Trospium chloride versus oxybutynin: a randomized, double-blind, multicentre trial in the treatment of detrusor hyper-reflexia.

OBJECTIVE: To compare trospium chloride (TCl), a quaternary ammonium derivative with atropine-like effects and predominantly antispasmodic activity, with oxybutynin (Oxy) in terms of efficacy and adverse effects. PATIENTS AND METHODS: In a randomized, double-blind, multicentre trial, 95 patients with spinal cord injuries and detrusor hyper-reflexia were studied. Treatment consisted of three doses per day over a 2 week period, with either Oxy (5 mg three times daily) or with TCl (20 mg twice daily) with an additional placebo at midday. The results were evaluated with regard to changes in objective (urodynamic) data and subjective symptoms as well as the incidence/severity of adverse effects. RESULTS: With both drugs there was a significant increase in maximum bladder capacity, a significant decrease in maximum voiding detrusor pressure and a significant increase in compliance and residual urine; there were no statistically significant differences between the treatment groups. The percentage of patients who reported severe dryness of the mouth was considerably lower (4%) in those receiving TCl 2 x 20 mg/day than in those receiving Oxy (23%) 3 x 5 mg/day. Withdrawal from treatment was also less frequent in those receiving TCl (6%) than in those receiving Oxy (16%). CONCLUSION: Trospium chloride and oxybutynin, judged in terms of objective urodynamic parameters, are of substantially equal value as parasympathetic antagonists. However, assessment of tolerance in terms of adverse drug effects showed that TCl had certain advantages.

Early modifications of biochemical markers of bone metabolism in spinal cord injury patients. A preliminary study.

Spinal cord injury is associated with the development of a rapid and severe osteoporosis which might reflect uncoupling between bone formation and resorption. A prospective study was made in 6 spinal cord injury patients followed up to 2-3 months after onset with various markers of a) bone formation: osteocalcin and C-terminal peptide of type I procollagen, b) bone resorption: pyridinolines and C-terminal telopeptide of type I collagen, c) connective tissue metabolism: amino-terminal propeptide of type III collagen (PIIINP). Preliminary results show that early after onset, bone formation was depressed as compared to dramatically increased bone resorption. Low bone formation rate lasted two weeks before it began to raise, while bone resorption showed a continuous tendency to increase. The dramatic increase in PIIINP levels might represent some attempt of bone to repair. This paper describes the evolution of various biochemical markers of bone and connective tissue metabolism after onset of paralysis and critically reviews the use of those markers in patients with spinal cord injury.

[Acute-stage para- and tetraplegia]. / Para- et tétraplégie au stade aigu.

A quarter of a century ago, in October 1964, the first spinal cord injury center in Switzerland was opened at Geneva University Hospital. At that time all para- and tetraplegics were classified as "high-risk" patients. Early mortality, covering the initial four weeks following trauma, was still around 15%. The available resources for diagnostic assessment were limited to clinical examination and neuroradiological assessment (subsequently improved by the introduction of tomography and gas myelography). A great many patients suffered a deteriorated neurological level due to inadequate, multiple transfers between hospitals. Most patients who are paralyzed following a road-traffic accident show severe polytrauma. Their chances of survival and functional recovery have greatly improved in recent years due to efficient emergency transport by helicopter, admission to an intensive care unit (respiratory therapy, prophylactic anticoagulation, gastrointestinal cytoprotection, prevention of pressure sores, etc.) and a comprehensive medico-surgical team approach (orthopedic surgeons, neurosurgeons, ICU specialists, internists, etc.). Evaluation of the spine and spinal cord by NMR and CT scan allows precise assessment of the extent of CNS damage and provides additional guide-lines regarding efficient surgical reposition and spinal fusion. Ongoing experimental research in neurophysiology and neurobiochemistry of the brain and spinal cord is presently yielding some interesting results which hold out new hopes for functional recovery in some specific types of incomplete spinal cord trauma.

The influence of CLS 2210 on the course of myocardial infarction: a pilot study in man.

To assess the effect of CLS 2210 (a new formulation of calcium dobesilate) on the evolution of acute myocardial infarction, 100 patients presenting their first infarct were distributed, according to their sequential admissions to the hospital, into CLS 2210-treated group (50 patients) or a comparison group (50 patients not receiving CLS 2210). The two groups were similar in age, sex, predisposing factors, and site of infarction. Intravenous infusion of CLS 2210 was begun within six hours of onset of chest pain and continued for seventy-two hours. Thereafter, it was given, as oral capsules, in a dose of 1,000 mg every eight hours throughout the hospitalization. Before and during the trial, blood samples were drawn for the measurements of serum concentrations of creatine kinase (CK), and twelve-lead electrocardiograms (ECGs) were obtained serially in each patient. All objective data were analyzed on a coded basis without reference to the treatment. In the comparison group, thirty-six to forty-eight hours was required for CK to fall to 50% of the baseline value, whereas in the CLS 2210-treated group it reached 50% of the baseline in eighteen to twenty-four hours. For each infarction site, a statistically significant fall was reached earlier in the CLS 2210 group. CK, the ECG index, and the sum of the ST segments showed earlier and more rapid improvement in the CLS 2210 group than in the comparison group. The consumption of narcotic analgesic agents and nitroglycerin was substantially less in the CLS 2210 group than in the comparison group.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral immunotherapy in paraplegic patients with chronic urinary tract infections: a double-blind, placebo-controlled trial.

In a 6-month, double-blind, placebo-controlled clinical trial with cross-over, we investigated the efficacy and tolerance of an orally administered bacterial extract in 70 spinal cord injury patients with chronic lower urinary tract infections. In the treated patients, compared to those given placebo, there was a statistically significant decrease in the degree of bacteriuria, a considerably decreased incidence of infectious episodes and a lesser requirement for antibiotics.

Salvage of ischemic myocardium by CLS 2210 in the dog: a preliminary double-blind study.

To assess whether a cardiac lymphagogue, CLS 2210, would reduce myocardial infarct size after coronary artery ligation, studies were performed in 14 dogs. The left anterior descending coronary artery was ligated in each dog, and the dogs were randomized to either placebo or CLS 2210 treatment, which was carried on for seven days. After seven days the animals were sacrificed and the volume of infarcted myocardium was determined macroscopically on a double-blind basis, supported by histologic examination. CLS 2210 treatment resulted in a highly significant reduction in the volume of infarcted myocardium (p less than 0.001). Since CLS 2210 is chemically and pharmacologically unrelated to hyaluronidase but shares an action with hyaluronidase as a cardiac lymphagogue, the results offer further support for a role of myocardial lymphatics in the evolution of myocardial necrosis following coronary artery occlusion and provide an explanation for the mechanism by which these agents reduce myocardial infarction size.

[Treatment of infections of the lower urinary tract caused by multiresistant gram-negative pathogens, with ceftazidime in monotherapy of patients with spinal cord injuries]. / Die Behandlung von Infektionen der unteren Harnwege durch multiresistente gramnegative Erreger mit Ceftazidim in Monotherapie bei Patienten mit Rückenmarksverletzungen.

In 53 spinal cord injury patients with neurogenic bladder suffering from severe infections caused by multiresistant gram-negative pathogens, treatment with ceftazidime at a fixed dosage schedule of 2 g i.m. for seven days, yielded an overall cure rate of 86.5%. In view of the fact that 28 episodes (52.8%) of acute infection were caused by highly resistant strains of Pseudomonas aeruginosa and considering the many aggravating factors due to the recent polytrauma and paraplegia, we consider the therapeutic results as highly satisfactory. In spinal cord injury patients in whom urinary tract infections are notoriously difficult to cure, repetitive therapy with the potentially nephrotoxic aminoglycosides should be avoided. Ceftazidime offers a valuable alternative with minimal risk of drug toxicity.

CLS 2210, hyaluronidase and the cardiac lymphatic system.

Earlier studies have shown that hyaluronidase exerts a potent influence upon the lymphatic system of the myocardium and that it reduces the size of myocardial infarcts after coronary occlusion. In this study we compared, in mongrel dogs, the effect of intravenous hyaluronidase or CLS 2210 upon the cardiac lymphatic vessels. We observed that in CLS 2210-treated animals the number of visualized cardiac lymphatic vessels was significantly higher than in the hyaluronidase-treated control group. We have previously demonstrated a cardioprotective effect of hyaluronidase in the treatment of acute myocardial infarction. The present experimental data indicate that intravenous CLS 2210 may have a definite role in the management of acute coronary occlusion. Further studies are needed to confirm these preliminary findings.

Computed tomography of the spine and spinal cord; limitations and applications.

The author presents a comprehensive review of the literature on spinal computerized tomography in the evaluation of spinal fractures and fracture-dislocations, degenerative processes with bony encroachment into the spinal canal, disc protrusion, cystic degeneration of the cord, communicating hydro-syringomyelia, intra- and extramedullary neoplasms and congenital malformations. Critical analysis of all published data and additional personal experience gained over the past three years make it possible to better define the clinical applications and practical limitations of spinal CT scans.

Porcine xenografts in the treatment of pressure ulcers.

Porcine heterografts are effective in the treatment of cutaneous ulcers as biological bandages that promote healing by: speeding the processes of granulation and epithelialization; maintaining a clean covering over the wound; reducing loss of fluid and protein; and preventing bacterial encroachment.

Clinical and urodynamic assessment of alpha-adrenolytic therapy in patients with neurogenic bladder function.

The efficacy of alpha-adrenolytic treatment with oral phenoxybenzamine chloride (40 mg per day during three to four months) has been assessed both clinically and urodynamically among 249 patients with neurogenic bladder function. The results were significantly better in patients with autonomous (n = 95) than in the ones with automatic (n = 154) bladders (urethral sphincter spasticity and detrusor sphincter dyssynergia dominating the clinical picture in the latter event). A further striking difference was noticed when the data were analysed with regard to the patient's age, a far better therpeutic response being regularly recorded in subjects below age 35, while minimal and inconsistent improvements were observed in the older age group. No major side effects were encountered. Caution is however required in tetraplegics where phenoxybenzamine may aggravate orthostatic hypotension. On the other side the drug proves highly beneficial in these same patients in that it markedly lowers the incidence of dysreflexic states.

Intra-medullary pressure and intra-osseous phlebography in paraplegia.

Intra-medullary pressure and intra-osseous phlebography have been studied in the femurs of ten paraplegics. These methods are reliable for studying bone circulation. Results show that there exists an increase of intra-medullary pressure of more than twice the normal value and signs of delayed blood flow as well as a diaphyseal reflux in the bone. The blood gases are also modified (O2 saturation; pO2 and pCO2). These signs indicate that there is a venous stasis. These circulatory disturbances are due to an autonomic nervous system lesion. Furthermore it seems that these vascular modifications below the neurological lesion have an influence on the osteoporosis in paraplegia.

Spinal cord involvement in systemic lupus erythematosus.

A review is made of the literature on central nervous system involvement in systemic lupus erythematosus (CNS-SLE). Particular attention is focused on lupus myelopathy. Referring to two well-documented personal cases, the authors describe the characteristic multisystem involvement, protean clinical pattern, serum and cerebrospinal fluid changes, histoimmunologic findings, response to corticosteroids and immunosuppressive agents and some prognostic features.