Combination of TMS and fMRI reveals a specific pattern of reorganization in M1 in patients after complete spinal cord injury.

PURPOSE: After a spinal cord injury (SCI), which was complete, deafferentation of the body representation caudal to the lesion height results in drastic changes in the cortical representation. The underlaying processes are poorly understood. METHODS: We investigated cortical representation sites of upper limb muscles using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) in five patients suffering from thoracic complete SCI and one with an incomplete SCI in the height of L1. RESULTS: In comparison to healthy controls fMRI demonstrated a displacement of elbow movement representations in the precentral gyrus in patients with complete SCI into the direction of the deafferented cortical thoracic representation. Changes increased with time after the incidence of SCI. TMS revealed reduced excitability and prolonged silent periods for muscles more distant to the deafferented area. CONCLUSIONS: Whereas fMRI demonstrated changes in representation sites adjacent to the deafferented area, TMS excitability changes were also observed more distant to the deafferented area and silent periods were prolonged in comparison to healthy controls. TMS changes might depend on both: the distance to the deafferented area and the time of persistence of deafferentation.

Analgesic effect of fluproquazone in postoperative patients.

In 4 double-blind, randomized, stratified, parallel group studies, single oral doses of fluproquazone (75 to 200 mg), a new nonsteroidal anti-inflammatory analgesic, were compared with aspirin (1,000 mg) and placebo in a total of 672 hospitalized patients with moderate or severe pain following episiotomy or other surgical interventions. A dose-dependent effect of fluproquazone which was highly significantly superior to placebo and which resembled the effect of aspirin with respect to onset, degree, and duration was noted in all studies. Fluproquazone, 100 to 150 mg, was found to be approximately equiactive to 1,000 mg of aspirin and better tolerated.

Reorganization in the primary motor cortex after spinal cord injury - A functional Magnetic Resonance (fMRI) study.

Activation maps in the primary motor cortex (M1) were investigated in three patients with complete spinal cord injury (SCI) at level TH3, TH7 and TH9 and in one patient with an incomplete spinal cord injury at level L1 during right elbow (4 patients), right thumb (4 patients), bilateral lip (2 patients) and right foot (3 patients during imagined, 1 patient during executed) movements using functional Magnetic Resonance Imaging (fMRI). Compared to controls fMRI activation maps of patients with complete paraplegia showed a cranial displacement of the activation maxima in the contralateral primary motor cortex during elbow movement of 13.3mm, whereas the maxima of thumb and lip movements were not altered. The patient with an incomplete spinal cord injury revealed no displacement of elbow activation maxima. The reorganization is likely to occur on the cortical and not on the spinal level.

Sonographic patterns of ovarian tumors: prediction of malignancy.

Four hundred four women with suspected pelvic masses or histories suggesting ovarian cancer (eg, low abdominal pain) entered a prospective study designed to assess the accuracy of sonography in confirming or excluding the presence of ovarian cancer. Three hundred twelve of these patients were operated on and evaluated within three weeks after sonography. The predictive value of the sonographic evidence of malignancy was 73% (38 of 52 patients), whereas benign tumors were predicted correctly in 95.6% (177 of 185). Sonographic reassessment of masses with patterns suggesting benign disease may be an alternative to immediate surgical exploration in a selected population (ie, those with poor surgical risk). The sonographic detection of ovarian malignancy requires further improvement; as a diagnostic tool it continues to present a challenge.

Motor thresholds in humans: a transcranial magnetic stimulation study comparing different pulse waveforms, current directions and stimulator types.

OBJECTIVES: To evaluate the stimulation effectiveness of different magnetic stimulator devices with respect to pulse waveform and current direction in the motor cortex. METHODS: In 8 normal subjects we determined motor thresholds of transcranial magnetic stimulation in a small hand muscle. We used focal figure-of-eight coils of 3 common stimulators (Dantec Magpro, Magstim 200 and Magstim Rapid) and systematically varied current direction (postero-anterior versus antero-posterior, perpendicular to the central sulcus) as well as pulse waveform (monophasic versus biphasic). The coil position was kept constant with a stereotactic positioning device. RESULTS: Motor thresholds varied consistently with changing stimulus parameters, despite substantial interindividual variability. By normalizing the values with respect to the square root of the energy of the capacitors in the different stimulators, we found a homogeneous pattern of threshold variations. The normalized Magstim threshold values were consistently higher than the normalized Dantec thresholds by a factor of 1.3. For both stimulator types the monophasic pulse was more effective if the current passed the motor cortex in a postero-anterior direction rather than antero-posterior. In contrast, the biphasic pulse was weaker with the first upstroke in the postero-anterior direction. We calculated mean factors for transforming the intensity values of a particular configuration into that of another configuration by normalizing the different threshold values of each individual subject to his lowest threshold value. CONCLUSIONS: Our transformation factors allow us to compare stimulation intensities from studies using different devices and pulse forms. The effectiveness of stimulation as a function of waveform and current direction follows the same pattern as in a peripheral nerve preparation (J Physiol (Lond) 513 (1998) 571).

Maculopathy in patients with diabetes mellitus type 1 and type 2: associations with risk factors.

AIM: To examine possible relation between diabetic maculopathy and various risk factors for diabetic complications in patients with diabetes mellitus type 1 and type 2. METHODS: Cross sectional study of two cohorts of diabetic patients, comprising 1796 patients with type 1 diabetes (mean age 47 years, mean duration of diabetes 24 years) and 1563 patients with type 2 diabetes (mean age 62 years, mean duration of diabetes 16 years). Retinopathy levels (R0-RV) and maculopathy were assessed by fluorescence angiography and fundus photography and binocular biomicroscopy. Diabetic neuropathy was assessed by means of computer assisted electrocardiography and by thermal and vibratory sensory examination. Patients were classified as normoalbuminuric (<20 microg/min) or microalbuminuric (20-200 microg/min) according to their albumin excretion rates measured in urine collected overnight. Using univariate analyses, the effects of selected patient characteristics on the presence of maculopathy were evaluated. Multiple logistic regression analyses were performed to determine independent effects of risk variables on diabetic maculopathy. RESULTS: Background retinopathy (RII) was found to be present in 28% of type 1 diabetic patients and in 38% of type 2 diabetic patients. The prevalence of maculopathy in these patients was remarkably high (42% in type 1 and 53% in type 2 diabetic patients). Patients with maculopathy had significantly impaired visual acuity. Multiple logistic correlation analysis revealed that in both types of diabetes maculopathy exhibited independent associations with duration of diabetes and with neuropathy (p <0. 01); in type 1 diabetic patients there were significant associations with age at diabetes onset, serum triglyceride and total cholesterol levels (p <0.05); in type 2 diabetes with serum creatinine levels and with hypertension (p <0.05). CONCLUSIONS: Irrespective of the type of diabetes, diabetic patients with long standing diabetes have a high risk for the development of diabetic maculopathy. Diabetic maculopathy is closely associated with diabetic nephropathy and neuropathy and with several atherosclerotic risk factors which suggests that these factors might have an important role in the pathogenesis of maculopathy. However, prospective trials are necessary to evaluate the predictive value of such factors. The findings of the present cross sectional study reinforce the arguments of previous studies by others for tight control of hypertension and hyperglycaemia.

Acute effects of calcium sodium citrate supplementation of a test meal on mineral homeostasis, oxalate, and calcium oxalate crystallization in the urine of healthy humans--preliminary results in patients with idiopathic calcium urolithiasis.

Calcium, in the form of regular food supplementation, can improve bone metabolism, but it can also increase the risk for renal calcium stones, and may aggravate pre-existing calcium urolithiasis. To study the first of these two aspects, ten healthy volunteers were given a conventional test meal (breakfast; calcium content 28 mg) with or without two dosages of calcium (as calcium-sodium citrate, CSC 1, 680 mg; CSC 2 1,360 mg), taken after an overnight 12 h fast. To study the latter aspect, patients with idiopathic recurrent calcium urolithiasis (ICU) received a balanced test meal of fixed composition, containing 1,000 mg calcium either as CSC (Meal + CSC3; n = 6) or as calcium gluconate (Mcal; n = 8). In normals, CSC induced a dose-dependent increasing intestinal absorption of calcium, and a decrease in oxalate absorption; in serum, CSC increased calcitonin and suppressed parathyroid hormone, but left unchanged the markers of bone turnover, serum osteocalcin and bone alkaline phosphatase. In urine, CSC decreased bone resorption markers (collagen crosslinks) and phosphaturia increased citrate, created signs of metabolic alkalosis, and inhibited several parameters of CaOx crystallization. In ICU, the CSC3 load failed to promote the crystallization of CaOx and calcium phosphate. It was concluded that CSC supplementation of a meal: (1) is well tolerated by healthy subjects and ICU patients, renders calcium highly available to bone, and prevents post-prandial oxaluria from rising; and, (2) is followed by the inhibition of crystallization of renal stone forming calcium-containing substances. Long-term studies aimed at evaluating the usefulness of CSC in preserving healthy bone, and in the metaphylaxis of renal stones would appear justified.

Acute oral calcium-sodium citrate load in healthy males. Effects on acid-base and mineral metabolism, oxalate and other risk factors of stone formation in urine.

The currently preferred calcium preparations for supplementation of food vary widely with respect to calcium availability, effects on systemic mineral metabolism, acid-base status, and the calciuria-induced risk of urinary tract stone formation. In eight healthy males we studied the response to an acute load with alkali(sodium)-containing soluble calcium citrate (CSC) (molar ratio calcium/sodium/citrate approx. = 1/1/1), when taken in three different doses (10, 20, 30 mmol calcium) together with a continental breakfast. Intestinal calcium absorption, serum calcium, calcitonin, parathyroid hormone (PTH) other markers of bone metabolism, net acid excretion and calcium oxalate crystallization in urine were evaluated. CSC evoked a dose-dependent increase in calcium absorption, calcium in serum and urine, but no overt hypercalcemia, and calciuria was low relative to the excess calcium ingested; PTH fell and calcitonin rose (p < 0.05 vs. breakfast alone), but the diet-independent markers of bone resorption declined only insignificantly, while the markers of bone formation and turnover remained unchanged. There was a significant "once-daily" effect (= cumulative 24 h postload response) of CSC: a decrease in urinary cyclic AMP, phosphorus, and ammonium, and an increase in urinary bicarbonate. Soon after CSC intake, urinary calcium oxalate and hydroxyapatite supersaturation increased dose-dependently, the calcium oxalate crystal diameter was increased, but crystal aggregation time, which is crucial for stone formation, remained statistically unchanged. Thus, CSC provides calcium in a bioavailable form, creates mild systemic alkalinisation and inhibition of bone resorption, but leaves the risk of developing urinary stones unchanged. Comparative long-term studies on bone growth and the maintenance of bone health, using alkali-containing versus alkali-free calcium citrate, appear worthwhile.

[Gallstone ileus. A report of 104 cases]. / Der Gallensteinileus. Ein Bericht über 104 Beobachtungen.

An analysis of 104 cases of gallstone ileus in 102 patients is presented. Biliary stones reach the intestinal tract through a biliodigestive fistula in 80-85% and on natural way in 15-20%. Clinical symptoms depend on mechanism of obstruction. It shows 3 forms of course: peritonitical form (20%), remittent form (30%) and typical intestinal obturation (50%). Roentgenological findings show aerobilia in 36%, dystope radiopaque stones in 8% and signs of obstruction in 97% of investigations. The main concern in gallstone ileus should be to relieve the intestinal obstruction and not cholelithiasis. The mortality rate declined during reported time from 40-50% to 25%.

[A clinical approach in neuromuscular diseases in childhood]. / Neuromuskuläre Erkrankungen im Kindesalter: Klinisches Vorgehen.

The group of neuromuscular disorders includes disorders of the motor neurons in the medulla oblongata and myelon, the peripheral nerves, the neuromuscular junction, and of the muscle. Clinical manifestation varies from pre-/perinatal to adulthood. The prevalence of all neuromuscular disorders is about 1:1500. In the last years, knowledge of genetic defects in neuromuscular disorders has dramatically increased. This is due to an increase in knowledge of the underlying genetic defects. Hence the classification of the neuromuscular disorders is still changing. In clinical practice the history and the clinical examination of patients with suspected NMDs is very important in the correct selection of the necessary investigations. Many investigations are possible, but should be chosen according to the patient's symptoms. Careful interpretation of the results most often defines diagnosis. The aim of this article is to establish a work-up according to the patient's symptoms and problems in childhood.

Continuous glucose monitoring reveals associations of glucose levels with QT interval length.

BACKGROUND: QTc interval lengthening during hypoglycemia is discussed as a mechanism linked to sudden death in diabetes patients and the so-called "dead in bed syndrome." Previous research reported a high interindividual variability in the glucose-QTc association. The present study aimed at deriving parameters for direction and strength of the glucose-QTc association on the patient level using combined Holter electrocardiogram (ECG) and continuous glucose monitoring. METHODS: Twenty type 1 diabetes patients were studied: mean (SD, range) age, 43.6 (10.8, 22-65) years; gender male (n [%]), 10 (50.0%); mean (SD) hemoglobin A1C, 8.5% (1.0%); and impaired hypoglycemia awareness (n [%]), six (30.0%). Continuous interstitial glucose monitoring and Holter ECG monitoring were performed for 48 h. Hierarchical (mixed) regression modeling was used to account for the structure of the data. RESULTS: Glucose levels during nighttime were negatively associated with QTc interval length if the data structure was accounted for (b [SE] = -0.76 [0.17], P = 0.000). Exploratory regression analysis revealed hypoglycemia awareness as the only predictor of the individual strength of the glucose-QTc association, with the impaired awareness group showing less evidence for an association of low glucose with QTc lengthening. CONCLUSIONS: Mixed regression allows for deriving parameters for the glucose-QTc association on the patient level. Consistent with previous studies, we found a large interindividual variability in the glucose-QTc association. The finding on impaired hypoglycemia awareness patients has to be interpreted with caution but provides some support for the role of sympathetic activation for the QTc-glucose link.

A syringe exchange programme in prison as prevention strategy against HIV infection and hepatitis B and C in Berlin, Germany.

In two prisons in Berlin, Germany, provision of sterile injection equipment for injecting drug users (IDUs) started in 1998. To assess the programme's impact, the frequency of injecting drug use and syringe sharing, and the incidence of HIV, HBV, and HCV infection were determined in a follow-up study. Of all IDUs (n=174), 75% continued to inject. After the project start the level of syringe sharing declined from 71% during a 4-month period of previous imprisonment to 11% during the first 4 months of follow-up, and to virtually zero thereafter. Baseline seroprevalences for HIV, HBV, and HCV were 18, 53, and 82%. HIV and HCV seroprevalence at baseline was significantly associated with drug injection in prison prior to the project start. No HIV and HBV seroconversions, but four HCV seroconversions occurred. The provision of syringes for IDUs in appropriate prison settings may contribute to a substantial reduction of syringe sharing. However, the prevention of HCV infection requires additional strategies.