Autoantibodies to B lymphocytes in a patient with hypoimmunoglobulinemia. Characterization and pathogenic role.

In a young woman with ulcerative colitis, hypoimmunoglobulinemia, and humoral immunodeficiency, lymphocyte counts vary between 600 and 1,000 per mm(3) with 0.5-1.5% bone marrow-derived (B) cells and 98-99% thymus-derived (T) cells. Anti-lymphocyte antibodies were detected by immunofluorescence and by microlymphocytotoxicity with increased reactivity at +4 degrees C. They belonged to the IgM class and were polyclonal. Studies performed with various normal lymphocyte subpopulations, several lymphoblastoid cell lines and lymphocytes from immunodeficiency patients showed that these antibodies reacted with B cells. The corresponding antigen(s) is distinct from membrane-bound immunoglobulins, is not an alloantigen, and is probably unrelated to the la-like molecules. Pokeweed mitogen stimulated B cells appear to lose this antigen. Cells from various lymphoproliferative disorders were tested. T-derived and "non T-non-B" leukemic cells did not react with the antibody. Malignant cells from B-derived lymphomas and prolymphocytic leukemias were reactive. The incidence of positivity of the leukemic cells among patients with common B chronic lymphocytic leukemia was surprisingly low (one-third of the patients). The autoantibody nature of the anti-B-cell antibodies and their pathogenic role in the genesis of the patient's hypoimmunoglobulinemia was demonstrated by the effect of removal of antibodies by massive plasmaphereses which were followed by a dramatic and transitory increase of B-cell figures. Whereas most primary immunodeficiency syndromes appear to result from an arrest in the differentiation capabilities of immunologically competent cells, autoantibodies to circulating B lymphocytes may be incriminated in the pathogenesis of some cases of hypogammaglobulinemia.

A novel phenotype related to partial loss of function mutations of the follicle stimulating hormone receptor.

A single natural loss of function mutation of the follicle stimulating hormone receptor (FSHR) has been described to date. Present in the Finnish population it markedly impairs receptor function, blocking follicle development at the primary stage and presenting as primary amenorrhea with atrophic ovaries. When Western European women with this phenotype were examined for FSHR mutations the result was negative, suggesting that other etiologies corresponding to this clinical pattern are markedly more frequent. We now describe a novel phenotype related to mutations provoking a partial loss of function of the FSHR. A woman with secondary amenorrhea had very high plasma gonadotropin concentrations (especially FSH), contrasting with normal sized ovaries and antral follicles up to 5 mm at ultrasonography. Histological and immunohistochemical examination of the ovaries showed normal follicular development up to the small antral stage and a disruption at further stages. The patient was found to carry compound heterozygotic mutations of the FSHR gene: Ile160Thr and Arg573Cys substitutions located, respectively, in the extracellular domain and in the third intracellular loop of the receptor. The mutated receptors, when expressed in COS-7 cells, showed partial functional impairment, consistent with the clinical and histological observations: the first mutation impaired cell surface expression and the second altered signal transduction of the receptor. This observation suggests that a limited FSH effect is sufficient to promote follicular growth up to the small antral stage. Further development necessitates strong FSH stimulation. The contrast between very high FSH levels and normal sized ovaries with antral follicles may thus be characteristic of such patients.

Effect of a fermented milk containing Bifidobacterium animalis DN-173 010 on the health-related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double-blind, controlled trial.

BACKGROUND: Health-related quality of life (HRQoL) has been rarely evaluated as a primary endpoint in the assessment of the effect of probiotics on the irritable bowel syndrome (IBS). AIM: To study the effects of fermented milk containing Bifidobacterium animalis DN-173 010 and yoghurt strains on the IBS in a multicentre, double-blind, controlled trial. METHODS: A total of 274 primary care adults with constipation-predominant IBS (Rome II) were randomized to consume for 6 weeks either the test fermented milk or a heat-treated yoghurt (control). HRQoL and digestive symptoms were assessed after 3 and 6 weeks on an intention-to-treat population of 267 subjects. RESULTS: The HRQoL discomfort score, the primary endpoint, improved (P < 0.001) in both groups at weeks 3 and 6. The responder rate for the HRQoL discomfort score was higher (65.2 vs. 47.7%, P < 0.005), as was the decrease in bloating score [0.56 +/- (s.d.)1.01 vs. 0.31 +/- 0.87, P = 0.03], at week 3 in the test vs. the control group. In those subjects with <3 stools/week, stool frequency increased (P < 0.001) over 6 weeks in the test vs. control group. CONCLUSIONS: This study suggests a beneficial effect of a probiotic food on discomfort HRQoL score and bloating in constipation-predominant IBS, and on stool frequency in subjects with <3 stools/week.

Review article: bifidobacteria as probiotic agents -- physiological effects and clinical benefits.

Bifidobacteria, naturally present in the dominant colonic microbiota, represent up to 25% of the cultivable faecal bacteria in adults and 80% in infants. As probiotic agents, bifidobacteria have been studied for their efficacy in the prevention and treatment of a broad spectrum of animal and/or human gastrointestinal disorders, such as colonic transit disorders, intestinal infections, and colonic adenomas and cancer. The aim of this review is to focus on the gastrointestinal effects of bifidobacteria as probiotic agents in animal models and man. The traditional use of bifidobacteria in fermented dairy products and the GRAS ('Generally Recognised As Safe') status of certain strains attest to their safety. Some strains, especially Bifidobacterium animalis strain DN-173 010 which has long been used in fermented dairy products, show high gastrointestinal survival capacity and exhibit probiotic properties in the colon. Bifidobacteria are able to prevent or alleviate infectious diarrhoea through their effects on the immune system and resistance to colonization by pathogens. There is some experimental evidence that certain bifidobacteria may actually protect the host from carcinogenic activity of intestinal flora. Bifidobacteria may exert protective intestinal actions through various mechanisms, and represent promising advances in the fields of prophylaxis and therapy.

Effects of cyclic (nocturnal) total parenteral nutrition and continuous enteral nutrition on circadian rhythms of blood lipids, lipoproteins and apolipoproteins in humans.

The aim of the present study was to investigate the occurrence and characteristics (acrophase, amplitude) of circadian rhythms of serum total cholesterol, free-fatty acids (FFA), triglycerides, lipoproteins (HDL-, LDL-, and VLDL-cholesterol), apolipoproteins A and B, glucose and total proteins in hospitalized patients fed with 12 h nocturnal total parenteral nutrition (TPN) (from 8 PM to 8 AM) including lipids, patients fed with continuous enteral nutrition over 24 h daily spans, and patients eating 3 meals a day serving as controls. All the subjects were synchronized with diurnal activity and nocturnal rest in the hospital routine. The results showed the following: 1) circadian rhythms of total cholesterol, triglycerides, FFA, HDL-, LDL-cholesterol, apolipoprotein A and total proteins were detected in both TPN patients and controls, rhythms of apolipoprotein B and glucose in TPN patients only; in enteral nutrition patients, rhythms were detected for total proteins, glucose and triglycerides only; 2) a significant shift in triglyceride and FFA acrophases was observed in TPN patients, as compared with controls; 3) 24 h mean of both triglyceride and cholesterol concentrations remained unchanged after one month, in both TPN and enteral nutrition patients. The present approach, by extending results of previous investigations, leads one to conclude that, on both a metabolic and a chronobiological basis, cyclic nocturnal TPN is well-tolerated.

Effects of prolonged, purine-free total parenteral and enteral nutrition on urate homeostasis in man.

The influence on human urate homeostasis of prolonged, totally purine-free nutritional support, using total parenteral (TPN) or elemental enteral (EN) nutrition, is not well known. In a prospective study, we measured weekly serum uric acid, renal urate excretion and clearance, together with parameters of hydration, in 58 normally hydrated patients receiving prolonged (15 to 170 days) purine-free TPN (30 patients) or EN (28 patients) for various gastrointestinal disorders. A marked, early and sustained decrease (p less than 0.001) in serum uric acid was observed in TPN (155 +/- 9 mumol/l at day 7 versus 318 +/- 13 mumol/l before nutrition, mean +/- SEM) as well as in EN patients (192 +/- 11 mumol/l at day 7 versus 320 +/- 16 mumol/l before nutrition), together with a significant (p less than 0.01) rise in renal urate clearance. The urate clearance/glomerular filtration rate ratio increased significantly, while there was no significant change in natremia or plasma osmolarity. Serum urate and urate clearance returned to normal within 8 days of refeeding with a normally purine-containing diet. Replacement of TPN by EN or vice versa, or substitution of glucose by fructose resulted in no change in hypouricemia. A 4-day oral supply of purines (125 mg/day) in EN patients was associated with a 53% rise (p less than 0.01) in serum urate. We conclude that prolonged, purine-free TPN and elemental EN are a new cause of marked hypouricemia which is mainly due to increased urate clearance, the mechanism of the latter is still poorly known, but is not related to extracellular volume expansion.

A prospective assessment of cytomegalovirus infection in active inflammatory bowel disease.

BACKGROUND: The prevalence and clinical significance of cytomegalovirus infection is reportedly high in patients with refractory inflammatory bowel disease but is unknown in unselected patients with active disease. METHODS: In patients admitted for active inflammatory bowel disease, we prospectively studied the presence and significance of cytomegalovirus infection using anti-cytomegalovirus antibodies, cytomegalovirus viraemia and antigenaemia and cytomegalovirus inclusions and cytomegalovirus immunochemistry staining in ileocolonic biopsies. RESULTS: A total of 64 patients were included (ulcerative colitis, n = 23; Crohn's disease, n = 41), 18 of whom had been on high-dose oral steroids and 11 on immunosuppressants. Anti-cytomegalovirus IgG and IgM were positive in 42 (66%) and 3 (5%) patients respectively. Blood or urine cytomegalovirus replication markers were found in 4 (6%) patients, all of whom had ulcerative colitis. Three patients had cytomegalovirus viraemia and received anti-viral treatment with ganciclovir. Only one of these patients had cytomegalovirus antigenaemia and also associated biopsy-proven cytomegalovirus colitis, probably as a primary cytomegalovirus infection. This patient is the only one who benefitted from anti-viral therapy. CONCLUSIONS: Cytomegalovirus infection is infrequent in in-patients with active inflammatory bowel disease. Systematic search of cytomegalovirus replication markers should not be performed. Isolated viraemia without associated antigenaemia or direct demonstration of cytomegalovirus in ileocolonic biopsies does not warrant anti-viral therapy.

Severe hypoxemia in a case of midgut carcinoid tumor.

A 33-year-old woman treated for carcinoid tumor developed severe hypoxaemia. This hypoxaemia may have been related to an extracardiac right-to-left shunt. The pathogenic role of vasoactive agents is discussed and comparisons made with cirrhosis-associated hypoxaemia.

Cyclic parenteral nutrition in hospitalized adult patients: a 9-year experience.

We are reporting our 9-year experience of cyclic parenteral nutrition with 200 in-patients (mean age 52 years) treated 64 +/- (SEM)3 days (range: 15-230) for Gl diseases. During the first period (A, n = 38), all-in-one nutritive bags with intralipid 10% were used; in a second period (B, n = 135), intralipid 10% was infused separately over the first 6 h of nutrition; in the final period (C, n = 27), Intralipid 20% was used in all-in-one nutritive bags. Indications for parenteral nutrition were non-malignant digestive diseases in 89.5% of the cases. The frequency of complications appearing during cyclic parenteral nutrition was the following: catheter-related sepsis 8%, catheter obstruction 8%, hypertriglyceridemia 33%, hypercholesterolemia 14.7%, liver function test abnormalities 28% and biliary sludge and/or lithiasis 31.6%. 5 patients, with chronic obstructive small bowel disease, developed jaundice with no identifiable cause other than parenteral nutrition. The prevalence of catheter obstruction significantly decreased (P < 0.01) during period B, as compared with periods A and C. The prevalence of liver function test abnormalities decreased significantly (P < 0.01) during periods B and C, as compared with period A. Mortality rate related to cyclic parenteral nutrition was 3%. These results suggest that a) the separate infusion of lipid emulsion reduces the prevalence of catheter obstruction; b) as compared with 10% intralipid in all-in-one nutritive bags, the separate infusion of 10% Intralipid or the 20% Intralipid given in all-in-one nutritive bags is associated with a decreased prevalence of liver function test abnormalities; c) chronic small intestine obstruction seems to play a key role in parenteral-associated jaundice.

Cholesterol-lowering effect of continuous enteral nutrition in man.

We have studied the effect of polymeric cholesterol-free enteral nutrition (EN) on serum lipid and apolipoprotein levels in 30 consecutive non-diabetic, non-hyperlipaemic gastrointestinal patients. EN-40 +/- (SEM) 2 kcal/kg/day including 35% vegetable lipids (50% highly polyunsaturated fat, 50% medium chain triglycerides)-was delivered continuously (24h) via the gastric route for at least 2 weeks (mean duration: 35 +/- 4 days). In the entire group, serum total cholesterol decreased by 10.5% (p < 0.01) on day 7 and 17.5% (p < 0.01) on day 28 (n = 12); this was accompanied by 21% and 20% decreases in LDL-cholesterol and apolipoprotein B (p < 0.05) levels respectively, on day 28. In the 19 patients who were normocholesterolaemic on day 0, serum total cholesterol decreased by 15% (p < 0.01) on day 7 and by 28% (p < 0.05) on day 28 (n = 7). Conversely, in the other 11 patients with a low (<3.7 mmol/L) pre-EN serum total cholesterol level, no significant changes were observed during EN. We conclude that continuous, cholesterol-free EN has, in normocholesterolaemic patients, a marked cholesterol-lowering effect; the respective role of the composition of the diet and the continuous delivery of nutrient within the gut have yet to be investigated.

Techniques for the provision of parenteral nutrition.

Parenteral nutrition should be provided by a regularly trained nutrition team. The objectives of nutritional support should be decided by considering both the prognosis of the disease to be treated and the risk-to-benefit ratio of parenteral nutrition. Only when other nutritional therapy has failed should the costly and complicated protocol of parenteral nutrition be implemented. Although patients' consent to artificial nutrition is usually implicit, the goals and modalities of parenteral nutrition should be explicit. This approach avoids misunderstanding and may allow patients to participate in their own care, thus decreasing the likelihood of complications, especially those of a technical type, and possibly increasing the quality and efficacy of parenteral nutrition.

Computer simulation of metal ion equilibria in biofluids. Part 3. Trace metal supplementation in total parenteral nutrition.

Computer simulation models have been developed to investigate the effect of intravenous infusions of nutritive amino acid solutions metal equilibria in plasma. The distribution of Ca(II), Mg(II), Zn(II), Cu(II), and Mn(II) among the ligands in the nutritive fluid is calculated and used to estimate the amounts of each metal that should be included in future preparations.

[The digestive system and pancreas in 1982]. / Appareil digestif et pancréas en 1982.

The present review is concerned with the main pathophysiological, clinical and therapeutic progresses in the following fields: gastro-esophageal reflux, gastric antisecretory drugs, chronic inflammatory bowel diseases, cancer of colon and esophagus, pancreatic diseases (chronic pancreatitis, pancreatic carcinoma), acute bacterial diseases of the digestive tract, acquired immunodeficiency syndrome of the adult, diffuse nodular lymphoid hyperplasia of the adult small bowel.

Laparoscopic ileocecal resection in Crohn's disease: a case-matched comparison with open resection.

BACKGROUND: Despite some encouraging preliminary results, the role of laparosropic surgery in the treatment of Crohn's disease (CD) is a subject of controversy and still under evaluation. The aim of this case-matched study was to compare the postoperative course of laparoscopic and open ileocecal resection in patients with CD in order to define the potential role of laparoscopic surgery in CD. METHODS: From 1998 to 2001, 24 consecutive patients with isolated Crohn's terminal ileitis treated by laparoscopic ileocecal resection (laparoscopy group) were compared with 32 patients matched for age, gender, duration of disease, preoperative steroid treatment, fistulizing disease, and associated surgical procedure, and treated by open resection (open group). RESULTS: In the laparoscopy group, four procedures (17%) were converted. There were no deaths. The morbidity rate was 20% in the laparoscopy group and 10% in the open group (NS). There was no significant difference between the two groups in operating time, size of bowel resection and resection margin, postoperative morphine requirement, resumption of intestinal function, tolerance of solid diet, or length of hospital stay. CONCLUSIONS: Laparoscopic ileocecal resection in CD is safe and effective, even for fistulizing disease. There are no significant differences between laparoscopic and open ileocecal resection, especially in terms of the mortality and mortality rates. Consequently, because laparoscopic surgery seems to offer cosmetic advantages, it should be considered the procedure of choice for patients with ileocecal CD.

[Biological hepatic abnormalities, cholestatic jaundice and hospital artificial nutrition. A comparative study in adults with cyclic total parenteral nutrition and enteral nutrition]. / Anomalies biologiques hépatiques, ictères cholestatiques et nutrition artificielle à l'hôpital. Etude comparée, chez des adultes en nutrition parentérale totale cyclique et en nutrition entérale.

Two hundred and fourteen hospitalized nonsurgical, nonacutely stressed adult patients, who were receiving, either prolonged (greater than 21 days) cyclic total parenteral nutrition (n = 106) or enteral nutrition (n = 108), including lipids, for gastrointestinal disorders, and who were free of prenutrition liver function test abnormalities were prospectively investigated for hepatic dysfunction: 41 p. 100 and 17 p. 100 of parenteral and enteral nutrition patients, respectively, developed abnormalities of liver function tests after 25 +/- 5 and 21 +/- 4 days (p less than 0.01). This prevalence was unrelated to catheter sepsis, blood transfusion, caloric load, site of digestive disease or initial nutritional status, and decreased by 50 and 40 p. 100 before the end of total parenteral nutrition and enteral nutrition respectively. In the parenteral nutrition group, separate infusion of lipids, as compared with mixed infusion, was associated with a lower rate of hepatic dysfunction (29 vs 54 p. 100; p less than 0.02). Nine (8.5 p. 100) parenteral nutrition but no enteral nutrition patients developed severe cholestatic jaundice, 47 +/- 39 days after the onset of liver function test abnormalities; no identifiable cause excepting parenteral nutrition per se was found in 3 patients with diffuse obstructive small intestinal disease; jaundice led to death from noncirrhotic hepatic failure in the 2 patients who remained totally parenteral nutrition-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

[Continuous ambulatory enteral feeding in hospitalized adults: prospective experience in 98 patients]. / Nutrition entérale continue ambulatoire à l'hôpital, chez l'adulte: expérience prospective chez 98 malades.

The goal of this study, which describes a personal technique of continuous enteral nutrition (CEN) in hospitalized adults on an ambulatory basis, was: to prospectively evaluate, over a 2-year period, its efficacy and tolerance in 98 patients requiring CEN for at least 15 days; to compare its efficacy and tolerance with those of conventional non-ambulatory CEN on a prospectively randomized basis in 16 patients. Ambulatory CEN was given at the rate of 35-45 kcal/kg/d (lipids: 35 p. 100; carbohydrates: 45 p. 100); during day-time, a portable system, including pump, tubes and low-viscosity nutrient solutions, allowed ambulation. Ninety-eight consecutive patients with a minimal level of physical autonomy were treated for intestinal (n = 47), pancreatic (n = 20), esophagogastric (n = 17) diseases, or for malnutrition of other causes for an average of 38 days (15 to 141). The average weight gain (m +/- SD) was 1.2 +/- 5.5 p. 100 of ideal body weight (IBW) and the average nitrogen gain was 0.7 +/- 3.8 g/24 h; weight gain proved significantly lower in patients with inflammatory bowel disease receiving steroids. The clinical tolerance proved excellent, except for 5 cases of transient diarrhea and 9 cases of reposition of the nasogastric tube. A decrease in cholesterolemia below 3.9 mmol/l was noted in 25 p. 100 of patients during CEN. No significant difference between ambulatory and non-ambulatory CEN was observed in terms of evolution of body weight and other anthropometric variables, nitrogen balance, albuminemia, and oxygen consumption; conversely, the CEN experience, evaluated by patients on analogical visual scales, was significantly better endured in the ambulatory group.(ABSTRACT TRUNCATED AT 250 WORDS)

[Anti-endomysium and anti-reticulin antibodies in adults with celiac disease followed-up in the Paris area]. / Anticorps anti-endomysium et anti-réticuline chez des adultes atteints de maladie coeliaque suivis en région parisienne.

OBJECTIVES: Circulating IgA class anti-endomysium and anti-reticulin antibodies are reliable serological markers for the diagnosis of coeliac disease. The aim of this study was to evaluate their diagnostic sensitivity and specificity, and their prevalence in a group of coeliac adults taking a gluten-free diet followed in Ile-de-France. METHODS: One hundred and forty-five sera from 134 patients were examined for IgA and IgG anti-endomysium and anti-reticulin antibodies by indirect immunofluorescence. Sixty-eight patients were confirmed coeliacs; 8 patients with noncoeliac (unresponsive to a gluten-free diet) duodenal villous atrophy and 58 patients with no villous atrophy served as controls. RESULTS: In active coeliac disease, the sensitivity of anti-endomysium and anti-reticulin antibodies was 88% and 50%, respectively. Their specificity was 100%: they were never detected in case of noncoeliac villous atrophy. Under a strict gluten-free diet, their prevalence was 7% and 0%, respectively. CONCLUSION: In the studied population, the diagnosis accuracy of IgA anti-endomysium antibodies confirms their usefulness in screening and follow-up of coeliac disease. The absence of anti-endomysium and anti-reticulin antibodies in those cases with noncoeliac villous atrophy suggests that in the latter, different immunopathologic mechanisms, as compared with coeliac disease, are concerned.

[Metabolism of plasma cholesterol and lipoproteins after total resection of the small intestine in patients with parenteral nutrition. Effects of the amount of phospholipids infused]. / Métabolisme du cholestérol et des lipoprotéines plasmatiques après résection totale de l'intestin grêle chez l'homme en nutrition parentérale. Effets de la quantité de phospholipides infusés.

The aim of this study was to investigate the plasma lipoprotein profile in 2 patients treated by parenteral nutrition for total small bowel resection over a 15 month period. According to the amount of infused phospholipids (6 g/d vs 3 g/d), infused during 4 non consecutive 6 month or 6 week periods, HDL-cholesterol, apolipoproteins AI and B plasma levels were 30 to 50% below normal values. During the higher phospholipid supply, cholesterolemia seemed normal; each phospholipid supply decrease was followed by a reduction of cholesterol, phospholipids and apolipoprotein B plasma levels of 40, 50 and 25%, respectively, while HDL-cholesterol and apolipoprotein AI plasma levels remained unchanged. Density gradient ultracentrifugation showed that plasma cholesterol changes were mainly due to cholesterol changes (as free cholesterol associated with phospholipids) located in the density range of 1.019-1.040, reflecting the presence of lipoprotein X-like particles, whose levels remained unchanged during each period. An apolipoprotein E, CII and CIII enrichment of plasma was observed and was more pronounced when patients received higher phospholipid infusion. These results show that, in patients without a small bowel, minor changes in phospholipids supply are responsible for serious alterations of the lipoprotein profile; formation of lipoprotein X-like particles could be favored by the low HDL levels in these patients.