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Background: Most moderate-severe juvenile Crohn's disease (CD) patients are in a constant catabolic state resulting in poor weight gain and growth failure. Anti-inflammatory, immunomodulatory, and monoclonal antibody drugs, as well as growth hormone (GH), frequently fail to achieve sustained remission or reverse growth failure.Objective: To test whether an exclusion diet with nutraceutical therapy (DNT) could induce sustained clinical remission and weight gain, and if so does this enhance the ability for GH to reverse growth failure.Methods: An uncontrolled prospective case study was undertaken in six moderate- severe CD patients, two of whom had completed growth. All were treated with DNT. Adequate caloric and protein ( ≥ 3g/kg/d) intake for catch up weight was prescribed. Dairy products, certain grains and carrageenan containing foods were eliminated. Nutraceuticals, consisting of fish peptides, bovine colostrum, boswellia serrata, curcumin and a multivitamin were administered daily. Lactobacillus GG, a probiotic, was administered twice weekly. Recombinant human GH (rhGH) was administered daily.Results: Within 2 months of starting DNT all six patients went into remission, with discontinuation of all pharmacological drugs. Three patients have remained in sustained remission for 4 to 8 years. One patient with very severe CD had recurrence of CD symptoms after being in complete remission for 18 months, one patient was in remission for 3 years but symptoms recurred when she became less compliant to DNT and one recently treated patient remains in remission after 6 months. With the addition of rhGH, the 4 growing patients had good-excellent growth responseConclusion: DNT engendered prolonged remission and restoration of normal weight in moderate-severe juvenile CD patients, providing conditions that enabled rhGH to stimulate growth. These findings justify larger controlled trials to evaluate the long-term benefit of compliance to DNT in both juvenile and adult CD patients.

In muscular dystrophy (MD) the imbalance between muscle protein synthesis and degradation may be an important factor leading to muscle wasting. The three major pathways of muscle proteolysis identified in skeletal muscle are: the lysosomal cathepsin pathway, the calcium-dependent calpain pathway, and the ATP-dependent ubiquitin pathway. Insulin-like growth factor I (IGF-I) and a high-protein diet (HPD) have been shown to reduce proteolysis in skeletal muscle. We examined the effect of 6 weeks of recombinant human IGF-I (rhIGF-l) alone or in combination with HPD treatment on the proteolytic pathways in skeletal muscle of 129 ReJ dystrophic (dy) mice. (A group of normal (Norm) nondystrophic (129 J) mice were included as controls). Untreated dymice exhibited increased net proteolysis (P< 0.05), elevated net calpain activity (P< 0.01), and increased ubiquitin levels when compared to control mice (P< 0.05). Our evidence suggests that HPD and rhIGF-l decrease proteolysis in the 129 ReJ dymouse. This effect appears attributable, at least in part, to reduced calpain-mediated myofibrillar breakdown (P< 0.05) due to decreased calpain autolysis or increased calpastatin levels. In contrast to calpain, cathepsin B activity was increased in HPD and rhIGF-l + HPD-treated dymuscle (P< 0.05) and unaltered in the rhIGF-l treated animals. Levels of free and protein-conjugated ubiquitin were also increased in rhIGF-l, and rhIGF-l + HPD treated dyanimals (P< 0.05). The amelioration of muscle wasting in the 129 ReJ dymodel by HPD and/or rhIGF-l may have potential implications in the treatment of human MD.

• Clinical, hematologic, and immunologic findings were reviewed in 21 patients with glycogenosis lb. Fifteen of the patients suffered from moderate to severe bacterial infections. Ten patients had excessive epistaxis or bleeding from surgical sites, and eight suffered oral and anal mucosal ulceration. Sixteen of 21 patients exhibited chronic neutropenia associated with abnormalities In myelold maturation and decreases in the bone marrow storage and peripheral marginating pools. Diminished neutrophil motility was documented in 14 of 15 patients tested, and adherence was decreased in three patients studied. Neutrophil microbicidal activity, reduction of nitroblue tetrazolium, and ingestion were normal in all patients tested. Bleeding times were prolonged in five of eight patients, and results of platelet function studies were abnormal in five individuals. Excessive bleeding in patients with glycogenoses la and lb are similar and may be secondary to the functional deficiency of glucose-6-phosphatase. However, neutropenia, neutrophil dysfunction, and the resulting Infectious complications are specific for lb disease and may be related to abnormal glucose-6-phosphate transport.(AJDC 1985;139:691-697)

Progressive muscle weakness in acid maltase deficiency (AMD) is associated with intralysosomal accumulation of glycogen and altered myofibrillar morphology. A rapid fall in circulating branched chain amino acids after protein ingestion in a child with AMD suggested that increased net muscle protein catabolism may play a part in the pathogenesis of this condition. To reduce this muscle catabolism, the patient was treated with a high-protein diet for 12 months. This has reversed the weakness and wasting, with improvement in muscle function, exercise tolerance, and growth.

In muscular dystrophy (MD) there is an imbalance between muscle protein synthesis and protein degradation, which results in a net muscle catabolism, along with muscle wasting and weakness. Using a dystrophic hamster model (BIO 53.58), we examined the chronic (8 weeks) effects of two factors that may enhance muscle protein synthesis and inhibit protein degradation, namely, insulin-like growth factor-I (rhlGF-I) and high-protein diet (HPD). Protein synthesis was determined by measuring the incorporation of 14C phenylalanine into perfused leg muscle, while protein degradation was calculated from the release of tyrosine from the same perfused muscle. Urinary 3-methylhistidine excretion was used as an indicator of myofibrillar degradation. Treatment of dystrophic hamsters with rhlGF-I, HPD, or a combination of the two for 8 weeks resulted in significant decreases in total and myofibrillar degradation when compared with untreated dystrophic animals (P< 0.05) but had minimal effects on protein synthesis. Significant morphologic improvements (P< 0.05), including a normalization and greater uniformity of muscle fibers, were also seen in rhlGF-l- and rhlGF-l + HPD-treated animals. rhlGF-l and HPD were effective in reducing the excessive proteolysis seen in dystrophic muscle, and this reduced proteolysis resulted in improvement of muscle morphology.