Sustained-release Madopar HBS compared with standard Madopar in the long-term treatment of de novo parkinsonian patients.

In this Danish-Norwegian randomized double-blind parallel-group multicentre study, we compared the therapeutic response of slow-release Madopar HBS to standard Madopar in 134 de novo patients with idiopathic Parkinson's disease during a 5-year period. The drugs were dosed according to the individual need of the patients. The Webster, NUDS, UPDRS and Hoehn & Yahr scales were used for evaluation of symptoms. Addition of a morning dose of standard Madopar 62.5 mg was allowed after 6 months. Bromocriptine could be administered but not Selegiline. Sixty-five patients got Madopar HBS and 69 standard Madopar. Surprisingly, no differences were found as to the mean daily levodopa dose, the mean number of daily doses or the use of the doses of bromocriptine. Unexpectedly, we found a trend towards a more frequent use of a morning dose of standard Madopar in the group treated with the standard formulation. No differences were observed in the occurrence of motor fluctuations or dyskinesia, the incidence of which was relatively low. Sustained-release Madopar (HBS) thus proved to be as effective as standard Madopar in the long-term treatment of de novo parkinsonian patients, but the drug showed no advantage in postponing or reducing the long-term levodopa treatment problems.

A multicenter review of 839 laparoscopic-assisted vaginal hysterectomies.

A multicenter review of 839 cases of laparoscopic-assisted vaginal hysterectomy (LAVH) was conducted to contribute to the clinical decision-making process regarding the procedure, which has been the subject of much debate in recent years. The results suggest that patients undergoing LAVH experience complication rates no higher than those having any other type of hysterectomy, and that efficacy is identical to that of vaginal hysterectomy. Furthermore, the laparoscopic approach affords better visualization of pelvic pathology and better adnexal access for the accomplishment of concurrent pelvic procedures. Mean hospital stay is 1.7 days and mean recovery time 20 days. The notion of a learning curve as described by diminishing procedure time and declining complication rates over time is not supported by this data set. Patients who may traditionally have faced abdominal hysterectomy due to putative or demonstrated pelvic pathology may benefit the most from LAVH.

Laparoscopic bladder neck suspension using hernia mesh and surgical staples.

A laparoscopic colposuspension technique for the correction of urinary stress incontinence has been described in the recent literature. Herein we describe a laparoscopic adaptation of the Burch procedure, used in the treatment of urinary stress incontinence since 1958. The use of titanium hernia staples and Prolene mesh in place of traditional suture material eliminates the need for laparoscopic suturing in the confined pelvic space, a practice that often poses difficulty for inexperienced surgeons. Of 40 female patients treated, with a mean 6-month follow-up, there has been no relapse of stress incontinence. Complications in this modest population have been minor and self-limiting. As with any laparoscopic procedure, the results obtained here may be influenced by the extensive experience of the laparoscopist.

The neuropathology in toxoplasmosis-like infection caused by a newly recognized cyst-forming sporozoon in dogs.

The pathomorphological changes in the central nervous system associated with an infection with a previously reported, Toxoplasma-like, cyst-forming sporozoon were studied by means of light microscopy, including immunohistochemistry, and transmission electron microscopy in seven dogs, aged 4 months to 2 years. Tachyzoites (endozoites) within parasitophorous vacuoles were found in neurons, astrocytes, macrophages, vascular pericytes and probably also in fibroblasts, while cyst stages were only observed in cells showing features of neurons. Proliferating tachyzoites were associated with lesions of a necrotic/granulomatous type. Perivascular accumulations of lymphocytes and plasma cells, together with an activation of astrocytes and perivascular fibroblasts resulting in marked sclerosis, were prominent features in all cases. The grey matter was most seriously affected in the brain, while the white matter was most often the site of inflammation in the spinal cord. The structural similarity to the newly reported Neospora caninum suggests that we are dealing here with the same parasite. However, the present infection and toxoplasmosis have so many features in common, including the light microscopical morphology of the organisms and host/parasite relationship, that a definite etiological diagnosis should be based on ultrastructural and/or immunohistochemical examinations.

Immuno-histochemical and ultrastructural characteristics of a cyst-forming sporozoon associated with encephalomyelitis and myositis in dogs.

Light-microscopy, including immuno-histochemical staining, and transmission and scanning electron microscopy were applied for the characterization of a Toxoplasma-like parasite associated with encephalomyelitis and myositis in dogs of the boxer breed. Most parasites were tachyzoites, occurring in clusters, up to 60 micron in diameter, in parasitophorous vacuoles of host cells. Cyst stages with a definite cyst wall were few, but could be demonstrated in all cases. Immunostaining with antiserum against Toxoplasma gondii was negative, while both tachyzoites and bradyzoites were stained with serum from affected dogs. Ultrastructurally, the parasite was characterized by a great number of rhoptries, few amylopectin granules, lack of micropores in the tachyzoites, and the occurrence of numerous dense bodies in the bradyzoites. Numerous intravacuolar tubules were present in the space of the parasitophorous vacuole. The cyst wall resembled that of T. gondii. Until a definite host is found, the parasite may be regarded as an "orphan", cyst-forming sporozoon that is ultrastructurally different from other known protozoan parasites. It has a light-microscopical similarity to T. gondii but is antigenically different.

Selegiline (1-deprenyl) and low-dose levodopa treatment of Parkinson's disease. A double-blind crossover trial.

Fifteen parkinsonian patients previously untreated with levodopa were treated with daily doses of 200 mg Madopar and randomized to addition of 10 mg selegiline (1-deprenyl) in a double-blind, placebo controlled, crossover trial. According to the patients own evaluations 6 reported additional therapeutic effect from selegiline to Madopar; 2 reported possible additional effect, whereas a further 6 reported no improvement; 1 did not complete the trial. Statistically significant positive therapeutic effect of selegiline could not be found on Webster's rating scale or on a sensimotoric test designed for parkinsonian disabilities. Side effects of selegiline were minimal. It is concluded that selegiline may be of some value in addition to levodopa in early treatment of parkinsonian patients, but positive therapeutic effect has to be tested individually. Even in these patients the additional therapeutic effect of selegiline to levodopa seems to be quantitatively small.

Effects of denervation, immobilization and cachexia on fibre size in the anterior tibial muscle of the rat.

The effects of denervation, immobilization and cachexia on the size of the various histochemical fibre types were studied in the anterior tibial muscle of male Wistar rats aged 60-100 days. Denervation was induced by unilateral sectioning of the sciatic nerve, immobilization by a plaster cast on one hindlimb and cachexia by restriction of food intake. In the anterior tibial muscle of the normal rat, three fibre types can be identified by myofibrillar ATPase stain after alkaline preincubation. These fibres were called dark (D-fibres), intermediate (I-fibres) and light fibres (L-fibres), respectively. The I-fibres correspond to the fast-twitch type 2 fibres and the L-fibres to the slow-twitch type 1 fibres. The D-fibres have intermediate characteristics, but they probably belong to the type 2 group. The three fibre types reacted differently to denervation, immobilization and cachexia. Denervation caused progressive atrophy of the D- and I-fibres and almost no change of the L-fibres. Immobilization caused minor reduction in size of the D- and I-fibres during the first days and no change thereafter, whereas the L-fibres showed transitory hypertrophy. Cachexia, on the other hand, resulted in progressive atrophy of all three fibre types but a predominant affection of the D- and I-fibres. The different susceptibilities of the various fibre types suggest different mechanisms for atrophy of muscle in these three conditions.

Randomized double-blind cross-over study of iohexol and Amipaque in cerebral angiography.

Iohexol was compared with Amipaque (metrizamide) in a double-blind study in one pair of injections in each of 20 patients referred for routine cerebral angiography. Catheter position, patient position, injection pressure, contrast medium volume, and concentration (300 mg l/ml) were the same in the two injections, with iohexol and Amipaque being used alternately. Except for these two injections iohexol was used throughout. The parameters studied included diagnostic information obtained (quality of the examination), circulation time, and comparison of patient reactions to the pair of injections (e.g., electrocardiogram, heart rate, and subjective reactions). The patients' reactions to the noncomparative part of the examination were evaluated also, and the patients were observed for possible adverse reactions after the examination. No difference could be detected between the two contrast media in this series. No serious adverse reactions occurred.

Deprenyl (selegiline) combined with levodopa and a decarboxylase inhibitor in the treatment of Parkinson's disease.

The purpose of this double-blind placebo controlled study was to estimate how much the levodopa dosage can be reduced, when deprenyl is used, without worsening the disease and to see whether deprenyl can reduce the "off-periods". The trial included 40 patients of both sexes with at least 3 years history of Parkinson's disease who were undergoing stabilized levodopa therapy. The deprenyl dosage was 5 mg daily in the first 4 weeks. The levodopa dosage was reduced until there was demonstrable impairment. The trial demonstrates that with deprenyl the levodopa dosage can be reduced considerably without prejudicing the therapeutic outcome. Some patients showed improvement, and the "off-periods" were reduced in many cases.

Cerebral angiography with iohexol. A multicentre clinical trial.

An open multicentre clinical trial with the new non-ionic contrast medium iohexol is reported. A total of 38 adult patients were included in the series. No serious side effects or complications occurred. The impression was that subjective reactions were less marked with iohexol than what is usually observed with conventional ionic contrast media.

Dopaminergic agonist Ro 8-4650 in Parkinson's disease. II. Patients not treated with dopa.

An isoquinolone derivative Ro 8-4650 (rac-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-7-methoxy-2-methylisoquinoline hydrochloride) with dopaminergic properties was studied in a randomized crossover trial. The group studied comprised 37 patients with idiopathic parkinsonism, not previously treated with levodopa or dopamin agonists. The trial drug was significantly more effectve than placebo, but the clinical improvement, according to the Webster rating scale, was small. No significant difference was observed as regards involuntary movements, but the trial drug led to more frequent minor side effects. It can be concluded that the trial drug, despite its proven effect in Parkinson's disease, has only limited clinical value.

Diagnostic problems in extrapyramidal disorders.

The diagnostic problems of extrapyramidal disorders (ED) are reviewed. Many of the wide range of ED occur rarely, and clinical experience is difficult to obtain. Despite great advances in pathophysiology and pathological anatomy the diagnosis of ED is still mainly a clinical diagnosis, and the diagnostic problems are discussed principally in relation to the involuntary movements and partly with regard to muscle tone. Except in a few diseases, biochemical and microbiological analyses, EEG, EMG and X-ray examinations offer little contribution to the solution of diagnostic problems in these disorders.

Parkinson's disease treated with Sinemet or Madopar. A controlled multicenter trial.

92 patients with Parkinson's disease not previously treated with levodopa were considered as eligible for this triple-blind trial. Patients were allocated at random to treatment with either levodopa + benserazide ratio 4:1 (Madopar) or levodopa + carbidopa ratio 10:1 (Sinemet) using dosage schedules recommended by the manufacturers which they had to adhere to for 6 months. Unless prohibitive side-effects occurred daily maximum dosage of 800 mg levodopa + 200 mg benserazide respectively 1,500 mg levodopa + 150 mg carbidopa were obtained after 6 weeks and 3 weeks, respectively. The effect of the two schedules on the Parkinsonian symptoms were equal and appeared equally fast. The frequency of gastrointestinal side-effects and involuntary movements were significantly higher and more severe for Sinemet than for Madopar. These side effects are usually symptoms of levodopa overdosing, but whether or not a different dosage schedule with Sinemet would have given fewer side-effects without concurrent lower efficacy remains open to speculation. The treatment schedules did not differ with regard to other side-effects and influence on blood pressure. Neither treatment seemed to influence liver function, renal function and hematological parameters in a statistically way.

Metrizamide, the new water-soluble non-ionic contrast medium for myelography. Clinical experience.

A survey is made of the development of water-soluble contrast media and of the experimental and preliminary clinical investigations of the new water-soluble contrast medium metrizamide. The experiences with the medium indicate that its use in the subarachnoid space is safe and reliable.

Levodopa alone and in combination with a peripheral decarboxylase inhibitor benserazide (Madopar) in the treatment of Parkinson's disease: A controlled clinical trial.

A combination of levodopa and the extracerebrally acting decarboxylase inhibitor benserazide (ratio 4:1) (Madopar), was compared with levodopa alone in a controlled double-blind clinical multicenter trial on 94 patients with Parkinson's disease. During 4 months of therapy levodopa + benserazide proved superior to levodopa on several accounts. Nausea and vomiting occurred with statistically significant less severity and frequency. Clinical improvement expressed through improvement in Webster rating occurred sooner and was all together greater. The treatment schedules did not differ with regard to other side effects, in particular involuntary movements and reduction in supine blood pressure. Neither treatment seemed to influence liver function, renal function and hematological parameters.