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Biomedical subjects

E Goldin

Publications and source records attributed to E Goldin.

At least 37 records · Page 2Linked to original sources
PubMed2000

Time course of nitric oxide synthase generation after gluten exposure in the rectal mucosa of gluten-sensitive patients.

BACKGROUND: Nitric oxide is thought to play an important role in modulating chronic inflammatory responses as well as in immune-mediated inflammation. We reproduced a gluten-mediated mucosal response in the rectum of celiac and control subjects in order to determine the role of inducible and constitutive nitric oxide synthases in the pathogenesis of this process. MATERIAL: Nine patients with confirmed celiac disease and five healthy controls underwent a long-term rectal gluten challenge (48 h) after an enema of 6 g of crude gluten, and constitutive and inducible nitric oxide synthase activity were determined in rectal biopsies. The histological localization of inducible nitric oxide synthase was determined by immunohistochemistry. RESULTS: Activity of both isoforms of nitric oxide synthase in control subjects did not change significantly after gluten instillation. In celiac patients, constitutive nitric oxide synthase on rectal mucosa also showed no significant changes after challenge with gluten. Inducible nitric oxide synthase isoform exhibited a modest increase 4 h after gluten instillation in celiac patients (mean increase 35% compared with baseline levels) but, 8 h after challenge, generation of iNO synthase was significantly higher: 54% more than pre-challenge production (P < 0.05) and higher than control values (P < 0.05). Inducible nitric oxide synthase staining was mostly localized in mononuclear cells of the epithelium and the lamina propria. After gluten instillation, the enhanced staining was mainly localized in subepithelial areas of the lamina propria. CONCLUSION: Our data suggest a role for nitric oxide, generated by inducible nitric oxide synthase, in the process of rectal mucosa injury by local gluten instillation in sensitized patients. We could not, however, determine if the role of nitric oxide in the ensuing injury of this gluten-induced immune inflammation model is a protective one, or merely a by-product generated by the activation of the inflammatory cells.

Adult↗
PubMed2000

Treatment of experimental colitis by oral tolerance induction: a central role for suppressor lymphocytes.

OBJECTIVE: Inflammatory bowel diseases (IBD) are immune-mediated disorders wherein an imbalance between proinflammatory (Th1) and antiinflammatory (Th2) cytokines is thought to play a role in the pathogenesis. The aim of this study was to test whether induction of oral tolerance to proteins extracted from inflammatory colon alleviates experimental colitis, and whether oral tolerization mediated by suppressor cells can induce immune tolerance. METHODS: Colitis was induced in rats by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS). Rats received five oral doses of colonic proteins extracted from TNBS-colitis colonic wall. Splenocytes harvested from tolerized and control rats were transplanted into irradiated naive rats. RESULTS: Feeding of colitis-extracted proteins ameliorated colonic inflammation, as shown by reduction of colonic ulcerations, as well as decreased diarrhea, intestine and peritoneal adhesions, wall thickness, and edema. A marked reduction of the fraction of injured colonic area and colon weight, and decrease in colon weight, were observed in tolerized rats versus controls. Histological parameters for colitis were markedly improved in tolerized animals that showed significant reduction in inflammatory response and mucosal ulcerations. Tolerized rats developed an increase in TGFbeta1 and a decrease in IFNgamma serum levels. TNBS-induced colitis was significantly attenuated in naive recipients of splenocytes from tolerized rats, compared with rats that received splenocytes from control donors. CONCLUSIONS: Induction of oral tolerance to colitis-extracted proteins downregulates the anticolon immune response, thereby ameliorating experimental colitis. Suppressor lymphocytes mediate the tolerance by induction of a shift from a proinflammatory to an antiinflammatory immune response.

Administration, Oral↗
PubMed2000

[Randomized prospective study to compare the efficiency between standard plastic and polyurethane stents in biliary tract malignant obstruction].

UNLABELLED: The aim of this paper is to compare the efficiency between standard plastic stents and polyurethane stents used in biliary tract malignant obstruction. The main problem of the plastic prosthesis is their early occlusion. On the other hand there is the hypothesis that due to the less porousness of the polyurethane surface, there might be lesser adherence and consequently a late occlusion. Thirty-eight patients in two groups of 19 were evaluated prospectively and at random in the Jerusalem Hadassah Hospital and the HIGA San Martín La Plata. They had biliary tract obstruction due to inoperable tumors. Biliary endoprosthesis (plastic standard or polyurethane 10 French diameter) were placed, according to the randomization, after a previous staging with clinical examination, laboratory analysis and images. The follow-up with the same parameters was monthly done. Twelve of the 38 patients were female and 26 male; age average 62.73 (range 81-49). The stents were placed in 17 patients with biliary cancer, 14 pancreatic cancer, 2 papila cancer, 2 gallbladder cancer with bile duct invasion and 3 liver metastasis with biliary tract compression. The clinical and laboratory parameters in 36 patients at 30 days improved. On the contrary, 2 (1 plastic standard and 1 polyurethane stent) did not improve. There were 29 deaths due to the basic illness and not related to the endoscopic method. The mean obstruction occurred at 12.76 weeks (range 32-4) in the standard stents and 12.05 (range 24-2) in the polyurethane ones. CONCLUSION: There were no significant differences in the two groups patients.

Aged↗
PubMed1999

Mucolipidosis IV consists of one complementation group.

Mucolipidosis IV (MLIV) is an autosomal recessive disorder of unknown etiology characterized by severe visual impairment and psychomotor retardation. Recently, there has been considerable interest in positional cloning of the MLIV gene. It is unknown whether MLIV is a genetically homogenous disorder. In this paper, we present experiments that determined whether the MLIV phenotype in fibroblasts could be corrected by fusing normal cells to MLIV cells and fusing fibroblasts from pairs of patients. All of our MLIV patients fulfilled several diagnostic criteria that we developed. In addition, we found high sensitivity to chloroquine in cultured fibroblasts from MLIV patients. We found that normal cells corrected the MLIV phenotype. Fusion products of normal and MLIV fibroblasts, but not MLIV fibroblasts themselves, were relatively protected against chloroquine selection. In addition, 74% of the normal-to-patient fusion products had reduced levels or total loss of MLIV characteristic autofluorescence. However, there was no complementation of the phenotype in fibroblast cultures from any of our MLIV patients, including those of non-Jewish ancestry. In fusion products of MLIV cultures from 24 patients, 90-100% of the cells remained autofluorescent. These results indicate that all of our known MLIV patients, regardless of ancestry or severity of the developmental defect, have a single mutated gene.

Amines↗
PubMed1999

Mapping of the mucolipidosis type IV gene to chromosome 19p and definition of founder haplotypes.

Mucolipidosis type IV (MLIV) is a lysosomal storage disorder characterized by severe neurologic and ophthalmologic abnormalities. It is a rare autosomal recessive disease, and the majority of patients diagnosed, to date, are of Ashkenazi Jewish descent. We have mapped the MLIV gene to chromosome 19p13.2-13.3 by linkage analysis with 15 markers in 13 families. A maximum LOD score of 5.51 with no recombinants was observed with marker D19S873. Several markers in the linked interval also displayed significant linkage disequilibrium with the disorder. We constructed haplotypes in 26 Ashkenazi Jewish families and demonstrate the existence of two founder chromosomes in this population. The localization of MLIV to chromosome 19 will permit genetic prenatal diagnosis in affected families and will aid in the isolation of the disease gene.

Chromosome Mapping↗
PubMed1999

Lysosomal inclusions in gastric parietal cells in mucolipidosis type IV: a novel cause of achlorhydria and hypergastrinemia.

Mucolipidosis type IV (ML-IV) is an autosomal recessive lysosomal storage disease that causes severe neurologic abnormalities. The brain disease is characterized by pigmented cytoplasmic granules in neurons and accumulation of lamellated membrane structures in lysosomes. The gastrointestinal disease in ML-IV was not previously recognized. Clinical examination of 20 patients with ML-IV (age range, 2-23 years) at the National Institutes of Health showed hypergastrinemia and constitutive achlorhydria. Endoscopic biopsy specimens from the gastric fundus, body, and antrum and from the duodenum of four such patients (ages 4, 6, 7, and 22 years) were evaluated histologically and by electron microscopy. Histologically, all gastric fundus and body biopsy specimens showed parietal cells in normal numbers. However, a striking cytoplasmic vacuolization of parietal cells was seen on hematoxylin and eosin stain. Electron microscopy showed the parietal cells to be markedly distended by large lysosomes containing lamellar, concentric, and cystic membranous inclusions. Additionally, chronic atrophic gastritis and enterochromaffin-like (ECL) cell hyperplasia were observed. Foveolar and chief cells in stomach and duodenum biopsy specimens were normal. We conclude that the cytoplasmic lysosomal inclusions in gastric parietal cells is a unique histologic feature of gastric biopsy in ML-IV.

Achlorhydria↗
PubMed1999

The prevalence of chronic diarrhea among diabetic patients.

OBJECTIVE: The prevalence of chronic diarrhea in patients with type I and type II diabetes is uncertain, most data being available from tertiary referral centers. We report the prevalence and etiology of chronic diarrhea in 861 heterogeneous diabetic patients attending a primary care diabetic outpatient clinic. METHODS: All patients attending the clinic were asked to fill in a questionnaire relating to their bowel habits. Patients who fulfilled the criteria for chronic diarrhea underwent a comprehensive workup to define the cause of the diarrhea. Additional parameters were the mean duration of diabetes, hemoglobin-Alc levels, and the presence of autonomic neuropathy. RESULTS: Chronic diarrhea was diagnosed in 32 patients (overall prevalence of 3.7%). The prevalence of nondiabetic diarrhea was higher among type I diabetic patients than among type II patients (3.29% vs 2.3%), although it did not reach statistical significance. Diabetic diarrhea was more common among type I than type II diabetic patients (5.2% vs 0.4%, respectively, p < 0.01). The most common cause of nondiabetic diarrhea was medication induced (metformin). CONCLUSIONS: Chronic diarrhea is more frequent in type I diabetic patients. The higher prevalence of diarrhea in this population can be attributed to diabetic diarrhea (which is quite rare in type II patients). The most common cause of nondiabetic diarrhea is drug therapy with metformin.

Adolescent↗
PubMed1998

Neurochemical alterations in the cerebellum of a murine model of Niemann-Pick type C disease.

Niemann-Pick disease Type C (NPC) is a progressive neurovisceral metabolic disorder that is caused in most patients by a defect in a recently found gene, NPC-1. Neurological damage includes visual disorders such as vertical supranuclear gaze palsy, movement disorders such as dystonia and ataxia, dementia, and seizures. So far the biochemical deficit, most likely manifested by delayed intracellular cholesterol transport, has not been correlated with the progressive neurological damage. A mutant Balb/C mouse with a defect in the same gene is used as a model to study NPC. Pathological examination of brain tissue obtained by autopsy from NPC patients or brains of affected NPC mice of different ages, revealed signs of extensive damage throughout the brain, including neurofibrillary tangles and intracellular storage of various compounds. Loss of cerebellar Purkinje cells was the most significant specific damage. The present study examined whether the neurochemical changes present in the NPC mouse brain were related to the pathological changes. The results show major alterations in the levels of serotonin and its main metabolite, 5-hydroxyindoleacetic acid, in the cerebellum and cortex of NPC mice. The levels of the inhibitory amino acid glycine were threefold higher in the cerebellum of NPC mice and those of glutamate and GABA decreased in the cortex. Tyrosine hydroxylase immunoreactivity was present in Purkinje cells, and the levels of L-DOPA increased specifically in the vermis of the cerebellum. These results are the first to indicate changes in neurotransmitters in NPC and that these could be correlated with some of the neuropathology of this disease.

Amino Acids↗
PubMed1998

Constitutive achlorhydria in mucolipidosis type IV.

Mucolipidosis type IV is an autosomal recessive lysosomal storage disease of unknown etiology that causes severe neurological and ophthalmological abnormalities. In an attempt to obtain insight into the nature of the metabolic abnormality in this disorder, we prospectively evaluated 15 consecutive patients, aged 2 to 23 years, over a period of 22 months. The finding of iron deficiency in some of the patients led us to the discovery that all patients but one had markedly elevated blood gastrin levels. None had vitamin B12 deficiency. Gastroscopy in three patients showed normal gross appearance of the mucosa in two patients, 4 and 7 years old, and mucosal atrophy in a 22-year-old. Parietal cells were present in normal numbers and contained large cytoplasmic inclusions that were confirmed immunohistochemically to be lysosomal in nature. Other gastric epithelial cells appeared normal. Parietal cells contained very few tubulovesicular membranes, suggesting cellular activation, whereas apical canaliculi appeared relatively nonactivated. Both subunits of the parietal cell H+/K+-ATPase were present, and both partially colocalized with f-actin at the apical membrane. We conclude that patients with mucolipidosis type IV are constitutively achlorhydric and have partially activated parietal cells. We hypothesize that the defective protein in this disease is closely associated with the final stages of parietal cell activation and is critical for a specific type of cellular vacuolar trafficking between the cytoplasm and the apical membrane domain.

Achlorhydria↗
PubMed1998

Treatment of chronic anal fissure with isosorbide dinitrate: long-term results and dose determination.

PURPOSE: Anal fissure is a tear of the anoderm, which eventually can become an ulcer. Chronic anal fissure is perpetuated by contraction of the internal sphincter, believed to reduce perfusion. Nitric oxide is a neurotransmitter mediating vasodilation and internal anal sphincter relaxation. The aim of the present study was to evaluate both the effect and the effective dose regimen of isosorbide dinitrate, a nitric oxide donor, as a treatment for chronic anal fissure. METHODS: Isosorbide dinitrate, Isoket spray (Schwarz-Pharma, Mannheim, Germany), was used to treat 41 patients with chronic anal fissure. Anal manometry was performed in all patients before they entered the study. The treatment program consisted of digital application of isosorbide dinitrate in a dose of 1.25 mg or 2.5 mg three times each day for four weeks. At the end of the trial, patients were followed up for an average time of 11 +/- 1 months. RESULTS: In 34 (83 percent) patients, the fissure healed within one month of treatment (mean, 3 +/- 0.1 weeks). The average time for symptoms to disappear was 6.5 +/- 0.7 days. In six (14.6 percent) patients the anal fissure did not heal even after four weeks of further treatment, and they underwent lateral sphincterotomy. Six patients relapsed during the follow-up period, but responded to another course of treatment. A dose of 2.5 mg of isosorbide dinitrate caused a greater reduction in maximum anal resting pressure than a dose of 1.25 mg. CONCLUSIONS: Topical isosorbide dinitrate is an effective and safe treatment for chronic anal fissure. In our experience the optimal dose regimen is 2.5 mg three times each day.

Administration, Topical↗
PubMed1998

EsophaCoil: long-term results in 81 patients.

BACKGROUND: Cancer of the esophagus and gastric cardia cause progressive dysphagia. Half of patients are not amenable to surgical resection; of those who are, about 20% will suffer either from local recurrence or anastomotic strictures. Self-expandable metallic stents of diverse characteristics have been used in these clinical conditions. However, expandable metallic stents have several drawbacks: low radial force, migration, epithelial trauma, and tumor ingrowth. We herein report our long-term experience with EsophaCoil, a self-expandable esophageal metallic coil, in 81 patients. METHODS: From January 1993 to July 1996, 84 stents were placed in 81 consecutive patients (53 men and 28 women, mean age 69.8 years (range 40 to 90 years). 41 patients had esophageal squamous cell carcinoma, 32 adenocarcinoma of the esophagus and cardia, 5 mediastinal metastasis, 1 sarcoma, and 2 had benign esophageal strictures. Five patients had bronchoesophageal fistulas. Mean dysphagia score before treatment was 3.5, mean stricture length 6 cm. Most patients were hospitalized for at least 24 hours after stent implantation. Patients were followed and early and late complications were recorded. RESULTS: Stents were successfully placed in all patients. Dysphagia improved in 96% of patients (score dropped from 3.5 to 1.2). Mean patient survival after stent insertion was 4 months (range 0.5 to 20 months). Bronchoesophageal fistulas were closed in all 5 cases. Early complications occurred in 11 patients. These were severe in 3 (esophageal perforation) and mild in 8 patients (precordial pain lasting 24 to 48 hours). Late complications occurred in 18 patients and included migration to the stomach (5 patients), stent breakage (5 among the first 20 cases), food impaction (5), tumor overgrowth (2), and bleeding (1). CONCLUSIONS: In a long-term follow-up, EsophaCoil was effective in the palliative treatment of dysphagia caused by malignant esophageal strictures, including cases of fistulas, having low malfunction and migration rates. No tumor ingrowth was seen.

Adenocarcinoma↗
PubMed1998

Increased serum CA 19-9 antibodies in Sjögren's syndrome.

A 67-year-old woman with a history of thyroiditis presented with recent intermittent epigastric pain and nausea. Hyperamylasaemia, oedema of the pancreas, and high serum levels of lipase and CA 19-9 were found. Xerostomia and dry eyes developed later, accompanied by an abnormal Schirmer's test. The diagnosis of Sjögren's syndrome was confirmed by increased anti-Ro and anti-La antibodies and the histological findings of parotid gland biopsy. Two additional cases of Sjögren's syndrome with elevated serum CA 19-9 are also described. These observations of elevated serum lipase and serum CA 19-9 in Sjögren's syndrome without evidence of malignancy may reflect pancreatic involvement in this disorder.

Adult↗
PubMed1997

Nitrous oxide inhalation as sedation for flexible sigmoidoscopy.

BACKGROUND: Flexible sigmoidoscopy is usually performed without sedation in screening programs for colorectal cancer. Most patients report some degree of discomfort or pain during the procedure. The aim of this study was to evaluate self-administered nitrous oxide as a method to reduce patient discomfort, thereby improving the procedure and conceivably increasing patient compliance and motivation. METHODS: In a double-blind, randomized, placebo-controlled study, 38 patients undergoing sigmoidoscopy self-administered 60% nitrous oxide (n = 18) or oxygen (n = 20) by mask. The endoscopist recorded the depth of insertion of the sigmoidoscope, duration of the procedure, and time to patient recovery. Patients scored the degree of pain and discomfort felt during the examination. RESULTS: There were no significant differences between the groups with regard to patients' age, gender, pain or discomfort, duration of procedure, or depth of insertion. Recovery time was significantly longer in the nitrous oxide group (3.3 +/- 0.6 minutes vs 0.5 +/- 0.5 minutes; p = 0.02), but this finding was of no practical or clinical consequence. CONCLUSIONS: The addition of "on demand" nitrous oxide did not improve sigmoidoscopy performance or diminish pain and discomfort. However, further studies using improved administration techniques and larger study groups are justified in the search for ways to increase compliance with and motivation for colorectal cancer screening.

Administration, Inhalation↗
PubMed1997

Decreased substance P content in the rectal mucosa of diabetics with diarrhea and constipation.

Substance P (SP), vasoactive intestinal polypeptide (VIP), and somatostatin content in rectal mucosa were determined by radioimmunoassay (RIA) in 38 diabetic patients (12 with normal bowel function, 13 with diabetic diarrhea, and 13 with constipation) and in 10 nondiabetic controls with normal bowel function. SP content (picograms per milligram) in the rectal mucosa of diabetics with normal bowel function was significantly higher than that of nondiabetic controls (P < .05). SP content in the rectal mucosa of diabetics with diabetic diarrhea and constipation was significantly lower than in diabetics with normal bowel habits and nondiabetic controls (P < .05). No differences were found in the rectal mucosa content of VIP and somatostatin between the different groups of diabetics and controls. Diabetic diarrhea is a condition with an intermittent nature and frequently alternates with constipation. Our findings showing low levels of rectal mucosa SP in both conditions suggest a possible common role of SP in the pathogenesis of diabetic diarrhea and constipation.

Adult↗