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Biomedical subjects

F Konikoff

Publications and source records attributed to F Konikoff.

At least 19 recordsLinked to original sources

Risk factors for severity and relapse of pseudomembranous colitis in an elderly population.

OBJECTIVE: Pseudomembranous colitis (PMC) is well recognized as an important cause of diarrhoea in patients receiving antibiotics, with significant consequences of morbidity and mortality. Mortality among elderly patients is high, and even with successful treatment, a significant number of patients relapse. To evaluate the outcome of elderly patients with PMC, and to try to identify risk factors that might influence mortality or relapse. METHOD: We studied 72 consecutive hospitalized patients with endoscopically proven PMC. The medical records of all patients with their clinical history and laboratory data were reviewed in detail. These data included: pre-hospitalization residence and physical status, background medical history, presenting symptoms, antibiotic history, haematological and biochemical parameters, treatment, duration of hospitalization, complications, mortality within 30 days of hospitalization and relapse. RESULTS: Of the 72 patients (M/F=34/38, mean age=77 years), 47% were nursing home residents. Prior to hospitalization, 91.6% of patients had received antibiotic treatment (cephalosporins - 64%, penicillins - 42% and quinolones - 28%), 26% of patients received antacid therapy and 36% had been fed with a nasogastric tube (NGT). Thirty-seven (51%) patients recovered without complications, 21 (29%) patients died within 30 days of hospitalization and 14 (19%) patients were re-hospitalized because of relapse of PMC. Multivariate analysis revealed that white blood cell count above 20 x 10(3)/mm3 (P=0.009), serum albumin level of less than 2.5 g/dl (P=0.02), and pre-hospitalization NGT feeding (P=0.01) were associated with high mortality. Treatment with acid-reducing drugs (P=0.01) and living at a nursing home (P=0.06) were associated with high relapse rates. CONCLUSION: Pseudomembranous colitis is an important complication of antibiotic therapy and is associated with high mortality and recurrence rate, especially in old and debilitated persons. Pre-admission NGT feeding, severe leucocytosis and hypoalbuminaemia on admission are associated with increased mortality. Pre-hospitalization acid reducing treatment and nursing home residency are associated with increased risk of recurrence.

Aged↗

CT findings of latrogenic complications following gastrointestinal endoluminal procedures.

Abdominal CT, a simple and safe imaging modality, plays an important role in evaluating patients suspected of having abdominal complications following nonsurgical gastrointestinal procedures, to accurately determine the presence or absence of such insults. This pictorial article reviews and demonstrates the CT findings of various complications following upper endoscopy, percutaneous endoscopic gastrostomy, endoscopic retrograde cholangiopancreatography, endoscopic US, colonoscopy, and enemas (barium as well as cleansing).

Barium Sulfate↗

Consecutive instances of gallstone ileus due to obstruction first at the ileum and then at the duodenum complicating a gallbladder carcinoma: a case report.

Ectopic gallstone obstruction, gallstone ileus, due to cholecystoenteric fistula is an infrequent condition. Its occurrence as a complication of a gallbladder (GB) carcinoma is even more rare. We describe an unusual case of a GB carcinoma complicated by a cholecystoduodenal fistula leading to first gallstone obstruction in the ileum and then, later, in the duodenum, in which an accurate preoperative diagnosis was based on pathognomonic computerized tomography (CT) features. A correct diagnosis of this may be crucial and requires prompt surgical intervention; radiologists should be familiar with their classic CT appearance.

Aged↗

Fatty acid bile acid conjugates (FABACs)--new molecules for the prevention of cholesterol crystallisation in bile.

BACKGROUND: Cholesterol gall stones are a frequent disease for which at present surgery is the usual therapy. Despite the importance of bile acids it has become evident that phospholipids are the main cholesterol solubilisers in bile. Even phospholipid components, such as fatty acids, have anticrystallising activity. AIM: To synthesise fatty acid bile acid conjugates (FABACs) and study their effects on cholesterol crystallisation in bile in vitro and in vivo. METHODS: FABACs were prepared by conjugation of cholic acid at position 3 with saturated fatty acids of variable chain length using an amide bond. Cholesterol crystallisation and its kinetics (crystal observation time, crystal mass) were studied in model bile, pooled enriched human bile, and fresh human bile using FABACs with saturated fatty acids of varying chain length (C-6 to C-22). Absorption of FABACs into blood and bile was tested in hamsters. Prevention of biliary cholesterol crystallisation in vivo was tested in hamsters and inbred mice. RESULTS: FABACs strongly inhibited cholesterol crystallisation in model as well as native bile. The FABACs with longer acyl chains (C-16 to C-22) were more effective. At a concentration of 5 mM, FABACs almost completely inhibited cholesterol crystallisation in fresh human bile for 21 days. FABACs were absorbed and found in both portal and heart blood of hamsters. Levels in bile were 2-3 times higher than in blood, indicating active secretion. Appreciable levels were found in the systemic circulation 24-48 hours after a single administration. Ingested FABACs completely prevented the formation of cholesterol crystals in the gall bladders of hamsters and mice fed a lithogenic diet. CONCLUSIONS: FABACs are potent inhibitors of cholesterol crystallisation in bile. They are absorbed and secreted into bile and prevent the earliest step of cholesterol gall stone formation in animals. These compounds may be of potential use in cholesterol gall stone disease in humans.

Animals↗

Pregnancy and the biliary tract.

Pregnancy induces many physiological changes, some of which may have pathological results. In population studies, gallstones were found in 6.5% to 8.4% of nulliparous women, and in 18.4% to 19.3% of women with two to three or more pregnancies. In women followed throughout pregnancy, neoformation of gallstones was documented in 3% to 8.1% depending on the population. Some 20% to 30% of these gallstones redissolve postpartum. The frequency of biliary colic during pregnancy is controversial, and the recommended therapeutic approach during pregnancy is conservative. When essential, invasive procedures are relatively well tolerated, preferably during the second trimester. Biliary sludge disappears postpartum in the great majority. Gallstones and sludge are most likely caused by biliary stasis, prolonged intestinal transit and increased cholesterol saturation of bile, which were all demonstrated to occur during pregnancy.

Bile↗

[Photodynamic therapy for dysphagia due to esophageal carcinoma].

Surgery is the mainstay in the treatment of esophageal carcinoma and is effective for palliation of dysphagia. Patients unfit for surgery are difficult therapeutic problems. We evaluated photodynamic therapy for palliation of dysphagia in this condition. Patients were given 5-aminolevulinic acid, 60 mg/kg, orally and 24 hour later gastroscopy was performed during which red light illumination (100 j/cm2 for 600 seconds) was administered. This was repeated 48 hours later. The degree of dysphagia was recorded before and 14 days after treatment. 8 patients with an advanced non-resectable tumor, or who were unfit for surgery, were thus treated. 4 had squamous cell carcinoma of the mid-esophagus and 4 had adenocarcinoma of the lower esophagus. There was mild, self-limited photosensitivity in all. Liver and renal function tests and blood count were not affected by the treatment. Dysphagia was improved in all except 1 patient. A patient with early stage disease continued to eat a normal diet. We believe that photodynamic therapy with systemic aminolevulinic acid as a photosensitizer and a non-laser light source is feasible and safe in advanced esophageal cancer. It is an effective modality for relief of dysphagia in that condition.

Adenocarcinoma↗

Photodynamic therapy of cancer of the esophagus using systemic aminolevulinic acid and a non laser light source: a phase I/II study.

BACKGROUND: Surgery is the mainstay for the treatment of carcinoma of the esophagus and is also considered to be effective for palliation of dysphagia. Patients who are unfit for surgery represent a difficult therapeutic problem. The goal of the present study was to evaluate the effects of photodynamic therapy by using systemic administration of 5-aminolevulinic acid and a non laser light source on carcinoma of the esophagus. METHODS: Patients were given 60 mg/kg 5-aminolevulinic acid orally. Twenty-four hours later gastroscopy was performed. After initial localization of the tumor with the use of white light, the light source was switched to the red light band at 100 J/cm2 for 600 seconds. Gastroscopy was repeated at 48 hours and 7 days after the treatment. The degree of dysphagia was recorded before and 14 days after treatment. RESULTS: Five patients with advanced nonresectable tumors or who were unfit for surgery were treated. Two patients had squamous cell carcinoma of the mid-esophagus and three had adenocarcinoma of the distal esophagus. Mild self-limiting photosensitivity was noted in all patients. Liver and renal function tests as well as hemoglobin level and white blood cell count were not affected by the treatment. Improvement of dysphagia was observed in four patients who had pretreatment dysphagia. The patient with the early stage of disease continued to eat a normal diet. CONCLUSIONS: Photodynamic therapy with systemic aminolevulinic acid as a photosensitizer and a non laser light source is feasible and safe in advanced-stage esophageal cancer. It can be an effective modality for the relief of dysphagia in these patients.

Adenocarcinoma↗

Elevated serum iron predicts poor response to interferon treatment in patients with chronic HCV infection.

To date, there are no firm clinical, demographic, biochemical, serologic, or histologic features predicting which patients with chronic hepatitis C are more likely to respond to therapy with interferon-alpha. Serum iron, total iron-binding capacity, transferrin saturation, and ferritin were measured in the fasting state. The amount of stainable iron in liver biopsy specimens was evaluated histochemically as well. All patients received subcutaneous recombinant human IFN-alpha 2a three million units thrice weekly by self-administration. Eleven of 13 (84%) responders had low to normal serum iron levels as compared to one of 26 (4%) nonresponders (P < 0.001). The serum transferrin was similar in both groups, but iron saturation was significantly lower in responders (30 +/- 10%) than in nonresponders (53 +/- 12%) (P< 0.001). Serum ferritin and hepatic iron content were higher in nonresponders (NS). It is suggested that increased serum iron and transferrin saturation blunt the action of interferon, as they have opposite effects on the immune system. Iron overload can thus lead to a poor response to interferon. It remains to be seen whether reducing iron overload will improve the response to interferon therapy.

Chronic Disease↗

Post-transfusion etiology and non-cirrhotic histology improve the remission rate of chronic hepatitis C during interferon treatment.

During a 29 month period, 46 patients with chronic hepatitis C virus (HCV) received recombinant human interferon alpha-2a for 6 months and were followed for another 6 months. The dose of interferon was three million units thrice weekly and was increased to six million units if amino transferase levels failed to return to normal after 2 months of therapy. At the end of the treatment 19 patients had a complete response, 6 had a near complete response, 2 patients had breakthrough during treatment, and the remaining 19 did not respond at all. Six months after treatment only 10 of the 19 responders remained in remission. Post-transfusion disease was associated with a significantly higher remission rate than sporadic disease (9/22 vs. 1/24, P < 0.001), as was also found in non-cirrhotic compared to cirrhotic patients (9/27 vs. 1/19, P < 0.001). Age, sex, duration of disease, serum aminotransferase, albumin, bilirubin, alkaline phosphatase, or Child's classification did not correlate with treatment response. Severe side effects necessitating cessation of treatment occurred in six patients, four of whom had major autoimmune phenomena. We conclude that careful selection of HCV patients with favorable response characteristics (post-transfusion etiology and non-cirrhotic liver) and without autoimmune manifestations can improve the remission rate and decrease the complication rate during interferon treatment.

Adult↗

The distribution of the biliary-anionic polypeptide fraction between cholesterol carriers in bile and its effect on nucleation.

The small (7 kD) biliary phospholipid and calcium binding polypeptide (anionic polypeptide fraction/calcium binding protein) has been found in higher concentrations in the bile of patients with pigment stones than in controls. In different model systems it was variously found to promote or retard cholesteral crystalization. In the present study we investigated its distribution between cholesterol carriers in bile and its effect on cholesterol crystalization in native and model biles. On gel chromatography anionic polypeptide fraction/calcium binding protein was found predominantly in three areas: in the vesicular fraction, in the non-vesicular lipid fraction and in another fraction unassociated with biliary lipids. It was much more concentrated in the vesicular than in the non-vesicular fraction, the mean anionic polypeptide fraction/phospholipid molar ratio being 219 +/- 181 vs. 30.4 +/- 16, respectively. Anionic polypeptide fraction/calcium binding protein was added at three dose levels, 0.14, 0.28, 0.42 mg/ml (representing approximately 18%-55% of the physiologic biliary concentration), to 19 human and five model biles. This did not produce any significant changes in the nucleation time. The addition of anionic polypeptide fraction/calcium binding protein at a dose level of 0.42 mg/ml to 13 different human biles did not induce changes in the distribution of cholesterol among its carriers. The present experiments do not support a role for anionic polypeptide fraction/calcium binding protein in the process of cholesterol nucleation in bile. Qualitative changes in the protein molecule, as demonstrated in other human secretions, cannot be excluded.

Apoproteins↗

Morphological transformation of Helicobacter pylori during prolonged incubation: association with decreased acid resistance.

The survival of clinical isolates of H pylori at two cultural ages (two and four days) at pH 2, in the presence of different buffers, with and without urea, was investigated. It was found that the morphological changes which occur with longer incubation of H pylori have an inverse correlation with its resistance to an acidic environment. The finding that the addition of urea almost reversed this phenomenon and prolonged survival of the cultures emphasises the role of urea in the survival of H pylori in acidic environments.

Acids↗

A multicenter, double-blind, randomized controlled study of omeprazole versus ranitidine in the treatment of duodenal ulcer in Israel.

A multicenter, double-blind, randomized, controlled study of 203 Israeli patients with endoscopically proven duodenal ulcer is described. The study compares the efficacy (i.e., ulcer healing and relief of symptoms) and safety of 20 mg omeprazole once daily in the morning, with those of 300 mg ranitidine once daily at night. The omeprazole group had significantly higher cumulative healing rates than the ranitidine group both at day 15 (71% vs. 55%, P < 0.03) and day 29 (94% vs. 86%, P < 0.05). The efficacy was unaffected by known risk factors such as smoking. The omeprazole group had significantly fewer days with pain than the ranitidine group (median 1 vs. 3.5 days) (P < 0.03). There were no differences in ulcer size, symptoms or healing rates between Ashkenazi and Sephardic patients who were born in Israel, or who had immigrated to Israel. In summary, the present study confirms the efficacy and safety of omeprazole in the treatment of duodenal ulcer. Omeprazole provides more rapid relief of the symptoms and heals a greater proportion of duodenal ulcers, within 2-4 weeks, than ranitidine.

Adult↗

Free fatty acids have nucleating effects in model biles.

Nucleating factors are thought to be responsible for the more rapid nucleation of gallbladder bile from patients with gallstones as compared to controls. Biliary proteins and, in particular, mucus and non-mucus glycoproteins are the focus of current research. Non-protein nucleating factors were not extensively investigated. In this study we studied the role of free fatty acids (FFA) as possible nucleating factors. Palmitic, oleic and linoleic acid were added to model biles in increasing concentrations from 0 to 20 mu mol/ml. The nucleation time of model biles decreased to 45%-60% of the initial following the addition of 0.5 to 1 mu mol/ml of each of the three fatty acids. Only a small further decrease in the nucleation time was noted with higher concentrations of up to 20 mu mol/ml. The pronucleating effect of FFA added to whole model bile was also examined in the isolated vesicular and non-vesicular fractions. The decrease in the nucleation time at each concentration of the three fatty acids was in the following order of magnitude: whole bile greater than vesicular phase greater than non-vesicular phase. The addition of each of the three fatty acids resulted in a partial solubilization of vesicles, with transfer of their lipid contents to the non-vesicular fraction. The effect was more marked with oleic acid and least marked with linoleic acid. The vesicular cholesterol to phospholipid ratio did not change following the addition of exogenous free fatty acids. Studies with labeled FFA showed that they migrated with the non-vesicular fraction on gel chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile↗

Oral colon lavage solutions containing polyethylene glycol may interfere with ELISA detection of tumor-associated antigens in colonic effluent.

Immunologic methods for detection of colorectal neoplasia based on examination of stool or colonic effluent are being developed. Most current oral lavage preparations contain polyethylene glycol (PEG), and if PEG adversely interferes with immunologic testing these tests may become less useful. We describe a decrease in sensitivity of ELISA for tumor-associated antigens (TAA) when effluent samples are diluted in PEG-electrolyte lavage solution, equivalent to a commonly used oral lavage solution based on PEG. Radioisotope-labeled antigen binding to plastic plates was decreased by dilution in the PEG lavage solution. Antigen binding, present in colonic effluent collected by the laxative purge method, was absent in effluent collected by PEG oral lavage from the same patient. We conclude that PEG and PEG-containing lavage solutions interfere with ELISA detection of TAA in colonic effluents. We speculate that the in vitro, and possibly the in vivo, effect occurs at the level of antigen binding to the plate either by a steric effect or alteration of charge by the nonpolar properties of PEG.

Absorption↗

A controlled trial of beclomethasone versus betamethasone enemas in distal ulcerative colitis.

Steroid enemas are widely used in distal inflammatory bowel disease (IBD). They are partly absorbed and suppress adrenocortical function. Beclomethasone dipropionate (BD) is a topically active steroid that undergoes rapid first-pass inactivation in the liver and is practically devoid of systemic side effects. We treated 32 consecutive patients with active distal ulcerative colitis (40 attacks) with 0.5 mg BD and/or 5 mg betamethasone phosphate (BP) enemas for 28 days. Clinical, laboratory, sigmoidoscopic, and histologic data were recorded before, during, and after the trial. The clinical efficacy of both treatments was similar. Betamethasone was slightly more effective in relation to the histologic improvement and disappearance of blood from the stools. Clinical signs of steroid overdosage were noted in patients on BP but not in patients on BD. Mean fasting plasma cortisol at the end of the trial was 2.9 micrograms/dl in the BP group and 15.3 micrograms/dl in the BD group. The adrenocorticotropin test was markedly suppressed in the BP group but not in the BD group. The absence of systemic steroid side effects makes BD enemas a useful addition in the therapy of IBD. Its oral administration should also be considered.

Adult↗