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Biomedical subjects

J Markowitz

Publications and source records attributed to J Markowitz.

At least 19 recordsLinked to original sources
PubMed1997

Genetic and morphological findings in progressive familial intrahepatic cholestasis (Byler disease [PFIC-1] and Byler syndrome): evidence for heterogeneity.

Byler disease (ByD) is an autosomal recessive disorder in which cholestasis of onset in infancy leads to hepatic fibrosis and death. Children who have a clinically similar disorder, but are not members of the Amish kindred in which ByD was described, are said to have Byler syndrome (ByS). Controversy exists as to whether ByD and ByS (subtypes of progressive familial intrahepatic cholestasis [PFIC]) represent one clinicopathological entity. The gene for ByD has been mapped to a 19-cM region of 18q21-q22. PFIC caused by a lesion in this region, including ByD, can be designated PFIC-1. Examination of haplotypes in siblings with ByS in two unrelated non-Amish families showed that the gene(s) responsible for their disorder(s) did not lie in the PFIC-1 candidate region. On light microscopy and transmission electron microscopy (TEM), liver tissue differed between Amish children with PFIC-1, who had coarsely granular bile and at presentation had bland intracanalicular cholestasis, and the children with ByS in the two non-Amish families, who had amorphous or finely filamentous bile and at presentation had neonatal hepatitis. Bile acid composition of bile also differed: In the Amish children with PFIC-1 and in one ByS family, the proportional concentration of chenodeoxycholic acid (CDCA) in bile was low compared with normal bile; in the other ByS family, it was only slightly reduced. Genetic analysis and light microscopy and TEM of liver may help distinguish PFIC-1 from other forms of ByS.

Bile↗
PubMed1997

Clinical outcome of ulcerative proctitis in children.

BACKGROUND: Although the course of ulcerative proctitis in adults has been well described, little data are available concerning its clinical behavior in children and adolescents. This study sought to characterize the presentation, response to therapy, and long-term course of ulcerative proctitis in the pediatric population. METHODS: A retrospective chart review was conducted at five pediatric gastroenterology centers. RESULTS: A total of 38 subjects (mean age 11.6 years) were identified with ulcerative proctitis (mean follow-up 4.3 years). Symptoms were mild at diagnosis in 74% and moderate or severe in 26%. Thirty-two percent had a complaint of constipation at presentation. Cessation of symptoms was noted in 68% within 3 months of therapy, an additional 24% within 6 months, and 8% were still symptomatic despite 6 months of therapy. During any subsequent yearly follow-up interval, -55% of patients were asymptomatic, 40% had a chronic intermittent course, and < 5% were continuously symptomatic despite therapy. Eight subjects were treated with oral corticosteroids, one with 6-mercaptopurine, and one with cyclosporine. Extension of inflammation proximal to the rectosigmoid occurred in 11 of 38 subjects (29%), 0.5-11.3 years postdiagnosis. Seven of the 13 subjects (54%) followed for > or = 5 years had proximal extension of disease, and two had undergone colectomy. CONCLUSIONS: Despite a mild presentation in most subjects, ulcerative proctitis seems to have a high risk of proximal extension of disease. The overall response to therapy seems to be similar to that reported for ulcerative colitis in children. Follow-up endoscopic evaluation of patients with ulcerative proctitis seems warranted, especially in the setting of recurrent or recalcitrant symptoms.

Adolescent↗
PubMed1997

Progesterone levels in preterm labor are not affected by ritodrin treatment.

Several in vitro studies reported on increased levels of progesterone secretion from placental tissue. This was not tested in vivo. To study the issue we examined progesterone levels in women presenting with premature labor before treatment, and 24 h and 48 h after beginning ritodrin treatment. A control group consisted of women treated with indomethacin for preterm labor. There were 13 women in the ritodrin group and 12 in the control group. The mean concentration of progesterone in the ritodrin group was 161.7 +/- 74.2, 132 +/- 50.2 and 145 +/- 49.8 ng/ml before treatment, and 24 and 48 h after ritodrin treatment, respectively. The mean progesterone concentration of the group treated with indomethacin was 129 +/- 45.6, 132 +/- 49.5 and 138.6 +/- 53.5 ng/ml before treatment, and 24 and 48 h after treatment, respectively. There were no statistically significant differences between the groups or within each group before and after treatment. Ritodrin treatment does not affect progesterone levels in vivo as demonstrated by in vitro studies.

Administration, Rectal↗
PubMed1997

Endoscopic screening for dysplasia and mucosal aneuploidy in adolescents and young adults with childhood onset colitis.

OBJECTIVES: In adults, the premalignant nature of ulcerative colitis (UC) has long been accepted. Currently there is increasing concern that Crohn's disease (CD) may be equally premalignant. As a consequence, most adults with long-standing UC and many with chronic CD are enrolled in ongoing endoscopic cancer surveillance programs. In contrast, the risk of colonic cancer in adolescents and young adults with either form of colitis is less well recognized, and the need for dysplasia and cancer screening in this population has not been systematically evaluated. We therefore report the prospective results of colonoscopic cancer screening in such a young population. METHODS: Thirty-five adolescents and young adults with long-standing colitis (18 UC, 17 CD; 21 +/- 3 yr old, 11 +/- 3 yr colitis duration) underwent colonoscopic cancer screening. All had multiple biopsies for flow cytometry and light microscopy. RESULTS: Seven subjects had aneuploidy (3/18 UC, 4/17 CD). Of these seven, only two had dysplasia [one high grade (UC), one low grade (CD)]. One additional subject had indefinite dysplasia with normal flow cytometry. The remaining 27 subjects had both normal flow cytometry and light microscopy. Five of the seven aneuploid subjects underwent surgery within 1 yr of screening. Four, including both subjects with dysplasia, had no evidence of colon cancer at surgery. However, a 24-yr-old female with a 14-yr history of UC and no evidence of dysplasia or cancer at screening had a Dukes C adenocarcinoma. CONCLUSIONS: Adolescents and young adults with childhood onset UC or CD are at risk for aneuploidy, dysplasia, and colon cancer. Aneuploidy can be evident 10 yr after the onset of colitis and in patients as young as 16 yr of age. Therefore, the risk for colon cancer in patients with childhood onset colitis must be based on the duration of the illness, not on their chronological age. Incorporation of flow cytometry into an endoscopic screening protocol appears to enhance the ability to identify individuals at highest risk for colon cancer.

Adolescent↗
PubMed1996

Clinical outcome of ulcerative colitis in children.

OBJECTIVES: To characterize the response to current medical therapies in children with ulcerative colitis, and to identify those factors that may predict the need for colectomy. DESIGN: Retrospective chart review at two large pediatric inflammatory bowel disease centers. RESULTS: We identified 171 subjects ranging in age from 1.5 to 17.7 years at diagnosis (mean 11.2 years). Mean follow-up was 5.1 years. Of these subjects, 43% had mild disease at presentation and 57% had disease that was classified as moderate or severe. After treatment 90% of the former group and 81% of the latter group had resolution of symptoms by 6 months. During any subsequent yearly follow-up interval, approximately 55% of the entire study population was symptom free, 38% had chronic intermittent symptoms, and 7% had continuous symptoms. A significantly lower risk of colectomy was noted for those with initially mild disease compared with those with moderate/severe disease. At 1-year the risk of colectomy was 1% among those with mild disease versus 8% with moderate/severe disease; at 5 years, the risk of colectomy was 9% in the mild disease group versus 26% in the moderate/severe disease group (p <0.03). CONCLUSIONS: In the majority of pediatric subjects with ulcerative colitis remission is achieved in the first 6 months after therapy; thereafter disease is inactive in about 50% of patients during any given year of follow-up. Severity of disease at presentation is a significant risk factor for colectomy during the first 5 years of follow-up. Future management protocols with more aggressive initial therapy may be warranted in children with moderate/severe disease.

Adolescent↗
PubMed1995

Highly destructive perianal disease in children with Crohn's disease.

The perianal complications of Crohn's disease (CD) seen in children and adolescents include skin tags, anal fissures, fistulae, and abscesses. While these lesions are often chronic and variably responsive to medical therapy, only rarely are they severely destructive. In this report, we characterize the frequency, severity, and clinical course of a highly destructive form of perianal disease (HDPD) that we have noted in a number of children and adolescents with Crohn's disease. A database containing records from 350 children with inflammatory bowel disease was reviewed to identify all children with CD treated between 1970 and 1993. For each, the occurrence or absence of significant perianal pathology, including fistula, abscess, and HDPD, was determined. Pertinent clinical details were recorded for all patients. In addition, the clinical characteristics of those children with HDPD were compiled, and the courses of those with HDPD characterized. A search of the database identified 230 children and adolescents with CD followed for a total of 1,518 patient years. Sixty-seven of these patients (29% of the CD population) had significant perianal pathology. This included 6 with HDPD, 8 with complicated fistulae [rectourethroperineal (1), rectovaginal (1), rectolabial (2), and multiple communicating perineal (4)], and 53 with simple perianal fistulae or abscesses. All six with HDPD had deeply destructive perineal ulcerations, marked undermining of the perineal and perirectal tissues, and copious exudate, and often there was a deeply cleaved or fileted perineum on separating the buttocks. Two children with HDPD had fecal incontinence.

Abscess↗
PubMed1993

A pilot clinical trial of the angiotensin-converting enzyme inhibitor ceranapril in Alzheimer disease.

This pilot clinical trial was a 15-week, double-blind, controlled, three-way crossover study evaluating cognitive effects of ceranapril in subjects with dementia of the Alzheimer type (age range 50-75 years). Computerized (CNTB) and noncomputerized cognitive test batteries revealed no significant results (p > 0.05). On further analysis of the data, however, a study of longer duration and/or higher dosages may be warranted.

Aged↗
PubMed1993

Growth failure in pediatric inflammatory bowel disease.

To assess whether children with inflammatory bowel disease (IBD) develop permanent impairment of linear growth, we analyzed records from 48 young adults who had IBD during childhood or early adolescence (Tanner I-III; 11.8 +/- 2.4 years old at diagnosis). All were fully grown (Tanner V; 21.1 +/- 3.0 years) at last examination. Adult heights were predicted from data obtained at or shortly after the diagnosis of IBD by three methods: height for age percentile, the Bailey-Pinneau (BP), and Roche-Wainer-Thissen (RWT) methods. Predicted adult heights were then compared with the actual ultimate height of each subject. Permanent growth failure occurred in 19-35% of subjects, depending upon the method used to assess growth. Overall, 31% (15 of 48) of the subjects had deficits of adult height identified by two or more methods, including 14 of 38 (37%) of those with Crohn's disease but only one of 10 with ulcerative colitis. Age at diagnosis of IBD, age at last examination, age at cessation of linear growth, and site of IBD did not differ between impaired and normal growth groups. Duration of corticosteroid use was longer (p < 0.05) in growth-impaired subjects. In addition, although 60% of all subjects had periods of poor growth that put them in height-for-age percentiles two or more major growth channels below previous percentiles, only 19% remained at these levels upon achieving their final adult heights. Permanent impairment of linear growth leading to clinically meaningful deficits of ultimate adult height is common in patients with IBD in childhood or early adolescence. New therapeutic approaches are needed to address this problem.

Adolescent↗
PubMed1993

Interleukin-2-responsive wound-infiltrating lymphocytes in surgical adjuvant cancer immunotherapy.

Wound-infiltrating lymphocytes (WIL) were assessed in murine models of localized sarcoma and carcinoma to evaluate the role of interleukin-2 (IL-2)-responsive lymphocytes in adjuvant immunotherapy. Following tumor resection, IL-2 or diluent was injected at the surgical site for 6 days. Surgical site tissues were harvested and digested in a triple enzyme mixture, and single cell suspensions were prepared. Thy 1.2+ lymphocytes were isolated by incubating cells with monoclonal anti-Thy 1.2 antibody-coated magnetic beads. Lymphocyte-bead complexes were extracted with a magnet and cultured in medium containing IL-2 (100 units/ml) for 1-3 weeks. Perioperative IL-2 immunotherapy led to a three- to four-fold increase in WIL yield. WIL from IL-2-treated mice also demonstrated enhanced cytolysis of the autologous tumor and bound to activated endothelial cells with greater avidity than did the controls. We conclude that perioperative IL-2 therapy augments the yield, as well as the cytolytic and adhesive properties, of wound-infiltrating lymphocytes.

Animals↗
PubMed1993

Atypical rectosigmoid histology in children with newly diagnosed ulcerative colitis.

BACKGROUND: In the untreated patient with inflammatory colitis, rectal sparing or patchy rectal inflammation is generally considered a sign of Crohn's disease (CD), rather than ulcerative colitis (UC). METHODS: The initial endoscopic rectosigmoid mucosal biopsies obtained at disease onset from 12 untreated children with UC who ultimately required surgery were blindly reviewed (randomly mixed with another 62 specimens obtained from children with CD or treated UC). Biopsies were classified as typical UC if there was diffuse, active inflammation and severe crypt destruction or distortion. Those with patchy, active inflammation and only mild crypt changes were classified as CD. Because all 12 subjects had ultimately been proven to have UC by examination of a subtotal colectomy specimen, for the purposes of this report biopsies read as either normal or CD were both considered evidence of atypical UC with rectal sparing. RESULTS: Five of 12 subjects (seven biopsies) had atypical histology. Mild, patchy inflammation was seen in six rectal or sigmoid biopsies, whereas one rectal biopsy was normal. The remaining seven subjects (10 biopsies) had diffuse inflammation. Two of five subjects with atypical biopsies had an endoscopically normal rectosigmoid, one had patchy inflammation, and the remaining two had diffuse endoscopic changes. All seven subjects with typical UC histology had diffuse endoscopic changes. Subjects with atypical findings could not be differentiated by age, duration, or types of symptoms at presentation, years of disease at colectomy, or indications for colectomy. CONCLUSIONS: Patchy or absent inflammation of the rectum and sigmoid can be present in untreated children with UC at disease onset. Because such children may be mistakenly diagnosed as having CD, these data must be considered when treatments or clinical research protocols are designed to include children with colitis.

Adolescent↗
PubMed1993

The morphologic relationship of sinus and fistula formation to intestinal stenoses in children with Crohn's disease.

Sinus and fistula (SF) formation in adults with Crohn's disease has been ascribed to increased intraluminal pressure from stenotic lesions or to inflammation. We retrospectively evaluated 55 surgically resected specimens from 30 children with Crohn's disease for stenotic lesions, sinuses, fistulas, and inflammation. Eighteen of 30 children had one operation, and there were 12 multiple surgeries. Thirty-one of 55 specimens (56%) contained stenoses. SF formation was seen in 16 of 31 specimens with stenosis; it developed proximal to the stenosis in seven patients, distal in five, and both proximal and distal in four. SF formation was also noted in 12/24 specimens without stenosis. In 93% of the cases, the SF was associated with moderate to severe inflammation. Although 56% of the patients had stenoses, SF frequently developed independent of stenosis. All SF were associated with inflammation. Therefore, inflammation rather than increased intraluminal pressure appears to be the primary factor in SF formation in children with Crohn's disease.

Adolescent↗