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Biomedical subjects

J Markowitz

Publications and source records attributed to J Markowitz.

At least 37 records · Page 2Linked to original sources

Immunosuppressive therapy in pediatric inflammatory bowel disease: results of a survey of the North American Society for Pediatric Gastroenterology and Nutrition. Subcommittee on Immunosuppressive Use of the Pediatric IBD Collaborative Research Forum.

We report the results of a survey of the membership of the North American Society for Pediatric Gastroenterology and Nutrition designed to determine pediatric gastroenterologists' attitudes toward the use of immunosuppressive therapy for inflammatory bowel disease (IBD), and to assess how these medications are actually being used in the treatment of children with IBD. One hundred five physicians (27% of surveys) responded. Eighty-eight (84%) had prescribed 6-mercaptopurine and/or azathioprine for IBD, and 66 believed that they were effective. Only 12 had used cyclosporine and four methotrexate. All physicians who had used immunosuppressives in IBD had prescribed them for patients with Crohn's disease, but only 50% had prescribed them for ulcerative colitis. The predominant indications for use included intractable symptoms despite traditional medical therapy (92%) and for corticosteroid-sparing effects (86%). Potential toxicities of greatest concern included marrow and immune suppression and malignancy. The vast majority of responders were not certain what to recommend with respect to the use of immunosuppressive agents prior to and during pregnancy. A clinical database was compiled from 165 retrospective case reports submitted by 45 physicians (33 medical facilities). At the start of immunosuppressive therapy, patients were 15.3 +/- 4.0 yr of age, and 52% were Tanner IV-V. Eighty-one percent had Crohn's disease, 8% ulcerative colitis, and 11% indeterminant colitis. One hundred twenty-two were treated with 6-mercaptopurine, and 43 with azathioprine. Five also received cyclosporine concomitantly. Overall, 68% of patients treated with an immunosuppressive improved. Complications requiring discontinuation of immunosuppressive therapy occurred in 6% of patients. It appears that immunosuppressives are commonly used to treat children with IBD despite a paucity of data regarding their safety and efficacy in this age group. Controlled, prospective trials are warranted to better define the role of immunosuppressive therapy in pediatric IBD.

Adolescent

Effect of electroconvulsive therapy on the electrocardiogram and echocardiogram.

Although electrocardiographic (ECG) ST segment depression is commonly induced by electroconvulsive therapy (ECT) for depression, it is unknown whether this reflects segmental myocardial ischemia, as is true under most circumstances, or a direct effect of central nervous system stimulation on cardiac repolarization in the absence of ischemic left ventricular regional wall motion abnormalities. We evaluated the association between ECG changes and left ventricular regional wall motion abnormalities detected by the echocardiograms performed before and after ECT in 11 patients. Immediately after ECT, three patients' ECGs revealed 1-mm downsloping or horizontal ST segment depression, one had a nonspecific ECG change (peaked T waves), and the ECG remained normal in seven. All patients had normal baseline echocardiograms. After ECT, at a time when the product of arterial blood pressure and heart rate was 100% above baseline values, five patients developed new left ventricular regional wall motion abnormalities that were confined to hypokinesia; no patient developed myocardial infarction or angina after ECT. Three patients with regional wall motion abnormalities developed ECG ST segment depression after ECT (sensitivity 60%), one had a nonspecific ECG change (peaked T waves), and the ECG of one patient remained normal. In conclusion, ECT may induce ECG changes with simultaneous regional wall motion abnormalities at a time when arterial blood pressure and heart rate are markedly elevated, findings that are highly suggestive of "demand" myocardial ischemia. In this small series, ECG or echocardiographic abnormalities did not predict clinical cardiac morbidity.

Adult

The use of a new radiopharmaceutical, 97Ru-DISIDA, and of 99Tcm-sulphur colloid for the simultaneous evaluation of duodenogastric reflux and gastric emptying.

There is no consensus or a uniform technique for measuring gastric emptying and numerous modalities have been reported. We report here the results obtained using a modification of the published techniques for the simultaneous measurement of duodenogastric reflux and gastric emptying utilizing simultaneously the recently developed radiopharmaceutical 97Ru-DISIDA, intravenously, and the oral administration of 99Tcm-sulphur colloid incorporated in a 'solid' test meal.

Administration, Oral

The appendix in inflammatory bowel disease in children.

The morphologic characteristics of the colon in ulcerative colitis and Crohn's disease are well established, but specific appendiceal pathology is less clearly defined. In addition, the frequency of appendiceal involvement in children with inflammatory bowel disease has also not been delineated. We have determined the prevalence of appendiceal involvement in 41 children with inflammatory bowel disease (24 with Crohn's disease and 17 with ulcerative colitis) who required colonic resection and have defined the histopathologic characteristics of the appendix in these diseases. All appendices were abnormal. Specific changes of Crohn's disease or ulcerative colitis were observed respectively in 50% and 56% of the appendices in our patient population. Nonspecific changes only such as fibrous obliteration, serosal fibrosis and lymphoid and/or neuronal hyperplasia were noted in the remaining appendices. The severity of ileocolonic and appendiceal inflammation was similar in about two thirds of the patients with either type of inflammatory bowel disease.

Adolescent

Erosion through the posterior gastric wall by a pancreatic pseudocyst secondary to gastric duplication.

Gastric duplications are the rarest form of enteric duplication. They account for about 20% of all gastrointestinal duplications. Delayed and missed diagnosis leads to prolonged morbidity and mortality. We report a case of a child with a gastric duplication cyst in the body of the pancreas, associated with a pancreatic pseudocyst that ultimately eroded into the posterior wall of the stomach.

Humans

Heterogeneity of clinical response during placebo treatment.

OBJECTIVE: The authors attempted to identify different patterns of improvement among patients receiving placebo during clinical trials. It was hypothesized that patients who improved abruptly would differ from patients whose improvement was gradual in that they would tend to improve earlier and would tend to have less persistent improvement. METHOD: The subjects were 144 patients who met the DSM-III criteria for depressive illness and were randomly assigned to placebo medication in four double-blind antidepressant drug trials. All studies lasted 6 weeks. Mood change was rated each week on a 7-point scale; a rating of 1 or 2 was considered an indication of improvement. Improvement was judged to be abrupt if the first score of 1 or 2 was immediately preceded by a score of 4 or worse, and it was classified as gradual if the first score of 1 or 2 was preceded by a score of 3 in at least 1 week. Improvement was considered persistent if a score of 1 or 2 was not followed by a score of 3 or worse in any subsequent week. RESULTS: Of the 144 patients, 72 showed clinical improvement during at least one weekly visit; 33 improved abruptly and 39 improved gradually. The abrupt improvements occurred significantly earlier in the trial and were less likely to persist than the gradual improvements regardless of when they occurred. CONCLUSIONS: These data suggest that among patients receiving placebo abrupt improvements are a form of placebo response and gradual responses may be the result of spontaneous remission. These preliminary observations require validation.

Adolescent

Different types of placebo response in patients receiving antidepressants.

OBJECTIVE: The authors studied the responses of drug-treated patients in an attempt to validate observations about abrupt and gradual improvements in patients receiving placebo. Since previous data suggested that in the first 2 weeks of antidepressant treatment specific drug effects are unlikely, the authors hypothesized that this improvement is a placebo effect. Therefore, in the first 2 weeks of antidepressant treatment abrupt and gradual improvements should have the characteristics of their placebo counterparts. METHOD: The subjects were 263 patients in controlled antidepressant trials lasting 6 weeks. RESULTS: The percentage of abrupt improvements that occurred in the first 2 weeks was higher than that for gradual improvements. Abrupt improvements during the first 2 weeks of drug treatment were also less persistent than gradual improvements with drug and no more persistent than improvements with placebo during the same period. However, in weeks 3, 4, and 5, abrupt and gradual improvements with drug were equally persistent and both were more persistent than abrupt improvements with placebo. CONCLUSIONS: These data support the authors' findings about placebo. Abrupt improvements during treatment with both drug and placebo are more likely during the first 2 weeks of treatment and are less likely to persist than gradual improvements. The fact that persistence of abrupt improvements with drug in weeks 1 and 2 appears different from that of gradual improvements but appears no different after week 3 suggests that the mechanism of action of abrupt improvement with drug changes after week 2.

Adolescent

Immunology of inflammatory bowel disease: summary of the proceedings of the Subcommittee on Immunosuppressive Use in IBD.

As outlined, scanty data exist with regard to immunologic therapy in children with IBD despite the fact that the pediatric population affords a unique opportunity for clinical evaluation. Children are less affected by modifying conditions such as smoking, alcohol ingestion, and the long-term use of medications, and because of their specific needs for ponderal and linear growth, children might benefit most from immunological therapy that has been proven to be steroid sparing. Therefore, clinical trials to evaluate the efficacy of 6-MP and/or azathioprine in growing children with Crohn's disease would appear to provide a fruitful avenue for collaborative research. Efforts to organize a multicenter evaluation of these agents have been initiated. The studies are crucial in evaluating the efficacy and safety of immunosuppressive therapy in the pediatric population with IBD.

Aminosalicylic Acids

Neuronal intestinal dysplasia: quantitative diagnostic criteria and clinical management.

Neuronal intestinal dysplasia (NID) clinically resembles Hirschsprung's disease but is characterized by hyperplasia rather than aganglionosis of the intramural plexus. Surgical intervention is common. We report the 5-year follow-up of an infant with the mixed form of NID managed medically and a method by which NID can be quantified histologically. Hyperganglionosis was determined by counting the number of ganglia per high-power field and the number of ganglion cells per ganglia from at least two biopsy specimens. The patient's biopsies and biopsies from "normal" and "inflamed" patients were compared. Normals contained 0.68 +/- 0.28 (mean +/- SD) ganglia per high-power field and 2.16 +/- 0.31 ganglion cells per ganglion. The inflamed biopsies were similar, 0.69 +/- 0.38 ganglia per high-power field and 2.63 +/- 0.40 ganglion cells per ganglion. The patient's initial rectal biopsy revealed 7.6 ganglia per high-power field and 3.8 ganglion cells per ganglion. Management of the patient included saline colonic irrigations and hyperalimentation with gradual reinstitution of breast-feeding. Clinical improvement was associated with normalization of manometry and biopsy findings, a phenomenon not documented previously in the literature. Irrigations were stopped at age 9 months, and the child is now asymptomatic.

Biopsy

Long-term 6-mercaptopurine treatment in adolescents with Crohn's disease.

Although 6-mercaptopurine is often used to treat adolescents with intractable Crohn's disease, its long-term efficacy has not yet been studied in this population. This study shows data derived from 36 adolescents (mean age +/- SD, 16.5 +/- 3.3 years; 27 males, 9 females) treated at least 6 months with 6-mercaptopurine (1.5 mg.kg-1.day-1, maximum of 75 mg/day). Sites of Crohn's disease at the start of 6-mercaptopurine therapy included 17 ileocolic, 9 pancolic, 7 small bowel, and 3 partial colon. All had received corticosteroids, sulfasalazine, antibiotics, and nutritional support for 5.0 +/- 3.0 years before administering 6-mercaptopurine, but intractable symptoms persisted. Disease activity lessened during the first year of 6-mercaptopurine, reflected by a higher Lloyd-Still disease activity score (pre, 64 +/- 9 vs. 6-mercaptopurine, 72 +/- 11; P less than 0.0001). General activity, physical examination, nutrition, and laboratory subscores all improved (P less than 0.004). Lessened disease activity occurred despite concomitant decrease in duration of prednisone use (pre, 9.5 +/- 4.2 vs. 6-mercaptopurine, 6.6 +/- 4.9 months/year; P less than 0.001) and cumulative annual prednisone exposure (pre, 3672 +/- 2106 vs. 6-mercaptopurine, 1964 +/- 1460 mg; P less than 0.0007). The frequency of perianal fistulae and abscesses also decreased (P less than 0.01) during treatment. Annual rates of hospitalization decreased in 44% of subjects during 6-mercaptopurine treatment, while increasing in only 22%. Follow-up beyond 1 year of 6-mercaptopurine treatment showed continued remission in 23 of 30 subjects. No serious complications were seen. 6-mercaptopurine is an effective long-term therapy for adolescents with intractable Crohn's disease. While inducing remission, it also has a significant steroid-sparing effect which may be of particular benefit to this population.

Abscess

Phenelzine and imipramine in mood reactive depressives. Further delineation of the syndrome of atypical depression.

Sixty patients who met Research Diagnostic Criteria for major, intermittent, or minor depressive disorder and had reactive mood without atypical symptoms were treated with imipramine hydrochloride, phenelzine sulfate, or a placebo. These patients, referred to as simple mood reactive depressives, were contrasted with previously published data from 180 atypical depressives. Atypical depressives had the presence of at least one vegetative atypical sign (hypersomnia, hyperphagia, leaden feeling, or rejection sensitivity) but were otherwise indistinguishable from simple mood reactive depressives. In contrast to the atypical depressives for whom phenelzine was effective and imipramine was relatively ineffective, both medications were equivalently good in simple mood reactive depressives. Since all groups did poorly when given a placebo and well when given phenelzine, the salient feature of atypical symptoms may be that they predict poor response to imipramine. Since the difference between imipramine and placebo depends on the diagnostic group, pharmacologic dissection suggests that atypical symptoms in patients with nonautonomous mood may delineate a qualitatively distinct subgroup.

Adult

Relevance of DMS-III depressive subtype and chronicity of antidepressant efficacy in atypical depression. Differential response to phenelzine, imipramine, and placebo.

One hundred ninety-four nonmelancholic depressed outpatients with features of atypical depression took part in a 6-week randomized trial of imipramine hydrochloride, phenelzine sulfate, and placebo. Their courses of illness were also rated for chronicity. Significantly more patients responded to phenelzine (71%) than to imipramine (48%), which benefited significantly more patients than placebo (26%). Both chronicity and DMS-III diagnosis predicted response on several outcome measures. For example, patients with dysthymic disorder responded better to treatment than did those with major depression, suggesting that dysthymic disorder can be treated with medication. Placebo response correlated inversely with chronicity, regardless of DMS-III diagnosis. Atypical depression and longitudinal course of illness may add to the usefulness of DMS-III depressive diagnosis as a predictor of antidepressant response.

Adolescent

Human ontogeny of the bile duct to portal space ratio.

Paucity of interlobular bile ducts is a common feature of cholestatic liver disease in premature infants. Whereas a bile duct to portal space ratio of 0.9 to 1.8 is cited by Alagille as the norm for children, there are no data regarding the normal bile duct to portal space ratio in preterm infants. In this study, by examining liver tissue obtained from autopsied fetuses and infants, we have determined that the bile duct to portal space ratio increases as a function of postconceptional age. After 38 weeks postconception, a ratio equal to or greater than 0.9 was seen in eight of nine subjects. Therefore, in evaluating premature infants for duct paucity, liver biopsies should be obtained only after 38 weeks. Prior to 38 weeks postconception, a bile duct to portal space ratio less than 0.9 may be physiologic.

Bile Ducts, Intrahepatic

Home nocturnal supplemental nasogastric feedings in growth-retarded adolescents with Crohn's disease.

We hypothesized that supplemental nutritional support delivered at home by nocturnal nasogastric feedings would result in accelerated growth in growth-retarded adolescents with Crohn's disease. Eight Tanner stage I adolescents with Crohn's disease, mean age 14 yr 5 mo, had a mean weight gain of 0.38 kg and height gain of 1.4 cm for the year before initiation of nasogastric feedings. All had been either asymptomatic or had only minimal symptoms in the year before the study, but were ingesting only 55%-80% of their daily required caloric intake. The subjects were taught to pass by themselves a nasogastric feeding tube, through which 1000-1500 ml of commercial, nonelemental isocaloric formula was infused during sleep to supplement their usual dietary intake. After 12 mo of nocturnal feedings, the subjects had a mean weight gain of 11.75 kg and a mean height gain of 6.98 cm. Six control subjects, matched for age and degree of growth and sexual retardation at the beginning of the study period, but who had refused the nasogastric feedings, had no change in weight and height during the same period of observation. We conclude that home nocturnal nasogastric feedings can achieve dramatic improvement in weight gain and linear growth in motivated adolescents with Crohn's disease and growth retardation.

Adolescent

Does proctosigmoiditis in inflammatory bowel disease presage the imminent onset of symptoms?

This study was undertaken to determine if asymptomatic children and adolescents with inflammatory bowel disease and moderate to severe anorectosigmoid inflammation might remain symptom-free for at least 12 months without specific intrarectal therapy. We prospectively studied 13 asymptomatic patients 6-21 years of age (four with Crohn's disease and nine with nonspecific colitis) with previously documented anorectosigmoid inflammation. Of these 13, four had moderate to severe anorectosigmoid inflammation both endoscopically and histologically. These four patients (two with Crohn's disease and two with nonspecific colitis) were entered into the second phase of the study. Three were receiving sulfasalazine, and one received methylprednisolone, 4 mg/day, and 6-mercaptopurine, 50 mg/day. None received intrarectal therapy. Clinical evaluation revealed that all four remained asymptomatic for 12 months despite the continued presence of moderate to severe anorectosigmoid inflammation. These results indicate that in children and adolescents with inflammatory bowel disease, the presence of inflammation of the anorectosigmoid does not necessarily correlate with or presage the onset of symptoms of proctosigmoiditis. Therefore, active inflammation of the anorectosigmoid is not the sole prerequisite for intrarectal therapy. The clinician should be guided by the symptoms of the patient, not by the presence or absence of active anorectosigmoid inflammation.

Adolescent

Amyloidosis in children with inflammatory bowel disease.

Reactive systemic or secondary amyloidosis occurs in 1-29% of adults with Crohn's disease, but only sporadic cases of amyloidosis have been recognized in children with inflammatory bowel disease. We therefore have studied operative specimens (ileal, ileocolonic, and colonic) from 46 children (30 with Crohn's disease and 16 with ulcerative colitis) to determine the frequency of amyloid deposits. Sections of bowel, skin, and lymph nodes (n = 940) were stained by Congo red and examined by light microscopy and by polarized light. Amyloid deposits were found in only one of 46 subjects, an 18-year-old girl who had had Crohn's disease for 6 years. Intestinal amyloid deposits, present 16 months before the clinical diagnosis of amyloidosis, were patchy and seen predominantly in the intestinal mucosa. We conclude that amyloidosis is rare in children requiring surgery for Crohn's disease and ulcerative colitis. Examination of Congo red-stained sections can detect even subclinical amyloidosis. The amyloid deposits in our patient, which were both patchy and consistently mucosal, suggest that multiple endoscopic biopsy samples, not necessarily containing submucosa, are sufficient for diagnosis.

Adolescent

Prognostic significance of epithelioid granulomas found in rectosigmoid biopsies at the initial presentation of pediatric Crohn's disease.

The prognostic significance of epithelioid granulomas in Crohn's disease (CD) remains controversial. We have determined the prognostic significance of epithelioid granulomas noted in endoscopic rectosigmoid biopsies obtained from untreated pediatric patients at initial presentation of CD. Data collected from 19 subjects with rectosigmoid granulomas and inflammation (Group 1) were compared to those obtained from another 37 subjects (Group 2) with CD of the rectosigmoid, but in whom no granulomas were present. Both groups had similar ages at disease onset [Group 1: 11.6 +/- 3.6; Group 2: 10.4 +/- 4.0 years (X +/- SD)]. At diagnosis, Group 1 had more extensive CD (small bowel and colon involvement, with Group 1 74% versus Group 2 30%; isolated rectosigmoid involvement, with Group 1 11% versus Group 2 35%; p less than 0.01). Perianal disease was also more common in Group 1 (58% versus 27% Group 2; p less than 0.05). However, CD activity scores and clinical laboratory findings were comparable. Duration of follow-up was identical (5.6 +/- 3.3 years) for both groups. By the end of the period of follow-up, 43% of Group 2 had developed small bowel involvement, but Group 1 continued to have more extensive CD (p less than 0.05). Perianal fistulae and abscesses and anal stenosis were more frequent in Group 1. Throughout this period, the need for oral and parenteral corticosteroids, 6-mercaptopurine, and nutritional support modalities were similar in the two groups. Although the number of subjects requiring hospitalization and the number of hospitalizations per patient were similar in both groups, Group 1 had more surgery (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy