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PubMed2026

Comparison of clinical efficacy and gut microbiota characteristics in children with ASD treated with fecal microbiota transplantation and ketogenic diet.

OBJECTIVE: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and interaction, along with restricted, repetitive patterns of behavior. It is often accompanied by gastrointestinal dysfunction and gut microbiota dysbiosis. Fecal Microbiota Transplantation (FMT) and the Ketogenic Diet (KD) are interventions targeting the gut microbiota for ASD. METHODS: 30 participants were diagnosed with ASD according to DSM-5 and ADOS-2. ASD core symptoms were evaluated with CARS and ABC. Gut microbiota composition was analyzed by shotgun metagenomic sequencing. RESULTS: Both groups demonstrated significant improvements in core symptoms. In the FMT group, the mean CARS score significantly decreased from 34.87 to 33.53 (p < 0.01); in the KD group, it declined from 35.13 to 33 (p < 0.01). The mean ABC score reduced from 79.93 to 69.33 (p = 0.064) in the FMT group and from 63.07 to 42.73 (p < 0.01) in the KD group. Following the intervention, no statistically significant changes were observed in α-diversity or β-diversity within either group. LEfSe analysis revealed distinct post-intervention microbial signatures: FMT significantly enriched butyrate-producing taxa (Wujia chipingensis, Eubacterium sp. MSJ-33, and Butyrivibrio crossotus), while KD elevated Blautia massiliensis and decreased propionate metabolism -associated taxa (Veillonella sp. S12025-13 and Veillonella nakazawae). KEGG enrichment analysis revealed that KD enriched propionate metabolism (Fold enrichment = 3.747, q = 0.010) and aromatic compound degradation (Fold enrichment = 3.591, q = 0.010). CONCLUSIONS: Both interventions significantly improved clinical symptoms among children with ASD, potentially through distinct patterns of gut microbiota modulation. CLINICAL TRIALS NUMBER: NCT06348433 (03/21/2024).

Child↗

PubMed2004

Assessment of intestinal permeability and absorption in cirrhotic patients with ascites using combined sugar probes.

Gastrointestinal dysfunction in patients with cirrhosis may contribute to complications such as malnutrition and spontaneous bacterial peritonitis. To determine whether cirrhotic patients with ascites have altered intestinal function, we compared intestinal permeability and absorption in patients with liver disease and normal subjects. Intestinal permeability and absorption were investigated in 66 cirrhotic patients (48 with ascites, 18 without ascites) and 74 healthy control subjects. Timed recovery of 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose in urine following oral administration was measured in order to assess active and passive carrier-mediated, and nonmediated, absorptive capacity, as well as intestinal large-pore/small-pore (lactulose/rhamnose) permeability. Test sugars were measured by quantitative thin-layer chromatography and results are expressed as a percentage of test dose recovered in a 5-h urine collection. Sugar excretion ratios relating to small intestinal permeability (lactulose/rhamnose) and absorption (rhamnose/3-O-methyl-D-glucose) were calculated to avoid the effects of nonmucosal factors such as renal clearance, portal hypertension, and ascites on the recovery of sugar probes in urine. Compared with normal subjects, the mean lactulose/rhamnose permeability ratio in cirrhotic patients with ascites was significantly higher (0.058 vs. 0.037, P < 0.001) but not in cirrhotic patients without ascites (0.041 vs. 0.037). Cirrhotic patients with ascites had significantly lower mean recoveries of 3-O-methyl-D-glucose (23.0 vs. 49.1%; P < 0.001), D-xylose (18.8 vs. 34.5%; P < 0.001), L-rhamnose (4.0 vs. 9.1%; P < 0.001), and lactulose (0.202 vs. 0.337%; P < 0.001) than normal subjects. However, the mean rhamnose/3-O-methyl-D-glucose ratio was the same in cirrhotic patients with ascites as normal subjects (0.189 vs. 0.189), indicating that the reduction in probe recovery was due to nonmucosal factors. Compared with normal subjects, cirrhotic patients with ascites have abnormal intestinal permeability, measured by urinary lactulose/rhamnose excretion, and normal small intestinal absorption, assessed by the urinary rhamnose/3-O-methyl-D-glucose ratio. Low urine recovery of sugar probes found in cirrhotic patients appears to be the result of nonintestinal factors affecting clearance rather than reduced intestinal absorption.

Analysis of Variance↗

PubMed2002

Poisoning as a result of barium styphnate explosion.

BACKGROUND: Acute barium poisoning is most often the result of accidental or suicidal ingestion of the rodenticide, barium carbonate. We describe a trauma patient whose condition was complicated by severe acute barium toxicity from an explosion of the propellant, barium styphnate. In addition to critical injuries, the patient manifested classic signs of barium toxicity including repeated profound hypokalemia, cardiac arrhythmias, respiratory failure, prolonged gastrointestinal dysfunction, paralysis, myoclonus, hypertension, and profound lactic acidosis. METHODS: The patient required lidocaine for ventricular bigeminy, massive infusions of potassium, prolonged ventilatory support, and parenteral nutrition to manage the effects of barium toxicity. RESULTS: He is the first reported case to demonstrate recurrent profound hypokalemia as an effect of blood transfusions. CONCLUSIONS: Considering the paucity of information concerning management of this life-threatening problem, the pathophysiology of barium toxicity, including the transfusion related hypokalemia, and its management is reviewed.

Accidents, Occupational↗

PubMed1979

The natural history of peripheral neuropathy in primary systemic amyloidosis.

The records of 31 patients with primary systemic amyloidosis and peripheral neuropathy seen during a 17-year period were analyzed to define the natural history of the neuropathy. Patients tended to be older men with a painful, distal, symmetrical sensorimotor neuropathy and prominent autonomic features. Loss of pain and temperature sensation was frequently more striking than loss of mechanoreception. Renal, cardiac, hematological, and gastrointestinal dysfunction often overshadowed the neuropathy. Clinical, neurophysiological, and histopathological studies pointed to axonal degeneration with predominant but not exclusive involvement of small myelinated and unmyelinated fibers. The neuropathy was progressive in all patients with or without treatment, but death was typically due to supervening medical complications.

Aged↗

PubMed1996

Pharmacokinetics of cyclosporine after renal transplant in children.

The pharmacokinetics of cyclosporine and the relationship between blood levels and average drug concentration were prospectively evaluated in 18 children 1 month after renal transplantation. All children had normal renal function and no hepatic or gastrointestinal dysfunction. Cyclosporine was administered after an overnight fast, and serial blood samples were drawn over a 24-hour period. Analysis of cyclosporine levels was performed by means of monoclonal radio immunoassay on whole blood. Children were divided into three age groups for comparison: 2-5 years, 5-10 years, and > 10 years. There were no differences between age groups in serum protein, serum lipids, or hemoglobin levels, or in the pharmacokinetic parameters of cyclosporine except as follows: significant differences were noted in cyclosporine dose based on body weight, apparent steady-state volume of distribution, and apparent blood clearance, with the youngest children (2-5) requiring higher doses, a relative greater distribution, and exhibiting more rapid drug clearance than those > 10 years of age. In addition, we observed diurnal variation in trough levels, with morning levels (0 hr) significantly higher than those obtained in the evening (12 hours after administration of cyclosporine). Trough levels demonstrated a fair correlation with area under the concentration-time curve (AUC) and average concentration (Cav), but an abbreviated kinetic profile using cyclosporine levels 1 and 3.5 hours after administration accurately predicted AUC.

Adolescent↗

PubMed1989

Denervation and hyperinnervation in the nervous system of diabetic animals. I. The autonomic neuronal dystrophy of the gut.

Peripheral neuropathy is a correlate of experimental diabetes induced in rats by means of a single injection of alloxan. The autonomic and enteric innervation of the gut are profoundly affected in the small intestine of such animals. A complex process of denervation and hyperinnervation of the gut wall of diabetic animals is observed. It was previously reported that the cholinergic parasympathetic innervation of the intestine is markedly reduced. We have found that noradrenergic sympathetic axons hyperinnervate the duodenum of diabetic rats, whereas noradrenaline levels are significantly reduced in the jejunum. The putative enteric neurotransmitter dopamine is also present in higher levels in the duodenum. The intrinsic peptidergic neurons of the gut are deeply affected as well in diabetic rats. Substance P and met-enkephalin content are remarkably reduced throughout the small intestine, whereas vasoactive intestinal polypeptide levels (VIP) are significantly increased in the duodenum. Indeed, immunocytochemical staining of the ileum did reveal hypertrophy of VIP-positive axons in diabetic rats. The intrinsic serotoninergic innervation of the gut is apparently unaffected. Our results indicate that the changes of gut innervation observed in experimental diabetes are consistent with increased content and also likely with hyperinnervation by the neuronal systems involved in smooth muscle relaxation and decreased content and with denervation by those systems with smooth muscle contraction properties. Such a perturbed gut innervation may be responsible of the gastrointestinal dysfunctions that are among the most common complications of diabetes.

Alloxan↗

PubMed1995

Site-dependent pathological differences in smooth muscles and skeletal muscles of the adult mdx mouse.

This study presents a survey of the morphometric characteristics, the regeneration rate, and the extent of muscle dystrophy in several smooth and skeletal muscles from adult mdx mice, an animal model of the Duchenne muscular dystrophy (DMD). Smooth muscles from adult mdx mice showed neither cell necrosis nor fibrosis. As compared to control C57 mice, the thickness of the mdx smooth muscle was normal in the vascular and urogenital layers but significantly reduced in the digestive layers, a finding relevant to clinical reports of gastrointestinal dilatation in DMD patients, and suggesting that gastrointestinal dysfunctions should be systemically searched for in DMD patients. Adult mdx skeletal muscles, however, presented different patterns of muscle suffering: either absent (esophagus); very mild (trunk and limb muscles); or severe (diaphragm). In these three conditions we studied the fiber diameters, the nuclei locations, and the regeneration rate. From this comparative study, it seems that severe dystrophy occurs in muscle tissues showing large fiber diameter and peripheral location of the nuclei. We showed that this combination occurs in the mouse diaphragm which is thus a realistic model for human DMD muscles.

Animals↗

PubMed1995

Early prenatal diagnosis of cartilage-hair hypoplasia (CHH) with polymorphic DNA markers.

Cartilage-hair hypoplasia (CHH) is an autosomal recessive disorder resulting in short stature and hypoplasia of hair. Associated features include impaired T-cell-mediated immunity, deficient erythropoiesis, gastrointestinal dysfunction, and an increased risk of malignancies. As the condition may, in some cases, be severe or even fatal during childhood, families with a previous history of CHH may wish to have prenatal diagnosis. We have previously assigned the gene for CHH to the proximal 9p by linkage analysis using several polymorphic DNA markers. Here we report the prenatal testing for CHH in three Finnish and one Australian family using three DNA markers closely linked to the CHH gene. In three cases a fetus unaffected with CHH was predicted at the probability level of more than 94 per cent. In one case, an affected fetus was predicted. The results were in concordance with ultrasonography performed for all fetuses. The three children born to date were unaffected as predicted. The DNA marker-based analysis thus provides a useful method for early prenatal testing for CHH.

Base Sequence↗

PubMed1999

Blindness as a consequence of a paraneoplastic syndrome in a woman with clear cell carcinoma of the ovary.

BACKGROUND: Paraneoplastic syndromes are rare conditions associated with cancer that result in serious disease states at unique sites. In 1982, a report of bilateral diffuse uveal melanocytic proliferation associated with nonocular cancers which resulted in blindness was reported. We present a case of a woman with recurrent ovarian cancer who developed this paraneoplastic syndrome. CASE: A 55-year-old woman had been diagnosed in 1990 with an ocular melanoma of her right eye and in 1994 with clear cell carcinoma of the ovary. With recurrence of ovarian cancer, new eye lesions were identified in both eyes. After enulcleation of her right eye, an ocular melanoma and diffuse bilateral melanocytic proliferation (BDUMP) were found. The sight in her left eye continued to deteriorate as other signs of BDUMP occurred in the eye. Within 1 month of diagnosis, the patient was blind. She subsequently succumbed to progression of ovarian cancer. CONCLUSION: Recurrent ovarian cancer is usually an intraabdominal disease that results in gastrointestinal dysfunction. This case illustrates a rare paraneoplastic syndrome associated with ovarian cancer that mimics metastatic disease to the eye, but has a different pathophysiology.

Adenocarcinoma, Clear Cell↗

PubMed1995

Is outpatient laparoscopic cholecystectomy wise?

The authors report a prospective analysis of their experience with 506 consecutive laparoscopic cholecystectomies to examine the appropriateness of outpatient or same-day laparoscopic cholecystectomy. Thirty-eight patients experienced at least one postoperative complication. The complication was clinically evident or suspected in only 4 of these 38 patients within 8 h following surgery. Thirty-nine percent and 76% of complications were clinically detected at 24 and 48 h, respectively. Nausea and vomiting occurred among 32% of all patients on the day of operation and extended into the 1st postoperative day in 10%. Compared to predicted values, forced vital capacity was 61 +/- 5% 1 h postoperatively in 32 patients studied. At 6 and 24 h postoperatively, forced vital capacity was 63 +/- 7% and 66% respectively. Postoperative analgesic medication requirement was determined in 220 patients who were provided with a patient-controlled intravenous morphine analgesia machine with no basal rate. Consumption of morphine was highly variable but substantial on the day of operation: 17 +/- 16 mg. Most complications of laparoscopic cholecystectomy, including life-threatening complications, are not apparent by 8 h postoperatively and may not be apparent at 24 h. The potential for delay in the diagnosis and treatment of complications, variable but substantial analgesic requirements, impaired postoperative ventilation, and postoperative gastrointestinal dysfunction argue for the need to use great caution in selecting patients for outpatient laparoscopic cholecystectomy. Criteria are proposed to identify patients who are safest for outpatient laparoscopic cholecystectomy.

Administration, Oral↗

PubMed1995

Prevalence of sexual abuse among patients with functional disorders of the lower gastrointestinal tract.

To evaluate the links between gastrointestinal disorders and sexual abuse, we asked 344 patients consulting in a specialized tertiary care university hospital or a gastroenterologist in private practice, if they had been sexually abused. Forty per cent of patients suffering from lower functional digestive disorder gave a history of having been victims of sexual abuse in contrast to only 10% of patients with organic diseases (P < 0.0003). The prevalence was similar in private practice and in the university hospital. Abused patients were more likely to complain of constipation (P < 0.03) and diarrhoea (P < 0.04). Anismus was more frequent in patients who had been sexually abused (P < 0.02). The prevalence of abuse was four times greater in patients with lower than with upper functional motor disorders of the gastrointestinal tract (P < 0.002). This study confirms the large prevalence of a past history of sexual abuse among patients consulting for gastrointestinal tract functional disorder, and this whatever the kind of recruitment may be. It shows the association to be much stronger in patients who have a lower rather than an upper gastrointestinal dysfunction, the major complaint of abused patients being constipation and diarrhoea.

Adolescent↗

PubMed1981

Morphometric analysis of autonomic neuropathology in the abdominal sympathetic trunk of the ketonuric diabetic Chinese hamster.

Fibers from the infradiaphragmatic portion of the sympathetic trunk of ketonuric diabetic Chinese hamsters were quantitatively analyzed by light and electron microscopy to determine frequency distribution and numerical density. Myelinated and unmyelinated fibers displayed a significant reduction in diameter which was exacerbated by increased duration of ketonuria. Mean numerical density of myelinated fibers was reduced whereas that of unmyelinated fibers was increased. The alterations in sympathetic nerve populations are believed to be a manifestation of previously observed demyelination and axonal degeneration. On the basis of axon diameter, it appeared that both visceral afferent and efferent fibers were affected. These data strongly suggest that autonomic neuropathology in the sympathetic trunk of the diabetic Chinese hamster may be a critical factor underlying gastrointestinal dysfunction.

Animals↗

PubMed1986

Enteric nerves in diabetic rats: electron microscopic evidence for neuropathy of vasoactive intestinal polypeptide-containing fibres.

Enteric nerves in the ileum of rats 8 weeks after streptozotocin-induction of diabetes were examined under the electron microscope before and after immunolabeling for vasoactive intestinal polypeptide (VIP). These studies have provided evidence of degenerative changes in the myenteric nerve fibres of diabetic rats, many of which were shown to contain VIP. It is suggested that VIP-ergic nerves in the gut may play a role in the development of gastrointestinal dysfunction in diabetes.

Animals↗

PubMed1979

Radiologic abnormalities and autonomic neuropathology in the digestive tract of the ketonuric diabetic Chinese hamster.

Barium x-ray patterns of ketonuric diabetic Chinese hamsters displayed marked dilatation of the stomach, small and large intestine. Hypomotility was manifested by flocculation of barium in the small and large bowel. Impaired transit time was further characterized by prolonged emptying of the stomach (mean 570 min diabetics; 200 min controls) and delayed stool formation (mean 230 min diabetics; and 100 min controls) and passage (mean 457 min diabetics; 210 min controls). Ultrastructural analysis of Auerbach's myenteric plexuses of the small intestine indicated acute degeneration in certain distal, unmyelinated axons. Swelling, deposition of glycogen, aggregation of neurofilaments and dense accumulation of lamellar bodies were observed. The severity and frequency of barium flocculation, glycogen deposition, aggregation of neurofilaments and lamellar inclusion bodies in axons were directly related to duration of ketonuria. The data strongly suggest that autonomic neuropathology in the plexuses of Auerbach may be a critical factor underlying gastrointestinal dysfunction in the ketonuric diabetic Chinese hamster.

Animals↗

PubMedDate not supplied

Neonatal necrotizing enterocolitis: experience with 100 consecutive surgical patients.

One hundred newborns with neonatal necrotizing enterocolitis (NEC) were treated surgically according to a uniform protocol between July, 1980 and June, 1988. The infants (53 females, 47 males) weighed between 600 and 3,800 g, averaging 1,500 g. Twenty-eight weighed less than or equal to 1,000 g, 38 weighed from 1,001 g to 1,500 g, and 34 weighed more than 1,500 g. Median age at the time of surgery was 14 days. Surgery was performed for pneumoperitoneum in 40, a "positive" paracentesis in 51, and for other reasons in 9 infants. A paracentesis was performed if intestinal gangrene was suspected clinically. Resection of gangrenous bowel with exteriorization was the usual procedure; in only 5 patients was primary closure performed. The hospital survival for the infants was 54% for the group weighing less than or equal to 1,000 g, 74% for the group weighing from 1,001 g to 1,500 g, and 79% for the group weighing more than 1,500 g. Overall hospital survival was 70%; it was 81% for those having a definitive procedure (excluding 14 infants with NEC "totalis"). There were 3 late deaths from causes unrelated to NEC. Significant long-term complications included failure-to-thrive in 23% and stricture formation in 30% of the survivors. Long-term follow-up showed gastrointestinal status to be normal in 74%; only 8% have persistent major gastrointestinal dysfunction. Mental and motor development was considered grossly normal in only 53% of the patients.

Birth Weight↗

PubMed1996

Modulation of gut substance P after whole-body irradiation. A new pathological feature.

Exposure to ionizing radiation induces gastrointestinal dysfunction and inflammatory reactions. The present study carried out in the rat, focuses on substance P, an inflammatory mediator implicated in the control of intestinal motility. We have investigated the effects of gamma irradiation on plasma and tissue substance P levels, ileal smooth muscle activity, and properties of specific receptors. Plasma and ileal (mucosa and muscle) substance P concentrations were measured by radioimmunoassay. At doses ranging from 1 to 8 Gy, plasma substance P levels increased in a dose-dependent manner up to four days after irradiation. Ileal mucosal concentration decreased rapidly 1 hr after a 6-Gy irradiation as compared to controls. A second class of binding sites appeared three days after 6 Gy irradiation. In addition, substance P contractile effects measured on isolated ileum showed a fourfold decrease of EC50, three days after 6 Gy irradiation. These results indicated that gamma irradiation induced an increase of plasma levels concomitant with a modification of gastro-intestinal substance P specific binding sites and contractile activity.

Animals↗

PubMed2004

Effects of dietary L-arginine supplementation on serum lipids and intestinal enzyme activities in diabetic rats.

We investigated whether dietary supplementation with L-arginine, the endogenous precursor of nitric oxide, might affect serum lipid levels and activities of intestinal mucosa enzymes in animals, in which diabetes was induced by administration of streptozotocin. Control and diabetic rats were fed diets with or without 2% L-arginine supplementation for 4 weeks. Diabetic rats had significantly higher concentrations of serum triglycerides and LDL-cholesterol than control rats. These alterations were partially reduced by L-arginine supplementation. Experimental diabetes did not influence the lactase and leucine aminopeptidase activity in the intestine, but the activity of alkaline phosphatase was increased. Furthermore, activities of maltase and sucrase in the intestinal mucosa were elevated in streptozotocin-induced diabetic rats and were restored to control levels after dietary L-arginine supplementation. On the basis of the present experimental evidence, dietary L-arginine supplementation appears to affect the metabolism of lipoproteins and might alleviate some gastrointestinal dysfunctions, commonly seen in diabetes mellitus.

Animals↗

PubMedDate not supplied

Clinical development of human polymerized hemoglobin as a blood substitute.

Although the efficacy of hemoglobin-based oxygen carriers was established more than 60 years ago, all prior clinical trials have demonstrated significant toxicity characterized by renal dysfunction, gastrointestinal distress, and systemic vasoconstriction. The mechanisms of these toxicities now appear to be understood. Tetrameric forms of the hemoglobin molecule extravasate from the circulation and interact with endothelium-derived relaxing factor, leading to unopposed vasoconstriction. Although numerous efforts are under way to chemically modify the native tetramer, it is likely that all tetrameric forms of the hemoglobin molecule will continue to extravasate. We have focused on developing a polymerized form of hemoglobin that is virtually free of unreacted tetramer. The development and characterization of this polymerized pyridoxylated hemoglobin solution (Poly SFH-P) is described. Clinical trials have been completed successfully in volunteers and are now under way to assess the safety and efficacy of Poly SFH-P as a clinically useful red blood cell substitute for treatment of acute blood loss in the setting of trauma and surgery.

Animals↗