Assessing disease activity in Crohn''s disease--are we there yet?

Many attempts have been made over recent years to assess accurately disease activity in Crohn's disease. We review some of these attempts, giving particular emphasis to the combination of serum levels of proinflammatory cytokines (interleukin-6, tumour necrosis factor alpha, recombinant interleukin-2 and acid alpha-1-glycoprotein).     

T cells and cytokines in Crohn''s disease

Complete-arch implant prostheses continue to exhibit horizontal and vertical misfit between frameworks and abutments. It has been suggested that these gaps may be eliminated and that restoration-induced stresses may be reduced by luting frameworks to screw-retained abutments intraorally. This study measured and compared the strains generated by clinically acceptable, conventional frameworks were made from a single master cast representing a bone simulant model of an edentulous mandible with five Nobel Biocare implants and 4-mm abutments. Two strain gauges were also embedded in the bone simulant model to measure strains at two locations. Resin-luted frameworks were made by securing abutments to the clinical model with five gold slot screws tightened to 10 Ncm. Strain-indicator readings were recorded at a standardized time following the initial fastening of each prosthesis (n = 3). Mean principal strains were determined and compared using a one-way repeated measures analysis of variance. A statistically significant difference was found in the principal strains between the conventional cast and the resin-luted frameworks. Overall, there was a decrease in the magnitude of strain for the resin-luted frameworks. Intraoral luting of frameworks may decrease the strains produced in the bone around implants.     

The central role of chemokines (chemotactic cytokines) in the immunopathogenesis of ulcerative colitis and Crohn''s disease

Rats with large thalamic lesions affecting the mediodorsal (MDn) and intralaminar (ILn) nuclei are impaired performing delayed matching to sample tasks (DMTS). To determine the neurological basis of this deficit, we trained rats to perform a place DMTS task and then compared the effects of excitotoxic lesions of the MDn, the ILn, and the lateral internal medullary lamina (L-IML). The MDn lesion had little effect. The ILn group was significantly impaired throughout 8 months of training. The L-IML group exhibited an intermediate level of impairment. Varying the sample response requirement, retention intervals, and trial-to-trial congruence in the side reinforced, had predicted effects, as did variations in response latency. However, none of these factors interacted with the treatment effects. These findings indicate that DMTS performance is disrupted by lesions of the ILn but not the MDn.     

Place of laparoscopic surgery in Crohn''s disease

PURPOSE: We describe our therapeutic strategy and correlate the anatomic results and clinical outcomes in patients who received immediate fibrinolytic therapy for thromboembolic complications occurring during endovascular treatment of an intracerebral aneurysm. METHODS: The medical records and angiographic examinations of 19 patients were reviewed. All endovascular procedures were performed with the patients under general anesthesia and fully heparinized. Thirteen patients received an intravenous bolus injection of aspirin. Thromboemboli occurred during catheterization or insertion of embolic material (Guglielmi detachable coils or mechanical detachable spirals) or in the first hours after the intervention. Clot distribution was within the MCA territory in 14 patients, the ACA in three patients, and the basilar trunk in two patients. A continuous intraarterial injection of urokinase was administered immediately, either superselectively distal to the thrombus or selectively within or closely proximal to the thrombus. In nine cases, chemical lysis was combined with mechanical clot fragmentation. Initial anatomic recanalization as well as clinical outcome at 3 months were evaluated. RESULTS: Ten patients showed complete recanalization and nine patients showed partial recanalization. Fourteen patients had a good clinical recovery. One patient was moderately disabled and two were severely disabled according to their scores on the Glasgow outcome scale. Two patients died, one as a consequence of the preexisting subarachnoid hemorrhage and the other because of a large intracerebral hematoma that developed after fibrinolysis. Of the 14 patients with a good clinical outcome, nine exhibited complete recanalization and five partial recanalization. CONCLUSION: Pharmacological thrombolysis seems to be a safe and efficient therapy that facilitates the natural fibrinolytic process, increasing the rate of recanalization in thromboembolic events. Clot fragmentation and superselective drug infusion appear to improve the rate of recanalization. Complete recanalization increases the chance of a better clinical outcome; however, clinical outcome does not always correspond to recanalization and vice versa.     

Effect of psychotherapy on the course of Crohn''s disease. Results of the German prospective multicenter psychotherapy treatment study on Crohn''s disease. German Study Group on Psychosocial Intervention in Crohn''s Disease

OBJECTIVES: To determine whether a combination of ciprofloxacin hydrochloride and metronidazole hydrochloride would be as effective or more effective than a combination of gentamicin sulfate and metronidazole hydrochloride for preventing infection in patients with penetrating abdominal trauma, to evaluate the factors associated with increased risk of infection, and to determine the serum peak and trough levels of gentamicin with the dosage regimen of 2.5 mg/kg every 12 hours. DESIGN: Randomized double-blind study. SETTING: Level I trauma center. PATIENTS: Eighty-four patients with penetrating intra-abdominal injuries (gunshot wound, 69; stab wound, 15) thought to require laparotomy. INTERVENTIONS: The patients were randomized during treatment in the emergency department to be given a combination of ciprofloxacin hydrochloride, 400 mg every 12 hours, and metronidazole hydrochloride, 500 mg every 6 hours, or a combination of gentamicin sulfate, 2.5 mg/kg every 12 hours, and metronidazole hydrochloride, 500 mg every 6 hours. RESULTS: Of 68 patients with intra-abdominal injuries who could be observed for at least 48 hours after laparotomy, posttraumatic infections developed in 12 (18%), and nosocomial infections developed in 6 (9%). The incidence of posttraumatic infections in patients who were given gentamicin and metronidazole (5/33 [15%]) was not significantly lower than the incidence in patients who were given ciprofloxacin and metronidazole (7 of 35 [20%]; P=.75). The presence of any infection increased the mean+/-SD length of hospital stay from 8.7+/-3.5 days to 23.3+/-10.9 days and increased the mean+/-SD hospital charges from $24 507+/-$9860 to $104920+/-$49083 (P<.001). Univariate analysis showed the factors most significantly associated with infection were as follows: (1) the use of blood transfusions (P<.001), (2) the penetrating abdominal trauma index of 35 or more (P<.002), (3) injury to the colon requiring a colostomy (P=.004), and (4) a trauma score of less than 12 (P<.02). Multivariate analysis showed the only significant factor was the receipt of blood transfusions (F=10.165; P<.005). CONCLUSIONS: Ciprofloxacin and gentamicin, each in combination with metronidazole, were equivalent in their ability to prevent infections after penetrating abdominal trauma; other factors, especially the receipt of blood transfusions, had much more effect on the incidence of infection. Infection greatly increases the length of hospital stay and hospital charges. The use of an increased dosing regimen of 2.5 mg/kg every 12 hours of gentamicin sulfate was effective at obtaining a therapeutic peak serum concentration.     

Effect of disease localization on the anthropometric and metabolic features of Crohn''s disease

Conjugated linoleic acid (CLA) is a potent anticarcinogen secreted in milk of ruminants, but it inhibits de novo fatty acid synthesis and desaturation in mammary cell cultures. The potential for increasing CLA content of milk fat and the effects of elevated CLA availability on milk fat secretion were investigated. Four Holstein cows were used in a single crossover design with repeated measures to determine milk fatty acid concentration in response to a 24-h infusion of 200 g linoleic acid (LA) or a mixture of 100 g LA plus 100 g CLA (LCLA). Milk and blood samples were obtained 12 h before infusion and at 12-h intervals from 0 to 72 h. Compared with LA infusion, total CLA concentration in blood plasma at 24 h in response to LCLA was elevated fivefold, whereas CLA content of plasma triglycerides was increased 10-fold. Milk fat yield from 24 to 72 h was approximately 34% lower in response to LCLA compared with LA, due primarily to reduced yield of fatty acids with six to 16 carbons. Amount of CLA in milk increased from 0.5 g/100 g total fatty acids at 0 h to 3.3 g/100 g at 36 h in response to LCLA. Concentration of stearic acid in milk fat at 36 h in response to LCLA was nearly double the stearic acid concentration in response to LA. Oleic and arachidonic acid concentrations in milk declined as stearic acid increased in response to LCLA. Results indicated CLA content of milk fat reflects the amount available for absorption from the small intestine, and CLA appeared to be a potent inhibitor of de novo fatty acid synthesis and desaturation in the mammary gland.     

Ulceration of the ileum in Crohn''s disease: correlation with vascular anatomy

Forty-five cases of gastroschisis and 85 of omphalocele were reviewed. The survival of gastroschisis has dramatically improved over the past 20 years, however, that of omphalocele still remained in the lower value, because the size of the defect and the presence of associated anomalies are prognostic factors. The primary fascial closure was first employed for the patients with gastroschisis and a silo chimney was used for limited cases. On the other hand, for the patients with omphalocele, primary closure was possible in 34 cases, silo chimney was used in 17, and 45 cases had nonoperative management with epithelialization. Among them, nonoperative management using painting was the most reliable therapeutic for omphalocele.     

Enterolithiasis, refractory anemia, and strictures of Crohn''s disease

It has been recently shown that NGF is not only involved in the survival and development of sympathetic and neural crest-derived sensory neurons, but also in some mechanisms of the immune system. For this reason, we studied the content of NGF in CSF samples from patients with diseases in which neuroimmunological mechanisms seem to be involved (multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer disease, chronic relapsing polyradiculoneuritis, Guillain-Barré syndrome, and tumors of the nervous system), as well as from a number of normal control subjects. We setup an ELISA aimed at the beta subunit of NGF, obtaining good validation tests and a detection limit of 28 pg beta NGF per ml. None of the samples was found to contain detectable levels of NGF and, when a concentration method for sample enrichment was used, only one patient was NGF-positive. This suggests that NGF is probably not involved in the neuroimmunological mechanisms underlying some inflammatory and degenerative diseases of the nervous system.     

An unusual case of Crohn''s disease in a West Indian child

A method is described for the determination of the intracellular concentration of sodium in individual cells using the electron microprobe analyzer. This method gives an accuracy equal to that obtained by using flame photometry on tissues with large cell populations. Intracellular sodium was precipitated in the cell by a fixative containing pyroantimonate. Cartilaginous needles from shark fins which were equilibrated in saline solutions of differing concentrations were used as biological standards.     

Polyamines as markers of response and disease activity in cancer chemotherapy

One hundred twenty-four patients with hematological and solid neoplasms had pretreatment urinary polyamine determinations. Putrescine, spermidine, and spermine were all significantly increased as compared to normals (p less than 0.001). Polyamine levels were directly related to disease activity and tumor burden. In patients with multiple myeloma, putrescine levels were significantly correlated with clinical disease activity as well as the in vitro labeling index of marrow plasma cells. Spermidine values reflected tumor cell burden. Serial studies in 56 patients indicated that greater than twofold rise in urinary spermidine during treatment was highly correlated with cell kill and subsequent clinical response (p less than 0.001). Serum polyamine levels in 17 patients were found to be comparable to urinary values. Our data indicate that polyamine determinations can potentially be clinically useful, i.e., baseline values as indicators of tumor cell mass and growth fraction, and increases in spermidine during treatment as an excellent marker of tumor cell kill.     

Life-threatening hemorrhage and exsanguination from Crohn''s disease. Report of four cases

This study evaluates the reproducibility of food intake reports in a 45-item self-administered food frequency questionnaire (FFQ) used for a diet study in a large cohort in New York State. The first FFQ was mailed in 1980, and a followup version containing 75 food items was mailed in 1988 to the eligible original participants. Reproducibility was evaluated by comparing the subjects' 1988 responses with their original 1980 responses. Spearman's correlations ranged from 0.27 (nuts other than peanuts) to 0.56 (summer squash) in men and from 0.25 (tomatoes) to 0.51 (summer squash) in women. Analyses stratified by age, education, marital status, body mass index, cigarette smoking, alcohol drinking, and special diet revealed few substantial differences in correlations. The moderate reproducibility of foods in this questionnaire indicates that brief FFQs may be a useful tool to study food intake and chronic disease relationships in this population.     

A randomized controlled study comparing elemental diet and steroid treatment in Crohn''s disease

To elucidate the mechanism underlying the interaction between the L-type Ca2+ channel and the dihydropyridines (DHPs), contribution of the repeat III was studied by constructing chimeras between the DHP-sensitive alpha1C and DHP-insensitive alpha1E subunits. The chimeras were transiently expressed in human embryonic kidney 293 cells and the whole-cell Ba2+ current (IBa) was recorded. Mutating Thr1061 to Tyr in IIIS5 of the alpha1C sequence completely abolished the inhibition and stimulation of IBa by the antagonist (+)-isradipine and agonist (-)-Bay K 8644, whereas mutating Gln1065 to Met in IIIS5 decreased the affinity for isradipine 100-fold without affecting the stimulating effect of Bay K 8644. The conserved amino acid residue Tyr1174 in IIIS6 of the alpha1C subunit was necessary for the high affinity DHP block. The DHP-dependent block and stimulation of IBa were transferred to the alpha1E channel by the mutation of two amino acid residues in IIIS5 (Y1295T, M1299Q), three residues in IIIS6 (F1406I, F1409I, V1414M) and three residues in IVS6 (I1706Y, F1707M, L1714I). The mutated alpha1E channel was stimulated 2.8-fold by 1 microM Bay K 8644 and blocked by isradipine with an IC50 value of 60 nM. These results show that mutation of Thr1061 in the alpha1C sequence results in a DHP-insensitive L-type channel and that transfer of the high affinity DHP sensitivity requires mutation of eight amino acid residues in the alpha1E sequence.     

Assessment of thalamic regional cerebral blood flow in patients with cerebrovascular disease

The thalamus is believed to play an integrative role in the central nervous system. In the present study, thalamic rCBF was measured in 65 CVD patients and 15 normal volunteers by stable Xe/CT scanning. ROIs were chosen in the thalamic slice at a level 5cm over the OM line, and mean CBF was 7 cm over the OM line. The clinical factors focused on in multiple regression analysis were: age (A), sex (Se), stage from onset (St), lesion side (Sd); unilaterality or bilaterality, size (Sz) thalamic lesion (Tl). GCS (G), HDS-R (H); Hasegawa dementia score (revised), symptoms (Ss) such as anxiety, dizziness, head-headed feeling and headache, and neurological deficits (N). Each factor was graded and scored. Statistically, there was a significant correlation between thalamic rCBF (Y) and mean CBF (X) in the less affected hemisphere: Y = 1.82X + 2.2, r = 0.801, p < 0.001, n = 65. Multiple regression analysis of the thalamic rCBF revealed that the Sz factor was significant (p < 0.0001) on the lesion side: Y = 76.7-10.2Sz, r = 0.644, p < 0.001, n = 51, while the Se, Sd and St factors were significant (p < 0.005) on the less affected side: Y = 71.9 + 9.7Se-6.8Sd-5.0St, R = 0.585, p < 0.001, n = 65. The thalamic index (X), an indicator of thalamic atrophy, and thalamic rCBF were significantly correlated: Y = 28.7X + 10.2, r = 0.386, p < 0.001, n = 80. In conclusion, thalamic rCBF appeared to reflect the degree of organic changes and time course in the cerebral hemisphere, because factors such as size, sex and stage were statistically significant.     

Surgical treatment for duodenal involvement in Crohn''s disease: report of a case

BACKGROUND: Aerobic bacterial pathogens are recovered from 65 to 85% of patients with acute otitis media (AOM). Although Chlamydia pneumoniae is a common pathogen of pediatric pneumonia, it has rarely been cultured from children with chronic otitis media and its role in AOM is unknown. METHODS: We cultured for C. pneumoniae in tympanocentesis aspirates and nasopharyngeal swabs from 101 consecutive, otherwise healthy children with AOM or refractory AOM. A control group of 50 similarly aged, healthy children was evaluated for nasopharyngeal carriage of C. pneumoniae. Specimens were also evaluated by PCR for C. pneumoniae. RESULTS: C. pneumoniae was recovered by tympanocentesis in 8 (8%) of 101 children with AOM. Among the 8 children with C. pneumoniae-positive-AOM, 5 had C. pneumoniae detected by PCR in middle ear fluid, none had C. pneumoniae recovered by nasopharyngeal culture or PCR and 5 were younger than 16 months. C. pneumoniae was the sole pathogen isolated in 2 patients. Copathogens included beta-lactamase-positive positive Haemophilus influenzae (2), beta-lactamase positive Moraxella catarrhalis (1), penicillin-resistant Streptococcus pneumoniae (2) and penicillin-susceptible S. pneumoniae (1). C. pneumoniae was recovered from nasopharyngeal culture in 2 additional patients with C. pneumoniae-negative AOM and in none of 50 healthy control children, although 2 controls were positive by PCR from the nasopharynx. CONCLUSIONS: This is the first study to report the isolation of C. pneumoniae in middle ear fluid of children with AOM.     

Cortical blood flow response to hypercapnia during anaesthesia in Moyamoya disease

Cortical blood flow (CoBF) was measured continuously by the laser-Doppler method to evaluate the effect of hypercapnia on cortical blood flow during ten surgical procedures in ten young patients (mean +/- SD 9.3 +/- 6.4 yr) with Moyamoya disease. The CoBF was 42.8 +/- 13.4 (ml.100 g-1.min-1) during normocapnia (PaCO2 = 39.0 +/- 2.4 mmHg), and 38.7 +/- 14.4 during hypercapnia (PaCO2 = 47.1 +/- 2.5 mmHg). There was a decrease in CoBF with hypercapnia (P < 0.05) so that the normal CoBF response to hypercapnia was impaired during surgery in the patients with Moyamoya disease. He concluded that patients with Moyamoya disease have a precarious cerebral circulation and hypercapnia may be detrimental to the cortical circulation. This suggests that normocapnia is preferable to hypercapnia in patients with Moyamoya disease during anaesthesia.     

Intrinsic hyperreactivity of mucosal T cells to interleukin-2 in pediatric Crohn''s disease

1. The basic etiology of Alzheimer's disease remains unknown, although four genes have so far been involved: beta-amyloid precursor protein, presenilin-1, presenilin-2 and apolipoprotein E genes. 2. The largest familial Alzheimer's disease (FAD) kindred so far reported belong to a point mutation in codon 280 that results in a glutamic acid-to-alanine substitution in presenilin-1 characterized in Antioquia, Colombia. 3. A hypothetical unified molecular mechanism model of cell death in FAD mediated by presenilin-1, beta-amyloid, and oxidative stress is proposed as an attempt to explain the mechanisms of neuronal loss in this neurodegenerative disorder.