible for each of the 165 patients completed a questionnaire. OUTCOMES MEASURED: Physicians had to indicate whether the FBC was routine or clinically indicated and how the FBC result influenced their patient management. RESULTS: In 67.9% of cases the FBC was considered to be clinically indicated, while in 32.1% of cases it was routine. Although it was felt that 76.4% of the clinically indicated tests influenced patient care, patient management was changed in only 24.7% of cases. In the case of routine tests, care was influenced in only 2.0% of cases. CONCLUSION: Routine tests have a very low clinical yield. There is no substitute for good clinical judgement and the practice of routine tests must be reviewed, as much time, money and patient discomfort could be saved by the elimination of unnecessary investigations.

District level information systems: two cases from South Africa.

The health system in South Africa has to date been fragmented and centralised. The priority of the new government is to establish an integrated and decentralised district health system of which a key element is the development of district health and management information systems (H & MIS). This paper presents experiences from two projects in the Western Cape in which a process to establish a district-based H & MIS was initiated and a situation analysis of the information systems was done. The two projects applied different research methods but the results show with remarkable consistency that much time is used on data collection, but information is not used at local level. The projects have applied different approaches towards developing a district H & MIS but in both important pre-requisites for a successful, action-led H & MIS include local ownership and motivation, a process based around existing local management structures and the active involvement of the community.

Demonstration of a bilateral projection from the rostral nucleus of the solitary tract to the medial parabrachial nucleus in rat.

This study examined the projection from the rostral nucleus of the solitary tract (rNST) to the medial parabrachial nucleus (mPBN) in male Wistar rats using DiI as a retrograde tracer and biotinylated dextran as an anterograde tracer. Following successful unilateral injection of DiI into the mPBN (n = 8), retrogradely labeled neurons were always found in the rNST both ipsilateral and contralateral to the pontine injection site. Significantly, approximately 25% of the total number of DiI-labeled neurons were located in the contralateral rNST. The labeled neurons were located throughout the rostral-caudal extent of the rNST with the most cells being located in the central portion of the nucleus, and the fewest located ventromedially and dorsolaterally. Supporting the findings of the retrograde labeling study, axons and terminals, anterogradely labeled by injecting biotinylated dextran unilaterally into the rNST (n = 4), were always found in both the ipsilateral and contralateral mPBN. Although the intensity of anterograde labeling was higher ipsilaterally, a mirror-image staining pattern consistently was present contralaterally. These results indicate that there is a substantial contralateral component of the projection from the rNST to the mPBN. This suggests that convergence of gustatory information from the two sides of the oral cavity may occur within the pons before processing in higher brain centers. These findings may have important implications as to where and how bilateral gustatory information is processed and integrated.