Neuronal activity in the globus pallidus of multiple system atrophy patients.

The pathophysiological changes in neural activity that characterize multiple system atrophy (MSA) are largely unknown. We recorded the activity of pallidal neurons in 3 patients with clinical and radiological features of MSA who underwent unilateral microelectrode-guided pallidotomy for disabling parkinsonism. Findings in these patients were compared with 4 control patients with a clinical diagnosis of Parkinson's disease (PD). The position, firing rates, and firing patterns of single neurons in the pallidal complex were analyzed in both MSA and PD patients. The mean spontaneous firing rate of neurons in the internal segment of the globus pallidus internus (GPii) was significantly lower in MSA than in PD patients. There were no significant differences between MSA and PD patients, however, in firing rates of neurons in the external globus pallidus (GPe) or in the external segment of GPi (GPie). In addition, no significant differences in firing pattern were found between MSA and PD patients. In conclusion, this study has shown that firing rates of neurons in GPii but not in GPie and GPe are different in MSA patients compared with that in PD patients, a finding that may reflect the poor clinical results of pallidotomy reported in patients with MSA.     

Acute interstitial nephritis: clinical features and response to corticosteroid therapy.

BACKGROUND: Acute interstitial nephritis (AIN) is a recognized cause of reversible acute renal failure characterized by the presence of an interstitial inflammatory cell infiltrate. METHODS: In order to evaluate the clinical characteristics and management of this disorder, we performed a retrospective study of all cases of AIN found by reviewing 2598 native renal biopsies received at our institution over a 12 year period. Presenting clinical, laboratory and histological features were identified, as was clinical outcome with specific regard to corticosteroid therapy response. RESULTS: AIN was found in 2.6% of native biopsies, and 10.3% of all biopsies performed in the setting of acute renal failure during the period analysed (n = 60). The incidence of AIN increased progressively over the period observed from 1 to 4% per annum. AIN was drug related in 92% of cases and appeared to be idiopathic in the remainder. The presenting symptoms included oliguria (51%), arthralgia (45%), fever (30%), rash (21%) and loin pain (21%). Median serum creatinine at presentation was 670 micromol/l [interquartile range (IQR) 431-1031] and 58% of cases required acute renal replacement therapy. Corticosteroid therapy was administered in 60% of cases. Serum creatinine at baseline was similar in the corticosteroid-treated and conservatively managed groups; 700 micromol/l (IQR 449-1031) vs 545 micromol/l (IQR 339-1110) P = 0.4. In this, the largest retrospective series to date, we did not detect a statistically significant difference in outcome, as determined by serum creatinine, between those patients who received corticosteroid therapy and those who did not, at 1, 6 and 12 months following presentation. CONCLUSION: The results of this study do not support the routine administration of corticosteroid therapy in the management of AIN.     

Should cervical ultrasonography be a routine staging investigation for lung cancer patients with impalpable cervical lymph nodes?

OBJECTIVES: Detection of cervical N3 lymph nodes is currently not a routine preoperative investigation for lung cancer patients. We designed a study to assess if the frequency and accuracy of detection of metastatic cervical lymph nodes using cervical ultrasonography (US) and fine needle aspiration (FNA) justify their routine use in all lung cancer patients with impalpable cervical lymph nodes. METHODS: Fifty patients with suspected and potentially operable non-small cell lung cancer were enrolled. Patients with palpable cervical lymph nodes were excluded. In addition to routine preoperative investigations, all patients received cervical US to determine the presence of cervical lymph nodes. Nodes suspicious of harboring malignancy according to a specific set of sonographic criteria (which include shape, echogenicity, nodal architecture, and vascular patterns) were subjected to biopsy by ultrasound-guided FNA. RESULTS: Normal cervical lymph nodes were detected by cervical US in 30 patients (60%). Cervical lymph nodes suspicious of harboring malignancy were detected in 10 patients (20%). FNA confirmed cervical nodal metastasis in four of these patients (8%). The TNM staging of two patients (4%) was revised up to stage IIIb as a result, excluding them from further surgery. Cost analysis suggests this technique to be cost-effective when used as a routine preoperative investigation to exclude patients from unnecessary surgical intervention. No mortality or complications were encountered in all patients. CONCLUSIONS: Cervical US and FNA is a safe and cost-effective method of evaluating the status of impalpable cervical lymph nodes in lung cancer patients. Further study is warranted to establish the role of cervical US and FNA in lung cancer staging algorithms.     

Influenza vaccination: a collaborative effort to improve the health of the community.

BACKGROUND: The need to improve influenza vaccination delivery in our community became painfully clear during the winter of 1997-1998 when high rates of respiratory illness led to congestion in the emergency department and a critical shortage of hospital beds. In response, the local hospital and the Department of Health launched a collaborative program to increase influenza vaccine coverage in the community. METHODS: The partnership was designed to increase the number of citizens receiving influenza vaccine and to moderate the severity of lower respiratory tract illness during the winter season. A variety of methods were used to increase public awareness, enhance vaccine delivery, and create a relatively seamless service for the community. RESULTS: During three seasons, influenza vaccination rates increased by a relative 150%. This represented immunization of 16% of the entire community and more than 75% of residents older than 65 years. Hospital employee vaccination rates also rose from 34% to 58%. When compared with other hospitals in the county, the campaign reduced the average number of annual visits to the emergency department for all respiratory diagnoses by 34% and exacerbations of chronic obstructive pulmonary disease by 46%. CONCLUSIONS: This influenza vaccination program illustrates the potential for synergy that exists between local departments of health and community hospitals in successfully increasing vaccine delivery to the community. Furthermore, it also suggests that such efforts can be successful in reducing use of the emergency department, resulting in a positive impact on the health of the community.     

International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson's disease: the NMSQuest study.

Nonmotor symptoms (NMS) of Parkinson's disease (PD) are not well recognized in clinical practice, either in primary or in secondary care, and are frequently missed during routine consultations. There is no single instrument (questionnaire or scale) that enables a comprehensive assessment of the range of NMS in PD both for the identification of problems and for the measurement of outcome. Against this background, a multidisciplinary group of experts, including patient group representatives, has developed an NMS screening questionnaire comprising 30 items. This instrument does not provide an overall score of disability and is not a graded or rating instrument. Instead, it is a screening tool designed to draw attention to the presence of NMS and initiate further investigation. In this article, we present the results from an international pilot study assessing feasibility, validity, and acceptability of a nonmotor questionnaire (NMSQuest). Data from 123 PD patients and 96 controls were analyzed. NMS were highly significantly more prevalent in PD compared to controls (PD NMS, median = 9.0, mean = 9.5 vs. control NMS, median = 5.5, mean = 4.0; Mann-Whitney, Kruskal-Wallis, and t test, P < 0.0001), with PD patients reporting at least 10 different NMS on average per patient. In PD, NMS were highly significantly more prevalent across all disease stages and the number of symptoms correlated significantly with advancing disease and duration of disease. Furthermore, frequently, problems such as diplopia, dribbling, apathy, blues, taste and smell problems were never previously disclosed to the health professionals.     

Localization by immunoelectron microscopy of spanning protein of triad junction in terminal cisternae/triad vesicles

Summary Polyclonal antibodies have been developed against the junctional feet or spanning protein from skeletal muscle triads. These probes in combination with immunogold labels have been used to localize the spanning protein by electron microscope of isolated vesicles from terminal cisternae/triads. The spanning protein antibodies specifically bind to the electron dense junctional feet. In vesicles permeabilized by hypotonic treatment or by saponin, some gold particles may be seen on the luminal side of the vesicle. Trypsin treatment of vesicles causes complete loss of the 300 K spanning protein from SDS gels while dot blots show that some but not all the antigenic activity is lost. This treatment is associated with the loss of the electron dense projections from the membrane surface and is coincident with the loss of immunogold staining when antibody is added to the intact vesicles. On the other hand, in experiments in which the luminal portions of the isolated vesicles have been made accessible to the polyclonal antibodies by sectioning lightly fixed vesicles before immunogold tagging, extensive gold labelling was found to occur in trypsin treated vesicles which have lost detectable projections from the cytoplasmic side of the membrane. These data support the view that the spanning protein projects from the sarcoplasmic reticulum towards the transverse tubules but further suggest that spanning protein extends into and probably through the sarcoplasmic reticulum membrane in accord with the proposition that it is a Ca²⁺ channel.Nomenclature SP spanning protein - SR sarcoplasmic reticulum - TC terminal cisternae - T-tubule transverse tubule - HMW high molecular weight - ELISA enzyme linked immunosorbent assay - PMSF phenylmethyl sulphonylfluoride - SDS sodium dodecyle sulphate