Biomedical subjects

M Groeneweg

Publications and source records attributed to M Groeneweg.

11 recordsLinked to original sources

PubMed2005

[Acute abdominal pain as the first sign of Henoch-Schönlein purpura; a hidden diagnosis in the absence of purpura].

2 girls with abdominal pain, aged 7 and 9 years, were admitted and underwent extensive evaluation: the first girl underwent colonoscopy and the second appendectomy, in which a negative appendix was removed. After 6 and 14 days, respectively, they developed skin lesions that did not disappear on pressure, characteristic of Henoch-Schönlein purpura (HSP). They recovered after treatment with prednisone. HSP is a systemic vasculitis, which can be diagnosed by its characteristic purpura of the skin. Diagnosis is more difficult if the patient does not present with skin lesions. HSP presenting with acute abdominal pain as an initial symptom can give rise to unnecessary additional investigation and even laparotomy. Apart from the other clinical features of HSP, i.e. bloody stools, oligo-articular arthritis and (microscopic) haematuria, diagnosis can be made earlier if biopsies of the normal skin or duodenum are taken and assessed for IgA depositions. Treatment of the abdominal pain with corticosteroids can be considered.

Abdominal Pain↗

PubMed2003

[From gene to disease; CD40 ligand deficiency as the cause of X-linked hyper-IgM-syndrome].

X-linked hyper-IgM syndrome (XHIM) is a rare congenital immunodeficiency disorder, characterised by a defect in both humoral and cellular immune responses. In XHIM, the membrane glycoprotein CD40 ligand (expressed on activated T-cells) is deficient, which compromises T-cell interactions with antigen-presenting cells. Patients with XHIM present with severe, recurrent infections, predominantly of the respiratory and gastrointestinal tract. The gene encoding the CD40 ligand is located on the long arm of the X chromosome.

CD4-Positive T-Lymphocytes↗

PubMed2003

[Two children with severe recurrent infections and the X-linked hyper-IgM syndrome].

A boy suffered from severe recurrent intestinal infections from the age of 8 months onwards; investigation into an immune disorder ultimately resulted in the diagnosis of 'hyper-IgM syndrome'. He was treated successfully with bone marrow transplantation, using an HLA-matched donor. Another boy had severe recurrent respiratory tract infections from the age of 3 months onwards. At the age of 6.5 years, 'hyper-IgM syndrome' was diagnosed. No suitable donor was available. In addition, he developed sclerosing cholangitis and end-stage liver disease, making a combined bone marrow and liver transplantation too risky. He died at 10.5 years of age. X-linked hyper-IgM syndrome is a rare congenital immunodeficiency disorder, characterised by a defect in both humoral and cellular immune responses. Deficiency in the membrane glycoprotein CD40 ligand (expressed on activated T-cells) compromises T-cell interactions with antigen-presenting cells. In a child with severe recurrent infections, and with dysgammaglobulinaemia with a normal or increased IgM level, the diagnosis of 'X-linked hyper-IgM syndrome' should be considered.

Bone Marrow Transplantation↗

PubMed2002

Is it a medical error if we do not screen cirrhotic patients for minimal hepatic encephalopathy?

Minimal hepatic encephalopathy (MHE) refers to subtle neurocognitive and neurophysiological defects in patients with liver cirrhosis without clinical signs of hepatic encephalopathy. Using appropriate diagnostic methods the prevalence of MHE is approximately 25-30%. MHE has clinical significance as it results in a diminished daily functioning, precedes overt hepatic encephalopathy and is associated with a poor prognosis. Treatment with non-absorbable disaccharides can reverse the neurocognitive and neurophysiological defects found in MHE. The failure to diagnose MHE in apparently normal cirrhotic patients could, therefore, be considered a medical error. However, whether treatment also improves patients' quality of life and prognosis remains to be determined.

Electrophysiology↗

PubMed2000

Screening of subclinical hepatic encephalopathy.

BACKGROUND/AIMS: Subclinical hepatic encephalopathy adversely affects daily functioning. The aim of this study was to determine which elements of daily life have predictive value for subclinical hepatic encephalopathy. METHODS: The study was performed in 179 outpatients with liver cirrhosis. Subclinical hepatic encephalopathy was diagnosed using psychometric tests with normal values corrected for age (Number Connection Test A and the Digit Symbol Test) and automated analysis of the electroencephalogram (EEG). Daily functioning was measured with the Sickness Impact Profile (SIP), a quality of life questionnaire, containing 136 statements. Patients with and without SHE were compared for differences in response to all statements by univariate analysis, and subsequently by multivariate analysis of potential discriminating statements. RESULTS: SHE was diagnosed in 48 patients (27%). Thirty-six statements were significantly more often true for patients with subclinical hepatic encephalopathy. Multivariate analysis showed that five statements of the SIP, related to alertness, sleep and rest, fine motor skills and work, have independent predictive power for subclinical hepatic encephalopathy. CONCLUSION: Combining these statements predictive for subclinical hepatic encephalopathy with patient characteristics enables physicians to assess the probability of subclinical hepatic encephalopathy in the individual cirrhotic patient at the bedside or in the outpatient clinic.

Electroencephalography↗

PubMed2000

The prognostic significance of subclinical hepatic encephalopathy.

OBJECTIVE: Subclinical hepatic encephalopathy may have prognostic significance with regard to the development of clinical hepatic encephalopathy and survival. METHODS: We studied 116 consecutive patients with histologically proven cirrhosis of the liver for subclinical hepatic encephalopathy, using Number Connection Test A, Digit Symbol Test, and spectral analysis of the electroencephalogram. RESULTS: Twenty-five patients (22%) were diagnosed as having subclinical hepatic encephalopathy. Patients with subclinical hepatic encephalopathy were older, had a higher Child-Pugh score, and more often had esophageal or gastric varices and episode(s) of clinical hepatic encephalopathy in their history. During a median follow-up of 29 months (range, 1-49 months), patients with subclinical hepatic encephalopathy significantly more often had episodes of clinical hepatic encephalopathy; survival, however, was similar to that of patients without subclinical hepatic encephalopathy, and was determined mainly by the Child-Pugh score. The Child-Pugh score was also superior to subclinical hepatic encephalopathy in predicting episodes of clinical hepatic encephalopathy. CONCLUSIONS: The prognostic significance of subclinical hepatic encephalopathy appears limited.

Adolescent↗

PubMed1998

Subclinical hepatic encephalopathy impairs daily functioning.

Subclinical hepatic encephalopathy (SHE) is assumed to have a negative effect on patients' daily functioning; therefore, treatment is recommended. However, no studies have been performed that document the clinical relevance of SHE. We performed a study in which the prevalence of SHE was determined in 179 outpatients with cirrhosis using two psychometric tests (Number Connection Test Part A [NCT-A] and the Digit Symbol Test [DGT]) and automated analysis of the electroencephalogram (EEG). SHE was defined by the presence of at least one abnormal psychometric test and/or abnormal slowing of the EEG. The influence of cirrhosis and SHE on patients' daily functioning was assessed using the Sickness Impact Profile (SIP) questionnaire. The distribution of SIP scores of the patients with cirrhosis differed from the reference scores of the general population. Patients with cirrhosis and SHE (n = 48) reported significantly more impairment in all 12 scales of the SIP, in the psychosocial subscore, the physical subscore, as well as in the total SIP score, compared with cirrhotic patients without SHE (n = 131). Multivariate analysis taking into account severity of liver disease (Child-Pugh score), presence of varices, and alcoholic etiology, showed that SHE independently was related to a diminished total SIP score. The reproducibility of the SIP was high when the test was repeated after a 3-month period. We conclude that SHE implies impaired daily functioning and warrants attempts at treatment.

Adolescent↗

PubMed1996

Effect of flumazenil on the electroencephalogram of patients with portosystemic encephalopathy. Results of a double blind, randomised, placebo-controlled multicentre trial.

The efficacy of the benzodiazepine antagonist flumazenil has been assessed clinically in a double blind, randomised, placebo-controlled multicentre study in patients with grade I-III portosystemic encephalopathy. In an ancillary study reported here the effect of flumazenil on the electroencephalogram (EEG) was analysed in 32 patients who had EEG grading according to protocol. Following the baseline observation period, patients were randomised to receive (at 1 min interval) 3 sequential bolus injections of flumazenil (0.4, 0.8 and 1 mg) or placebo followed by infusions of flumazenil (1 mg/h) or placebo for 3 h. Patients were monitored for 5 h after infusion. A positive response was defined as 1 point improvement in EEG grade. After independent analysis of the EEG gradings 5 out of 17 (29%) flumazenil treated patients showed an improvement in EEG grading (3 after bolus, 2 during follow-up) compared to 2 out of 15 (13%) placebo treated patients (1 after bolus, 1 during follow-up) (95% confidence interval of difference: -12% to + 50%). Of the 5 EEG responders after flumazenil, 3 also had an improvement in clinical PSE grading (none after bolus, 2 during infusion, 1 during follow-up), compared to neither of the 2 EEG responders after placebo. EEg responders did not differ from non-responders with respect to Child-Pugh score, basal EEG, PSE grade and positivity for benzodiazepines. In conclusion, treatment perspectives for flumazenil in portosystemic encephalopathy appear to be present for only a minority of patients; however, this study yields no support for a major role of benzodiazepine antagonists in the treatment of hepatic encephalopathy.

Adult↗

PubMed1996

Evaluation of the efficacy and safety of flumazenil in the treatment of portal systemic encephalopathy: a double blind, randomised, placebo controlled multicentre study.

BACKGROUND: Portal systemic encephalopathy (PSE) is a complex neuropsychiatric syndrome associated with hepatic failure. Small scale studies have shown the benzodiazepine receptor antagonist flumazenil to be effective in ameliorating PSE. AIMS: To determine the efficacy of flumazenil in patients with non-comatous mild to moderate PSE (stages I to III) due to severe chronic liver disease. PATIENTS: 49 male and female adults without symptoms of severe bleeding and sepsis and who screened negative for benzodiazepine in both blood and urine, were included in the study. METHODS: Patients were randomised to receive either three sequential bolus injections of flumazenil (0.4, 0.8, and 1 mg) or placebo at one minute intervals, followed by intravenous infusions of either flumazenil (1 mg/h) or placebo for three hours. Clinical PSE grading and vital signs were assessed hourly during baseline and post-treatment periods and half hourly during treatment. The main outcome measures were improvement in group average PSE score and reduction of two points in individual PSE score (clinically relevant improvement). RESULTS: The mean average improvement in the PSE score in the subjects treated with flumazenil was not statistically significantly different from placebo. However, for patients showing clinically relevant improvement, the difference between flumazenil and placebo was statistically significant (seven of 28 v none of 21; p = 0.015). Flumazenil was well tolerated. CONCLUSIONS: A subgroup of patients with PSE resulting from chronic liver disease may benefit from the administration of flumazenil.

Chronic Disease↗

PubMed1994

Encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit. A clinical and biochemical study.

To study the molecular basis of ammonia toxicity, highly reproducible models of acute liver failure and acute hyperammonemia in the rabbit were developed. Acute liver failure was induced by two-stage liver devascularization, and acute hyperammonemia by prolonged ammonia infusion such that the plasma ammonia pattern found in acute liver failure was simulated. Clinical symptoms, spectral analysis of the EEG, biochemistry (blood gases, renal function, electrolytes and markers of hepatic injury) and the presence of cerebral edema were studied. During acute liver failure severe encephalopathy developed after 10.2 +/- 1.9 h (n = 6, mean +/- SEM). Other liver-failure-associated abnormalities were cerebral edema, lactic acidosis, renal dysfunction, hypothermia and septicemia. During acute hyperammonemia, severe encephalopathy developed after 18.2 +/- 0.4 h (n = 6, mean +/- SEM). Other abnormalities found were cerebral edema and lactic acidosis. In both animal models comparable EEG changes were observed (a decrease in mean dominant frequency and theta-activity, and an increase in delta activity). However, these changes were not statistically significant, and non-specific as they also occurred in control rabbits despite their clinical wellbeing. This study demonstrates in the rabbit the similarity between encephalopathy due to acute ischemic liver failure and that due to hyperammonemia. An observed difference in hyperammonemia-induced encephalopathy was pronounced ataxia, which did not occur during acute liver failure, whereas hypothermia, sepsis and renal failure occurred exclusively in acute liver failure. Our models appear satisfactory for the study of hepatic encephalopathy and ammonia toxicity.

Ammonia↗

PubMed1993

Neuronal and glial marker proteins in encephalopathy associated with acute liver failure and acute hyperammonemia in the rabbit.

Neuronal and glial cell marker proteins were quantified in order to evaluate the possibility of increased proteolysis in the brain of rabbits with acute liver failure and acute hyperammonemia. Acute liver failure was induced by a two-stage devascularization procedure. Acute hyperammonemia was induced by a prolonged infusion of ammonium acetate, which simulates the plasma ammonia level in acute liver failure. Control animals received an infusion of sodium/potassium acetate. After development of severe encephalopathy, the animals were sacrificed (13.7 +/- 1.3 hours for rabbits with acute liver failure and 20.2 +/- 0.8 hours for rabbits with hyperammonemia) (x +/- S.E.M./n = 6) and their brains were dissected into cerebral cortex, hippocampus, cerebellum and brain stem. The total protein content and the concentrations of the neuronal cell marker proteins NSE (neuron specific enolase), NF68 and NF200 (68 kD and 200 kD neurofilament polypeptides) and the glial cell marker proteins GFAP (glial fibrillary acidic protein) and S-100 were determined. Total protein content was decreased in the brain stem in acute hyperammonemia only. The content of neuronal and glial cell markers was not affected in either of the two conditions. However, low molecular weight proteolytic fragments of the NF 68 kD polypeptide were observed in the hippocampus of three out of six animals in both experimental groups. No proteolytic degradation of GFAP was observed. The results show that, in experimental encephalopathy due to acute liver failure and acute hyperammonemia, no major changes occur in the marker proteins. The finding of proteolytic fragments of the NF68 polypeptide indicates that the neuronal population is affected prior to glial alterations. These findings are in agreement with the concept that acute hepatic encephalopathy is reversible and induces only slight structural changes.

Acute Disease↗