Detection of inflammatory bowel disease in adults and children: evaluation of a new isotopic technique.

The distribution of radioactivity after the oral administration of sucralfate labelled with technetium-99m was studied in 33 patients with Crohn''s disease (13 adults, 20 children), 10 with ulcerative colitis (four adults), and 29 controls (23 with upper intestinal disease, four irritable bowel, one hypolactasia, and one malrotation of the gut). Positive scans were obtained in all patients with ulcerative colitis and 29 of 31 with active Crohn''s disease. The scans of two patients with inactive Crohn''s disease were negative. There were two false negative scans in patients with Crohn''s colitis and one false positive scan. Overall, sensitivity was 95% and specificity 97%. Comparison with radiology in 39 patients showed similar distribution of disease in 24 and more extensive disease in 12. The scan was inexpensive, simple to perform, well tolerated, allowed small and large bowel to be visualised simultaneously, and used a lower dose of radiation than barium studies. It may prove useful as a screening test for inflammatory bowel disease and in the serial assessment of disease activity.     

The 99mTc-HMPAO leukocyte scan: an alternative to radiology and endoscopy in evaluating the extent and the activity of inflammatory bowel disease

Seventy-eight patients, 47 with Crohn's disease and 31 with ulcerative colitis, were studied using 99mTc-HMPAO-labelled leukocytes, in order to assess the reliability of the scan in evaluating the location and activity of the disease. The granulocyte integrity was assessed by evaluating the lung wash-out and the early liver and spleen uptake using a 20 minute initial dynamic study. The results of the leukocyte scan revealed a high correlation with radiological and endoscopic findings in the diagnosis of the inflamed bowel segments. The disease activity correlated well with uptake in the bowel, graded from 0 to 3. The leukocyte scan exactly documented the activity in the 9 cases of Crohn's disease located in the ileum and in 5 cases in which the endoscopic exploration was hampered by scarring. Four fistulae were correctly visualized. Moreover, the change in activity after therapy in 6 patients was documented. This technique provides images of excellent quality, superior to those obtainable with indium-111.     

Colonoscopy for unexplained rectal bleeding.

Two hundred and thirty-nine patients underwent colonoscopy for unexplained rectal bleeding. Local anorectal conditions were excluded by digital and proctosigmoidoscopic examinations and results of barium studies were negative for all patients. A cause for bleeding was found in 95 patients. Thirty-nine had adenomatous polyps, 24 had unrecognised inflammatory bowel disease, and most importantly 23 (10% of series) had carcinomas. Forty patients had diverticular disease, but nine of them were found to have an adenomatous polyp and four a carcinoma. Colonoscopy can contribute positively to the investigation and treatment of unexplained rectal bleeding and may prevent unnecessary laparotomy.     

Determinación de la certeza diagnóstica de la gammagrafía tiroidea con tecnecio 99 sestamibi en pacientes con nódulo tiroideo y resultado histopatológico definitivo

Background99mTc sestamibi scanning and aspiration biopsy can predict the histopathological result of a thyroid nodule fairly accurately.ObjectiveTo determine the accuracy of 99mTc sestamibi scanning in detecting malignancy in patients with thyroid nodule confirmed by definitive histopathological report after thyroidectomy.Material and methodsA total of 69 patients with a solitary thyroid nodule were studied. In all patients, fine needle aspiration, total thyroidectomy for suspected thyroid cancer, and histological analysis of the surgical specimen were performed. There were 54 patients with a positive 99mTc sestamibi scan; of these, malignancy was confirmed by histological analysis in 25 and excluded in 29. There were 15 patients with a negative 99mTc sestamibi scan; of these, three had a final diagnosis of cancer and 12 were confirmed as cancer-free.ResultsThe diagnostic accuracy of 99mTc sestamibi scanning in detecting malignancy in thyroid nodules was determined through a statistical analysis. 99mTc sestamibi scan for thyroid cancer had a sensitivity of 89.28% and a specificity of 29.25%. The positive predictive value was 46.29% and the negative predictive value was 80%.ConclusionsWe believe that 99mTc sestamibi scan should be routinely used in all patients with a thyroid nodule and an indeterminate result on fine needle aspiration. This procedure is most useful in excluding malignancy in patients with a negative 99mTc sestamibi scan.     

Detection of deep venous thrombosis by scanning of 99mtechnetium-labelled red-cell venous pool.

A comparative study of 32 patients with suspected deep venous thrombosis was carried out using blood-pool radionuclide scanning and conventional x-ray phlebography. Results of the two methods showed close agreement, the sensitivity (positive correlation) of the scan being 100% and its specificity 89%. We conclude that a patient''s red cells labelled with 99mtechnetium (99mTc) provide an excellent medium for this type of scanning. The technique has particular advantages in visualising the whole venous system, giving a persisting image, and obviating the need to inject into a vein of the affected limb. In view of the inherent disadvantages of contrast phlebography, 99mTc-red-cell scanning is clearly an acceptable alternative.     

Cytomegalovirus Infection in Inflammatory Bowel Disease Is Not Associated with Worsening of Intestinal Inflammatory Activity

Background

Cytomegalovirus is highly prevalent virus and usually occurs in immunocompromised patients. The pathophysiology and treatment of inflammatory bowel disease often induce a state of immunosuppression. Because this, there are still doubts and controversies about the relationship between inflammatory bowel disease and cytomegalovirus.

Aim

Evaluate the frequency of cytomegalovirus in patients with inflammatory bowel disease and identify correlations.

Methods

Patients with inflammatory bowel disease underwent an interview, review of records and collection of blood and fecal samples. The search for cytomegalovirus was performed by IgG and IgM blood serology, by real-time PCR in the blood and by qualitative PCR in feces. Results were correlated with red blood cell levels, C-reactive protein levels, erythrocyte sedimentation rates and fecal calprotectin levels for each patient.

Results

Among the 400 eligible patients, 249 had Crohn''s disease, and 151 had ulcerative colitis. In the group of Crohn''s disease, 67 of the patients had moderate or severe disease, but 126 patients presented with active disease, based on the evaluation of the fecal calprotectin. In patients with ulcerative colitis, only 21 patients had moderate disease, but 76 patients presented with active disease, based on the evaluation of the fecal calprotectin. A large majority of patients had positive CMV IgG. Overall, 10 patients had positive CMV IgM, and 9 patients had a positive qualitative detection of CMV DNA by PCR in the feces. All 400 patients returned negative results after the quantitative detection of CMV DNA in blood by real-time PCR. Analyzing the 19 patients with active infections, we only found that such an association occurred with the use of combined therapy (anti-TNF-alpha + azathioprine)

Conclusion

The findings show that latent cytomegalovirus infections are frequent and active cytomegalovirus infection is rare. We did not find any association between an active infection of CMV and inflammatory bowel disease activity.     

Organometallic 99mTc(III) '4 + 1' bombesin(7-14) conjugates: synthesis, radiolabeling, and in vitro/in vivo studies

Bombesin (BBN) peptide exhibits high selectivity and affinity for the gastrin-releasing peptide receptor (GRPr). The GRPr is overexpressed on many human cancer cell types, thus making BBN a potent delivery vehicle for radionuclide targeting. In this study, the biologically active minimal sequence BBN(7-14) was labeled using the novel Tc '4 + 1' mixed-ligand system, [Tc(NS3)(CN-R)], in which Tc(III) is coordinated by a monodentate isocyanide linker bearing the peptide and the tetradentate, tripodal chelator, 2,2',2'-nitrilotriethanethiol (NS3). BBN(7-14) was N-terminally modified with Gly-Gly-Gly, betaAla, and Ser-Ser-Ser spacer groups (X) and functionalized with 4-(isocyanomethyl)benzoic acid (L1) or 4-isocyanobutanoic acid (L2), resulting in a series of [M(NS3)(L-X-BBN(7-14))] conjugates (M = 99mTc, Re). The isocyanide ligand frameworks were introduced using novel bifunctional coupling agents. The spacer groups (X), the monodentate isocyanide units, and a tetradentate NS3 chelator bearing a pendant carboxylic acid (NS3COOH) were proposed as pharmacological modifiers. 99mTc-labeling was performed in a two-step procedure by first preparing 99mTc-EDTA/mannitol followed by reactions with the isocyanides and NS3 or NS3COOH ligand frameworks. The 99mTc complexes were obtained with a radiochemical yield of 30-80% depending on the amount of the isocyanide (20-100 nmol) used. These new conjugates were purified by reversed-phased high-performance liquid chromatography (RP-HPLC) to give a radiochemical purity of >or=95%. The 99mTc conjugates exhibited high in vitro stability (>90%, 24 h). Analogous nonradioactive Re conjugates were synthesized and characterized by electrospray ionization mass spectrometry (ESI-MS). RP-HPLC analyses of the Re conjugates indicated that they exhibited identical retention times to the corresponding 99mTc conjugates under identical HPLC conditions, demonstrating structural similarity between the two metalated species. The [Re(NS3)(L-X-BBN(7-14))] conjugates exhibited GRPr affinity in the nanomolar range as demonstrated by in vitro competitive binding assays using PC-3 human prostate cancer cells. In vitro internalization/externalization assays indicated that approximately 65% of [99mTc(NS3)(L2-betaAla-BBN(7-14))] conjugate was either surface-bound or internalized in PC-3 cells. Cell-associated activity for all other 99mTc conjugates was below 20%. Biodistribution studies of [99mTc(NS3)(L-betaAla-BBN(7-14))], L = L1 or L2, in normal, CF-1 mice showed minimal accumulation in normal pancreas (a tissue expressing the GRPr in high density in rodent models) and rapid hepatobiliary elimination. Introduction of a carboxyl group onto the NS3 ligand framework had only minimal effects to increase renal excretion. Activity distribution and accumulation was highly dominated by the relatively lipophilic '4 + 1' complex unit.     

Oesophageal carcinoma demonstrated by whole-body nuclear magnetic resonance imaging.

The quality of the images produced by nuclear magnetic resonance (NMR) imaging has steadily improved over the past five years. Images of the head, thorax, and abdomen have clearly shown the normal anatomy. A clinical trial of NMR imaging has therefore been started in Aberdeen to assess its diagnostic accuracy and compare it with conventional radiography and other imaging technique. The first patient examined by whole-body NMR imaging had carcinoma of the oesophagus diagnosed on barium meal examination. A technetium-99m-sulphur colloid liver scan also showed hepatic metastases. NMR imaging showed a large tumour in the lower third of the oesophagus, and areas of increased proton spin-lattice relaxation time (T1) on a section through the liver corresponded with the metastases shown on the radionuclide scan. Increased areas of T1 were present in some vertebrae, and a technetium-99m bone scan confirmed the presence of bone metastases. The NMR images in this patient compared well with the images from other techniques. The continuing clinical trial may show that NMR is an accurate diagnostic aid which will complement existing techniques for diagnosing intrathoracic and intra-abdominal conditions.     

Significant increase of interleukin 6 production in blood mononuclear leukocytes obtained from patients with active inflammatory bowel disease

In the present study, we compared the potency of interleukin 6 production in peripheral blood mononuclear leukocytes between paired patients with active stage and inactive stage of inflammatory bowel disease. Subjects included nine patients with ulcerative colitis, ten patients with Crohn's disease and sex-matched nine healthy volunteers. Mononuclear leukocytes were stimulated with concanavalin A for 24 h to induce interleukin 6 production. Interleukin 6 content in the culture medium was assayed by using specific ELISA and interleukin 6 dependent cell line MH-60. Interleukin 6 production was found to be significantly increased in mononuclear leukocytes from both active ulcerative colitis and Crohn's disease as compared to that from control subjects. There was no significant difference in interleukin 6 production between ulcerative colitis and Crohn's disease. The potency of interleukin 6 production was returned to the control level when the diseases became inactive. The present results, therefore, may indicate some important role of interleukin 6 in the pathogenesis of inflammatory bowel disease and also the potency of interleukin 6 production in mononuclear leukocytes can be an indicator of the activity of inflammatory bowel disease.     

Juvenile onset inflammatory bowel disease: height and body mass index in adult life.

OBJECTIVE--To establish the frequency of permanent growth failure in juvenile onset inflammatory bowel disease. DESIGN--Measurement of height and weight in a geographically based cohort at a mean of 14 (range 5.2-29.5) years after diagnosis. Comparison with data from surveys of British adults in 1980 and 1987. SETTING--NHS hospitals throughout Scotland. SUBJECTS--105 Children admitted to hospital during 1968-83 who fulfilled diagnostic criteria for Crohn''s disease or ulcerative colitis and lived in specified regions. 87 were aged over 18 and living in Britain at follow up. MAIN OUTCOME MEASURES--Height, weight, body mass index, and sexual maturity. RESULTS--All patients were sexually mature. 67 of the 70 patients examined were of normal height, and three women with Crohn''s disease were abnormally short. Weight and body mass index were normal in all patients with ulcerative colitis. Patients with Crohn''s disease had significantly lower weight than those with ulcerative colitis (men 66.8 (9.5) kg v 78.4 (13.8) kg, P = 0.04; women 51.5 (8.2) kg v 63.0 (12.1) kg, P < 0.02) irrespective of disease activity. Body mass index was also significantly lower than the normal distribution (P < 0.01). Growth retardation was not mentioned as a problem for any of the 17 patients interviewed only by telephone. CONCLUSIONS--Despite growth retardation in the teenage years most young people with inflammatory bowel disease will eventually achieve normal height. Reasons for lower weight in patients with Crohn''s disease remain to be established.     

Sigmoidoscopy/proctoscopy service with open access to general practitioners.

Many hospitals now offer barium enema examinations to general practitioners on an open access basis, so bypassing the traditional sequence of first carrying out a sigmoidoscopy. An open access sigmoidoscopy/proctoscopy service was therefore opened with requests for a barium enema being denied unless preceded by sigmoidoscopy. During the first three and a half years 1458 patients referred direct from their general practitioners were examined using a rigid sigmoidoscope. Patients were also examined with a proctoscope if thought appropriate. After the first year of the service a subsequent examination with a fibreoptic sigmoidoscope was also carried out if the presenting symptom was bleeding for which no cause could be found with the rigid instruments. A total of 516 abnormalities were found to account for symptoms in 506 patients giving a diagnostic rate of 35%. The most common lesion was piles (307 cases). Other relatively common disorders included inflammatory bowel disease (107 cases), benign tumours (44), and malignant tumours (38). Of 41 patients subsequently undergoing fibreoptic sigmoidoscopy a cause for the bleeding was found in 32, the most common being a malignant tumour (16). Most general practitioners in the district used the service and a questionnaire survey indicated that most found it very helpful. Requests from general practitioners for a barium enema fell substantially over the period.     

Technetium-99m-labeled medium-chain fatty acid analogues metabolized by beta-oxidation: radiopharmaceutical for assessing liver function.

External imaging of energy production activity of living cells with 99mTc-labeled compounds is a challenging task requiring good design of 99mTc-radiopharmaceuticals. On the basis of our recent findings that 11C- and 123I-labeled medium-chain fatty acids are useful for measuring beta-oxidation activity of hepatocytes, we focused on development of 99mTc-labeled medium-chain fatty acid analogues that reflect beta-oxidation activity of the liver. In the present study, monoamine-monoamide dithiol (MAMA) ligand and triamido thiol (MAG) ligand were chosen as chelating groups because of the stability and size of their complexes with 99mTc and their ease of synthesis. Each ligand was attached to the omega-position of hexanoic acid (MAMA-HA and MAG-HA, respectively). In biodistribution studies, [99mTc]MAMA-HA showed high initial accumulation in the liver followed by clearance of the radioactivity in the urine. Analysis of the urine revealed [99mTc]MAMA-BA as the sole radiometabolite. Furthermore, when [99mTc]MAMA-HA was incubated with living liver slices, generation of [99mTc]MAMA-BA was observed. However, [99mTc]MAMA-HA remained intact when the compound was incubated with liver slices in the presence of 2-bromooctanoate, an inhibitor of beta-oxidation. The findings in this study indicated that [99mTc]MAMA-HA was metabolized by beta-oxidation after incorporation into the liver. On the other hand, poor hepatic accumulation was observed after administration of [99mTc]MAG-HA.     

The mechanics of terminal lymph flow

The effects of external pressure on the terminal lymphatic clearance rate are studied. Sulfur colloid tagged with 99mTc is injected into the subcutaneous tissue in the hind thigh of canines. The activity of the tracer is measured over the injection site for 90 min to determine the lymphatic clearance rate of the sulfur colloid. Several experiments are performed at different external pressures applied to the surface of the canine thigh. A two-compartment model is defined to determine both the terminal lymphatic flow rate per unit volume of tissue and the diffusion constant (sulfur colloid/interstitial fluid) from the raw data. Experimental results indicate that increases in the external pressure applied to the skin cause terminal lymphatic clearance rates to increase until the pressure reaches 60 mm Hg. At this level, some test results showed reduced levels of clearance. At 75 mm Hg, the lymphatic clearance of sulfur colloid from the subcutaneous tissue was stopped suggesting occlusion of the vessels resulting from vessel collapse.     

Evaluation of axillary lymph nodes from the results of radioisotopic study

The purpose of the investigation was to study the pattern of 99mTc (MIBI) technitrile uptake in the metastatically involved lymph nodes in breast cancer, by applying the plain scintigraphic technique. The scintigraphic study of the breast and regional metastatic areas by means of the radionuclide 99mTc (MIBI) technitrile was made on a Millennium GE tomographic gamma chamber. The radiotracer 550 (MBq) dissolved in 10-20 ml of saline solution was intravenously injected into the arm cubital vein contralaterally to the lesion. Following 20 minutes of injection of the agent, plain scintigraphy was carried out in three standard projections: frontal and two oblique ones. The scintigraphy was performed using a high-resolution collimator recording a 128 x 128 matrix image. The detector was maximally approximated to the organ being examined. A plain scintigraphic scan was recorded on each side for 10 minutes. By the degree of axillary lymph nodal involvement, the patients were divided into 3 groups in accordance with the international TNM classification: N0 (n = 55), N1 (n = 13), N2 (n = 4). Among 72 patients, axillary lymph nodes could be detected in 6, in 2 of them changes were not diagnosed by X-ray and ultrasound studies. The final pathomorphological study of intraoperative materials revealed axillary lymph nodal metastatic involvement in 17 patients. A micrometastasis in one lymph node was found in 1 patient. None of the radionuclide studies showed tumor spread in 5 cases. The sensitivity, specificity, and precision of the technique were 35.3, 100, and 84.7%, respectively. Thus, a combination of the high cost of the procedure, its radiation load on a patient, and its low sensitivity make the use of plain scintigraphy of axillary regions inexpedient in the complex of studies of the extent of breast cancer in the present development of technology.     

An evaluation of flexible fibreoptic sigmoidoscopy.

Results of 350 flexible fibreoptic sigmoidoscopy examinations showed a diagnostic yield of 30% compared with 6.5% by rigid sigmoidoscopy of the same patients. The mean time for the examinations was eight minutes, a distance of over 50 cm being visualised in 65% of the patients. Preparation of the bowel with a single phosphate enema was adequate in 95% of the patients. As an outpatient investigation for clinicians fibreoptic sigmoidoscopy is a safe, quick, and useful addition to rigid sigmoidoscopy and should result in a decrease in the number of barium enema examinations required.     

Indium-111 autologous leucocyte scanning: comparison with radiology for imaging the colon in inflammatory bowel disease.

Indium-111 autologous leucocyte scanning was compared with barium enema for assessing the extent of colonic disease in Crohn''s colitis and ulcerative colitis. Scanning was shown to be as accurate as conventional radiology in colitis, reliably distinguishing active from inactive disease. The results suggest that 111In-leucocyte scanning is an accurate, non-invasive, alternative technique for imaging the extent of disease in colitis.     

Current possibilities of X-ray diagnosis of small intestine diseases using the agent Entero-view

The paper analyzes the current capacities of routine (classical) X-ray study in the diagnosis of organ diseases of the small bowel. The distinctive feature of the paper is that in addition to routine barium passage through the small bowel, the new barium contrast agent Entero-view specially designed for its exploration is used. Of the 115 examined patients with various gastroenterological diseases, 76 underwent Entero-view examination that revealed different organ pathology of the small bowel in 28 cases (Crohn's disease in 18, tuberculosis in 3, lymphomas in 5, and cancer in 2). A normal X-ray pattern of the small bowel was diagnosed in 48 cases. The authors highly appreciate this agent. In their opinion, it is essentially helpful in solving one of the most difficult problems in X-ray gastroenterology--present-day X-ray diagnosis of small bowel pathology. The paper describes a procedure for using this agent. It gives a normal X-ray pattern of the small bowel, the agent's use has provided a particularly vivid image of both a normal part of the ileum and its different organ pathology-associated changes.     

Aspects des complications ostéo-articulaires de la maladie de Gaucher de type 1 en scintigraphie osseuse planaire (infection exclue) : à propos d’un cas

Type 1 Gaucher disease is an autosomal recessive inheritance lysosome storage disorder, corresponding to an inherited deficiency of glucocerebrosidase. Bone complications are frequently revealing and constitute the main source of morbidity and disability. They can appear on the acute (osseous infarction, acute osteomyelitis) or chronic mode (bone modelling disorders, osteopenia, osteonecrosis, chronic osteomyelitis). The aim of our work is to evaluate the contribution of the 99mTc labeled diphosphonates bone scan in the case of a 28-year-old patient, followed up for type 1 Gaucher disease and presenting for 2 months knees and pelvis inflammatory pain with functional impotence. X-ray had shown a stage IV aseptic osteonecrosis of the right femoral head. The bone scan found other osteo-articular lesions of the left hip, knees and right tibia related to Gaucher disease with a high likelihood. Bone scan is a very sensitive procedure in the early diagnosis and in the follow-up of bone complications of type 1 Gaucher disease. Bone scan allows to clinically silent lesions on the whole skeleton.     

Diagnostic and therapeutic efficacy of barium meal examination: a prospective evaluation in general practice.

OBJECTIVE--To assess the efficacy of barium meal examinations in managing patients with dyspepsia in general practice. DESIGN--Prospective study by questionnaires completed by general practitioners before and within three to six months after the barium meal examination. Information was requested about the patients'' symptoms, current treatment, reason for requesting the examination, and the working diagnosis, including degree of certainty and, after the examination, about any change in diagnosis, diagnostic confidence, or management and to determine whether the examination was judged to be helpful or not. SETTING--Inner city health district. PATIENTS--133 Patients with dyspepsia referred by general practitioners for outpatient barium meal examination, 31 of whom failed to attend for the examination, or refused it on arrival, or did not have fully completed questionnaires. Two patients were not available for follow up. MAIN OUTCOME MEASURES--Prevalence of radiological abnormalities and the influence of the examination result on management, particularly changes in drug treatment. RESULTS--Fully completed pairs of questionnaires were available for 100 patients, 58 of whom were aged below 50. Most of the barium meal reports (64) were to confirm the clinical diagnosis; only 22 were to exclude serious disease. Ninety nine patients were already receiving treatment, with 39 taking an H2 receptor antagonist. Fifty eight barium meal examinations showed abnormalities (31 major abnormalities); there were no cancers and in only 18 patients was the working diagnosis changed as a result of the findings. Although the barium meal result increased management confidence (63 patients) and allayed patients'' anxiety (46), changes in management attributed directly to the examination occurred in only 22 patients. Management changes were minor, usually comprising interchange of antacids and H2 receptor antagonists. CONCLUSIONS--Young patients (aged below 50) with dyspepsia are still being overinvestigated. Although barium meal examination improves diagnostic confidence and allays patients'' anxiety, fully utilising communication skills at the initial consultation might allay anxiety more economically.