Effect of interleukin-8 on glomerular sulfated compounds and albuminuria

To evaluate the effect of interleukin-8 (IL8) on glomerular basement membrane (GBM) sulfated compounds and albuminuria, we infused IL8 in 1% bovine serum albumin (BSA) for 5 days into the left renal artery of Holtzman male rats at the rate of 10 μl/h using an osmotic pump. Control rats received 1% BSA. A significant increase in urinary albumin/creatinine ratio was seen on the last day of IL8 infusion (0.38±0.11, mean ± SEM) when compared with albumin/creatinine ratio prior to infusion (0.19±0.04, P = 0.04). No significant differences in urinary albumin excretion prior to and after infusion of 1% BSA were observed. On the last day of infusion, rats were injected with ³⁵sulfate (1.0 mCi/200 g body weight) intraperitoneally and killed after 8 h. Glomeruli were isolated and GBM obtained. After 5 days of IL8 administration, there was a significant increase in ³⁵sulfate uptake by GBM of the infused kidney (76±10 cpm/dry glomerular weight, mean ± SEM) compared with the uptake seen in the contralateral kidney (53±9, P = 0.05). The in vivo infusion of IL8 increased the ³⁵sulfate uptake by GBM and augmented the urinary albumin/creatinine ratio, suggesting that IL8 may induce albuminuria by altering the metabolism of the GBM sulfated compounds. This hypothesis needs to be confirmed by studies on glomerular charge selectivity and GBM anionic sites during the course of the infusion. Moreover, the persistence of the effect needs to be evaluated by prolonging the infusion for more than 5 days. Received June 3, 1996; received in revised form and accepted October 18, 1996     

Evaluating candidates for kidney transplantation: some recommendations still lack convincing clinical evidence.

Sir, The paper by Zeier and Ritz in the April 2002 issue of NDT [1]is a good reminder of the importance of evaluation and selectionof kidney transplant candidates. Also, this paper clearly demonstratesthe persisting lack of clinical evidence in this field, whichhas considerable impact on large numbers of end-stage renaldisease patients. We have previously demonstrated the unexplained variations inthe evaluation     

Efficacy and safety of xaliproden in amyotrophic lateral sclerosis: results of two phase III trials.

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal motor neuron disease. We carried out two randomized, double-blind, placebo-controlled, multi-centre, multi-national studies with xaliproden (a drug with neurotrophic effect) to assess drug efficacy and safety at two doses. Patients with clinically probable or definite ALS of more than 6 months and less than 5 years duration were randomly assigned to placebo, 1 mg or 2 mg xaliproden orally once daily as monotherapy in Study 1 (n=867); or to the same regimen with addition of riluzole 50 mg bid background therapy in Study 2 (n=1210 patients). The two primary endpoints were defined as: 1. Time to death, tracheostomy, or permanent assisted ventilation (DTP), and 2. Time to vital capacity (VC)<50% or DTP before (log-rank test) and after adjustment using a Cox proportional hazard model for prespecified prognostic factors. Secondary endpoints were rates of change of various functional measures. In Study 1, primary outcome measures did not reach statistical significance. For the 2 mg group, for time to VC<50% analysis (without DTP) a significant 30% RRR was obtained (95% confidence interval [CI]: 8.46, P=0.009). In Study 2, no significant results were obtained. However, there was a trend in favour of add-on 1 mg dose xaliproden vs. placebo (RRR 15% [-6.31, ns] for time to VC<50%; RRR 12% [CI: -6.27, ns] for time to VC<50% or DTP). Adjusted RR ratios were consistently more favourable for the xaliproden groups. Tolerability was good, and dose-dependent side effects were largely associated with the serotonergic properties of xaliproden. An effect of xaliproden on functional parameters, especially VC, was noted. Although this effect did not reach statistical significance, xaliproden had a small effect on clinically noteworthy aspects of disease progression in ALS.     

Noninvasive Intracranial Cerebral Flow Velocity Evaluation in the Emergency Department by Emergency Physicians

Transcranial Doppler (TCD) is an accepted modality for the evaluation of cerebral blood flow velocities. OBJECTIVES: The purpose of this study was to test the feasibility of bedside TCD measurement in the emergency department (ED) with critically ill, intubated patients. METHODS: A prospective convenience sample of patients presenting to a university hospital over a two-month period underwent TCD evaluation of the middle cerebral artery. Intubated patients with head trauma and any patient requiring tracheal intubation were eligible. A 2-MHz Doppler probe was positioned over the temporal bone to acquire blood flow velocities. An emergency medicine resident and research assistant obtained measurements. Continuous TCD tracings were recorded on a video cassette recorder tape for quality assurance review and data collection. Vital signs and therapeutic interventions were also recorded. Flow velocities were measured in cm/s; the peak Resistance Index (RI) was calculated for each patient. RESULTS: A total of 30 patients were enrolled in the study. Adequate tracings were obtained in 25 patients (83%) without a disruption of resuscitation. Tracings could not be obtained in five patients; they were listed as TCD failures. However, in two of these patients, adequate flow velocity tracings were obtained after resuscitation. Four patients were evaluated during tracheal intubation. One patient was monitored successfully during cardiopulmonary resuscitation. The median time required for data acquisition was 1.9 minutes. The mean highest RI for those who expired was 0.84. For those who survived, the mean highest RI was 0.52. The difference of 0.32 was statistically significant (p = 0.04). CONCLUSIONS: Noninvasive blood flow velocity monitoring of the middle cerebral artery using TCD is feasible in the ED when performed at the bedside on intubated patients with traumatic brain injury and others during tracheal intubation and resuscitation.     

Effect of anticholinergic agents upon acquired nystagmus: a double-blind study of trihexyphenidyl and tridihexethyl chloride

We conducted a randomized, double-blind, crossover trial of two anticholinergic agents--trihexyphenidyl and tridihexethyl chloride (a quaternary anticholinergic that does not cross the blood-brain barrier)--in patients with acquired nystagmus and measured visual acuity and nystagmus before and at the end of 1 month on each medication. Of the 10 patients admitted to the study, only five completed trials of both drugs due to intolerance of medication or intercurrent illness. Of six patients who completed the trial of trihexyphenidyl, only one showed improvement. Of six patients who completed a trial of tridihexethyl chloride, four showed improvement. We conclude that (1) trihexyphenidyl is not a reliable treatment for acquired nystagmus, although occasional patients may benefit; (2) anticholinergic agents may suppress nystagmus by peripheral rather than central mechanisms; and (3) the side effects of anticholinergic agents limit their effectiveness in the treatment of nystagmus.     

Endoscopic transthoracic sympathectomy: current indications and techniques

Zusammenfassung GRUNDLAGEN: Die endoskopische thorakale Sympathektomie (ETS) existiert seit 60 Jahren als effektive Therapie der primären Hyperhidrose. Nach wie vor gibt es in der medizinischen Welt teils Vorbehalte, teils Unwissen über die Methode selbst, ihre Erfolgs- und Komplikationsraten sowie Nebenwirkungen. METHODIK: Nach Einführung in die Symptome und Behandlung der primären Hyperhidrose (konservativ und chirurgisch) werden Operationsmethoden und Langzeitergebnisse der ETS-Operation vorwiegend anhand der Daten aus der eigenen Abteilung präsentiert. ERGEBNISSE: Von 1965–2001 wurden 734 Sympathikotomien (ETS2–4) und bis 2003 weitere 103 Sympathikusblockaden (ESB4) bei Patienten mit primärer palmarer und axillärer Hyperhidrose durchgeführt. Die Konversionsrate betrug 0,1 %. Seit Einführung der Video-Thorakoskopie 1991 trat kein postoperatives Horner-Syndrom auf (zuvor 2,2 %), Drainage-pflichtige Pneumothoraces waren in 1,1 % zu verzeichnen. Nach einem medianen Follow-up von 16 Jahren waren 93 % der Extremitäten trocken, 5 % fast trocken und 2 % feucht. Nebenwirkungen traten in Form von kompensatorischem Schwitzen am Stamm (55 % insgesamt, davon 5 % stark) und gustatorischem Schwitzen (33 %) auf. Seit Einführung der limitierten Sympathikusblockade auf Höhe T4 (ESB4) konnte (bei naturgemäß kurzer Nachbeobachtungszeit) das kompensatorische Schwitzen auf 8,5 % und das gustatorische Schwitzen auf 2,1 % gesenkt werden. Mit dem postoperativen Ergebnis waren 100 % der Patienten nach ESB4 zufrieden, nach ETS2–4 waren 80 % zufrieden, 14 % teilweise zufrieden und 6 % unzufrieden (meist wegen starken kompensatorischen Schwitzens). SCHLUSSFOLGERUNGEN: Die ETS-Operation bietet hohe langfristige Erfolgsraten bei niedrigen Komplikationsraten. Patienten sollten über die zu erwartenden Nebenwirkungen genau aufgeklärt werden, für unzufriedene Patienten mit starkem kompensatorischem Schwitzen besteht nun die Möglichkeit der thorakoskopischen Klip-Entfernung.     

The sympathetic trunk and its neural pathway to the upper limb: review of the literature

Zusammenfassung GRUNDLAGEN: Kenntnisse der Anatomie des Truncus sympathicus und des autonomen Nervensystems sind von großer Bedeutung in der Sympathikuschirurgie. Allerdings existiert eine Vielzahl an unterschiedlichen sympathischen Nervenverbindungen zur oberen Extremität, wobei der Großteil im ersten Zwischenrippenraum zu liegen kommt. Aus unterschiedlichsten Gründen führt die chirurgische Sympathektomie im Bereich der oberen thorakalen Ganglien zu einer Unterbrechung der sympathischen Innervation der oberen Extremität. Entscheidend ist, diese variablen Verbindungen zu durchtrennen, um optimale chirurgische Ergebnisse zu erzielen. METHODIK: Diese Arbeit basiert auf einer Durchsicht der Literatur der letzten 80 Jahre über die Anatomie des kranialen thorakalen Truncus sympathicus und seiner Verbindungen, die in der Sympathikuschirurgie von besonderer Bedeutung sind. Die Evaluation basiert auf einer Literaturrecherche in der Medline, ergänzt um Wissen aus Anatomiebüchern; es wird zudem eine Übersicht über die historische Entdeckung des sympathischen Systems gegeben. ERGEBNISSE: Zwei wichtige Ergebnisse liegen vor. 1. Intrathorakale Nervenverbindungen zwischen zweitem und erstem intrathorakalen Nerv dürften sympathische Fasern der oberen Extremität zuführen. Diese Verbindungen kommen bei mehr als 50 % der Menschen vor und dürften für Misserfolge und/oder Rezidive nach Sympathektomie verantwortlich sein. 2. Aktuelle chirurgische Studien weisen darauf hin, dass das Hauptganglion für die sympathische Innervation der oberen Extremität im Segment T4 liegen könnte. Dies steht jedoch im Gegensatz zur bisher anerkannten Ansicht, dass das Hauptganglion der sympathischen Innervation für die obere Extremität das T2-Ganglion sei. Bislang können diese klinischen Erkenntnisse nicht durch anatomisches Wissen erklärt werden. SCHLUSSFOLGERUNGEN: Profunde anatomische Kenntnisse sind eine unabdingbare Voraussetzung, um in der Sympathikuschirurgie optimale Ergebnisse zu erzielen.