Continuous CSF drainage in AD: results of a double-blind, randomized, placebo-controlled study.

BACKGROUND: Alzheimer disease (AD) has been associated with abnormal cerebral clearance of macromolecules, such as amyloid and microtubule-associated-protein tau (MAP-tau). We hypothesized that improving clearance of macromolecules from the CNS might slow the progression of dementia. OBJECTIVE: This prospective, randomized, double-blinded, placebo-controlled trial evaluated the safety and effectiveness of a surgically implanted shunt in subjects with probable AD. METHODS: A total of 215 subjects with probable AD by National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria received either a low-flow ventriculoperitoneal shunt or a sham (occluded) shunt for 9 months. Longitudinal CSF sampling was performed in both active and control subjects. Primary outcome measures were the Mattis Dementia Rating Scale and the Global Deterioration Scale. CSF Abeta((1-42)) and MAP-tau also were assayed. RESULTS: After a planned interim analysis, the study was halted for futility. Using the intent-to-treat population, no between-group differences were observed in the primary outcome measures. The surgical procedure and device were associated with 12 CNS infections, some temporally associated with CSF sampling. All were treated successfully. CONCLUSIONS: We found no benefit to low-flow CSF shunting in subjects with mild to severe Alzheimer disease. CSF infections, while treatable, occurred more frequently than expected, in some cases likely related to CSF sampling.

Fenoldopam, a dopamine agonist, for hypertensive emergency: a multicenter randomized trial. Fenoldopam Study Group.

UNLABELLED: Despite successful therapies for chronic hypertension, hospital admissions for hypertensive emergency more than tripled between 1983 and 1992. OBJECTIVE: To examine the safety and efficacy of fenoldopam, the first antihypertensive with selective and specific action on vascular dopamine (DA1) receptors, in a clinical trial involving emergency department patients with true hypertensive emergencies. METHODS: Patients with a sustained diastolic blood pressure (DBP) of > or =120 mm Hg and evidence of target organ compromise were randomized in a double-blinded manner to one of four fixed doses of intravenous fenoldopam (0.01, 0.03, 0.1, or 0.3 microg/kg/min) for 24 hours. The primary endpoint was the magnitude of DBP reduction in each of the three higher-dose groups after four hours of fenoldopam treatment compared with the lowest-dose group. RESULTS: One hundred seven participants from 21 centers were enrolled, and 94 patients received fenoldopam. Evidence of acute target-organ damage included new renal dysfunction or hematuria (50%), acute congestive heart failure or myocardial ischemia (48%), and papilledema or grade III-IV hypertensive retinopathy (34%). The DBP decreased in a dose-dependent fashion, with significant differences between the 0.1- and 0.3-microg/kg/min groups compared with the lowest-dose group. Treatment was well tolerated, and there were no deaths or serious adverse events during follow-up, up to 48 hours. All patients were successfully transitioned to oral or transdermal antihypertensives with maintenance of blood pressure control. CONCLUSIONS: Fenoldopam safely and effectively lowers blood pressure in a dose-dependent manner in patients with hypertensive emergencies. Observations supporting potential risk factors for hypertensive emergency are discussed.

[Relevant differences after post-traumatic and degenerative humeral head replacement (intermediate-term results)]. / Relevante Unterschiede nach posttraumatischem und degenerativem Humeruskopfersatz (mittelfristige Resultate).

INTRODUCTION: In a comparative study, mid-term findings after posttraumatic and degenerative hemi-prosthetic shoulder joint replacement were analyzed and compared with current reports in the literature. METHODS: The patient sample in the retrospective study consisted of 20 patients with proximal fractures of the humeral head (x = 64 years) and 6 patients (x = 61 years) with degenerative shoulder joint disease. In 14 patients the humeral head was replaced as a primary procedure at < 4 weeks after the trauma and in 6 patients as a secondary treatment at > 4 weeks. The follow-up period was 38-41 months on average. Evaluation was based on the Constant Score, subjective assessment by the patient, and conventional radiographs. RESULTS: After posttraumatic shoulder replacement, the patients achieved a Constant Score of 65 (+/- 19) and after degenerative replacement 74 (+/- 34) points. In the posttraumatic group, the Constant Score after primary implantation was better than after secondary implantation (68 +/- 16 versus 59 +/- 15 points). After posttraumatic replacement, the only improvement over time was in pain levels (p < 0.05). 92% of all patients were satisfied with the result and would accept the same treatment again. Radiologically, a clinical correlate could be found for the arrosions at the acromion and occasionally for the secondary upwards displacement of the humerus. The results correlated well with data from the literature. CONCLUSIONS: For posttraumatic conditions, hemiarthroplasty led to better results within four weeks and seemed to be a suitable alternative to other procedures, especially in older patients. Patients with primary osteoarthritis and idiopathic humeral head necrosis can expect good to excellent results after hemiarthroplasty. In both groups, the overall results depend mainly upon patient compliance and the state of the rotator cuff.

The effects of fenoldopam, a selective dopamine receptor agonist, on systemic and renal hemodynamics in normotensive subjects.

OBJECTIVE: Acute renal failure, frequently a consequence of renal vasoconstriction and subsequent renal ischemia, is a common problem for which no proven preventive or therapeutic agents exist. Fenoldopam is a new, selective, dopamine-1 receptor agonist that causes both systemic and renal arteriolar vasodilation. In hypertensive patients, fenoldopam rapidly decreases blood pressure, increases renal blood flow, and maintains or improves the glomerular filtration rate. We sought to determine a dose of fenoldopam that increases renal blood flow without inducing hypotension in normotensive patients and to explore the role of volume status (sodium replete vs. deplete) in these effects. DESIGN: Randomized, double-blind, placebo-controlled, cross-over study. SETTING: Clinical research unit. PATIENTS: Fourteen normal male volunteers. INTERVENTIONS: Renal plasma flow (para-aminohippurate clearance) and glomerular filtration rate (inulin clearance) were measured during three fixed, escalating doses of fenoldopam (0.03, 0.1, and 0.3 Lg/kg/min) on both a high-sodium and a low-sodium diet. MEASUREMENTS AND MAIN RESULTS: Fenoldopam significantly increased renal plasma flow in a dose-dependent manner compared with placebo: 670 + 148 vs. 576 + 85 mUmin at 0.03 iLg/kg/min; 777 + 172 vs. 579 + 80 mUmin at 0.1 tig/kg/min; and 784 + 170 vs. 592 + 165 mUmin at 0.3 ilg/kg/min (p < .05 fenoldopam vs. placebo at all three doses). Glomerular filtration rate was maintained. At the lowest dose (i.e., 0.03 ILg/kg/min), significant renal blood flow increases occurred without changes in systemic blood pressure or heart rate. At 0.1 and 0.3 Lgl/kg/ min, systolic blood pressure did not change, but diastolic blood pressure was slightly lower in the fenoldopam group than in the placebo group: 62.5 + 6.4 vs. 63.6 + 2.6 mm Hg, respectively, at 0.3 tg/kg/min (p < .05). None of the effects of fenoldopam were altered by volume status. CONCLUSIONS: Fenoldopam increased renal blood flow in a dose-dependent manner compared with placebo, and, at the lowest dose, significantly increased renal blood flow occurred without changes in systemic blood pressure or heart rate. These findings will be useful in designing future studies exploring the role of fenoldopam in preventing or treating renal failure in patients who are not hypertensive.

[Leg pain from the orthopedic viewpoint]. / Der Beinschmerz aus orthopädischer Sicht.

The purpose of this paper is to analyze the etiology of pain in the lower limb provoked by the locomotor apparatus. Vertebral, pseudoradicular, radicular syndromes, the hip pain including the acetabular rim syndrome, the generally localized knee and foot pain are discussed. Major symptoms and clinical findings necessary for an effective differential diagnosis of the lower limb pain are pointed out.

[Subtalar arthrodesis--minimal resection technique]. / Subtalare Arthrodese--Minimale Resektionstechnik.

INTRODUCTION: This is a prospective clinical and radiological study of the treatment of talocalcaneal deformity or degeneration by a modified technique of isolated talocalcaneal fusion. METHODS: Thirty-six patients were evaluated with clinical examination, plain dorso-plantar and oblique x-rays and CT-scan or magnetic resonance imaging in a follow-up of 32.5 months (range: 20-62). In 12 cases a posterior tibial tendon rupture with secondary osteoarthritis and in 24 cases a posttraumatic secondary osteoarthritis (18 calcaneal fractures, 3 talar fractures, 2 axial traumas with secondary talar necrosis and 1 rheumatoid arthritis with calcanear and talar fracture) were the indications for arthodesis. RESULTS: On a visual analog pain scale the patients graded their pain preoperatively at 4.4 and postoperatively at 1.1. The subjective results showed in 12 cases (33.3%) complete satisfaction, in 10 cases (27.7%) satisfaction with minor reservation, in 11 cases (30.5%) satisfaction with major reservation and in 3 cases (8.5%) dissatisfaction. The overall objective results were excellent in 17 (47.2%), good in 11 (30.5%), fair in 6 (16.8%) and poor in 2 (5.5%) cases. A further advantage of this type of talocalcaneal fusion is the remaining range of motion in the neighbouring joints, at the ankle (in 75.7% the same or better ROM than preoperatively) and at Chopart joint (in 69.4% the same or better ROM than preoperatively). The fusion rate was high with 94.5%. CONCLUSION: The modified isolated talocalcaneal fusion without disruption at the Chopart joint is a simple surgical technique in the hand of the experienced surgeon. The subjective and objective mid-term results of this prospective follow-up study are comparable to other technique described in literature.

Isolated talocalcaneal interposition fusion: a prospective follow-up study.

This is a prospective clinical and radiological study of the treatment of talocalcaneal deformity or degeneration by a modified technique of isolated talocalcaneal fusion. Thirty-six patients were evaluated with clinical examination, plain dorsoplantar and oblique radiographs, and computed tomography scanning or magnetic resonance imaging in a follow-up of 32.5 months (range, 20-62 months). Indications for arthrodesis were posterior tibial tendon rupture with secondary osteoarthritis (12 cases) and secondary posttraumatic osteoarthritis (24 cases). On a visual analog pain scale, the patients graded their pain at 4.4 before surgery and at 1.1 after surgery. The subjective results were 33% complete satisfaction, 28% satisfaction with minor reservation, 31% satisfaction with major reservation, and 9% dissatisfaction. The overall objective results were excellent in 47%, good in 31%, fair in 17%, and poor in 6% of cases. A further advantage of this type of talocalcaneal fusion is a large remaining range of motion in the neighboring joints, at the ankle (in 76% the same or better ROM than before surgery), and at Chopart's joint (in 69% the same or better ROM than before surgery). The fusion rate was high (95%).

Sympatholysis after neuron-specific, N-type, voltage-sensitive calcium channel blockade: first demonstration of N-channel function in humans.

SNX-111 is the first neuronal N-type, voltage-sensitive calcium channel (VSCC) blocker to enter clinical drug development. Areas of potential therapeutic utility include treatment of nociceptive and neuropathic pain and neuroprotection after ischemic brain injury. The data presented demonstrate that SNX-111 is biologically active in humans and indicate for the first time a neurophysiologic function of N-type VSCCs in humans.

[Comparison between magnetic resonance imaging and arthroscopy for the diagnosis of knee meniscal lesions]. / Comparaison entre l'imagerie par résonance magnétique et l'arthroscopie pour le diagnostic des lésions méniscales du genou.

PURPOSE OF STUDY: The authors evaluated the use of MR-imaging of the menisci compared to arthroscopy considered as the gold standard by which all noninvasive imaging procedures of the knee have to be measured. MATERIAL AND METHODS: In a prospective study, we evaluated the use of MRI in 50 patients with clinically suspected disorders of the meniscus, followed by an arthroscopic examination by an experienced arthroscopist. MRI studies were performed after clinical evaluation and were interpreted by an experienced radiologist, who had no knowledge of the clinical findings. RESULTS: The accuracy of the diagnosis from MRI was 78 per cent for the medial meniscus (sensitivity 79 per cent and specificity 78 per cent) and 94 per cent for the lateral meniscus (sensitivity 50 per cent and specificity 98 per cent). The average age of the patients was 34 years, with a range from 3 to 73 years. The imaging studies revealed 9 false positive test and suggested that the meniscus was either degenerated or form in the horizontal plane. In all 9 menisci the abnormal MR imaging signal was limited to the posterior horns. The positive predictive value was 59 per cent and the negative predictive value was 94 per cent representing a moderate level of diagnostic certainty, both in patients who had a positive result and in those who had a negative result. High predictive negative value of MRI indicates that a negative MRI is quite reliable for meniscal lesions. DISCUSSION: Problems of MR-imaging are the popliteus tendon sheath and the transverse ligament. This ligament is seen in association with a large branch of the lateral inferior geniculate artery, and may be mistaken for a grade 3 signal intensity in the anterior horn of the lateral meniscus. CONCLUSION: A normal MRI allows to eliminate a meniscal lesion and so there is no need for a diagnostic arthroscopy. But with a pathologic MRI there is a risk to establish too often the diagnostic of a meniscal lesion rather then to identify structural modifications as a degeneration.

[Juvenile hallux valgus]. / Der kindliche Hallux valgus.

Juvenile bunions have different etiologies and require specific operative approaches. Any operative procedure to correct a juvenile hallux valgus deformity should correct all the components of the deformity, i.e. pronation of the hallux, the increased hallux valgus angle, the enlarged medial eminence, the increased intermetatarsal angle, and hypermobility or obliquity of the first metatarso-cuneiform joint with the intention of decreasing the rate of recurrence.

[Surgical fusion of the subtalar joint--changing concepts in changing times]. / Versteifungseingriffe am unteren Sprunggelenk--wechselnde Konzepte im Wandel der Zeit.

Triple arthrodesis respects the functional unit of the subtalar joint, but shows several intraoperative difficulties such as surfaces of resection that are too large or wrong positions between the hind and the middle foot. Furthermore postoperative problems like walking on uneven pavements, a reduced range of motion in the adjacent joints and the development of osteoarthritis of the ankle are not easy to deal with. Therefore isolated fusions of the talocalcaneal, talonavicular and calcaneo-cuboidal joint with a minimal resection technique seem to present several advantages. Among them we would mention a minimal reduction of the range of motion, the preservation of a physiological position of the adjacent joints and the prevention of osteoarthritis in the adjacent joint which rarely appears and when it does only in an asymptomatic form. The subtalar implants and the astragaloplasty as possibilities to treat disorders of the subtalar joint complex are also discussed.

[Socio-professional aspects of ankylosing spondylitis in Switzerland]. / Sozio-professionelle Aspekte der Spondylitis ankylosans in der Schweiz.

In this study, using a questionnaire, data were collected about the disease, the working conditions and problems, the working ability, the unemployment and the invalidity of 1134 patients suffering from ankylosing spondylitis (Bechterew's disease). In 739 cases (65.2%) a statistical evaluation could be made. 62.2% had pain when working; the reasons were most often the long working time, the position at work, and the climatic factors at the workplace. The solutions to working problems were often applied too late or they did not correspond to the needs of the patients with ankylosing spondylitis. Generally the working ability was with 97.3% high and the invalidity with 2.7% low.

[Natural course of juvenile foot deformities]. / Spontanverlauf kindlicher Fussdeformitäten.

The spectrum of normal variations of children's feet is extremely broad and often difficult to separate from pathological conditions. Especially the flexible flatfoot and the pes adductus normally disappear during growth, and even if they do persist up to adult life, they hardly have any pathological significance. It therefore appears proper to see foot deformities of children from the prognosis point of view, that is, to differentiate between a benign, pain-free course of development with no functional restriction even under load, and pathological deformities which systematically require conservative or surgical therapy. However, definite pathological conditions like pes equinovarus, talus verticalis, or foot deformities due to development of defects, without therapy lead in most cases to well-known deformations and often to painful functional disorders. Early detection and treatment can contribute to a favorable prognosis in many cases.

The synthesis and evaluation of macrocyclic gadolinium-DTPA-bis(amide) complexes as magnetic resonance imaging contrast agents.

The authors found that DTPA bis(amide) macrocycles can be prepared in reasonable yields using simple methods and readily available starting materials. Gadolinium complexation is facile and gives rise to monomeric and dimeric species. The "pocket size" influences the solid state structure of the final complex, with Gd-DTPA-EAM existing as a dimer wherein the macrocycle bridges between two metal centers. Increasing the size of the bridging diamide moiety yields a macrocycle with a sufficiently large pocket to allow for the formation of nine-coordinant monomeric complexes. The solution behavior of all the complexes studied is consistent with the complex being present as monomers. All complexes display kinetic lability comparable to Gd-DTPA-BMA. The measured KTherm and KSel values of the complexes vary with the size of the pocket. Values similar to those observed for Gd-DTPA-BMA have been obtained with Gd-DTPA-OAM. There appears to be a good correlation between log K(Gd/Zn) and the acute toxicity for the complexes studied, with Gd-DTPA-OAM showing a toxicity value similar to that of Gd-DTPA-BMA. Although many of these complexes are chemically interesting, they do not offer any unique advantages as new magnetic resonance imaging contrast agents compared with the DOTA- and DTPA-based products currently used clinically.

[Epidemiological aspects of ankylosing spondylitis]. / Epidemiologische Aspekte der Spondylitis ankylosans.

Epidemiological aspects of ankylosing spondylitis of the pre- and post-HLA-B27-area are shortly presented. The prevalence, the incidence and the mortality of the disease are mentioned. The non specific risk factors such as age, sex, familiar clustering and racial distribution are described. The absence of specific risk factors is regretted.

[Correct and incorrect paths in the history of ankylosing spondylitis]. / Wege und Irrwege in der Geschichte der Spondylitis ankylosans.

This article retraces the history of ankylosing spondylitis. While the first part takes into consideration the paleopathological aspects of illness, the second part retains the main stages of the research on the subject from the 16th to the 19th century. This part refers to B.O. Connor, who in 1694 was the first to give a complete description of a characteristic skeleton. This part also mentions Benjamin Brodie who in 1850 wrote the first complete clinical description and Charles Fagge who in his work was the first to combine clinical and anatomical elements. The scientific discussion at the end of the 19th century between Adolf Strümpell. Wladimir von Bechterew and Pierre Marie is also part of this paragraph. The last part shows the important discoveries of the 20th century, specially useful for a better understanding of the pathogenesis of the disease.