Kenneth A. Huizenga

Crohn's Disease and Cancer

Abstract A follow-up study of 449 patients with Crohns enteritis, enterocolitis or colitis showed the incidence of colonorectal cancer to be 20 times greater in these cases than in a control population. Life-table methods were used for analysis, and complete follow-up observation was achieved in 442 (98.4 per cent) of the patients. (N Engl J Med 289:1099–1103, 1973)

Dysgammaglobulinemia associated with nodular lymphoid hyperplasia of the small intestine

Abstract A syndrome, noted in eight patients, is described. It is characterized by (1) dysgammaglobulinemia, consisting of virtual absence of the IgA and IgM immunoglobulins and a moderately decreased level of IgG immunoglobulin in the serum; (2) an unusual susceptibility to infections; (3) diarrhea, sometimes with steatorrheal features; (4) the presence of Giardia lamblia in the stools; and (5) nodular lymphoid hyperplasia of the small intestine. This combination of features allowed differentiation from gluten-sensitive idiopathic sprue and from acquired idiopathic hypogammaglobulinemia. The screening of patients with sprue-like syndromes also resulted in the detection of two patients with isolated IgA immunoglobulin deficiency. The nodular lymphocytic hyperplasia which may occur in association with dysgammaglobulinemia may be related to functional abnormalities of the so-called central lymphoid tissues. Of practical clinical importance are (1) the possibility of a presumptive diagnosis by roentgenographic studies which may show the nodules in the small intestine in most cases and (2) the suggestion that, in at least some of the patients, remission of the diarrhea may be achieved by the use of tetracycline. Also of clinical significance and of theoretical interest is an increased incidence of carcinoma of the gastrointestinal tract in patients with dysgammaglobulinemia and nodular lymphoid hyperplasia of the small intestine.

Inhibition of in vitro cytotoxicity of lymphocytes from patients with ulcerative colitis and granulomatous colitis for allogeneic colonic epithelial cells using horse anti-human thymus serum.

Summary This study reports the cytotoxic effects in vitro of lymphocytes from the peripheral blood of patients with granulomatous or ulcerative colitis on suspensions of allogeneic colonic epithelial cells after 4 hr of incubation at 37 C. It has shown also that this effect can be inhibited by preliminary incubation of the lymphocytes in the presence of 10% horse anti-human thymus serum but not normal horse serum. Preliminary incubation of the colonic epithelial cells with either serum did not produce any similar inhibitory effect. If the hypothesis is accepted that the cytotoxic effects of lymphocytes on colonic epithelial cells may have a role in the pathogenesis of granulomatous or ulcerative colitis, then it is suggested that a clinical trial of horse anti-human thymus serum, possibly in association with other immunosuppressives, might prove valuable.

Serum globulin deficiencies in non-tropical sprue, with report of two cases of acquired agammaglobulinemia

MONG the published cases of acquired agamA maglobulinemia, a sprue-like syndrome has been reported in at least eight [7-81; Gitlin and associates [9] estimated the incidence of this syndrome in such cases as about 20 per cent. Such an incidence appears to be far too great to be altogether coincidental. Our study of serum globulins in sprue was stimulated by the observation of two cases in which non-tropical sprue and agammaglobulinemia coexisted. It is our aim to report these two cases and to present evidence, obtained from a review of the records in 124 cases of non-tropical sprue, that deficiencies in serum globulin, with or without associated reductions in serum albumin, occur frequently in this disease. These data and also an increase in the concentration of gamma globulin toward normal in one of our patients during a remission of sprue suggest that malabsorption may be an important causative factor in some cases of acquired agammaglobulinemia.

Giant Hypertrophic Gastropathy (Ménétrier's Disease): Pharmacologic Effects on Protein Leakage and Mucosal Ultrastructure

Seven patients with giant hypertrophic gastropathy participated in a gastric intubation perfusion study to investigate the route and mechanism of protein leakage associated with this disease. All patients had gastric tight junctions wider than those in healthy controls. Acute administration of propantheline bromide reduced gastric albumin leakage (-50.7%, p less than 0.05) and concurrently decreased width of tight junctions (p less than 0.05) in all patients. Another antisecretory agent, cimetidine, had no consistent effect on protein leakage or on the width of tight junctions. Pentagastrin and bethanechol chloride increased protein loss but had no effect on the width of tight junctions. These results are consistent with the hypothesis that proteins may take a paracellular route via the tight junctions as they traverse the gastric mucosa and that this may have a cholinergic mechanism.

Modification of in Vitro Cytotoxicity of Lymphocytes from Patients with Chronic Ulcerative Colitis or Granulomatous Colitis for Allogenic Colonic Epithelial Cells

It has been shown that preliminary incubation of the lymphocytes from patients with chronic ulcerative colitis or granulomatous colitis with a lipopolysaccharide extract of Escherichia coli O119:1314 resulted in considerable diminution of their cytotoxic effects in vitro for allogenic colonic epithelial cells, but that this did not occur when the lymphocytes were incubated with phytohemagglutinin-P or the tuberculin preparation purified protein derivative. It is speculated that the E. coli extract could be a specific antigen and that its preincubation with sensitized lymphocytes resulted in their desensitization. If this view were correct, then the phenomenon of cytotoxicity for colonic cells might be a final expression of delayed hypersensitivity in vitro, but the arguments against this are reviewed and presently it remains highly theoretical.

Roentgenologic Features of Lymphoid Hyperplasia of the Small Intestine Associated with Dysgammaglobulinemia

In 1966 Hermans and his co-workers (1) reported eight cases of dysgammaglobulinemia associated with nodular lymphoid hyperplasia of the small intestine. Characteristically, these patients demonstrated an unusual susceptibility to infection, chronic or intermittent diarrhea, reduced concentration of gamma globulins, and roentgenologic evidence of nodular defects in the intestine. Since that report, two more patients have been observed with this combination of findings. The present report is primarily concerned with the roentgenologic appearance of these nodular defects in 10 patients. These tiny, nodular, filling defects are usually evident on films of the upper part of the small intestine and are located primarily in the duodenum and jejunum, although they may also be seen in the terminal part of the ileum and the right colon. Clinical Study All the 10 patients (6 men and 4 women) gave a history of either unusual susceptibility to infection or chronic diarrhea which had persisted for various periods. The ...

Association of gastric carcinoma with idiopathic late-onset immunoglobulin deficiency.

Abstract Among 39 patients with idiopathic late-onset immunoglobulin deficiency (LID) seen at the Mayo Clinic in the past 10 years, 3 had a concomitant carcinomatous gastric lesion (incidence, 7.7%...

Peptic ulcer with islet cell tumor: A reappraisal

Abstract Islet cell tumor-peptic ulcer relationships are reappraised and the findings discussed with regard to more general implications involving the development of peptic ulcer in patients with parathyroid or other endocrine tumors. Atypical features are frequent in patients with peptic ulcer and islet cell adenoma or carcinoma of the pancreas, whether or not the tumors are insulin- or noninsulin-producing. The findings often include clinical and gastric secretory characteristics of the Zollinger-Ellison syndrome, together with the presence of tumors of the parathyroids and other endocrine glands, and a family history of peptic ulcer or endocrinopathy. Even in some patients with less remarkable ulcer features, gastric secretagogue activity was isolated from extracts of the islet cell tumor; in addition, both gastrin- and insulin-secreting islet cell tumors may develop in the same patient. In the majority of instances, the Zollinger-Ellison syndrome may represent the gastrin-secreting islet cell tumor component of familial polyglandular endocrinopathy, although a primary islet cell carcinoma also gives similar ulcer and gastric secretory features.

Further studies of the kinetics of rectal epithelium in normal subjects and patients with ulcerative or granulomatous colitis

ALTHOUGH the cytodynamics of the human gastrointestinal tract has not been studied extensively, data indicate that the renewal time of the rectal epithelium in normal subjects is approximately three days a, 4 Shorter and co-workers s reported that the renewal time of rectal epithelium from patients with active ulcerative colitis was prolonged significantly compared with that of normal subjects, but that it was normal when the disease was in remission. Of considerable interest to us was a similar investigation of patients with granulomatous colitis. The purpose of this communication is to report the findings of a study of the kinetics of the rectal mucosae in normal subjects, patients with granulomatous colitis, and patients with chronic ulcerative colitis, both active and in remission.