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The risk of Pneumocystis carinii pneumonia among men infected with human immunodeficiency virus type 1. Multicenter AIDS Cohort Study Group.

We assessed the risk of pneumonia due to Pneumocystis carinii in 1665 participants in the Multicenter AIDS Cohort Study who were seropositive for human immunodeficiency virus type 1 (HIV-1) but did not have the acquired immunodeficiency syndrome (AIDS) and were not receiving prophylaxis against P. carinii. During 48 months of follow-up, 168 participants (10.1 percent) had a first episode of P. carinii pneumonia. The risk was greatly increased in participants with CD4+ cell counts at base line of 200 per cubic millimeter or less (relative risk, 4.9; 95 percent confidence interval, 3.1 to 8.0). Although most participants (60.7 percent) described no HIV-1-related symptoms at the clinic visit at which a CD4+ cell count of 200 per cubic millimeter or less was first noted, this finding during follow-up was also associated with an increased risk of P. carinii pneumonia. The development of thrush or fever significantly and independently increased the risk of P. carinii pneumonia in these patients (adjusted relative risks, 1.86 and 2.15 for thrush and fever, respectively). Most participants with CD4+ cell counts above 200 per cubic millimeter who had P. carinii pneumonia within six months were symptomatic. We conclude that P. carinii pneumonia is unlikely to develop in HIV-1-infected patients unless their CD4+ cells are depleted to 200 per cubic millimeter or below or the patients are symptomatic, and therefore that prophylaxis should be reserved for such patients.

Adolescent↗

Randomized comparison of mounted versus unmounted stents: the multicenter COMUS trial.

BACKGROUND: Although the use of premounted stents on a delivery balloon has almost completely eliminated the initially used hand-crimping procedure, no data are available that prove the superiority of one or the other approach on a randomized basis. Therefore, this study was designed to examine whether the use of premounted stents is comparable with the hand-crimping procedure. METHODS: A total of 123 patients (64 treated with unmounted stents, 59 treated with premounted stents) were examined in a multicenter, randomized, prospective study. There were no significant differences in patient characteristics between groups. RESULTS: Primary end points (acute, postinterventional [within 72 hours], and late complications related to the stenting procedure) were reached in 1 patient treated with an unmounted stent versus 2 patients with mounted stents (P = not significant). In patients with angiographic follow up (n = 84, mean follow-up period 6 +/- 1 months), the total rate of restenosis was 27% (unmounted 12, mounted 11, P = not significant). Secondary end points were procedural success of stenting and maximal balloon inflation pressure needed for optimal stenting results by use of angiography. There were no differences in secondary end points for both techniques. The mean balloon pressure was 12.56 +/- 2.1 atmospheres (unmounted) and 12.12 +/- 1.92 atmospheres (mounted, P = not significant). CONCLUSION: Stenting with premounted devices was demonstrated to have a similar clinical and angiographic outcome as the hand-crimping approach for maximal inflation pressure, procedural success, major cardiac events, and rate of restenosis after 6 months of follow up. Thus, the more convenient use of a premounted stent provides procedural safety and efficacy comparable with a hand-crimped system.

Angioplasty, Balloon, Coronary↗

Clinical evaluation of St Jude Medical Hemodynamic Plus versus standard aortic valve prostheses: The Italian multicenter, prospective, randomized study.

OBJECTIVE: Hemodynamic and clinical performances of 21-mm and 23-mm St Jude Medical Hemodynamic Plus aortic valves (St Jude Medical, Inc, St Paul, Minn) were compared with those of 21-mm and 23-mm St Jude Medical standard cuff aortic valves in the first such multicenter, prospective, randomized study. Hemodynamic Plus valves are mechanical, bileaflet prostheses suitable for the small aortic anulus. METHODS: Patients with 21-mm and 23-mm anulus diameters were randomized to receive either a Hemodynamic Plus or a standard cuff valve. Postoperatively and at 6 months after the operation, patients underwent 2-dimensional Doppler echocardiography. Ejection fraction, cardiac output, peak gradient, mean gradient, effective orifice area, effective area index, and performance index were calculated. Postoperative and 6-month echocardiographic measurements and their variations across observation times were analyzed statistically. RESULTS: Of the 140 patients enrolled, 5 died at operation and 1 died of aortic dissection during the follow-up period. Eight patients were lost to follow-up. A total of 125 patients completed the study. In 1 patient a sewing cuff escaped intraoperatively. At 6 months the 21-mm and 23-mm Hemodynamic Plus valves showed significantly lower peak gradients and mean gradients than those of the 21-mm and 23-mm standard cuff valves. The 21-mm Hemodynamic Plus valves had gradients similar to those of the 23-mm Hemodynamic Plus valves. The effective orifice area did not differ significantly between the Hemodynamic Plus and standard cuff valves at either measurement. No valve mismatch was found in the 4 groups of patients. A more enhanced decrease of peak gradients and mean gradients and a more enhanced increase of effective orifice areas, effective area indices, and performance indices were found across observation times for patients with Hemodynamic Plus valves compared with those with standard cuff valves. CONCLUSIONS: Clinical hemodynamic performances of 21-mm and 23-mm St Jude Medical Hemodynamic Plus valves correspond closely with those of standard cuff valves, and gradients are substantially better than those of standard cuff valves of the same diameter. Therefore, use of this valve may minimize the need for aortic anulus enlargement. Early follow-up results with the Hemodynamic Plus valves were excellent, although more time is required to confirm this outcome.

Aortic Valve↗

The Tertatolol International Multicenter Study (T.I.M.S.). Predicting factors of an efficient therapy.

The Tertatolol International Multicenter Study (T.I.M.S.) was aimed at assessing the efficacy and tolerability of 5 mg tertatolol (T) once daily over a one year period and at finding, among the clinical variables before treatment, parameters predicting a successful single beta-blocking therapy. The study was carried out in 230 patients (96 men, 134 women, mean age +/- standard error of the mean: (51.5 +/- 0.7 years) suffering from uncomplicated mild to moderate hypertension. After a one-month placebo run-in period (M0-M1) and a one-month double-blind placebo-controlled period (M1-M2), 213 patients entered and 166 completed the one-year open period (M2-M14). A diuretic (D) was added if blood pressure (BP) was inadequately controlled with the single therapy. After one year, 88.5% of patients were controlled (sitting diastolic BP less than or equal to 90 mm Hg): 56.3% on single therapy (T) and 32.2% on dual therapy (T + D), respectively. Statistical analysis performed on the controlled subjects showed that patients who were controlled with T alone had an initially lower standing diastolic BP and a higher standing heart rate, were younger and had a lower sitting systolic BP than those controlled with T + D. Using such discriminant parameters which are predictors, 83.5% patients (single therapy group) and 49% patients (dual therapy group) were classified in the therapeutic group to which they really belonged. This study confirms the antihypertensive efficacy of tertatolol, and highlights relevant parameters for a successful single beta-blocker therapy in clinical practice.

Adrenergic beta-Antagonists↗

A multicenter double-blind study of the efficacy and safety of once and twice daily dilevalol compared to propranolol.

Dilevalol, the R,R isomer of labetalol, is a non-selective beta-adrenergic blocking drug with vasodilator properties which differ from those of labetalol in that they are attributable to beta-2 agonism rather than alpha-1 blockade. This multicenter, double-blind, randomized study compares the antihypertensive efficacy and safety of dilevalol with propranolol and, in addition, compares the efficacy of dilevalol when given once daily with twice daily. Caucasian patients with mild and moderate essential uncomplicated hypertension were divided into three treatment groups and received either propranolol twice daily (N = 59), dilevalol twice daily (N = 60), or dilevalol once daily (N = 53). Patients were given increasing doses of these medications over a 2 to 10 week period to achieve a supine diastolic blood pressure (SuDBP) of less than 90 mm Hg. The three regimens were equally effective in lowering supine blood pressure (dilevalol daily and twice daily reduced SuDBP by 14 Hg and propranolol by 13 mm Hg). Patients with at least a 5 mm Hg reduction in SuDBP then entered a two month maintenance phase. Dilevalol, whether given once (N = 40) or twice daily (N = 55) maintained the supine systolic blood pressure more effectively (dilevalol daily--15 mm Hg, twice daily--13 mm Hg, P less than .05) than propranolol (N = 53, 11 mm Hg) and dilevalol given once daily maintained diastolic blood pressure more effectively than propranolol (17 mm Hg v 14 mm Hg, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Phase III multicenter randomized trial of amifostine as cytoprotectant in first-line chemotherapy in ovarian cancer patients.

BACKGROUND: A phase III multicenter randomized trial has been designed in order to address whether amifostine (WR-2721, Ethyol), an organic thiophosphate cytoprotector, can protect ovarian cancer patients from toxicity induced by carboplatin-paclitaxel chemotherapy. PATIENTS AND METHODS: Patients were randomly assigned to receive carboplatin [area under the curve (AUC) 5 mg.min/ml] and paclitaxel (175 mg/m(2)) with (arm A) or without (arm B) amifostine (910 mg/m(2)) every 21 days for six cycles. RESULTS: One-hundred and eighty-seven patients were accrued: 93 patients in arm A and 94 patients in arm B. There was no difference in terms of erythrocytopenia between the two arms; grade 3-4 thrombocytopenia was higher in arm A (3.3% versus 0.6%; P = 0.0010). There was no significant reduction of grade 3-4 leukopenia in arm A (11.8% versus 13.8%). The incidence of grade 3-4 neutropenia was lower in arm A (31.3% versus 37.9%; P = 0.03), as was the incidence of severe mucositis (4.7% versus 15.4% in arm A versus arm B, respectively; P <0.0001). Finally, amifostine appears to be protective against neurotoxicity (grade 3-4 neurotoxicity 3.7% versus 7.2%; P = 0.02). With a median follow-up of 24 months (range 2-41), time to progression was similar between the two groups. CONCLUSIONS: We showed that amifostine can exert some protection from the cumulative toxicity associated with this regimen. The results need to be confirmed in other randomized trials with this combination.

Adult↗

Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study.

BACKGROUND: Human papillomavirus (HPV), the causal agent of cervical cancer, appears to be involved in the etiology of cancer of the oral cavity and oropharynx. To investigate these associations, we conducted a multicenter case-control study of cancer of the oral cavity and oropharynx in nine countries. METHODS: We recruited 1670 case patients (1415 with cancer of the oral cavity and 255 with cancer of the oropharynx) and 1732 control subjects and obtained an interview, oral exfoliated cells, and blood from all participants and fresh biopsy specimens from case patients. HPV DNA was detected by polymerase chain reaction (PCR). Antibodies against HPV16 L1, E6, and E7 proteins in plasma were detected with enzyme-linked immunosorbent assays. Multivariable models were used for case-control and case-case comparisons. RESULTS: HPV DNA was detected in biopsy specimens of 3.9% (95% confidence interval [CI] = 2.5% to 5.3%) of 766 cancers of the oral cavity with valid PCR results and 18.3% (95% CI = 12.0% to 24.7%) of 142 cancers of the oropharynx (oropharynx and tonsil combined) with valid PCR results. HPV DNA in cancer biopsy specimens was detected less frequently among tobacco smokers and paan chewers and more frequently among subjects who reported more than one sexual partner or who practiced oral sex. HPV16 DNA was found in 94.7% of HPV DNA-positive case patients. HPV DNA in exfoliated cells was not associated with cancer risk or with HPV DNA detection in biopsy specimens. Antibodies against HPV16 L1 were associated with risk for cancers of the oral cavity (odds ratio [OR] = 1.5, 95% CI = 1.1 to 2.1) and the oropharynx (OR = 3.5, 95% CI = 2.1 to 5.9). Antibodies against HPV16 E6 or E7 were also associated with risk for cancers of the oral cavity (OR = 2.9, 95% CI = 1.7 to 4.8) and the oropharynx (OR = 9.2, 95% CI = 4.8 to 17.7). CONCLUSIONS: HPV appears to play an etiologic role in many cancers of the oropharynx and possibly a small subgroup of cancers of the oral cavity. The most common HPV type in genital cancers (HPV16) was also the most common in these tumors. The mechanism of transmission of HPV to the oral cavity warrants further investigation.

Adult↗

Acquired immunodeficiency syndrome (AIDS)-free time after human immunodeficiency virus type 1 (HIV-1) seroconversion in homosexual men. Multicenter AIDS Cohort Study Group.

To estimate the time interval between human immunodeficiency virus type 1 (HIV-1) seroconversion and acquired immunodeficiency syndrome (AIDS) diagnosis in homosexual men, prospective incident cohorts are difficult to obtain and, if assembled, provide few events owing to the long incubation time. Although seroprevalent cohorts are numerous in size and events, the information is limited due to the unknown times since seroconversion. To combine the information provided by 1,628 seroprevalent men (304 AIDS cases) and 233 seroconverters (12 AIDS cases) being followed in a multicenter study since 1984, the postseroconversion changes in hematologic variables occurring in the incident cohort were used to develop a model that allowed for the imputation of the unknown times since seroconversion for the seroprevalent cohort. Nonparametric life table methods incorporating truncation and censoring were applied for the estimation of the probability distribution of the AIDS-free time after seroconversion. The precision of the estimates was evaluated using bootstrap methods. The analysis suggested that AIDS is unlikely (less than 0.5%) in the first year; 78% of seropositive homosexual men remain AIDS-free 60 months after seroconversion; and the AIDS incidence increases for months 12-36 and levels off at 38 per 1,000 person-semesters for months 42-60. The nonparametric estimate of the incidence rate suggests a median AIDS-free time of 11 years, which is longer than previous estimates based on parametric models.

Acquired Immunodeficiency Syndrome↗

Antibiotic prophylaxis in acute nonperforated appendicitis. The Danish Multicenter Study Group III.

In a prospective, block-randomized, multicenter study, the safety and efficacy of cefoxitin in preoperative prophylaxis were studied. 1735 patients undergoing appendectomy were evaluable, and half of these patients received 2 g of cefoxitin before undergoing operation. The patients were divided into three groups: patients with a normal appendix, patients with an acutely inflamed appendix, and patients with a gangrenous appendix. The study showed for each group a significant reduction of the incidence of wound infection in patients receiving prophylaxis. However, intra-abdominal abscess formation was not influenced by preoperative antibiotic prophylaxis. Consequently, routine preoperative prophylaxis is recommended before appendectomy.

Abdomen↗

Pre- or postoperative radiotherapy in rectal and rectosigmoid carcinoma. Report from a randomized multicenter trial.

Between October 1980 and December 1985, 471 patients with a resectable rectal carcinoma entered a randomized multicenter trial for comparison of pre- and postoperative irradiation. Two hundred thirty-six patients were allocated to receive high-dose fractionated preoperative irradiation (total dosage, 25.5 Gy in five to seven days) and 235 patients to receive postoperative irradiation to a very high dosage level with conventional fractionation (60 Gy in a total 8 weeks). The postoperative treatment was delivered only to a high-risk group of patients (Astler-Coller stages B2, C1, and C2). The preoperative irradiation was well tolerated, with no immediate irradiation-related complications and no increased postoperative mortality (3%, 7 of 217 patients, compared to 5%, 10 of 215 patients in the postoperatively irradiated group). More patients in the preoperative irradiation group had perineal wound sepsis after abdominoperineal resection and this prolonged the stay in hospital after surgery. In 50% of the patients the postoperative treatment could not be commenced until more than 6 weeks after surgery. The postoperative treatment was not as well tolerated as the preoperative one. The local recurrence rate was statistically significantly lower after preoperative than after postoperative radiotherapy (12% versus 21%; p = 0.02). In both groups more patients developed a local recurrence if the bowel was perforated at surgery or if the resection line was microscopically close to the tumor. To date, with a minimum follow-up of 3 years and a mean follow-up of 6 years, there is no difference in survival rates between the two groups.

Adult↗

Nature, time course and dose dependence of zidovudine-related side effects: results from the Multicenter Canadian Azidothymidine Trial.

To characterize the nature, time course and dose dependency of zidovudine-related side effects, we undertook a multicenter, prospective, dose-range finding study. Our study group consisted of 74 HIV-positive homosexual men belonging to groups II B, III and IV C2 from the Centers for Disease Control (CDC) classification of HIV disease. Following a 3-week observation period, volunteers were treated with zidovudine 600 mg/day for 18 weeks, 900 mg/day for 9 weeks and 1200 mg/day for 9 weeks, followed by a washout period of 6 weeks after which they were re-started on 1200 mg/day or the highest tolerated dose at 8-hourly intervals. Subjects were randomly assigned to 4-hourly or 8-hourly regimens within CDC groups while taking 600 and 1200 mg/day. Clinical and laboratory evaluations were performed at 3-week intervals. Symptomatic adverse effects were present in 96% of subjects, most commonly nausea (64%), fatigue (55%) and headache (49%). These were generally self-limited, reappearing briefly at each dose increment. A decrease in hemoglobin occurred shortly after initiation of therapy. This was not dose dependent and reversed rapidly upon discontinuation of treatment. A red blood cell count decrease, a mean cell volume increase and a granulocyte count decrease developed early in a dose-independent fashion, reverting at least partially during the washout phase. The decrease in reticulocyte count was dose related between 600 and 900 mg/day with no further change when the dose was escalated to 1200 mg/day. Bone marrow changes occurred rapidly as demonstrated by megaloblastosis in 95% of 65 specimens at week 18.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A multicenter clinical trial of oral ribavirin in HIV-infected people with lymphadenopathy: virologic observations. Ribavirin-LAS Collaborative Group.

A double-blind, randomized, placebo-controlled trial comparing two daily doses of oral ribavirin (600 and 800 mg) and a placebo was performed at four medical centers geographically distributed throughout the USA. One hundred and sixty-four HIV-infected adult men with lymphadenopathy were enrolled over a 2-month period and received active treatment for 24 weeks followed by a 4-week interval during which they did not receive the study drug. A marked interlaboratory variation in HIV isolation from peripheral blood mononuclear cells was observed, underscoring the critical role of quality assurance in similar multicenter trials. Nevertheless, the combined data indicate that ribavirin did not significantly suppress HIV activity (on measurement of reverse transcriptase activity) after week 6 or reduce serum p24 antigenemia.

AIDS-Related Complex↗

Clinical activity and tolerability of trazodone, mianserin, and amitriptyline in elderly subjects with major depression: a controlled multicenter trial.

The aim of this multicenter study was to compare trazodone (TRA) with two reference drugs, amitriptyline (AMI) and mianserin (MIA), under double-blind conditions, in an elderly population, to ascertain age-related patterns for efficacy and tolerability. One hundred six elderly depressed inpatients, ranging in age from 60 to 83 years, diagnosed as having major depression according to DSM-III, were treated with 75 mg AMI (37 patients), 60 mg MIA (33 patients) or 150 mg TRA (36 patients) p.o.t.i.d. for 5 weeks. There were no differences in the clinical outcome among the three groups of patients at the end of the trial, with a significant amelioration (p less than 0.01) for the Hamilton Rating Scale for Depression (HRS-D) and the Geriatric Depression Scale (GDS). TRA showed a lower overall prevalence of side effects than AMI or MIA, particularly for anticholinergic (p = 0.03 vs. AMI) and cardiovascular (p = 0.05 vs. MIA) effects. For these data GDS seems to be most reliable in detecting changes in elderly depressive symptomatology; moreover a comparable therapeutic response (among the three drugs) but a better tolerance for atypical antidepressants, particularly TRA, make advisable the use of the latter drug in the elderly population.

Aged↗

A multicenter Italian study of amineptine (Survector 100).

This study reports the antidepressant efficacy and the safety of amineptine (Survector 100) in a national multicenter open clinical trial (32 hospital centers). Three hundred twenty-four patients with depressive disorders, selected according to DSM-III Diagnostic Criteria and INSERM classification, were treated with amineptine (200 mg/day) for 40 days (mean). Amineptine proved to be significantly effective with a rapid onset of action (beginning on the 7th day) on depressive symptoms, as shown by the decrease in the Hamilton Depression Rating Scale total score. The assessment of the results in the different diagnostic subgroups confirmed the wide-spectrum antidepressant activity of amineptine. Particularly in reactive and neurotic depression (nonpsychotic depression according to INSERM) and dysthymic disorders according to DSM-III, amineptine induced an improvement in 90% of patients. Nevertheless, amineptine was also effective in psychotic depression (INSERM) and in major depressive episodes (DSM-III), in which improvement occurred in 76% of patients. The low frequency of side effects and the remarkable acceptability (clinical, biological, and cardiovascular) of amineptine were also confirmed.

Adult↗

The beneficial effects of amineptine (Survector 100) in the treatment of depression: preliminary results of an Indian multicenter trial.

A multicenter study of the efficacy and safety of amineptine in the treatment of depression has been performed in India. Patients fulfilling the DSM-III criteria for depression were included in this open clinical trial and treated with amineptine for 6 weeks. They received one 100-mg tablet or two (100 mg) tablets of amineptine per day. Efficacy of treatment was assessed using the Hamilton Depression Rating scale on D0, D7, D14, D21, D35, and D42. Liver function and cardiovascular function were examined on D0 and D42 to assess possible adverse effect of treatment. The preliminary results in 32 patients showed that amineptine was effective as soon as the 7th day of treatment and that this effect improved continuously throughout the study. Amineptine was found to be safe.

Adult↗

Evaluation of the efficacy of amineptine in a population of 1,229 depressed patients: results of a multicenter study carried out by 135 general practitioners.

To assess the efficacy, tolerance, and safety of amineptine in ambulant treatment of depressive states, an open multicenter trial was performed by 135 general practitioners in a large number of depressed patients (1,229) with different nosologies and living in all areas of Portugal. The protocol included criteria of inclusion and exclusion and the full methodology was discussed with the practitioners in previous meetings coordinated by a psychiatrist. Daily dosage was 200 mg (two tablets); other psychotropic drugs were associated rarely and only when strictly necessary. Assessments were made at day 0, 7, 28, and 56, using the Clinical Global Impressions (CGI), Hamilton Depression Rating Scale (HDRS), diagram HARD, and a list of side effects. Results were analyzed statistically with calculation of statistical significance. The calculation of the correlation coefficients between the different measurement instruments was also made. There were 84 dropouts mainly due to missed appointments and intolerance of the medication. It is worth noting that 50% of the patients were treated with monotherapy, and that other psychotropics used were almost always anxiolytic drugs. Efficacy of amineptine was very good and rapid since there was a statistically significant difference in all observations with the different instruments of measurement used. Results were good in all types of depression, mainly in the neurotic and reactive ones. Moderate or severe side effects were seldom observed and transient. The acceptability was good or very good in 97.1% of the cases.

Adolescent↗

Prevention of pneumonia in an intensive care unit: a randomized multicenter clinical trial. Intensive Care Unit Group of Infection Control.

In a randomized multicenter clinical trial on antibiotic prophylaxis, 1,319 patients in 23 ICUs were enrolled over a 4-month period. The end-point of the study was the prevention of early onset pneumonia (EOP), defined as acquired pneumonia diagnosed within 4 days of ICU admission; this accounted for greater than 50% of overall pneumonia. Patients eligible for the study were divided into three groups which received either cefoxitin (2 g iv for three doses/8 h), penicillin G (2 million U iv for four doses/6 h), or no antibiotic (control group). In the overall population, the incidence of EOP was 6.1% in the prophylaxis recipients vs. 7.2% in the control group (a 15.3% reduction). No statistically different rates of pneumonia or death were found among the groups. Patients with impaired reflexes on admission or prolonged ventilatory support were noted to have a lower incidence of EOP and an improved outcome when treated with cefoxitin.

Adolescent↗

Diagnostic significance of epithelioid granulomas in Crohn's disease in children. Multicenter Paediatric Crohn's Disease Study Group.

Out of 528 children with Crohn's disease in a Multicenter Paediatric Crohn's Disease Study Group, 37 cases had epithelioid granulomas but did not fulfill defined radiographic criteria of the disease. Follow-up studies including clinical, biochemical, radiological, endoscopic, and histological investigations were done in these patients. Initially, all patients showed clinical symptoms and 27 of them had biochemical signs of chronic inflammation. After a mean follow-up of 3 years, all 37 children treated for Crohn's disease got a complete upper gastrointestinal series with small bowel followthrough and 8 children in addition had barium enemas. Colonoscopies were done in 23 patients. Radiographic examination revealed Crohn's disease in 14 and endoscopy additionally confirmed Crohn's disease in 8 further cases. One child was diagnosed as having chronic granulomatous disease. Thirteen children still remained unclassified after these follow-up studies including radiographs and endoscopy. An interval of 3 years may in some cases be too short to express the complete radiographic pattern of Crohn's disease. Our studies demonstrate that in addition to initial radiological, endoscopic, and histological investigations, a thorough follow-up is necessary in early diagnosed patients. In these children, epithelioid granulomas are of high diagnostic validity preceding radiological changes of Crohn's disease often for years.

Adolescent↗