Bone metastasis from gastrinoma without hepatic involvement. Utility of the scintigraphy with 111 In-pentetreotide

The case of a 54 year old patient suffering from gastrinoma (within a type I multiple endocrine neoplasm) is presented. In 1990, she underwent a surgical resection. Eight years later, she suffered from a pain in the left thigh. The 99mTc-MDP bone scintigraphy showed bone metastasis. The CT scan did not show any hepatic involvement and the scintigraphy with 111In-Pentetreotide verified bone metastasis of a neuroendocrine tumor as a single expression of the recidive. In this case, the utility of the scintigraphy with octreotide to facilitate the localization and extent of the neuroendocrine tumors is demonstrated.     

Gastroenterology: a career for a lifetime

Following is an edited reprint of the Presidential Address delivered by Donald O. Castell, M.D., during the AGA Plenary Session at Digestive Disease Week 1999.     

Inherited disorders of 3-methylcrotonyl CoA carboxylation

The clinical course of 4 patients who had reduced activities of 3-methylcrotonyl CoA carboxylase (also called 3-methylcrotonylglycinuria) is described. Two children presented with a metabolic acidosis, one in the neonatal period and the other with episodes of acidosis that started in the second year of life. In the other 2 children neurological symptoms were prominent, one having infantile spasms and the other developmental regression with a skin rash and alopecia. Three of the children responded well to oral biotin and dietary protein restriction but the fourth, despite a biochemical response to biotin, has a severe neurological handicap. The clinical presentation of inborn errors of 3-methylcrotonyl CoA carboxylase is variable. Metabolic acidosis may not be conspicuous and instead neurological features may predominate.     

In vitro identification of the cytochrome P450 isoform responsible for the metabolism of alpha-dihydroergocryptine

1. The in vitro metabolism of alpha-dihydroergocryptine (DHEC, Almirid), an ergot-derived dopamine agonist for the treatment of Parkinson's disease, has been studied in cultured cell lines following incubation with DHEC. Human hepatocytes as well as two sets of metabolically competent cell lines expressing one single human cytochrome P450 (1A1, 1A2, 1B1, 2A6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4) were used. 2. Mono- and dihydroxy metabolites of DHEC could only be detected in the culture media of the cell line expressing human cytochrome CYP3A4. The same metabolites were found in the media of cultured human hepatocytes derived from three different donors. After 24-h incubation with 1 microM DHEC, approximately 60% mono- and approximately 20% dihydroxy metabolites were detected, i.e. approximately 80% of DHEC was metabolized. Further, DHEC demonstrated an inhibitory effect on CYP3A4-mediated testosterone metabolism and additionally could induce CYP3A4 and CYP2E1 mRNA when added at 10 microM to cultured human hepatocytes. 3. The data suggest that DHEC metabolism in humans is primarily mediated by the CYP3A4 isoform. The results are in accordance with findings derived from other ergot alkaloids.     

Anti-immunoglobulin antibody detection in adjuvant arthritis by an ELISA technique

Sprague-Dawley rats, injected in the hind paw with heat-killed mycobacteria dispersed in oil, develop a severe polyarthritis. In this paper, we detected and quantified by a micro-ELISA technique autoantibodies against immunoglobulins in rats with adjuvant arthritis. Increased total anti-immunoglobulin antibodies levels were found from 3 days after induction and remained elevated until day 42. IgG anti-immunoglobulin antibodies in arthritic animals were significantly elevated during days 35-42. These results show that alterations in the humoral immune response (synthesis of anti-immunoglobulin antibodies) are present in adjuvant arthritis as they are in human rheumatoid arthritis.     

Proxy‐reported health‐related quality of life of patients with juvenile idiopathic arthritis: The pediatric rheumatology international trials organization multinational quality of life cohort study

Objective

To investigate the proxy‐reported health‐related quality of life (HRQOL) and its determinants in patients with juvenile idiopathic arthritis (JIA).

Methods

In this multinational, multicenter, cross‐sectional study, HRQOL of patients with JIA was assessed through the Child Health Questionnaire (CHQ) and was compared with that of healthy children of similar age from the same geographic area. Potential determinants of HRQOL included demographic data, physician's and parent's global assessments, measures of joint inflammation, Childhood Health Assessment Questionnaire (CHAQ), and erythrocyte sedimentation rate.

Results

A total of 6,639 participants (3,324 with JIA and 3,315 healthy) were enrolled from 32 countries. The mean ± SD physical and psychosocial summary scores of the CHQ were significantly lower in patients with JIA than in healthy children (physical: 44.5 ± 10.6 versus 54.6 ± 4.0, P < 0.0001; psychosocial: 47.6 ± 8.7 versus 51.9 ± 7.5, P < 0.0001), with the physical well‐being domain being most impaired. Patients with persistent oligoarthritis had better HRQOL compared with other subtypes, whereas HRQOL was similar across patients with systemic arthritis, polyarthritis, and extended oligoarthritis. A CHAQ score >1 and a pain intensity rating >3.4 cm on a 10‐cm visual analog scale were the strongest determinants of poorer HRQOL in the physical and psychosocial domains, respectively.

Conclusion

We found that patients with JIA have a significant impairment of their HRQOL compared with healthy peers, particularly in the physical domain. Physical well‐being was mostly affected by the level of functional impairment, whereas the intensity of pain had the greatest influence on psychosocial health.     

A training program on exclusive breastfeeding in maternity wards.

OBJECTIVES: To estimate whether a 3-day training program for health professionals was followed by changes in maternity ward practices and in the rate of exclusive breastfeeding. METHODS: A retrospective study in the maternity ward of a French university hospital involved two cross-sectional samples of 323 mother-infant pairs in 1997 and 324 in 2000. RESULTS: The rate of exclusive breastfeeding at discharge increased from 15.8% (12.0-20.2) in the before sample to 35.2% (30.0-40.6) in the after sample (P<0.01). This result persisted in the multivariable analysis [adjusted odds ratio, 2.74 (1.72-4.37)]. Infants in the before sample were less likely to be breastfed within 1 h of birth (9.2% vs. 16.9%, P=0.01), to room-in 24 h/day (56.6% vs. 72.6%, P<0.01), and were more likely to receive formula supplementation (77.6% vs. 54.0%, P<0.01). CONCLUSIONS: A training program for health professionals can be effective in improving maternity ward practices and increasing exclusive breastfeeding rate at discharge.     

Human mesenchymal stem cells from adipose tissue: Differentiation into hepatic lineage.

Adipose tissue represents an accessible source of mesenchymal stem cells (ADSCs), with similar characteristics to bone marrow-derived stem cells. The aim of this work was to investigate the transdifferentiation of ADSCs into hepatic lineage cells in vitro. ADSCs were obtained from human adipose tissue from lipectomy. Cells were grown in medium containing 15% AB human serum. Cultures were serum deprived for two days and exposed to a two-step protocol with two different media using growth factors and cytokines. Hepatic differentiation was assessed by RT-PCR of liver-marker genes. ADSCs exhibited a fibroblastic morphology that changed to a cuboidal shape when cells differentiated. Expression of liver genes increased when using one of the two studied media consisting of DMEM supplemented with HGF, bFGF and nicotinamide for 14 days. The results indicate that, under certain specific inducing conditions, ADSCs can be induced to differentiate into hepatic lineage in vitro. Adipose tissue may be an ideal source of high amounts of autologous stem cells.