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Biomedical subjects

E Goldin

Publications and source records attributed to E Goldin.

At least 19 recordsLinked to original sources
PubMed2006

Relationships between hypoglycaemia and gastric emptying abnormalities in insulin-treated diabetic patients.

We hypothesize that hypoglycaemia in insulin-treated diabetic patients may result from gastric emptying abnormalities causing insulin and food absorption mismatching. We tested gastric emptying in insulin-treated diabetic patients with unexplained hypoglycaemia and without dyspepsia and in diabetic patients without hypoglycaemia, prospectively. Thirty-one diabetic patients with unexplained hypoglycaemic events within 2 h of insulin injection and 18 insulin-treated diabetic patients without hypoglycaemic events underwent gastric emptying breath tests, glycaemic control and autonomic nerve function. Gastric emptying tests were abnormal in 26 (83.9%) and in four (22.2%) patients with and without hypoglycaemia, respectively (P < 0.001). Gastric emptying was significantly slower in hypoglycaemic diabetic patients (t1/2 139.9 +/- 74.1 vs 77.8 +/- 23.3 and t(lag) 95.8 +/- 80.3 vs 32.84 +/- 16.95 min, P < 0.001 for both comparisons; t-tests). A significant association between hypoglycaemic patients and abnormal values of t1/2 and t(lag) was found (P < 0.001). Gastric emptying abnormalities were more frequent in hypoglycaemic patients. We suggest gastric emptying tests for diabetic patients with unexplained hypoglycaemic events.

Aged↗
PubMed2005

Safety and tolerability of antagonist anti-human CD40 Mab ch5D12 in patients with moderate to severe Crohn's disease.

BACKGROUND: The ligation of CD40 by CD154 is a critical step in the interaction between APC and T cells. In animals, antagonizing CD40L-CD40 has been shown to reduce the severity of several autoimmune and inflammatory disorders, including experimental colitis. AIM: To investigate tolerability and safety of an antagonist chimeric monoclonal anti-human CD40 antibody (ch5D12) for treatment of Crohn's disease. METHOD: ch5D12 was administrated to 18 patients with moderate to severe Crohn's disease in a single dose, open-label dose-escalation phase I/IIa study. RESULTS: ch5D12 plasma concentrations increased dose-dependently after infusion. Two patients developed an anti-ch5D12 antibody response. Overall response and remission rates were 72 and 22%, respectively with no evidence for a dose-response effect. Treatment with ch5D12 reduced microscopic disease activity and intensity of the lamina propria cell infiltrate, but did not alter percentages of circulating T and B cells. ch5D12 was well tolerated, although some patients experienced headache, muscle aches, or joint pains, which may have been related to the study drug. CONCLUSIONS: Antagonizing CD154-CD40 interactions with ch5D12 is a promising therapeutic approach for remission induction in Crohn's disease.

Adolescent↗
PubMed2005

Anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as predictors of inflammatory bowel disease.

BACKGROUND AND AIMS: Several antibodies have been reported in the sera of patients with Crohn's disease (CD) and ulcerative colitis (UC). The most commonly described are anti-Saccharomyces cerevisiae mannan antibodies (ASCA) in CD and perinuclear antineutrophil cytoplasm antibodies (pANCA) in UC. Familial clustering of these antibodies has been described, suggesting they might be genetic markers. Our aim was to investigate the presence of these antibodies before the emergence of overt clinical manifestations. METHODS: Since 1980, the Israeli Defense Force (IDF) Medical Corps Serum Repository has stored serum samples obtained systematically from 5% of all recruits on enlistment, and from the same population on discharge from compulsory military service. We evaluated serum samples obtained from 32 subjects with CD and eight with UC before they were clinically diagnosed, along with samples from matched controls. RESULTS: ASCA were present in 10/32 (31.3%) CD patients before clinical diagnosis compared with 0/95 (0%) controls (p<0.001). None of the eight patients with serum samples available before diagnosis of UC were ASCA positive. ASCA was positive in 54.5% of patients after diagnosis of CD. The mean interval between ASCA detection and diagnosis was 38 months. In 90% of patients, antibodies were detected in the first available serum sample; therefore, measurements of the average time from the presence of ASCA to diagnosis may be even longer. pANCA were present in 2/8 (25%) patients with available sera before the diagnosis of UC. None of their 24 matched controls were positive (p = 0.014). CONCLUSIONS: ASCA and pANCA may predict development of inflammatory bowel disease years before the disease is clinically diagnosed.

Adult↗
PubMed2004

Complicated endoscopic pediatric procedures using deep sedation and general anesthesia are safe in the endoscopy suite.

BACKGROUND: Complicated upper and lower endoscopic procedures of the gastrointestinal tract are performed in children for a variety of diagnostic and therapeutic reasons. Unlike adult patients, who receive conscious sedation, children usually require deep sedation (DS) or general anesthesia (GA). The aim of this study is to assess the safety parameters of complicated endoscopic procedures under DS or GA performed in children in the endoscopy suite rather than in the operating theatre. METHODS: Between May 1997 and December 2002, 296 patients (mean age 4.5 years, range 3 weeks to 16 years), defined as ASA I-III, underwent either DS or GA for endoscopic foreign body extraction, endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous endoscopic gastrostomy (PEG) insertion. ASA physical status I was found in 15%, II in 57% and III in 28%. The pathologies included neuromuscular diseases, genetic syndromes, nesidioblastosis, biliary atresia, hematologic, respiratory (cystic fibrosis) and cardiac disorders. Propofol was the drug of choice (63%) followed by a combination of propofol and midazolam (16%). RESULTS: Transient desaturation (O2 saturation <90%) was the only complication recorded in 21/296 (7.09%) patients. Only two patients with severe respiratory underlying disease were hospitalized for follow-up for a 24-h period. CONCLUSIONS: The use of DS and GA for complicated endoscopies in a moderately high-risk pediatric population was found to be safe. The very low complication rate found in this study suggests that complicated pediatric patients can be managed successfully outside the operating theatre, provided that all the safety criteria for ambulatory DS or anesthesia are present.

Adolescent↗
PubMed2003

Topical capsaicin--a novel and effective treatment for idiopathic intractable pruritus ani: a randomised, placebo controlled, crossover study.

PURPOSE: Pruritus ani is a common and embarrassing proctological condition which can be very difficult to treat. We report the results of a double blind placebo controlled study of treatment with capsaicin. METHODS: Firstly, a pilot open study was carried out on five patients to establish which of two doses was the most acceptable by comparing effectiveness and side effects. Secondly, a double blind, placebo controlled, crossover study of topical capsaicin was performed. This study involved two four week treatment phases separated by a one week washout phase. Forty four patients were randomised to receive locally either active capsaicin (0.006%) or placebo (menthol 1%) ointment over a four week period (22 patients per group). After four weeks of treatment and a one week washout period, the placebo group began to receive capsaicin while the treated group received placebo (menthol 1%) for another four weeks. At the end of the controlled study, responders from both groups continued with capsaicin treatment in an open labelled manner. RESULTS: Thirty one of 44 patients experienced relief during capsaicin treatment periods and did not respond to menthol; all patients not responding to capsaicin also failed on menthol (p<0.0001). In 13 patients, treatment with capsaicin was unsuccessful: eight patients did not respond to capsaicin treatment, one responded equally to capsaicin and placebo, and four others dropped out because of side effects. During the follow up period (mean 10.9 (SD 5.8) months), 29 "responders" needed a mean application of capsaicin every day (1.6 (SD 1.2); range 0.5-7 days) to remain symptom free (or nearly symptom free). CONCLUSION: Capsaicin is a new, safe, and highly effective treatment for severe intractable idiopathic pruritus ani.

Administration, Topical↗
PubMed2003

[Cholangiocarcinoma in primary sclerosing cholangitis: "chronicle of a death foretold"?].

Primary sclerosing cholangitis (PSC), a condition usually associated with inflammatory bowel disease, is a chronic inflammatory state of the biliary tract characterized by fibrotic strictures of intrahepatic and extrahepatic bile ducts. Between 5-15% of patients with PSC will develop cholangiocarcinoma. The diagnosis of cholangiocarcinoma in patients with PSC is difficult, as it is often impossible to distinguish benign PSC-related strictures from lesions associated with cholangiocarcinoma. Consequently, most patients are diagnosed with advanced disease and have a dismal prognosis at the time of diagnosis. The importance of characterizing patients with PSC who have an increased risk of developing cholangiocarcinoma and of developing means for early detection of this disease cannot be over-emphasized. Detection of cholangiocarcinoma in asymptomatic patients is additionally important, as this condition is considered a contraindication for liver transplantation. We describe a patient with longstanding Crohn's disease and PSC who developed cholangiocarcinoma, and review the literature regarding risk factors for cholangiocarcinoma, early detection of cholangiocarcinoma and the significance of existing cholangiocarcinoma in the context of liver transplantation.

Adult↗
PubMed2003

[Complications of endoscopic retrograde cholangiopancreatography].

INTRODUCTION: Endoscopic sphincterotomy (ES) is commonly used to remove bile-duct stones and to treat other problems. We prospectively investigated complications and mortality of endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS AND METHODS: Between june 6, 1998 and june 6, 1999 553 ERCP were performed in our centers. Inclusion criteria for protocol were: ERCP indication, complete follow-up and informed consent. We prospectively studied complications of ECRP in consecutive patients treated at 2 institutions (San Martin Hospital, La Plata, Argentina and Hadassah University Hospital, Jerusalem, Israel). The follow-up was done during 365 days with a clinical examination, laboratory test and ultrasonography to determine the possible complications. RESULTS: Of 553 ERCP, 43 had a complications; including pancreatitis in 16 cases, cholangitis in 12, hemorrhage in 5, perforation in 3 and miscellaneous in 7. 3-1) ES frequency: 241 patients (pts). 3-2) FOLLOW-UP: 365 days in 504 pts. 3-3) Sex and age: women 274 pts, men 230 pts. Age range 1 month to 90 year old. 3-4) Final diagnoses: choledocholitiasis (38.8%), strictures (18%), pancreatic cancer (4.3%), ampullary cancer (2.3%) and normal ERCP (24.4%). CONCLUSIONS: The rate of complications after ES can vary in different circumstances and is primarily related to the indication for the procedure and to endoscopic technique. Our percentage of complications (7.53%) coincide with consulted studies. Today, diagnostic ERCP has been challenged by magnetic resonance cholangiography (MRC). MRC provides images of the billary and pancreatic ducts that are nearly equal to those of ERCP without the procedural risk associated.

Adolescent↗
PubMed2002

The neurogenetics of mucolipidosis type IV.

BACKGROUND: Mucolipidosis type IV (MLIV) is an autosomal recessive disease caused by mutations in the MCOLN1 gene that codes for mucolipin, a member of the transient receptor potential (TRP) gene family. OBJECTIVE: To comprehensively characterize the clinical and genetic abnormalities of MLIV. METHODS: Twenty-eight patients with MLIV, aged 2 to 25 years, were studied. Ten returned for follow-up every 1 to 2 years for up to 5 years. Standard clinical, neuroimaging, neurophysiologic, and genetic techniques were used. RESULTS: All patients had varying degrees of corneal clouding, with progressive optic atrophy and retinal dystrophy. Twenty-three patients had severe motor and mental impairment. Motor function deteriorated in three patients and remained stable in the rest. All had a constitutive achlorhydria with elevated plasma gastrin level, and 12 had iron deficiency or anemia. Head MRI showed consistent characteristic findings of a thin corpus callosum and remained unchanged during the follow-up period. Prominent abnormalities of speech, hand usage, and swallowing were also noted. Mutations in the MCOLN1 gene were present in all patients. Correlation of the genotype with the neurologic handicap and corpus callosum dysplasia was found. CONCLUSIONS: MLIV is both a developmental and a degenerative disorder. The presentation as a cerebral palsy-like encephalopathy may delay diagnosis.

Adolescent↗
PubMed2002

Mast cells involvement in the inflammation and fibrosis development of the TNBS-induced rat model of colitis.

BACKGROUND: Mast cells have been implicated in chronic inflammatory conditions resulting in fibrosis, such as Crohn disease. However, a link between inflammation, fibrosis and mast cells has not been demonstrated in human or animal intestinal diseases. This work was undertaken to analyze whether mast cells play a role in inflammation and fibrosis in the TNBS-induced rat colitis. METHODS: Rats were rectally instilled 2,4,6,-trinitrobenzene sulfonic acid in ethanol, and immediately or 4 days later injected daily i.p. with nedocromil sodium, a mast cell stabilizer, compound 48/80, a mast cell activator, or saline. Rats were sacrificed 5 days post-TNBS, or on day 21. Intestinal inflammation and fibrosis were assessed by gross and histopathological evaluation. Colonic mast cell numbers (toluidine blue) and collagen (type I mRNA expression) were evaluated. Mast cell sonicate was added to rat colon fibroblasts. Fibroblast proliferation (3H-thymidine), collagen synthesis (3H-proline) and contractile activity (tridimensional collagen lattice contraction) were then assessed. RESULTS: Nedocromil reduced inflammation and fibrosis possibly by decreasing mast cell numbers and activation and consequent collagen production. Compound 48/80 slightly enhanced the severity of the disease by activating mast cells. Mast cells increased fibroblast proliferation, collagen production and contractile activity. CONCLUSIONS: Mast cells are involved in the gastrointestinal tract inflammation and fibrosis of the TNBS-colitis rats.

Animals↗
PubMed2002

Wheat grass juice in the treatment of active distal ulcerative colitis: a randomized double-blind placebo-controlled trial.

BACKGROUND: The use of wheat grass (Triticum aestivum) juice for treatment of various gastrointestinal and other conditions had been suggested by its proponents for more than 30 years, but was never clinically assessed in a controlled trial. A preliminary unpublished pilot study suggested efficacy of wheat grass juice in the treatment of ulcerative colitis (UC). METHODS: A randomized, double-blind, placebo-controlled study. One gastroenterology unit in a tertiary hospital and three study coordinating centers in three major cities in Israel. Twenty-three patients diagnosed clinically and sigmoidoscopically with active distal UC were randomly allocated to receive either 100 cc of wheat grass juice, or a matching placebo, daily for 1 month. Efficacy of treatment was assessed by a 4-fold disease activity index that included rectal bleeding and number of bowel movements as determined from patient diary records, a sigmoidoscopic evaluation, and global assessment by a physician. RESULTS: Twenty-one patients completed the study, and full information was available on 19 of them. Treatment with wheat grass juice was associated with significant reductions in the overall disease activity index (P=0.031) and in the severity of rectal bleeding (P = 0.025). No serious side effects were found. Fresh extract of wheat grass demonstrated a prominent tracing in cyclic voltammetry methodology, presumably corresponding to four groups of compounds that exhibit anti-oxidative properties. CONCLUSION: Wheat grass juice appeared effective and safe as a single or adjuvant treatment of active distal UC.

Adult↗
PubMed2001

A physical and transcript map of the MCOLN1 gene region on human chromosome 19p13.3-p13.2.

Mutations in MCOLN1 have been found to cause mucolipidosis type IV (MLIV; MIM 252650), a rare autosomal recessive lysosomal storage disorder found primarily in the Ashkenazi Jewish population. As a part of the successful cloning of MCOLN1, we constructed a 1.4-Mb physical map containing 14 BACs and 4 cosmids that encompasses the region surrounding MCOLN1 on human chromosome 19p13.3-p13.2-a region to which linkage or association has been reported for multiple diseases. Here we detail the precise physical mapping of 28 expressed sequence tags that represent unique UniGene clusters, of which 15 are known genes. We present a detailed transcript map of the MCOLN1 gene region that includes the genes KIAA0521, neuropathy target esterase (NTE), a novel zinc finger gene, and two novel transcripts in addition to MCOLN1. We also report the identification of eight new polymorphic markers between D19S406 and D19S912, which allowed us to pinpoint the location of MCOLN1 by haplotype analysis and which will facilitate future fine-mapping in this region. Additionally, we briefly describe the correlation between the observed haplotypes and the mutations found in MCOLN1. The complete 14-marker haplotypes of non-Jewish disease chromosomes, which are crucial for the genetic diagnosis of MLIV in the non-Jewish population, are presented here for the first time.

Chromosome Mapping↗
PubMed2001

The effect of traffic policing on road safety in Israel.

We use panel data on road sections to investigate the effect of traffic policing on non-urban road accidents in Israel. Traffic policing is measured indirectly by the number of police reports issued for driving offences. Our main findings are: (1) only large-scale enforcement has any measurable effect on road accidents while small-scale enforcement has no apparent effect. (2) The enforcement effect is slightly larger in the long run than it is in the short-run. (3) The effect of enforcement tends to dissipate rapidly after the dosage of enforcement is reduced. (4) Enforcement has no effect on fatal road accidents. (5) The evidence that the effect of policing in one road section spills over onto other road sections is weak.

Accidents, Traffic↗
PubMed2001

Topical nitrates potentiate the effect of botulinum toxin in the treatment of patients with refractory anal fissure.

BACKGROUND: Anal fissure is perpetuated by high sphincter pressures and secondary local ischaemia. Pharmacological approaches include topical nitrates and botulinum toxin (BT) which act to reduce anal pressure. BT lowers anal pressure by preventing acetylcholine release from nerve terminals while topical nitrates act by donating nitric oxide (NO). The aims of the present study were to compare the therapeutic effect and lowering action on internal anal sphincter pressure of BT injection and local application of isosorbide dinitrate (ID) compared with BT given alone, in patients with chronic anal fissure (CAF) refractory to treatment with ID. METHODS: Thirty consecutive patients with CAF who did not respond to previous topical ID treatments were randomly assigned to receive one of the following treatments: group A, injection of BT (20 U into the internal anal sphincter) and subsequent daily applications of ID (2.5 mg three times daily for three months); and group B, BT injection only (20 U). If at the end of six weeks following BT injection no improvement was seen in group B, ID was added. A series of anal pressure measurements, including resting basal pressure and resting pressure following topical ID (1.25, 2.5, and 3.75 mg), was carried out both before and two weeks after 20 U of BT injection into the internal anal sphincter. At the end of the trial, patients were followed up for an average period of 10 months. FINDINGS: At six weeks the fissure healing rate was significantly higher in group A patients (10/15 (66%)) compared with group B (3/15 (20%)) (p=0.025). At eight and 12 weeks, no significant differences were seen: 11/15 (73%) v 11/15 (73%) and 9/15 (60%) v 10/15 (66%), group A v group B, respectively. Maximum anal resting pressure (MARP) was significantly lower two weeks after BT injection than baseline MARP (90 (4) v 110 (5) mm Hg; p<0.001). A significantly greater reduction in MARP following local application of ID was achieved after BT injection compared with that achieved before BT injection (p=0.037) INTERPRETATION: (1) Combined BT injection and local application of ID in patients with CAF who failed previous treatment with ID was more effective than BT alone. This treatment modality appears to be safe and promising. (2) ID application induced a greater reduction in MARP following BT injection compared with ID application before BT injection. The improved potency of ID on MARP after BT injection suggests a primary cholinergic tonus dominance in some patients and not, as previously claimed, anal sphincter insensitivity to nitrates.

Adult↗
PubMed2001

Substance P in rectal mucosa of children with chronic constipation.

Substance P content was determined by radioimmunoassay in rectal mucosa of 17 children with idiopathic constipation and 9 with normal bowel movements who were used as controls. In children with chronic idiopathic constipation, rectal mucosa substance P levels were lower than levels in the control group: 47.6 +/- 11 vs. 79.4 +/- 11 pg/mg net weight respectively (differences not statistically significant). Substance P levels in rectal mucosa of children with soiling (11/17) did not differ from those of chronically constipated children without soiling (46.0 +/- 16 vs. 50.5 +/- 19 pg/mg net weight). In children with constipation, substance P levels did not correlate either with age or duration of symptoms. Substance P levels in normal controls were similar to levels previously observed in non-constipated adults, whereas levels in constipated children were intermediate between levels observed in healthy subjects and levels in adults with chronic constipation. These findings may point to a motility derangement as a possible factor in the pathogenesis of chronic constipation in childhood.

Case-Control Studies↗
PubMed2000

Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel.

Mucolipidosis type IV (MLIV) is a developmental neurodegenerative disorder characterized by severe neurologic and ophthalmologic abnormalities. The MLIV gene, ML4 (MCOLN1), has recently been localized to chromosome 19p13.2-13.3 by genetic linkage. Here we report the cloning of a novel transient receptor potential cation channel gene and show that this gene is mutated in patients with the disorder. ML4 encodes a protein, which we propose to call mucolipin, which has six predicted transmembrane domains and is a member of the polycystin II subfamily of the Drosophila transient receptor potential gene family. The role of a potential receptor-stimulated cation channel defect in the pathogenesis of mucolipidosis IV is discussed.

Amino Acid Sequence↗
PubMed2000

Self-expandable metal coil stents in the treatment of benign esophageal strictures refractory to conventional therapy: a case series.

BACKGROUND: Benign, refractory esophageal strictures are an important therapeutic challenge. Metallic self-expandable stents developed to treat malignant strictures have occasionally been used in the treatment of benign stenoses. This is a report of the use of 14 esophageal metallic stents in 10 patients with severe benign strictures. METHODS: Ten patients with peptic, post-surgical, or post-radiation esophageal strictures were treated with metallic stents. All patients had previously been treated, unsuccessfully, by endoscopic dilatation. Their strictures, although benign, gave rise to the same problems as malignant ones. RESULTS: In all patients, marked improvement of dysphagia was achieved with the use of metallic stents. They were inserted without early complications except for chest pain in one patient. Late complications were proximal and distal migration (in three patients) and a proximal stricture in one other patient. The best results were achieved in post-radiation strictures. CONCLUSIONS: Metallic stents can be considered as a therapeutic alternative in selected patients with severe benign esophageal strictures refractory to conventional treatment.

Aged↗