Mean Villous Height Research Articles

Quantitative histology as a diagnostic tool for celiac disease in children and adolescents

ObjectiveTo measure the villous height, the crypt depth, and the number of intraepithelial lymphocytes/100 enterocytes of the small intestinal mucosa of children and adolescents with celiac disease; and to classify these findings according to Q- Marsh and Q-histology scales. MethodsRetrospective study of a database from the Department of Pathology of biopsies from the second portion of the duodenum of pediatric patients. According to the histological report, three groups were established: celiac disease at diagnosis (n = 50), controls (n = 26), giardiasis (n = 10). In each biopsy, software (cellSens and Image J) evaluated 5 villous heights, 5 crypt depth and the number of intraepithelial lymphocytes/100 enterocytes. ResultsThe celiac group had the lowest mean villous height (197.83 μm) of all three groups (control = 477.70 μm; giardiasis = 397.04 μm. The celiac group's villous:crypt ratio (0.78) was significantly lower than the control group (1.89). The number of intraepithelial lymphocytes ≥25 was exclusive to the celiac group, with a sensitivity and specificity of 100 %. Only celiac patients were included in types 2 and 3 of the Q-histology classification. ConclusionCeliac disease patients showed shorter villous height than other groups, and the number of intraepithelial lymphocytes ≥25 was the best parameter to differentiate celiac from controls and giardiasis groups. Intraepithelial lymphocytes ≥25/100 enterocytes associated with any degree of villous atrophy, the classic Marsh 3 type, set the histological parameters of celiac disease. Quantitative histology is a valuable tool for diagnosing celiac disease, enabling histological changes in a short time, and the Q-histology scale appears to be more suitable than the Q-Marsh scale.

Prevalence and pathologic study of porcine epidemic diarrhea in Jeju

From April 2014 to September 2015, 153 piglets from 52 farms in Jeju were diagnosed with porcine epidemic diarrhea (PED). The major PED cases were focused on suckling piglets (144 piglets, 94.1%), particularly in 1-7-day-old piglets. Histopathologically, severe villous atrophy was observed in the small intestine, especially in the jejunum and ileum. The mean villous height to crypt depth ratios of the jejunum and ileum were 1.4:1 and 1.5:1, respectively. The major histopathologic findings of the small intestine were cytoplasmic vacuolation, cuboidalization, squamation, and exfoliation of the mucosal enterocytes in the villi. The cytoplasmic vacuolations in the enterocytes were the most prevalent lesions in the small intestine and were more severe in the ileum than in the jejunum. According to immunohistochemistry methods, the PED virus (PEDV) antigens were presented in the cytoplasms of the enterocytes, and were distributed more prevalently in the ileum than in the jejunum. PEDV antigens were also detected in the colon of 29 piglets (19.5%). Sequence comparison and phylogenetic analysis indicated that 12 PEDV had more than a 98.9% homology with each other. These PEDV strains were highly homologous with the genogroup 2 North American group.

Randomised clinical trial: adjunctive induction therapy with oral effervescent budesonide in newly diagnosed coeliac disease

The healing of the mucosal lesion in patients with coeliac disease is slow. To determine whether concurrent budesonide and gluten-free diet hasten small bowel healing and symptomatic improvement in patients with newly diagnosed coeliac disease. In a pilot, randomised, double-blind trial, effects on Marsh grading and quantitative duodenal morphometry of 10weeks' effervescent budesonide (initially 9mg/day) or placebo were assessed after 8 and 52weeks. Multiple clinical measures and adverse events were assessed. Nineteen patients were randomised to budesonide and 18 to placebo. No differences (all P>0.32) were observed for the week-8 mucosal response (Marsh 0 or 1) (budesonide: 37% vs placebo: 28%), week-8 remission (Marsh 0) (32% vs 17%), week-52 response (63% vs 44%) and week-52 remission (42% vs 33%). Likewise, the improvement from baseline in villous-height:crypt-depth ratio was not different for the treatment groups. There were no statistically significant differences in clinical measures or adverse events between the treatment groups. No corticosteroid adverse effects were observed. In a post hoc analysis of all patients, Marsh 3C was present at the diagnostic biopsy in 1/9 achieving mucosal remission at 8weeks versus 18/23 not (P<0.001) and mean villous-height:crypt-depth ratio was 1.06 (SD: 0.73) versus 0.46 (0.38) (P=0.005). In this pilot trial, induction therapy with budesonide had no significant effect on mucosal healing in patients with coeliac disease concurrently initiated on a gluten-free diet. Mucosal remission at 8weeks occurred in approximately one in four patients and was associated with less severe histological lesions at diagnosis.

Investigation of Morphological and Functional Changes in the Small Intestine With Pancreatic Disease.

The aim of this study was to investigate the relationship between pancreas and small intestine evaluating the endoscopic and histopathologic findings of the proximal small intestine in pancreatic diseases. Fifty patients (18 patients with chronic pancreatitis, 17 patients with pancreatic cancer, 15 control subjects) underwent enteroscopy using a prototype enteroscope. The villous height of the jejunum on bioptic specimens was measured, and the mean values of the villi were compared among the 3 groups. Exocrine function was calculated by the pancreatic function diagnostic test, and the correlation between the recovery rate of p-aminobenzoic acid and the villous height was assessed. Finally, the distribution of the K cells secreting glucose-dependent insulinotropic polypeptide and the L cells secreting glucagon-like peptide 1 in the duodenum and jejunum was investigated using immunohistochemistry for glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1. The mean villous height in chronic pancreatitis (328 ± 67 μm) was significantly lower than that in pancreatic cancer (413 ± 57 μm) and control subjects (461 ± 97 μm) (P = 0.004 and P < 0.0001, respectively). A positive correlation was found between the recovery rate of p-aminobenzoic acid and the villous height (r = 0.52, P = 0.0001). The presence of K and L cells was verified in the duodenum and the jejunum. Close relationship between pancreas and small intestine was demonstrated.

Comparison of the biological activities of Saccharomyces cerevisiae-expressed intracellular EGF, extracellular EGF, and tagged EGF in early-weaned pigs.

Epidermal growth factor (EGF) ameliorates stress and prevents incomplete gastrointestinal development in early-weaned piglets in commercial swine farming. This study aimed to further analyze the biological activities of intracellularly expressed EGF (IE-EGF), extracellularly expressed EGF (EE-EGF), and tagged EGF (T-EGF) from Saccharomyces cerevisiae in early-weaned pigs. In this study, we assigned 24 pigs to each of 5 groups that were provided a basic diet (the control group) or a diet supplemented with empty vector-expressing S. cerevisiae [the INVSc1(EV) group], T-EGF-expressing S. cerevisiae [the INVSc1-TE(-) group], EE-EGF-expressing S. cerevisiae [the INVSc1-EE(+) group], or IE-EGF-expressing S. cerevisiae [the INVSc1-IE(+) group]. All treatments were delivered at a dose of 60 μg EGF/kg body weight (BW) everyday. All the piglets were sacrificed after 21 day to determine their physio-biochemical indexes, immune functions, and intestinal development. In the piglet experiments, recombinant S. cerevisiae survived throughout the intestinal tract. The BW and intestinal development (e.g., mean villous height, crypt depth, villous height:crypt depth ratio (IVR), and total protein, DNA, and RNA contents) of the piglets were significantly enhanced in the INVSc1-IE(+) group compared with the animals in the INVSc1-EE(+) and INVSc1-TE(-) groups (P < 0.05). In addition, increased proliferating cell nuclear antigen (PCNA) staining was observed in the piglets that received the INVSc1-IE(+) treatment (approximately 80 %) compared with those that received the INVSc1-TE(-) (approximately 70 %) and INVSc1-EE(+) treatments (approximately 70 %). The levels of lactate dehydrogenase (LDH), creatine kinase (CK), alkaline phosphatase (ALP), immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) were also significantly increased in the INVSc1-IE(+) group compared with the INVSc1-EE(+) and INVSc1-TE(-) groups (P < 0.05). Furthermore, the proliferation of piglet enterocytes was also significantly stimulated by both IE-EGF and EE-EGF compared with T-EGF in vitro (P < 0.05). Our data further demonstrate the previously reported hypothesis that IE-EGF is more suitable than EE-EGF or T-EGF for applications in early-weaned pigs.

Analysis of the biological activities of Saccharomyces cerevisiae expressing intracellular EGF, extracellular EGF, and tagged EGF in early-weaned rats.

A growing number of studies suggest that epidermal growth factor (EGF) plays an important role in early-weaned animals. The objective of this experiment was to compare the biological activity of intracellularly expressed EGF (IE-EGF), extracellularly expressed EGF (EE-EGF), and tagged EGF (T-EGF) from Saccharomyces cerevisiae (S. cerevisiae) both in vivo and in vitro. Strains of S. cerevisiae expressing IE-EGF, EE-EGF, and T-EGF were designated INVSc1-IE(+), INVSc1-EE(+), and INVSc1-TE(-), respectively. The production performance, intestinal development, physio-biochemical indexes, and immunological function of early-weaned rats were measured in vivo to evaluate the biological activity of IE-EGF, EE-EGF, and T-EGF. In addition, the proliferation of rat enterocyte was also measured in vitro. In the in vivo experiment, the recombinant S. cerevisiae was shown to survive throughout the intestinal tract. The production performance (e.g., body weight) and intestinal development (e.g., mean villous height, crypt depth, total protein, DNA, and RNA) of the rats were significantly enhanced in the INVSc1-IE(+) group compared with the INVSc1-EE(+) and INVSc1-TE(-) groups (P < 0.05). However, the levels of lactate dehydrogenase (LDH), immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) showed no difference in the INVSc1-IE(+) group compared to the INVSc1-EE(+) and INVSc1-TE(-) groups (P > 0.05), with the only significant difference being found for creatine kinase (CK) (P < 0.05). In the in vitro experiment, the proliferation of enterocyte was significantly stimulated by both IE-EGF and EE-EGF compared with T-EGF (P < 0.05). Herein, IE-EGF is more suitable for application to early-weaned animals compared with EE-EGF and T-EGF.

High dose multiple micronutrient supplementation improves villous morphology in environmental enteropathy without HIV enteropathy: results from a double-blind randomised placebo controlled trial in Zambian adults.

BackgroundEnvironmental enteropathy (EE) is an asymptomatic abnormality of small bowel structure and function, which may underlie vaccine inefficacy in the developing world. HIV infection co-exists in many of these populations. There is currently no effective treatment. We conducted a secondary analysis of a randomised controlled trial of high dose multiple micronutrient (MM) supplementation on small bowel architecture in EE in participants with or without HIV infection.MethodsIn a double-blind parallel-group trial of the effect of MM on innate immune responses to oral vaccines, consenting Zambian adults were randomised to receive 6 weeks of 24 micronutrients as a daily capsule or placebo. HIV status was established after randomisation. Proximal jejunal biopsies were obtained after the supplementation period. Villous height, crypt depth, villous width, villous perimeter per 100 μm muscularis mucosa (a measure of epithelial surface area), and villous cross sectional area per 100 μm muscularis mucosa (a measure of villous compartment volume) were measured in orientated biopsy sections using semi-automated image analysis. Analysis was by intention to treat.Results18 patients received MM and 20 placebo. 6/18 MM and 9/20 placebo patients had HIV. In HIV negative patients given MM compared to placebo, mean villous height was 24.0% greater (293.3 v. 236.6 μm; 95% CI of difference 17.7–95.9 μm; P = 0.006), mean villous area was 27.6% greater (27623 v. 21650 μm2/100 μm; 95% CI of difference 818–11130 μm2/100 μm; P = 0.03), and median villous perimeter was 29.7% greater (355.0 v. 273.7 μm/100 μm; 95% CI of difference 16.3–146.2 μm/100 μm; P = 0.003). There was no significant effect on crypt depth or villous width. No effect was observed in HIV positive patients. There were no adverse events attributable to MM.ConclusionsMM improved small bowel villous height and absorptive area, but not crypt depth, in adults with EE without HIV. Nutritional intervention may therefore selectively influence villous compartment remodelling. In this small study, there was a clear difference in response depending on HIV status, suggesting that EE with superimposed HIV enteropathy may be a distinct pathophysiological condition.

Generation of epidermal growth factor–expressing Lactococcus lactis and its enhancement on intestinal development and growth of early-weaned mice

Background: Epidermal growth factor (EGF) plays an important role in intestinal proliferation and differentiation. Previous studies by others have shown that administration of EGF into the ileum lumen enhances intestinal development.Objective: The objective was to examine the feasibility of expressing and delivering EGF via Lactococcus lactis to early-weaned mice to enhance intestinal development at this critical transition stage.Design: EGF-expressing L. lactis (EGF-LL) was generated with a recombinant approach. Early-weaned mice were orally gavaged with the recombinant bacteria. Body weight, mean villous height, and crypt depth in the intestine were measured to examine the influence of EGF-LL on the intestinal development of early-weaned mice in vivo.Results: Populations of EGF-LL were shown to survive throughout the intestinal tract, and the recombinant EGF protein was also detected in intestinal contents. Weight gain was significantly greater in mice that received EGF-LL than in control mice fed phosphate-buffered saline or L. lactis transformed with the empty vector backbone but was comparable with that of the positive control mice that received recombinant human EGF. EGF-LL increased mean villous height and crypt depth in the intestine. Immunohistochemistry also confirmed that enterocyte proliferation was enhanced in mice that received EGF-LL, as evidenced by the greater number of cells stained with proliferative cell nuclear antigen in the intestine.Conclusions: This study showed that EGF-LL had beneficial effects on the intestinal growth of newly weaned mice. The combination of growth factor delivery and a probiotic approach may offer possibilities for formulating dietary supplements for children during their weaning transition stage.

Effects of Early Versus Delayed Nutrition on Intestinal Mucosal Apoptosis and Atrophy After Traumatic Brain Injury

To determine the optimal time to start nutritional support after traumatic brain injury (TBI). Rats were divided into six groups of seven. All but one of these groups were subjected to moderate closed head trauma under general anesthesia. Groups Ia and Ib were commenced on immunonutrition and standard enteral nutrition, respectively, 8 h later; groups IIa and IIb were commenced on immunonutrition and standard enteral nutrition, respectively, 72 h later; and group III was commenced on a parenteral saline infusion 8 h later. Group IV was a control group fed a laboratory diet and not subjected to trauma. The rats were killed 7 days later, and ileal segments were examined using light and electron microscopy. We used the deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) technique to detect intestinal mucosal apoptosis. Group III had a lower body weight than the other groups (P < 0.005). The mean villous height was highest in groups Ia and IV and lowest in group III. The villi count was lower in groups Ib, IIa, IIb, and III than in group IV (P < 0.005). The apoptotic index counts were higher in groups IIa, IIb, and III than in group IV (P < 0.005). The addition of enriching immunonutrients to early enteral feeding helps preserve an almost normal gut mucosa.

The effects of transplacental porcine circovirus type 2 infection on porcine epidemic diarrhoea virus-induced enteritis in preweaning piglets

The effects of transplacental porcine circovirus type 2 (PCV2) infection on porcine epidemic diarrhoea virus (PEDV)-induced enteritis were examined in neonatal piglets. Six pregnant sows were randomly allocated to an infected ( n = 3) or control group ( n = 3). Three pregnant sows were inoculated intranasally with 6 mL of tissue culture fluid containing 1.2 × 10 5 tissue culture infective doses 50% (TCID 50)/mL of PCV2 strain SNUVR000470 three weeks before the expected farrowing date. Three control pregnant sows were similarly exposed to uninfected cell culture supernatants. Thirty piglets from PCV2-infected sows were randomly assigned to two groups (A and B) of 15 piglets each. Another 30 piglets from noninfected sows were randomly assigned to two groups (C and D) of 15 piglets each. The piglets in groups A and C were dosed orally at three days of age with 2 mL of virus stock (1 × 10 6.5 TCID 50/mL) of the PEDV strain, SNUVR971496, at the third passage. The mean villous height and crypt depth (VH:CD) ratio in PEDV-infected piglets from PCV2-infected sows (group A) were significantly different from those of the PEDV-infected piglets from PCV2 negative sows (group C) at 36, 48, and 72 h post-inoculation (hpi) ( P < 0.05). In PEDV-infected piglets from PCV2-infected sows (group A), significantly more PEDV nucleic acid was detected in the jejunal tissues ( P < 0.05) at 24 hpi than in the same tissues of the PEDV-infected piglets from PCV2 negative sows (group C). Thereafter, at 36, 48, 60, and 70 hpi significantly more PEDV nucleic acid ( P < 0.05) was detected in the jejunal tissues of the PEDV-infected piglets from PCV2 negative sows (group C) than those of the PEDV-infected piglets from the PCV2-infected sows (group A). It is concluded that the clinical course of PEDV disease was markedly affected by transplacental infection of PCV2.

Optical Coherence Tomography to Identify Villous Morphology in Patients with Suspected Celiac Disease

Introduction: The prevalence of celiac disease (CD) is currently increased compared to our experience in the past. Serological findings are very useful in increasing our screening capacity, but histology remains the gold standard in the diagnosis of CD. OCT is a new imaging technique, similar to B-mode ultrasound (US), but its resolution is far greater (5-10 ìm) near to histology. No data are actually available on the use of OCT in the small intestine and, in particular, in the diagnosis of CD. Aim & Methods: Aim of our study is to test the utility of OCT in patients with serological positivity to antigliadine and antiendomisial antibodies undergone to esofago-gastro-duodenoscopy (EGDS) for histological diagnosis. We enrolled 5 patients with suspected CD and 5 normal subjects who underwent EGDS for dyspepsia. OCT scanning of descending duodenum was performed during diagnostic EGDS and biopsies of the same area of the duodenum were taken. Evaluation of OCT images and histological specimens was blind, the analysis being performed independently by a gastroenterologist and a pathologist. Three patterns of intestinal villous morphology were considered (1 = no atrophy; 2 = mild atrophy; 3 = total atrophy). Results: We obtained the same results about villous pattern into the two group with the two techniques, and similar data about mean villous height in celiac group (0.25 mm in the OCT measures vs 0.28 mm in the histological measures) but with an increased value in the data performed by OCT into the normal subjects group (mean villous height: 0.70 mm vs 0.40 mm). Conclusions: There is a good concordance between histology and OCT to identify villous pattern of CD. However measurements of intestinal villous height show an increased value in OCT, particularly in control patients, possibly due to the villous rhitidosis after histological handling. OCT appears to be a promising technique to identify CD during endoscopy. An unsolved problem remains the impossibility to detect, at present, lymphocitic infiltrate and crypt's hypertrophy, two specific tools in the diagnosis of CD. Our preliminary data must be confirmed by further studies. Introduction: The prevalence of celiac disease (CD) is currently increased compared to our experience in the past. Serological findings are very useful in increasing our screening capacity, but histology remains the gold standard in the diagnosis of CD. OCT is a new imaging technique, similar to B-mode ultrasound (US), but its resolution is far greater (5-10 ìm) near to histology. No data are actually available on the use of OCT in the small intestine and, in particular, in the diagnosis of CD. Aim & Methods: Aim of our study is to test the utility of OCT in patients with serological positivity to antigliadine and antiendomisial antibodies undergone to esofago-gastro-duodenoscopy (EGDS) for histological diagnosis. We enrolled 5 patients with suspected CD and 5 normal subjects who underwent EGDS for dyspepsia. OCT scanning of descending duodenum was performed during diagnostic EGDS and biopsies of the same area of the duodenum were taken. Evaluation of OCT images and histological specimens was blind, the analysis being performed independently by a gastroenterologist and a pathologist. Three patterns of intestinal villous morphology were considered (1 = no atrophy; 2 = mild atrophy; 3 = total atrophy). Results: We obtained the same results about villous pattern into the two group with the two techniques, and similar data about mean villous height in celiac group (0.25 mm in the OCT measures vs 0.28 mm in the histological measures) but with an increased value in the data performed by OCT into the normal subjects group (mean villous height: 0.70 mm vs 0.40 mm). Conclusions: There is a good concordance between histology and OCT to identify villous pattern of CD. However measurements of intestinal villous height show an increased value in OCT, particularly in control patients, possibly due to the villous rhitidosis after histological handling. OCT appears to be a promising technique to identify CD during endoscopy. An unsolved problem remains the impossibility to detect, at present, lymphocitic infiltrate and crypt's hypertrophy, two specific tools in the diagnosis of CD. Our preliminary data must be confirmed by further studies.

Villous height and crypt depth in piglets in response to increases in the intake of cows' milk after weaning

AbstractThe hypothesis tested in this experiment was that the structure and function of the small intestine of piglets given a milk liquid diet after weaning depends on their level of energy intake. At weaning (28 days), 42 piglets were allocated to one of five treatments: (1) control group killed at weaning; (2) piglets offered a dry starter dietad libitum; (3) piglets given cow's fresh milk at maintenance energy intake (Ma); (4) piglets given cow's fresh milk at 2-5 Ma; and (5) piglets given cow's fresh milkad libitum. On the 5th day all piglets were killed and samples of gut were taken for histological and biochemical examination. Piglets given milkad libitumgrew faster (P &lt; 0·001) than piglets on all other treatments. Piglets offered the dry starter diet ingested similar quantities of dry matter and energy, and grew at the same rate as piglets given cows' milk at 2·5 Ma. As predicted, piglets given milk at maintenance energy intake grew slower (P &lt; 0·001) and consumed less food (P &lt; 0·001) than piglets in all other treatments. For piglets given both cows' fresh milk and the dry starter diet, there were significant linear relationships (r = 0·72 to 0·82,P&lt; 0·05) between villous height and crypt depth with dry matter (energy) intake after weaning. In turn, mean villous height in both milk-fed and starter-fed piglets was significantly correlated (r = 0·68 to 0·79,P&lt; 0·05) to empty body-weight gain in the first 5 days after weaning. Estimates of digestive enzyme activity and absorptive capacity of the gut did not corroborate the large differences seen between treatments in villous height and crypt depth, and possible reasons are discussed. These data illustrate the interdependence between voluntary food intake and mucosal architecture in determining piglet performance after weaning.

The importance of luminal factors in neomucosal growth

Growing neomucosa on patched intestinal defects has been investigated as a method of expanding the intestinal absorptive area. The purpose of this study was to determine the effect of luminal factors on the rate of growth and function of neomucosa in rabbit ileum. A 2 × 5-cm distal ileal defect was patched with adjacent colon serosa in 10 New Zealand white male rabbits. A similar defect was patched in a bypassed ileal segment in an additional 10 rabbits. Five animals in each group were sacrificed at 4 and 8 weeks for determination of the gross and microscopic growth of neomucosa, glucose uptake, and disaccharidase activity. In addition, tritiated thymidine uptake was measured in neomucosa and incontinuity ileum at the 4-week sacrifice. Grossly, the patched defects were covered in nearly all animals by 4 weeks and coverage was complete at 8 weeks. Microscopically, the mucosa was less well developed in the bypassed group with a mean villous height significantly less than the incontinuity group (139.9 ± 13.9 μm vs 212.33 ± 30.3 μm, P < 0.0005). In vitro uptake of [ 3H]thymidine was significantly higher in neomucosa in bypassed segments when compared with neomucosa in incontinuity segments (692.5 ± 347.8 vs 278.0 ± 134.8, P < .05, expressed as percentage of normal incontinuity ileum). Glucose uptake was similar in both groups but disaccharidase activity was significantly less in the bypassed group. The increased uptake of [ 3H]thymidine in neomucosa in the bypassed segment may reflect the histologic immaturity of this tissue with a greater proportion of DNA synthesizing cells. Morphologically and functionally, the intestinal neomucosa appears better developed in incontinuity segments compared to bypassed segments. Thus, the growth of neomucosa appears to be influenced by luminal contents.

Congenital lactase deficiency. A clinical study on 16 patients.

There are at least 20 rare autosomal recessive disorders that are excessively common in Finland of which congenital lactase deficiency is one. During the last 17 years we have found 16 cases. In each case the mother noted watery diarrhoea, generally after the first feed of breast milk, and at the latest, by age 10 days. The lactose malabsorption was verified at a mean age of 36 (range 3-90) days, by which time the infants were dehydrated and 15 of them weighed less than at birth (mean weight for age was -2.8 SDs). On a lactose-free elimination diet (a group of 6 on Nutramigen and a group of 10 on soy-based formula) the children caught up in growth. One infant in each group showed allergic symptoms. While the infants were being breast fed their faeces contained 20 to 80 g/l lactose. In 24 peroral lactose tolerance tests, the greatest rise in blood glucose concentration was 0.8 mmol/l. Only 2 patients showed abnormal absorption when tested within a week of lactose elimination, and in each absorption tests became normal during the elimination period. Slight to partial villous atrophy of the jejunum was present in 4 early specimens, but in later ones the mean villous height was normal. The mean height of the epithelial cells was reduced and there were fewer intraepithelial lymphocytes in patients. The lactase activities in jejunal biopsy specimens were lower than in most patients with acquired lactase deficiency, with some overlap. The maltase and sucrase activities were normal.

Adaptative changes in the small intestine following bypass operation for obesity. A radioglocal and histological study.

Roentgenographic follow-up studies were made in 7 patients before and at different intervals after jejuno-ileal bypass operation. Length measurements were made by a modified intubation technique, and intestinal transit time was estimated after a standardized contrast meal. Microscopical measurements of mucosal biopsies were done in 6 patients before, and 6 and 12 months after, the operation. A significant increase in the diameter of the functioning small intestine was found 4 months after the operation; in repeated investigations up to 18 months no further dilatation occurred. A gradual increase in intestinal length was demonstrated up to 18 months postoperatively. This compensatory growth appeared earlier and was most pronounced in the ileal part of the functioning intestine. Whereas the emptying time of the stomach and the intestine were unchanged, an increase in transit time was found 12 and 18 months after the operation. Measurements of mucosal biopsies showed an increase in mean villous height of the functioning jejunum of 14% and in the functioning ileum of 32%, 6 months after the operation. One year after operation the increase was 55% and 66% respectively. In the bypassed ileum atrophic changes were found with a decrease in villous height of approximately 18%. Probably the demonstrated hypertrophic changes in the functioning small intestine and the increase in transit time represent the basis for the functional adaptation that occurs in patients with a short gut.

Studies of Small Bowel Adaptation After Intestinal Resection in the Rat

Fasting rats were killed 5 to 6 weeks after a 50-cm resection of either proximal or distal small bowel or sham operation. Remaining intestinal segments appeared increased in both thickness and diameter. The mean villous height was greater in proximal and distal bowel remnants of resected animals than in comparable segments of sham animals of the same age and weight. The number of epithelial cells per μ of villous surface increased in proximal and distal villi. Lactase, sucrase, and maltase activities were significantly lower in homogenates of both whole mucosa and isolated villous epithelial cells collected from proximal remnants. With the exception of sucrase, disaccharidase activity was also significantly lower in whole mucosa and isolated epithelial cells collected from distal remnants. Isolated epithelial cells collected from proximal and distal remnants were incubated with C14-labeled glucose and C14-labeled leucine. The ratios of glucose or leucine counts per min per ml of cell water to counts per min per ml of incubation medium indicated active transport and were equal to ratios obtained from cells collected from control segments. However, when uptake of glucose and leucine was determined as a function of the number of cells, the net transport of both substrates was reduced in cells collected from the distal remnant. Glucose transport in everted gut sacs prepared from proximal remnants was significantly less than control segments. In the early steady state after small bowel resection, the remaining segment shows hyperplasia with an increase in the number of epithelial cells lining the villous surface. These presumably less mature and smaller cells have diminished disaccharidase and transport activity.

Jejunal biopsy in malignant disease.

SUMMARYThe appearance of the small bowel mucosa and mucosal measurements are described in 45 patients with various malignant conditions and compared with the findings in 25 control subjects. The mean villous height and mean total mucosal thickness were significantly reduced in the patients with malignant disease. The mucosa in malignant disease was normal in 38%, and showed simple atrophy in 31%, partial villous atrophy in 29% and subtotal villous atrophy in 2% of cases. The mucosal changes were related to the duration of illness and the degree of loss of weight. They were less frequently detected in patients with bronchial carcinoma. The presence of metastases, the treatment given, the interval before death and the presence of steatorrhœa were not related to the abnormal mucosa. Steatorrhœa was detected in one‐third of the patients, but it was usually slight. Steatorrhœa did not account for weight loss and abnormalities in the small bowel mucosa appeared to be unrelated to the steatorrhœa.