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Biomedical subjects

L Freund

Publications and source records attributed to L Freund.

At least 37 records · Page 2Linked to original sources
PubMed1991

Final report on a placebo-controlled, double-blind, randomized, multicentre trial of cyclosporin treatment in active chronic Crohn's disease.

In a previous report we published the immediate results of a 3-month placebo-controlled trial (n = 34) showing that cyclosporin (n = 37) has a beneficial therapeutic effect in active chronic Crohn's disease. Here we report on the final outcome of the patients. During the 3-month tapering-off period eight initially improved patients (36%) in the cyclosporin group worsened, as did six (55%) in the placebo group. The therapeutic gain of cyclosporin treatment was consistently significant during this period. It ranged from 22% to 25% (95% confidence limits, 2-46%). An outcome ranking showed that 7 patients of the cyclosporin group (19%) were substantially improved, 7 (19%) moderately improved, and 23 (62%) not improved after the tapering off. In contrast, no significant differences were seen during the 6-month follow-up period. Four patients of the cyclosporin group (11%) were substantially improved, 3 (8%) moderately improved, and 30 (81%) not improved at final follow-up. Significant interactions between cyclosporin and prednisolone treatment were demonstrated both at the end of the initial treatment period and at the end of the tapering-off period. We conclude that a short course of cyclosporin treatment does not result in long-term improvement in active chronic Crohn's disease.

Chi-Square Distribution↗
PubMed1991

Neuroanatomy in fragile X females: the posterior fossa.

The relative homogeneity of the neuropsychiatric phenotype in individuals with fragile (fra) X syndrome suggests that there are consistent central nervous system (CNS) abnormalities underlying the observed cognitive and behavioral abnormalities. In this study, the neuroanatomy of the posterior fossa and other selected CNS regions in 12 young fra X females were compared with those of a group of 12 age-, sex-, and IQ-matched females without evidence of the fra X syndrome. Fra X females were shown to have decreased size of the posterior cerebellar vermis and increased size of the fourth ventricle, findings that are identical to those previously reported for fra X males. When compared with fra X male and nonfra X control groups, the distribution of the posterior-vermis and fourth-ventricle variables for the fra X female group was intermediate. These results support the hypothesis that the fra X genetic abnormality leads to hypoplasia of the posterior cerebellar vermis, a neuroanatomical variation of potential importance to both developmental and neuropsychiatric syndromes.

Adolescent↗
PubMed1990

Fragile X syndrome.

Fragile X syndrome is the most important X-linked etiology of mental retardation and developmental disability currently known. Accumulating evidence also indicates that male and female carriers of the fragile X genetic abnormality demonstrate a relatively specific pattern of psychiatric disturbance. Fragile X males frequently manifest behaviors from the autistic spectrum whereas females show dysfunction in social interaction, thought processes, and affective regulation. In this review, an overview of the fragile X syndrome is presented with a focus on the occurrence of particular neuropsychiatric characteristics in males and females. Relevant data from recent genetic and neurobiological research is also described. The ability to study individuals with a specific genetic cause of psychopathology such as fragile X syndrome makes this condition of particular interest to biological psychiatry.

Autistic Disorder↗
PubMed1990

Fragile X syndrome, DSM-III-R, and autism.

Although reports of autistic behavior in fragile X males have been published for 8 years, there is little information about specific behaviors shown by fragile X males that are suggestive of the diagnosis of autism. The new diagnostic criteria for autistic disorder contained in the DSM-III-R provided the opportunity for more closely investigating the topography of autistic behavior in 17 fragile X males and the effects of age and IQ on its occurrence. The criteria most frequently met by these subjects were related to deficits in social interaction with peers, abnormalities in verbal and nonverbal communication, stereotypic motor behavior, and unusual responses to sensory stimuli. Fragile X subjects did not frequently show abnormalities in attachment behaviors and reciprocal interaction with caregivers. There were no discernable age or IQ effects. The importance and implications of these findings are discussed and the need for greater exploration of autism "subtypes" is emphasized.

Adolescent↗
PubMed1989

A placebo-controlled, double-blind, randomized trial of cyclosporine therapy in active chronic Crohn's disease.

We randomly assigned 71 patients with active chronic Crohn's disease who were resistant to or intolerant of corticosteroids to treatment with oral cyclosporine (5 to 7.5 mg per kilogram of body weight per day) or placebo for three months. Disease activity was assessed on a clinical grading scale without knowledge of the treatment given. At the end of the treatment period, 22 of the 37 cyclosporine-treated patients (59 percent) had improvement, as compared with 11 of the 34 placebo-treated patients (32 percent) (P = 0.032). During cyclosporine treatment, there was significant improvement in plasma orosomucoid levels (P = 0.0025) and the Crohn's Disease Activity Index (P = 0.00012). The effect of treatment became evident after two weeks. In the subsequent three months, during which the patients were gradually withdrawn from treatment, the improvement continued in 14 of the 37 patients (38 percent) in the cyclosporine group and in 5 of the 34 (15 percent) in the placebo group (P = 0.034). No serious adverse events were observed. We conclude that cyclosporine has a beneficial therapeutic effect in patients with active chronic Crohn's disease and resistance to or intolerance of corticosteroids.

Administration, Oral↗
PubMed1989

[Liver transplantation undertaken on Danes abroad].

The indication for liver transplantation is the end stage of liver disease. Liver transplantations are not carried out in Denmark at present, one of the reasons being that it requires introduction of the brain death criterion, because the donor liver must be removed during maintained circulation. To date (November 1988), liver transplantations have been carried out abroad on seven Danes. One of these died after operation, one has chronic rejection and is to have retransplantation while the remaining five patients are well. In Europe (including Sweden, Norway and Finland) and USA, more than 5,000 patients have been liver transplanted. The one-year survival is approximately 75%. After this, only few liver-related deaths occur and the majority of patients can resume their previous activities. A total of 18 Danes have been assessed in transplantation centres abroad: Two are waiting for transplantation in the near future and seven have been accepted for transplantation at a later date, depending on the course of the disease. In a number of Danes, liver transplantation has been considered indicated but has not been effectuated because the disease was so advanced at the time of referral, that the patient died before transfer or the patient did not desire operation abroad.

Adolescent↗
PubMed1989

Low-dose cyclosporin for Crohn's disease: implications for clinical trials.

Cyclosporin is a potent immunosuppressant, which has gained recent interest as a possible treatment for Crohn's disease. Chronic nephrotoxicity, however, has recently been demonstrated as a result of early treatment with high initial cyclosporin doses. We report the effect of a 3-month treatment with low-dose cyclosporin (5-7.5 mg kg-1 day-1) in 11 chronically active, therapy-resistant Crohn's disease patients. Eight of the 11 patients (72%) improved according to a clinical grading score and the Dutch Activity Index whereas 9/11 (82%) improved according to the Crohn's Disease Activity Index (P less than 0.05) after 1 month. Three patients were withdrawn despite clinical improvement. One developed arterial hypertension, one dropped out and one required surgical treatment due to a small bowel stricture. Five patients (45%) completed the treatment period with improved clinical scores. After tapering-off, two patients (18%) were better at follow-up. No serious side-effects were encountered and it is concluded that low-dose cyclosporin treatment should be further investigated in Crohn's disease.

Adult↗
PubMed1989

Differentiation between Bernard-Soulier syndrome and immune thrombocytopenia by immunostaining of peripheral blood.

Peripheral blood smears from seven patients with Bernard-Soulier syndrome were examined by an immunocytochemical staining procedure using a monoclonal antibody specific for platelet glycoprotein Ib. No platelet staining was observed except for very slight staining of the large sized platelets from one of the patients. Application of the assay to blood smears from 12 patients with immune thrombocytopenia showed that their peripheral platelets stained normally, so the assay can be used to differentiate between immune thrombocytopenia and Bernard-Soulier syndrome and to confirm a diagnosis of the syndrome.

Adolescent↗
PubMed1989

Parental inheritance and psychological disability in fragile X females.

Studies of adult female carriers of the fragile X chromosome indicate that certain psychological problems occur with a greater frequency and severity than expected. This study examines the association of parental origin of the fragile X chromosome and of fragility detected in the karyotype with measures of social, educational, and psychological functioning in a group of adult fragile X females of normal intelligence. The results show that, as a group, women who inherit the fragile X chromosome from their mother and who demonstrate positive fragility in the karyotype (MI+ group = [maternal inheritance with positive fragility]) manifest significantly more impairment of social, educational, and psychological functioning when compared with fragile X females with paternal inheritance or negative fragility or with a matched control group comprising non-fragile X women. In particular, MI+ women show lower levels of both educational achievement and socioeconomic status and a greater degree of disturbance in communication, socialization, affect, and thought processes. These clinical findings are consistent with the recently advanced hypothesis which proposes that a two-stage process leading to chromosome imprinting in a preoogonial cell causes the fragile X syndrome.

Anxiety Disorders↗
PubMed1988

Preliminary communication: neuroanatomical variations of the posterior fossa in men with the fragile X (Martin-Bell) syndrome.

Four men with fragile X (fra (X], or Martin-Bell, syndrome were studied by magnetic resonance imaging (MRI) to determine whether detectable abnormalities of the cerebellum were present. The cerebellum was chosen because of the apparently increased tendency for fra (X) patients to demonstrate autistic behavior and accumulating evidence implicating cerebellar abnormalities in autism. Compared with a control group of four normal men, fra (X) patients had a significantly decreased area of the cerebellar vermis, particularly the posterior portion, on planimetric analysis in the midsagittal plane. The pons and fourth ventricular areas also were decreased and increased, respectively, in the fra (X) men. Neuroanatomical and animal research increasingly implicates the cerebellar vermis as an important component in functional brain systems subserving sensory and motor integration, learning, and modulation of affect, motivation, and social behavior. Thus, vermis dysfunction could account for many of the behavioral and cognitive abnormalities observed in fra (X) males, particularly those which overlap with the behavioral syndrome of autism.

Adult↗
PubMed1988

Positive Coombs' test associated with ulcerative colitis. A prevalence study.

Among 112 patients with ulcerative colitis (UC), a positive Coombs' test was detected in two cases. The immunoglobulins were IgG and no complement could be detected on the red cells. None of the two patients showed laboratory evidence of hemolysis, although reduced red cell survival was suspected in one patient with a 6-year history of UC, previous autoimmune hemolytic anemia and a positive in vitro monocyte-macrophage phagocytosis test. The HLA-antigens in the two patients were different except for the common antigen HLA-A1.

Adolescent↗
PubMed1984

Aclarubicin in the treatment of acute nonlymphocytic leukemia refractory to treatment with daunorubicin and cytarabine: a phase II trial.

Aclarubicin (ACR) was administered in a prospective cooperative phase II trial to 44 patients with possibly refractory acute nonlymphocytic leukemia who were previously treated with daunorubicin and cytarabine. Induction treatment consisted of 80 mg/m2 of ACR iv daily for 3 days, followed by 80 mg/m2 iv daily for 2 days in patients not obtaining a complete remission (CR) after 2-4 weeks. CR was observed in eight patients (18%) and partial remission was observed in six (14%). On monthly maintenance chemotherapy with ACR and cytarabine, the duration of CRs varied between 10 and 58 weeks. Achievement of remission was not related to age, presence or absence of Auer bodies, cytogenetic characteristics, or previous response to daunorubicin and cytarabine. Side effects were nausea and vomiting observed in 86% and diarrhea in 34% of the patients, whereas mucositis and alopecia were uncommon. Disturbances of cardiac function arousing suspicion of acute ACR toxicity were observed in seven patients. No case of chronic cardiotoxicity was observed, despite the fact that 20 patients received ACR doses greater than 400 mg/m2, with seven of the 20 having had a previous daunorubicin dose greater than 400 mg/m2. As CR was obtained in four of 14 patients with primary therapy-resistant leukemia and in two of 16 patients with relapse and no response to re-treatment with daunorubicin and cytarabine, ACR does not seem to show clinical cross-resistance to daunorubicin. Evaluation of ACR in first-line chemotherapy of acute nonlymphocytic leukemia appears justified.

Aclarubicin↗
PubMed1982

The effect of prednisone on platelet function tests.

Ivy bleeding time, capillary fragility, threshold ADP concentration for secondary platelet aggregation and platelet adhesiveness were found to be unchanged by 2 d and 6 weeks of treatment with prednisone in 22 consecutive patients with collagen or haematological diseases. Initial high platelet counts were unchanged after 2 d of treatment, but after 6 weeks of treatment the increase was significant. It is concluded that in patients of this category a 6-week treatment with commonly used doses of prednisone does not significantly affect platelet function.

Antigens↗