Increased dopamine receptor binding in duodenal mucosa of duodenal ulcer patients

High-affinity and saturable membrane-bound dopamine binding sites have been characterized in rat and human gastrointestinal tissues. Although their role in experimental ulcerogenesis has been suggested, dopamine receptor activity in peptic ulcer disease has not been investigated. Radioligand binding studies were performed with mucosal tissue homogenates obtained from the antrum and duodenum of six male healthy volunteers and six male duodenal ulcer patients. The binding assay was performed in triplicate with a crude membrane fraction using [³H] dopamine as a ligand at a final concentration of 1 nM at 22 °C in the dark. Nonspecific binding (which usually comprised about 30% of total binding) was determined in the presence of a 100-fold excess of unlabeled dopamine. A significant (P<0.05) increase of [³H]dopamine binding was found in duodenal mucosa of duodenal ulcer patients. [³H]Dopamine binding in stomach (antrum) of normal and duodenal ulcer patients did not differ significantly. These findings provide preliminary evidence for a role of dopamine receptors in duodenal ulcer and suggest that biochemical abnormalities of gut dopamine function may be operative in the pathogenesis of peptic ulcer disease.     

Pulsed doppler echocardiography in diagnosis of pulmonary regurgitation: Its value and limitations

Ninety-eight patients were studied with two dimensional echocardiography combined with pulsed Doppler echocardiography to assess the usefulness and limitations of the Doppler technique in the diagnosis of pulmonary regurgitation. The diagnosis of pulmonary regurgitation by pulsed Doppler echocardiography depended on subjective interpretation of the audio signal and objective interpretation of the time interval histogram for the presence of wide frequency dispersion. During cardiac catheterization in 53 of the 98 patients, indocyanine green was injected into the pulmonary artery, and simultaneous sampling was performed from the right ventricle and femoral artery to diagnose pulmonary regurgitation. Pulmonary regurgitation was confirmed by pulmonary arteriogram in one patient. Among 62 patients with adequate pulsed Doppler echocardiographic studies, diastolic turbulence was noted in 21. When diastolic turbulence was less than 50 percent of the period of diastole, no pulmonary regurgitation was demonstrated in patients studied by indicator-dilution technique. However, three of the four patients with diastolic turbulence greater than 50 percent had positive evidence of pulmonary regurgitation. Audio output was more sensitive than the time interval histogram, and only five patients' findings suggested pulmonary regurgitation. Three of these patients underwent dye-dilution studies; two studies were positive for pulmonary regurgitation and one was negative.Thus, interpretation of pulmonary regurgitation based on the time interval histogram alone produces a large number of false positive results. When diastolic turbulence is greater than 50 percent of the period of diastole, both the sensitivity and specificity of diagnosis of pulmonary regurgitation are increased. Combining audio output and the time interval histogram results in improved diagnostic capability.     

Studies of oral neutrophil levels in patients receiving G-CSF after autologous marrow transplantation

Patients are at risk of mucositis and infections in the oral cavity during the neutropenic period after chemotherapy, which are significant causes of morbidity. In phase I/II studies with the haemopoietic growth factor granulocyte colony stimulating factor (G-CSF), a reduction in post-chemotherapy mucositis has been observed in addition to haematologic effects. To understand this phenomenon better in patients receiving G-CSF following high-dose chemotherapy with autologous bone marrow transplantation (ABMT), we studied the effects of G-CSF on levels of neutrophils recoverable from the oral cavity using a quantitative mouthrinse assay. In normal subjects, mouthrinses contained 472 +/- 329 x 10(3) neutrophils/mouthrinse. After chemotherapy followed by ABMT, mouthrinse neutrophil levels decreased to undetectable levels during the neutropenic period, but recovered 1-2 and 3-9 d before circulating neutrophil levels reached 0.1 and 1 x 10(9)/l respectively, whether or not patients received G-CSF. In patients who received G-CSF, the mean cumulative mucositis score was reduced from 35 +/- 9 to 21 +/- 12 (P < 0.05), and the maximum mean daily mucositis score was reduced from 2.8 +/- 0.5 to 1.7 +/- 0.9 (P < 0.01), compared to patients who did not receive G-CSF after ABMT. These studies provide in vivo evidence that neutrophils produced during G-CSF therapy are available to leave the circulation and enter tissues where their function is required for host defence. Since the usual temporal relationship between oral and peripheral blood neutrophil recovery was preserved during G-CSF administration after ABMT, these data support the hypothesis that the reduction in post-ABMT mucositis observed with G-CSF therapy may reflect a beneficial effect of G-CSF on the kinetics of oral mucosal neutrophil recovery in addition to the effect of G-CSF to accelerate peripheral blood neutrophil recovery.     

Maintenance zinc therapy after initial penicillamine chelation to treat symptomatic hepatic Wilson’s disease in resource constrained setting

Background

Experience with zinc in treating symptomatic hepatic Wilson’s disease (WD) is limited.

Aim

To study the efficacy of Penicillamine followed by zinc in treating symptomatic hepatic Wilson’s disease.

Methods

We retrospectively analyzed case records of 31 symptomatic hepatic WD patients for whom disease severity scores (Child’s, model for end-stage liver disease (MELD), Nazer’s, and New Wilson Index (NWI) score) and 24-h urinary copper were compared at 3-time points—baseline at presentation, at transition from penicillamine to zinc and at end of follow up.

Results

Thirty-one patients (median age 11 [5–24] years) with symptomatic hepatic WD were studied; ten had associated neuropsychiatric manifestations of WD. Penicillamine was changed to zinc sulfate either due to financial constraints (28 patients) or due to adverse effects of penicillamine (3 patients). At presentation (baseline), six patients belonged to Child’s class A, five to Child’s B, and 17 to Child’s C. Duration of initial penicillamine chelation therapy was 134 (2–320) weeks, and of subsequent zinc therapy was 363 (35–728) weeks. There was a significant improvement in liver function tests and disease severity scores (Child’s, MELD, Nazer’s, and NWI score) at the transition from penicillamine to zinc compared to baseline. This improvement was maintained until the end of study period with 90% survival at 10 (2–20) years. Fifteen of the 17 Child’s C cirrhotic patients showed significant improvement in disease severity scores from baseline until end of follow up.

Conclusions

Penicillamine followed by zinc may be a safe and effective treatment in resource-constrained setting for symptomatic hepatic WD patients in all grades of baseline disease severity. Some patients with decompensated cirrhosis due to WD may be managed with medical treatment, avoiding liver transplantation.

     

Rheumatoid arthritis in a population sample in the gulf: Clinical observations

Summary In our practice we had constantly been under the impression that most Arab patients with RA tend to have a non-aggressive and rather nondisabling disease. Therefore, the spectrum of RA was studied in 42 hospital patients with classic or definite forms. Their mean age was 41.2 years and the mean duration of illness was 5.25 years. F:M ratio was 3.6:1. Seropositivity and radiological findings were observed in 59.5% and 45.2% of the patients respectively. They showed a marked lack of nonarticular manifestations with insignificant functional incapacity. The over-all assessment appeared to be in agreement with the initial clinical impression.     

Hodgkin's disease presenting as cholestatic hepatitis with prominent ductal injury

In advanced stages of Hodgkin's disease, liver involvement is common. However, Hodgkin's disease mimicking cholestatic hepatitis at presentation is rare. We describe a patient with Hodgkin's disease who was initially considered to have acute cholestatic hepatitis. Liver biopsy demonstrated prominent bile duct injury associated with a florid inflammatory reaction. These changes may represent an early stage of ductal injury, subsequently leading to vanishing bile duct syndrome, a recently documented mechanism of cholestasis in Hodgkin's disease.