Deep Brain Stimulation of the Pallidum is Effective and Might Stabilize Striatal D(2) Receptor Binding in Myoclonus-Dystonia.

PURPOSE: To assess clinical efficacy of deep brain stimulation (DBS) of the pallidum in Myoclonus-Dystonia (M-D) patients, and to compare pre- and post-operative striatal dopamine D2 receptor availability. METHODS: Clinical parameters were scored using validated rating scales for myoclonus and dystonia. Dopamine D2 receptor binding of three patients was studied before surgery and approximately 2 years post-operatively using 123-I-iodobenzamide Single Photon Emission Computed Tomography. Two patients who did not undergo surgery served as controls. RESULTS: Clinically, the three M-D patients improved 83, 17, and 100%, respectively on the myoclonus rating scale and 78, 23, and 65% on the dystonia rating scale after DBS. Dopamine D2 receptor binding did not change after surgery. In the two control subjects, binding has lowered further. CONCLUSION: These findings confirm that DBS of the pallidum has beneficial effects on motor symptoms in M-D and suggest this procedure might stabilize dopamine D2 receptor binding.

Severity of dystonia is correlated with putaminal gray matter changes in myoclonus-dystonia.

BACKGROUND: Myoclonus-dystonia (M-D) is an autosomal dominantly inherited movement disorder characterized by myoclonic jerks and dystonic postures or movements. Morphometric studies have been performed in other, mainly heterogenous, types of dystonia producing conflicting results. However, all these studies agree on abnormalities in sensorimotor structures, mainly in the basal ganglia. We aimed to study gray matter (GM) volumes in sensorimotor brain structures with magnetic resonance imaging (MRI) in a genetically homogeneous form of dystonia, M-D. METHODS: Twenty-five clinically affected DYT11 mutation carriers (MC) and 25 matched control subjects were studied using T1-weighted 3D anatomical images of the entire brain, obtained with a 3.0 Tesla MRI. MC were clinically scored using the Burke Fahn Marsden dsytonia rating scale (BFMDRS) and the unified myoclonus rating scale (UMRS). GM volumes in sensorimotor cortices and basal ganglia of patients and controls were compared, and multiple regression analyses were used to correlate the GM volumes of patients with the clinical rating scales BFMDRS and UMRS. RESULTS: No significant differences were found between groups, but dystonia severity in MC was strongly correlated with increased GM volume in bilateral putamina. CONCLUSIONS: This study provides further evidence for the involvement of putamina as important motor structures in the pathophysiology of (myoclonus-) dystonia. Changes in these structures are associated with the severity of dystonia.

Reduced striatal D2 receptor binding in myoclonus-dystonia.

PURPOSE: To study striatal dopamine D(2) receptor availability in DYT11 mutation carriers of the autosomal dominantly inherited disorder myoclonus-dystonia (M-D). METHODS: Fifteen DYT11 mutation carriers (11 clinically affected) and 15 age- and sex-matched controls were studied using (123)I-IBZM SPECT. Specific striatal binding ratios were calculated using standard templates for striatum and occipital areas. RESULTS: Multivariate analysis with corrections for ageing and smoking showed significantly lower specific striatal to occipital IBZM uptake ratios (SORs) both in the left and right striatum in clinically affected patients and also in all DYT11 mutation carriers compared to control subjects. CONCLUSIONS: Our findings are consistent with the theory of reduced dopamine D(2) receptor (D2R) availability in dystonia, although the possibility of increased endogenous dopamine, and consequently, competitive D2R occupancy cannot be ruled out.

[Small-bowel obstruction as the expression of hereditary non-polyposis colorectal carcinoma]. / Dunnedarmobstructie als uiting van heriditair non-polyposiscolorectaal carcinoom.

A 25-year-old man underwent periodic coloscopy due to the occurrence of colon carcinoma in the family. At the age of 41, a mutation in the MSH2-gene was detected. More than a year after resection of the sigmoid for recurrent diverticulitis, he developed ileus in the small intestine; in the resected specimen of a non-viable portion of small intestine an adenocarcinoma was found. One year after a wide repeat resection, the patient is doing well. The prevalence of small-bowel tumours in patients with hereditary non-polyposis colorectal carcinoma (HNPCC) is relatively high, but low in absolute terms. There are no good options for screening patients for small-bowel tumours. HNPCC patients presenting with complaints that could be due to obstruction should undergo gastroduodenoscopy, coloscopy or, if these yield negative results, wireless capsule endoscopy to reveal obstruction. In case of iron deficiency anaemia or symptoms that cannot immediately be related to an obstruction, one should be careful with a diagnostic laparotomy. In any other case the threshold for a diagnostic laparotomy should be quite low.

Cholecystogastric fistula presenting with haematemesis: diagnosed by endoscopic retrograde cholangiography.

The case is reported of a 72-year-old woman suffering from morbid obesity, who presented with haematemesis while on anti-coagulant therapy. The source of the bleeding proved to be the gastric exit of a cholecystogastric fistula. Subsequent cholangitis was successfully treated by endoscopic retrograde cholangiography (ERC) and endoscopic sphincterotomy (ES) while simultaneously the extent of the fistula was established. Cholecystectomy and closure of the fistula was contraindicated because of her morbid obesity. She remained well for 6 months but then presented with a gallstone ileus while another stone was found to be escaping from the gastric fistula. Her morbid obesity resulted in surgical procrastination, which eventually proved fatal. This patient experienced both of the most common types of complication in cholecysto-enteral fistulation, cholangitis and gallstone ileus. Although cholecysto-enteral fistulas (CEF) are probably less common than several decades ago, they are now most likely to be diagnosed during ERC. Gastroenterologists therefore need to be aware of their potential to contribute to the diagnosis and treatment of this surgical condition.

Delvotest SP for detection of cloxacillin and sulfamethoxazole in milk: IDF interlaboratory study. International Federation Dairy.

Under the auspices of the International Dairy Federation's Group E503, a collaborative study of the Delvotest SP multiplate microbial inhibitor test was performed to gain information about the detection limits of 2 antimicrobial agents (a beta-lactam and a sulfa compound), the variation of test results between users and 2 batches of the test, and the reasons for deviating results. Lyophilized milk samples spiked with various concentrations of cloxacillin or sulfamethoxazole were analyzed. Each substance/concentration combination was tested with each of 2 test batches 14 or 15 times per participating laboratory. Test results were to be read by more than one person and reported on separate forms. Results were obtained from 29 laboratories, which included 5 with no experience and 11 with limited experience with this test. Detection limits for cloxacillin (22.5 or 30 micrograms/kg, depending on batch) and sulfamethoxazole (45 micrograms/kg) were established from dose-response curves. A small difference in cloxacillin detection levels between the 2 test batches was observed. Analyses of samples gave almost unanimous results (> or = 95%). Of deviating results, defined as anomalous results (1.4% of readings), half could be attributed to human errors and half to procedural errors.

Food impaction in a duodenal diverticulum as an unusual cause of biliary obstruction: case reports and review of the literature.

We present two patients with upper abdominal complaints and symptoms of biliary obstruction. Endoscopic retrograde cholangiopancreatography showed that the common bile duct was obstructed by a juxtapapillary duodenal diverticulum filled with a food bezoar. There were no gallstones or other potential causes of obstruction. The bile flow was restored and symptoms disappeared after rinsing the diverticulum. Eventually, both of the patients were treated surgically because of recurrent symptoms.

[African sleeping sickness in The Netherlands]. / Afrikaanse slaapziekte in Nederland.

Of the four most dangerous protozoal infections acquired in (sub)tropical regions, falciparum malaria, amoebic abscess of the liver, visceral leishmaniasis (kala azar) and African trypanosomiasis (sleeping sickness) only the fourth was up to now unreported in the Dutch medical literature. Two case histories are presented: a Cameroonian woman, resident in the Netherlands for two years, suffering from West African type sleeping sickness, and a Dutch tourist who acquired East African trypanosomiasis while travelling through Zimbabwe. Although the parasites are morphologically identical, clinical and epidemiological characteristics are distinctly different. The West African type, rarely if ever observed in Europeans, has an insidious chronic course leading to the features of classical sleeping sickness. Differential diagnosis is difficult. The East African variety runs an acute course in Europeans leading to death within days due to myocarditis. It is therefore mandatory for the diagnosis to be made as soon as possible in order to initiate specific therapy. Both patients recovered after specific therapy.

Pancreatic pseudocyst as a cause of upper gastrointestinal bleeding.

A 67-year-old man with a history of an attack of pancreatitis was repeatedly investigated for recurrent gastrointestinal bleeding necessitating blood transfusions. Routine investigations did not reveal the source of bleeding. Repeated angiograms also were not diagnostic. A hot spot identified on a 99mTc-pertechnate-labelled erythrocyte scan prompted an endoscopic retrograde cholangio-pancreatography (ERCP), which showed bleeding through the papilla of Vater. The source of bleeding appeared to be a small pancreatic pseudocyst. The patient was treated with a duodenopancreatectomy in which the pylorus was preserved. No rebleeding occurred since the operation. Pancreatic pseudocysts must be considered as a source of upper gastrointestinal bleeding in patients with bleeding of "obscure" origin. 99mTc-pertechnate-labelled erythrocyte scanning and ERCP may be helpful, even when angiography is normal.

Oral pharmacokinetics of cyclosporin in patients with primary biliary cirrhosis and patients with skin diseases.

The pharmacokinetics of cyclosporin after oral administration were studied in seven patients with non-end stage primary biliary cirrhosis (PBC) without previous cyclosporin treatment (Group I), a control group of nine patients with skin diseases (mainly psoriasis; Group II) and six patients with PBC after prolonged cyclosporin treatment (Group III). Whole blood concentrations of cyclosporin were measured using a non-specific (N) radioimmunoassay (RIA) and--in a majority of the cases--also by a RIA specific (S) for the parent drug. No difference in cyclosporin absorption was observed between patients with PBC and those with a skin disease. The mean values for the area under the blood concentration-time curve for the first 6 h after the test dose (AUC0-6) and the maximal blood concentrations (Cmax) were significantly higher for Group I compared with Group II patients (P = 0.007 and 0.03, respectively), but the time to maximal blood concentrations (tc,max) did not differ. There was a trend toward higher mean AUC0-6 (P = 0.08) and Cmax (P = 0.08) values for Group III compared with Group I patients. Tc,max values were not influenced by prolonged cyclosporin treatment. The ratio of cyclosporin whole blood concentrations measured by the non-specific and specific RIA's (N/S ratio) increased with time without obvious differences between the three groups. These data suggest that cyclosporin absorption and its biotransformation in the liver are not impaired in patients with non-end stage PBC and that neither is affected by prolonged treatment.

Serial determination of type III procollagen amino propeptide serum levels in patients with histologically progressive and non-progressive primary biliary cirrhosis.

We examined the value of serum procollagen III amino propeptide (PIIIP) for predicting the histological progression of primary biliary cirrhosis (PBC). Serial PIIIP measurements were obtained for nine patients with histologically progressive PBC and nine patients with histologically stable early disease, assessed by repeated liver biopsies and followed for up to 13 years. The means of the follow-up PIIIP concentrations were elevated in 39% of the cases; moreover, PIIIP levels were elevated at least once during follow-up in 72% of the cases. Mean follow-up PIIIP concentrations did not differ significantly between progressive and non-progressive patients. In addition, in the progressive group, histological progression was not reflected by PIIIP levels. No difference was found between the serum PIIIP levels corresponding to the histological stages I, II and III. The individual coefficients of the correlation between serum PIIIP and biochemical variables (bilirubin, alkaline phosphatase, ASAT, albumin) and histology showed a wide distribution without a consistent trend towards positive or negative. Treatment with cyclosporin A or cyclosporin A combined with prednisone did not influence serum PIIIP levels. Treatment with penicillamine combined with prednisone, however, resulted in a significant decrease in PIIIP concentrations (p less than 0.05). We conclude that serum PIIIP measurements are of no value for predicting the histological progression of PBC.

Bone mass in women with primary biliary cirrhosis: the relation with histological stage and use of glucocorticoids.

To assess the impact of primary biliary cirrhosis on bone mass in general and the relative importance of the stage of the liver disease and of treatment with glucocorticoids for the possible development of osteoporosis, bone mineral mass was measured by single and dual photon absorptiometry in 55 unselected female patients with longstanding primary biliary cirrhosis. Although most of the patients had a bone mineral density within the normal range, the bone mineral densities of the lumbar spine and distal and proximal forearm were 8% (P less than 0.004), 8% (P less than 0.03), and 5% (NS) respectively, lower than in age-matched healthy women. Multiple regression analysis showed that the histological stage of the liver disease (early stage vs. late stage) was an independent determinant of axial bone mineral density, whereas the use of glucocorticoids resulted in only a moderate and not significant bone loss. Serum calcium proved to be significantly lower in the patients with late-stage primary biliary cirrhosis than in those with early-stage disease, whereas no significant differences were found in these groups with regard to several biochemical parameters of bone metabolism. In conclusion, in patients with primary biliary cirrhosis, bone loss was only moderate and related to the histological stage. The effect of low-dose glucocorticoids on bone mass seemed not significant.