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Biomedical subjects

T M Rossi

Publications and source records attributed to T M Rossi.

At least 19 recordsLinked to original sources

Celiac disease in a patient with a congenital deficiency of intestinal enteropeptidase.

We report on a 40-yr-old man with both primary enteropeptidase deficiency and celiac disease. He suffered from severe intestinal malabsorption and growth failure as a child. Enteropeptidase deficiency was found and pancreatic enzyme replacement therapy resulted in a growth spurt. Enteropeptidase levels in his intestinal mucosa and intraluminal fluid remained very low throughout childhood and early adult life. Celiac disease was confirmed by characteristic abnormalities in tests of intestinal function and in mucosal biopsies, which recovered when he instituted a gluten-free diet. He remains clinically intolerant to gluten as an adult. Enteropeptidase levels have remained abnormally low whether or not his intestinal mucosa has been normal in response to gluten restriction. Enteropeptidase levels have previously been shown to be normal in untreated celiac patients. The relationship between the two disorders remains unclear.

Adult↗

Gastrointestinal bleeding in children: an overview of conditions requiring nonoperative management.

Gastrointestinal bleeding in infants and children is a common problem in the practice of general pediatrics. This report outlines the diagnosis and management of gastrointestinal bleeding in children that does not require surgical or invasive intervention. The spectrum of responsible entities are quite diverse and include a variety of immune-mediated diseases, peptic diseases, drug induced disorders, infections, and coagulation disorders. Through understanding the nature of the above-described problems, appropriate diagnostic and management principles can be applied.

Adolescent↗

Oncogene expression in patients with familial polyposis coli/Gardner's syndrome.

We evaluated whether c-myc and ras P-21 oncogene expression could identify familial polyposis coli/Gardner's syndrome patients at risk for colon cancer. Monoclonal antibodies recognizing c-myc and ras P-21 proteins were used in immunohistochemistry to stain 26 paraffin-embedded tissue specimens collected over 12 years from 5 familial polyposis coli/Gardner's syndrome patients at various stages of their disease. Differences in staining intensity between specimens were noted with each of the two tissues markers; however, c-myc showed also a distinct cellular staining pattern in patients with advanced histologic features. The c-myc oncogene exhibited strong homogeneous cytoplasmic staining in all adenocarcinoma specimens; weak cytoplasmic staining was found in normal biopsies and in 5/10 familial polyposis coli/Gardner's syndrome specimens in the early stage of disease. In contrast, a heterogeneous staining pattern with a strong supranuclear and weak nuclear and cytoplasmic staining was demonstrated in specimens with advanced histologic features of familial polyposis coli/ Gardner's syndrome and also in postoperative ileal specimens. Anti-ras P-21 antibody, on the other hand, demonstrated a homogeneous cytoplasmic staining pattern in all specimens. We feel that the c-myc oncogene expression, in distinction to that of ras P-21, has potential as a genetic tissue marker to distinguish early from more progressive disease.

Adenocarcinoma↗

Serum soluble interleukin-2 receptor, soluble CD8 and soluble intercellular adhesion molecule-1 levels in Crohn's disease, celiac disease, and systemic lupus erythematosus.

We investigated soluble interleukin-2 receptor (sIL-2R), soluble CD8 (sCD8) and soluble intercellular adhesion molecule-1 (sICAM-1) levels in the sera of patients with non-malignant diseases believed to have an autoimmune or immunosuppressive component, Crohn's disease, celiac disease, and systemic lupus erythematosus (SLE). Sera of healthy blood donors served as controls. All samples were analyzed by commercial ELISA kits for sIL-2R, sCD8, and sICAM-1. Our control level of sIL-2R (x +/- S.D) was 395 +/- 84 units/ml, sCD8 (x +/- S.D.) 263 +/- 90 units/ml and sICAM-1 405 +/- 118 ng/ml. The 8 Crohn's disease patients had an average sIL-2R level of 920 +/- 329 units/ml, and an average sCD8 level of 355 +/- 91 units/ml, and sICAM-1 952 +/- 329 ng/ml. The four celiac disease patients had an average sIL-2R concentration of 1740 +/- 1071 units/ml, a sCD8 level of 460 +/- 320 units/ml and sICAM-1 1221 +/- 720 ng/ml. The three systemic lupus erythematosus patients had an average sIL-2R of 1023 +/- 123 units/ml, and an average sCD8 of 395 +/- 69 units/ml, and sICAM-1 1153 +/- 219 ng/ml. Thus, sIL-2R and sICAM-1 were significantly elevated over control levels in all 3 patient groups, and sCD8 was mildly elevated. These results indicate enhanced immune activation which may be a common feature in the onset and/or progression of these idiopathic illnesses.

Adult↗

Small intestinal mucosa changes, including epithelial cell proliferative activity, of children receiving total parenteral nutrition (TPN).

We examined the small intestinal histology disaccharidase activities as well as the incorporation of [3H]thymidine into DNA of biopsies maintained in organ culture from seven children (ages 9 months to 5 years) receiving total parenteral nutrition (TPN). Three children suffered from inflammatory bowel disease and received TPN for one month (short term). Four required long-term TPN (> 9 months) for short-bowel syndrome. DNA was extracted from the samples following serial precipitation with perchloric acid. Results were compared to those from 22 age-matched children investigated for abdominal pain or chronic diarrhea. Short-term TPN resulted in slightly lower lactase, sucrase, and palatinase activities that were not statistically different from controls. Long-term TPN resulted in focal mild villus atrophy and a decrease in disaccharidase activity in two patients. Biopsies from long-term TPN patients incorporated less thymidine compared to those of controls (P < 0.001) when data was expressed per total biopsy (3.6 +/- 1.1 vs. 8.4 +/- 1.1 fmol) or per milligram of tissue (1.0 +/- 0.12 vs 2.7 +/- 0.7 fmol). The above data are in general agreement with the hypoplastic effect of TPN in animals. However, in children, much longer periods of TPN are required to realize the changes.

Adolescent↗

Incidence of celiac disease identified by the presence of serum endomysial antibodies in children with chronic diarrhea, short stature, or insulin-dependent diabetes mellitus.

We determined the incidence of celiac disease in the western New York area to be 1.29 per 10,000 live births. Celiac disease occurred in 29 children with gastrointestinal symptoms. Two children (1.7%) of 117 with short stature and 10 (4.0%) of 211 with diabetes mellitus had serum anti-endomysial antibodies. We conclude that the incidence of childhood celiac disease in our area is much less than that reported in Europe.

Adolescent↗

Stromal cells derived from spleen or bone marrow support the proliferation of rat natural killer cells in long-term culture.

Rat nylon wool nonadherent bone marrow cells were propagated for up to 75 days in co-culture with stromal cells derived from either spleen or bone marrow. Interleukin (IL) 1 enhanced the ability of spleen stroma to support the long-term culture of natural killer (NK) cells, ostensibly by inducing these support cells to synthesize other cytokines. Flow cytometry studies indicated that the nylon wool separation procedure enriched the concentrations of mature NK cells from 7.9% to 38.1% for splenocytes and from 3.8% to 19.5% for bone marrow cells. Analyses of the adherent zones of suspended nylon screen NK cell cultures revealed substantial numbers of large granular lymphocytes that expressed NK 323+/MOM/3F12/F2- phenotypes. The presence of both mature and immature cells of the NK lineage in this matrix was inferred by the presence of both IL-2 receptor (IL-2R) positive and IL-2R negative, and OX-8+ and OX-8- NK 323+ cells over the greater than 4-month experimental period. Suspended nylon screen cultures displayed a greater potential for producing cytolytic cells than either co-cultures of bone marrow nonadherent cells on stroma monolayers or suspension cultures. The large granular lymphocytes produced in suspended nylon screen cultures could be transformed into active killers of YAC-1 targets by IL-2. In contrast to bone marrow nonadherent cells, more splenic nylon-wool-passed cells displayed a mature NK phenotype, but their proliferative potential and ability to be transformed into cytolytic cells by IL-2 decreased rapidly in culture. In the suspended nylon screen culture system, NK cells migrate from the underlying stroma in stages as they mature, retain their cytolytic potential, and manifest a capacity for self-renewal. Cultured cells were routinely dissociated into single cell suspensions via enzyme treatment and were reinoculated onto "fresh" nylon screen/stromal cell templates after passage through nylon wool columns. These co-cultures continued to generate cytolytic cells in numbers greater than those of the initial inoculum.

Animals↗

Immunology of inflammatory bowel disease: summary of the proceedings of the Subcommittee on Immunosuppressive Use in IBD.

As outlined, scanty data exist with regard to immunologic therapy in children with IBD despite the fact that the pediatric population affords a unique opportunity for clinical evaluation. Children are less affected by modifying conditions such as smoking, alcohol ingestion, and the long-term use of medications, and because of their specific needs for ponderal and linear growth, children might benefit most from immunological therapy that has been proven to be steroid sparing. Therefore, clinical trials to evaluate the efficacy of 6-MP and/or azathioprine in growing children with Crohn's disease would appear to provide a fruitful avenue for collaborative research. Efforts to organize a multicenter evaluation of these agents have been initiated. The studies are crucial in evaluating the efficacy and safety of immunosuppressive therapy in the pediatric population with IBD.

Aminosalicylic Acids↗

Human intestinal disaccharidase activities: correlations with age, biopsy technique, and degree of villus atrophy.

The relationship between intestinal morphology, disaccharidase activity, and disaccharide absorption is controversial. A retrospective study of 798 consecutive biopsies was performed to determine whether disaccharidase activities varied by subject age, biopsy technique, and degree of villus atrophy. Lactase activity was inversely correlated with age in the absence or presence of villus atrophy; sucrase, maltase, and palatinase activities did not correlate with age. Biopsies obtained by capsule or endoscopy had similar disaccharidase activities. In subjects 24 months of age or younger, the degree of mucosal injury was inversely correlated with lactase activity. In subjects older than 24 months, the degree of mucosal injury was inversely correlated with maltase and, to a lesser extent, lactase activities. The data suggest that disaccharidase activities in mucosal biopsies, whether obtained by endoscopy or capsule, are diminished in the presence of mucosal injury and correlate inversely with the degree of injury.

Adolescent↗

Laser-based detectors in chromatographic analysis.

Advances in detection technology have been a vital part of the development of microscale chromatographic techniques. Separation techniques such as microbore liquid chromatography impose severe constraints on the permissible volume of detector cells. The use of lasers to construct a new generation of chromatographic detectors has satisfied the need for low volume detection and high sensitivity. The unique properties of laser radiation have been used to advantage in designing new approaches to the detection of optical absorbance through fluorescence emission and thermal effects. New approaches to monitoring refractive index changes and optical rotation have also been developed. Together, the combination of microscale-separation techniques and highly sensitive detection provide a powerful tool for analysing small quantities of samples. Yet, there are practical limitations arising from the cost and complexity of much of the instrumentation reported to date, as well as the difficulties of preparing small samples for analysis which have limited the wide-scale application of these methods to solve practical problems. Recent advances in laser technology such as the advent of diode lasers may be useful in overcoming some of these limitations.

Chromatography↗

Carnitine ester excretion in pediatric patients receiving parenteral nutrition.

Carnitine plasma concentrations and the excretion of carnitine and individual carnitine esters were determined in 25 children and adolescents with gastrointestinal diseases receiving carnitine-free parenteral nutrition for at least 1 mo using radiochemical and radioisotopic exchange HPLC methods. Children less than 12-y-old usually had carnitine plasma concentrations less than -2 SD from the normal mean for age, whereas patients greater than 12-y-old had carnitine plasma concentrations within the normal range. Age was the only variable to correlate significantly with plasma carnitine concentrations during parenteral nutrition. Free carnitine (FC) excretion was closely correlated with plasma FC concentrations and minimal at values less than 25 mumols/L. The excretion of FC and short-chain acylcarnitines was reduced by an order of magnitude in younger compared with older patients and controls, but the excretion of "other" acylcarnitines was less affected. Some of the latter were tentatively identified using gas-liquid chromatographic and mass spectroscopic techniques as unsaturated and/or branched medium-chain carnitine esters with a carbon chain of C8-C10. The results suggest that FC and short-chain acylcarnitine are conserved by the kidney in nutritional carnitine deficiency but that there may be an obligatory renal excretion of other carnitine esters that contributes to the development of hypocarnitinemia in the younger age group.

Absorption↗

High-fat semielemental diet in the treatment of protracted diarrhea of infancy.

The capacity for greater fat absorption relative to carbohydrate absorption in protracted diarrhea of infancy was studied in a developed and a developing country (Buffalo, NY, and Bangkok, Thailand). Fifty patients with protracted diarrhea in the first year of life (defined as liquid stools of more than 20 mL/kg per day with more than a 14-day duration) were randomly assigned to receive either a standard semielemental diet (Pregestimil) or a high-fat semielemental diet that contained 40% more fat. The increased fat was largely in the form of medium-chain triglycerides, with the new diet providing 60% of the fat as medium-chain triglycerides compared with 40% in the standard diet. Tolerance to both diets was good in both studies. Both groups showed adequate weight gain and an improvement in anthropometric and biochemical parameters. The patients receiving the high-fat diet showed no initial weight loss, however, and their weight gain was initiated earlier. Cumulative weight gain was also higher in the group receiving the high-fat semielemental diet. Fecal fat analyses were performed after 1 week of therapy. There was no difference observed in the coefficient of fat absorption between the groups receiving the two formulas, indicating that infants with protracted diarrhea may be able to tolerate a higher fat intake than is normally provided. As carbohydrate intolerance is known to be a complicating factor when using semielemental enteral feeds for infants with protracted diarrhea, a higher-fat semielemental diet may be the most appropriate way to provide adequate caloric intake.

Diarrhea, Infantile↗

Quantitation of urinary carnitine esters in a patient with medium-chain acyl-coenzyme A dehydrogenase deficiency: effect of metabolic state and L-carnitine therapy.

Urinary carnitine esters were quantitated in an infant with medium-chain acylcoenzyme A dehydrogenase deficiency by means of a highly sensitive and specific radioisotopic exchange high-pressure liquid chromatography method. During fasting, the excretion of free carnitine and of acetylcarnitine, octanoylcarnitine, and hexanoylcarnitine was increased. The fractional tubular reabsorption of free carnitine was decreased, suggesting a renal leak of free carnitine. In the symptom-free, fed state, only minor amounts of free carnitine and of short-chain acylcarnitine, octanoylcarnitine, and hexanoylcarnitine were present in urine, and carnitine loss occurred in the form of "other" carnitine esters not exceeding that of control subjects. During L-carnitine therapy, the excretion of free carnitine, short-chain acylcarnitine, octanoylcarnitine, and hexanoylcarnitine, and particularly of "other" carnitine esters, was increased, suggesting a possible detoxifying effect of administered carnitine that is not confined to the elimination of octanoic and hexanoic acids. The employed method detects very low urinary concentrations of octanoylcarnitine and hexanoylcarnitine (less than 1 mumol/L) characteristic of medium-chain acyl-coenzyme A dehydrogenase deficiency and may be useful in screening for this disease, which has been associated with sudden infant death.

Acetylcarnitine↗

Serum antibodies to cow's milk proteins in pediatric inflammatory bowel disease: Crohn's disease vs. ulcerative colitis.

Serum antibodies to five cow's milk proteins, alpha-casein, bovine serum albumin (BSA), beta-lactoglobulin A and B (BLG-a, BLG-b) and alpha-lactalbumin (ALA) were investigated in young patients with inflammatory bowel disease, 56 with Crohn's disease (CD), 24 with ulcerative colitis (UC). IgG antibodies against BSA and BLG-a and -b were higher in Crohn's disease patients as compared to those with ulcerative colitis and controls. The IgG anti-BSA were higher in the group of CD patients with higher score of disease activity. Additionally, IgA antibodies to alpha-casein were higher in CD and UC compared to control. These findings may be due to increased uptake of dietary antigens or enhanced immunological response occurring in CD patients.

Adolescent↗

Serum antibodies to cow's milk proteins in pediatric inflammatory bowel disease. Crohn's disease versus ulcerative colitis.

Serum antibodies to five cow's milk proteins (alpha-casein, bovine serum albumin, beta-lactoglobulin A and B, and alpha-lactalbumin) were investigated in young patients with inflammatory bowel disease (56 Crohn's disease, 24 ulcerative colitis). IgG antibodies against bovine serum albumin, beta-lactoglobulin A and beta-lactoglobulin B were higher in Crohn's disease patients than in those with ulcerative colitis or the controls. IgG anti-bovine serum albumin antibodies were higher in those Crohn's disease patients who had higher scores of disease activity. Finally, IgA antibodies to alpha-casein were higher in patients with Crohn's disease and ulcerative colitis when compared to controls. These findings may be due to increased uptake of dietary antigens or enhanced immunological response occurring in Crohn's disease patients.

Adolescent↗

Selectivity of quercetin inhibition on stimulated amylase release in rat pancreatic acini.

Quercetin (Q) has been shown to inhibit Ca2+-dependent processes. The present study evaluates the effect of Q on amylase release stimulated by various agonists in dispersed rat pancreatic acini. Q inhibited amylase release stimulated by an optimal concentration of carbachol. The inhibition was dependent on Q concentration. Preincubation with Q was not necessary. Maximal inhibition (up to 60% of control) was reached at 50 microM of Q and was completely reversible. Full responsiveness of the acini to agonist stimulation was reestablished as early as 5 min upon the removal of Q. At 50 microM, Q inhibited stimulated amylase release by optimal concentrations of tetradecanoylphorbol-13-acetate (TPA) (10(-6) M), A23187 (3 x 10(-6) M), cholecystokinin C-terminal octapeptide (CCK-OP) (10(-9) M) and carbachol (3 x 10(-6) M), but not by vasoactive intestinal polypeptide (VIP) (3 x 10(-7) M). Instead, Q promoted amylase release stimulated by VIP. The inhibition of amylase secretion by Q occurred only at near optimal, optimal, and supraoptimal concentrations of TPA, A23187, CCK-OP, and carbachol. The potentiation effect of Q on VIP-stimulated amylase secretion was, however, seen at all concentrations of VIP used (10(-8) to 10(-6) M). Quercetin also inhibited protein kinase C activity from rat pancreas in a dose-dependent manner. Maximal inhibition (approximately 85%) was seen at 100 microM of Q. These results provide further support that the intermediary steps for stimulated enzyme secretion in pancreatic acini by TPA, A23187, CCK-OP, and carbachol involve calmodulin and/or protein kinase C, whereas VIP does not.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗

Nutritional assessment of children with short-bowel syndrome receiving home parenteral nutrition.

Serial nutritional assessments using arm anthropometry, computed tomography of the thigh, and serum biochemical indexes during an eight-month period were performed on nine children with short-bowel syndrome receiving home parenteral nutrition. The mean patient age at the beginning of the study was 3.0 years. In anthropometric measurements, the mean body weight of our test population did not deviate from that of the normal population. Most patients were below the normal median for height. The mean midarm muscle area was 114% of the normal median, and the mean midarm fat area was 98% of the normal median. The mean weight and height velocities were 148% and 122% of the standard, respectively. Retinol-binding protein values, albumin levels, and total lymphocyte counts of the patients were low, while levels of aspartate aminotransferase and alanine aminotransferase were slightly elevated. Midarm muscle and fat compartment sizes were highly correlated with thigh muscle and fat compartment sizes, as demonstrated by computed tomography. Our results demonstrate that children with short-bowel syndrome receiving home parenteral nutrition can maintain normal growth characteristics and extremity compartment sizes.

Anthropometry↗