Low molecular weight heparin as adjuvant therapy in active ulcerative colitis.

BACKGROUND: Heparin given intravenously has shown beneficial effects in the treatment of refractory ulcerative colitis in open trials. Low molecular weight heparin (LMWH) offers advantages in the method of administration but have not been evaluated in inflammatory bowel disease conditions. AIM: To assess the tolerability and safety of subcutaneous self-administered LMWH in outpatients with refractory ulcerative colitis and to evaluate any potential adjuvant therapeutic effect. PATIENTS AND METHODS: Twelve patients with mild to moderately active ulcerative colitis were included in the trial. The patients had either responded poorly to treatment with conventional therapy, including oral and/or rectal glucocorticosteroids, or had experienced a rapid relapse during or shortly after GCS therapy. Dalteparin sodium 5000 units s.c. injection was administered twice daily for 12 weeks. Patients were monitored for possible adverse events and changes in clinical symptoms, and endoscopic and histological scores were analysed. Leucocyte scanning was performed at inclusion and at the end of the study. RESULTS: Tolerability and compliance were excellent and no serious adverse events occurred. Eleven patients improved symptomatically and six (50%) attained complete remission after 12 weeks of treatment. Endoscopic, scintigraphic and histological scores were found to be significantly improved. CONCLUSION: Self-administered LMWH given s.c. may be a safe adjuvant therapy for patients with active, glucocorticosteroids-refractory ulcerative colitis. A controlled trial should be undertaken to confirm the positive effects found in this study.

Scintigraphic study of the major salivary glands in pediatric bone marrow transplant recipients.

Total body irradiation (TBI) at bone marrow transplantation (BMT) is shown to cause salivary gland dysfunction in children. The aim of the investigation was to study the function of major salivary glands in long-term surviving children following treatment with TBI, using salivary gland scintigraphy (SGS). Thirteen patients (seven male, six female), who had received TBI before the age of 13 years and survived more than 4 years, participated in the study. A reference group of 10 patients (nine male, one female) was examined shortly before they were to undergo BMT. The mean age was 14.1 +/- 4.1 years in the TBI-treated group and 12.8 +/- 5.9 years in the reference group. Unstimulated and stimulated whole salivary secretion rates were measured for 15 and 5 min, respectively, before SGS was performed. The percentage of stimulated secretion was 44.7 +/- 18.1% in the TBI-treated group compared to 58.4 +/- 13.0% in the reference group (P = 0.0438). Slower reaccumulation after excretion was found in the TBI-treated patients compared to the reference group (P = 0. 0300). The function of the major salivary glands in long-term survivors treated with TBI at BMT before the age of 13 years was found to be diminished, as shown by the reduced trapping rate and reduced emptying capacity, compared to prior to BMT. Bone Marrow Transplantation (2000) 26, 775-779.

Intraosseous compared to intravenous infusion of allogeneic bone marrow.

Thirty-eight patients (> or = 18 years) receiving marrow transplants from HLA-identical or one antigen-mismatched related donors were randomized to intraosseous (i.o.) + intravenous (i.v.) (n = 10), i.o. (n = 8) or i.v. (n = 20) infusions of bone marrow. There were no significant differences in patient characteristics. PMN/l more than 0.5 x 10(9) occurred on days 19 (median), 20 and 18.5 in the i.o. + i.v., i.o. and i.v. groups, respectively. We found a significant reduction in the number of days on total parenteral nutrition (P = 0.03) and a tendency to a reduction in the number of days on antibiotics (P = 0.06) in the i.o. compared to the i.v. group. Bacteraemia did not occur in the i.o. group, but was seen in 30% of the i.v. group (NS). The incidences of acute and chronic graft-versus-host disease, transplantation-related mortality, relapse and patient survival rates were similar in the three groups. Five patients examined with bone marrow scintigraphy showed the same distribution of granulocytes in the bone marrow directly after transplantation and 3 weeks after transplantation, whether the bone marrow was given by the i.o. or by the i.v. route. We conclude that allogeneic bone marrow transplantation can safely be performed by i.o. infusion, but haematopoietic recovery is not improved.

Adsorption of some technetium-99m radiopharmaceuticals onto disposable plastic syringes.

OBJECTIVE: The purpose of this study was to determine the adsorption behavior of some widely used, commercially available 99mTc radiopharmaceuticals onto different types of plastic syringes. METHODS: Kits were reconstituted with 99mTc-pertechnetate diluted with 0.9% saline to produce maximum radioactive concentrations, as stated by the manufacturers. Aliquots of the solutions were transferred to four different brands of 2-ml syringes. The activity in the syringes was measured before and after injections or simulated injections. The amount adsorbed to the plastic syringe barrel and plunger before and after washout also was measured at different time intervals. Comparisons between products from different manufacturers were made for 99mTc succimer (DMSA) and 99mTc macroaggregated albumin (MAA). RESULTS: Some 99mTC preparations undergo significant adsorption to plastic syringes. Adsorption differs considerably between products from different manufacturers. There was significantly higher residual activity in some types of syringes. In some cases the residual was as high as 40%-50% of the initial activity, and most of the adsorption occurred within 15 min of filling the syringe. CONCLUSION: The data suggest that the extent of adsorption depends on pharmaceutical excipients in the kits and/or the type of syringe used. When inappropriate syringes are used, the reduction in the administered activity may result in poor-quality images. Therefore, the compatibility between radiopharmaceutical and syringe should be investigated under normal conditions of preparation and use every time a new brand of syringe or a new radiopharmaceutical comes into use in diagnostic nuclear medicine.

Bone marrow imaging of bone marrow transplanted multiple myeloma patients.

Eighteen bone marrow transplanted multiple myeloma patients had imaging studies on 24 occasions with radiography as well as bone and bone marrow scintigraphy within 2 months. Twelve of the radionuclide bone marrow studies were performed with Tc-99m human serum albumin colloid and 12 were performed with a Tc-99m tagged monoclonal antigranulocyte antibody. The total detection rate of bone marrow lesions increased by 5% when the findings on bone marrow scintigraphy were combined with the findings and at radiography bone scintigraphy. For lesions in the spine and sacrum, the increase was 25% and 33% respectively, including patients with focal radiotherapy. Peripheral red bone marrow expansion was noted in 17 patients. In a comparison of Mab and Tc-99m HSA colloid imaging, Mab resulted in a higher bone marrow to soft tissue uptake and to a much smaller part of the skeleton being obscured by liver and spleen uptake. It is concluded that bone marrow imaging is valuable for showing red bone marrow distribution. It thereby shows possible sites for malignant lesions; it also shows that Mab imaging is superior to Tc-99m HSA colloid imaging in bone marrow transplanted multiple myeloma patients.

Dynamic scintigraphy of bone and bone marrow in multiple myeloma patients with bone-marrow transplants.

PURPOSE: To determine whether dynamic registration at bone and bone-marrow scintigraphy produces additional information compared to subsequent static registrations of bone-marrow transplants in multiple myeloma patients. MATERIAL AND METHODS: In a prospective study, 8 dynamic bone and 6 dynamic bone-marrow scintigraphies were performed in 10 patients. The dynamic scintigraphies were compared with conventional radiography, MR images, and static scintigraphies of bone and bone marrow. RESULTS: No additional information was revealed by the dynamic registration method; on the contrary, 4 of the 8 known lesions were not discerned at dynamic registration. An incidental observation was that the time-activity curves of both radiopharmaceuticals had a specific pattern. CONCLUSION: Dynamic registration at bone and bone-marrow scintigraphy was not useful for detecting disease in multiple myeloma lesions.

Gastrointestinal activity following bone marrow scintigraphy with technetium-99m nanocolloid in patients with multiple myeloma.

Unexpected abdominal activity was registered later than 1 h post injection in technetium-99m bone marrow scintigrams of 13 multiple myeloma patients and of five controls. The activity was considered to be localised in the gastro-intestinal tract. It is attributed to accumulation of degradation products of the used nanocolloid tracer. Corresponding results are known in patients with inflammatory bowel disease when scintigraphy is performed with other radiopharmaceuticals.

Correlation between quantitative salivary gland scintigraphy and salivary secretion rates in children and young adults treated for hematological, malignant and metabolic diseases.

OBJECTIVES: To study the correlation between whole salivary secretion rates and different variables from the radionuclide time-activity curve and to determine a reliable region for background correction in salivary gland scintigraphy. METHODS: Salivary gland scintigraphy (SGS) was performed before bone marrow transplantation or more than 4 years later in 23 patients aged 13.5 (s.d. 4.9) years. Unstimulated and stimulated whole salivary secretion rates were measured before SGS. Six different methods for background correction were evaluated. RESULTS: The unstimulated secretion rate was significantly correlated (P < 0.05) with the percentage stimulated secretion (S) and reaccumulation-slope (RS) after stimulation. The stimulated secretion rate was significantly correlated with RS, S and down-slope (DS). The temporal region above the parotid glands and the area above the thyroid gland was used for subtraction of background radiation for the parotid and submandibular glands respectively showed a strong correlation between repeated measurements of the variables analysed. The mean maximum uptake was 0.73-1.34% of total dose injected. CONCLUSIONS: The salivary scintigraphic variables which correlated more strongly with salivary secretion rates were RS, S and DS. The temporal region above the parotid gland and the area above the thyroid gland can be used reliably for correction background radiation in the analysis of the time-activity curve in SGS of the parotid and submandibular glands respectively.

Improvements of the lipoprotein profile after coronary bypass surgery: additional effects of an exercise training program.

We have followed physical working capacity and the plasma lipoprotein pattern in 37 males who underwent coronary artery surgery for severe disabling angina pectoris. In order to evaluate the effect of exercise training, 18 patients were randomized to a supervised bicycle training programme three times a week for 12 weeks starting 6 weeks after surgery. Before surgery, working capacity was severely reduced in all subjects. The mean HDL cholesterol level was low (0.8 +/- 0.2 mmol l-1) and the mean plasma LDL concentration moderately elevated (4.6 +/- 0.9 mmol l-1). In the non-training group, physical working capacity increased significantly, and 18 weeks after surgery reached a plateau about 45% above the preoperative values. In the training group, a further improvement to about 60% above preoperative levels was registered at the end of the training program. In the non-training group, HDL cholesterol concentrations rose rapidly to levels between 10 and 15% above the preoperative values. One year after surgery, HDL cholesterol levels were 20% higher than before surgery. There was a parallel rise in apolipoprotein A1 concentrations by about 10% which indicates that the increase in HDL occurred mainly in the lipid rich HDL2 subfraction. There were no changes in plasma lipids or in LDL cholesterol concentrations. In the training group, the increase in HDL was about 20% during the first 26 weeks. One year after surgery, HDL levels were 23% above preoperative values. In this group, we also registered a significant decrease in plasma triglyceride levels by about 25% after two months of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

In-hospital exercise therapy in patients with severe angina pectoris.

The authors evaluated physiologic, psychologic and metabolic effects of a nine-week in-hospital training program on 14 men with severe disabling angina pectoris. The exercise program consisted of intensive interval training on an ergometer bicycle for two 30 min sessions daily. The physical performance increased by about 40% (p less than 0.001). Plasma insulin levels were reduced and glucose tolerance improved significantly. There was a decrease in plasma triglyceride and low-density lipoprotein (LDL) cholesterol levels, but no change in high-density lipoprotein (HDL) cholesterol, apolipoprotein AI and B concentrations. Plasma triglyceride (p less than 0.05) and LDL cholesterol (p less than 0.05) levels remained low three weeks after completion of the training period and the physical performance remained improved (p less than 0.01) even six months post-training. Four of the patients who had been disabled for at least five months were able to return to work. The authors suggest that comparatively short and intensive in-hospital rehabilitation of patients with coronary heart disease may be an attractive alternative to prolonged training on an outpatient basis, especially in patients with severe angina pectoris.

Rehabilitation after coronary bypass surgery: coping strategies predict metabolic improvement and return to work.

Thirty-six consecutive male patients who underwent coronary bypass surgery were investigated before and repeatedly up to 5 years after surgery. We followed the patients' physical capacity, dietary and exercise habits, mood, perception of health and return to work. Discriminant analysis identified four variables from the preoperative interview and the psychological tests which correctly classified 22 out of 24 patients into either metabolic responders--who were characterized by favourable changes in their lipoprotein profile, related to a successful clinical outcome--or non-responders. Responders were found to acknowledge subjective, emotional aspects of their situation whereas non-responders minimised their disease. Six preoperative variables successfully predicted the classification of all but one patient into full-time workers or not, one year after surgery. Full-time workers were more frequent among minimizers. The results suggest that whereas minimising of disease is adaptive in a short-term perspective, acknowledgement may be successful in the long run.

Development of hypertension over 6 years in a birth cohort of young middle-aged men: the Cardiovascular Risk Factor Study in southern Sweden (CRISS).

OBJECTIVES: To explore the development of hypertension (HT) in a cohort of young middle-aged men. DESIGN: Prospective birth-cohort study of men surveyed over 6 years. SETTING: Helsingborg County Hospital, Sweden, 1990-97. SUBJECTS: A total of 628 men born in 1953-54, all surveyed at 37, 40 and 43 years of age. MAIN OUTCOME MEASURES: Systolic blood pressure (SBP), diastolic blood pressure (DBP), S-cholesterol, body mass index (BMI), alcohol consumption, ethnicity. HT was defined as SBP > or = 140 mmHg and/or DBP > or = 90 mmHg, or ongoing treatment. Using SBP < 130 mmHg and DBP < 85 mmHg as reference, the odds of conversion to HT in men with high normal blood pressure (BP) (SBP 130-139 mmHg and DBP 85-89 mmHg) was investigated. RESULTS: At age 37, 243 men (39%) had reference BP, 167 (26%) had high normal BP and 218 (35%) were hypertensive. Corresponding numbers at age 40 were 265 (42%), 166 (27%) and 197 (31%); and at age 43, 180 (29%), 142 (22%) and 306 (49%), respectively. High normal BP at baseline was associated with the development of HT both at age 40 (odds ratio (OR)=2.45 confidence interval (CI): 1.42-4.22) and at age 43 (OR=2.46, CI: 1.59-3.80), independent of other cardiovascular disease risk factors and ethnicity. The progression to HT was predicted also by S-cholesterol, alcohol consumption, BMI and weight gain. CONCLUSIONS: Over a short-term period, a substantial proportion of young middle-aged men with high normal BP develop HT with overweight and alcohol consumption as important determinants. These findings have implications for the prevention, screening and medical care of HT in this target population.

Associations between body height, body composition and cholesterol levels in middle-aged men. the coronary risk factor study in southern Sweden (CRISS).

BACKGROUND: Short body height is associated with increased risk for coronary heart disease; however, mechanisms are not fully explained. In this study, associations between body height and serum cholesterol, non-high-density lipoprotein (non-HDL cholesterol) and high-density lipoprotein (HDL cholesterol) were investigated. METHODS: Prospective cohort study of middle-aged men from Helsingborg, Sweden starting 1990. Two birth-year cohorts were invited at 37, 40 and 43 years of age; participation at baseline was 991 (68%). Serum and HDL cholesterol, systolic and diastolic blood pressure, weight, height, waist and hip circumferences were measured. Non-HDL cholesterol, body mass index (BMI) and waist/ hip ratio (WHR) were calculated. The participants completed a questionnaire covering lifestyle variables. RESULTS: There were statistically significant inverse correlations between body height and serum cholesterol (-0.11) and non-HDL cholesterol (-0.12). One standard deviation, 6.7 cm, taller body height was associated with a lower serum cholesterol (-0.12 mmol/l) and a lower non-HDL cholesterol (-0.13 m mol/l; p < 0.001). These associations remained when adjusted for BMI and WHR. Men with serum cholesterol equal to or above 6.5 mmol/l were significantly shorter (mean 178.71 cm) than men with serum cholesterol below 6.5 mmol/l (mean 179.71 cm). In addition, BMI and WHR were positively associated with serum and non-HDL cholesterol and inversely associated with HDL cholesterol. The change in cholesterol levels over the six-year follow-up was significantly associated to the change in BMI and WHR. CONCLUSIONS: Body height had an independent and inverse relation to serum cholesterol and non-HDL cholesterol in middle-aged men, and the lipid pattern suggests that the underlying mechanism might be different from the traditional association between lipids and the metabolic syndrome. Although the direct clinical implication is limited, our results may help to explain the association between short height and risk of myocardial infarction.

The molecular mechanism for the genetic disorder familial defective apolipoprotein B100.

Familial defective apolipoprotein B100 (FDB) is a genetic disorder in which low density lipoproteins (LDL) bind defectively to the LDL receptor, resulting in hypercholesterolemia and premature atherosclerosis. FDB is caused by a mutation (R3500Q) that changes the conformation of apolipoprotein (apo) B100 near the receptor-binding site. We previously showed that arginine, not simply a positive charge, at residue 3500 is essential for normal receptor binding and that the carboxyl terminus of apoB100 is necessary for mutations affecting arginine 3500 to disrupt LDL receptor binding. Thus, normal receptor binding involves an interaction between arginine 3500 and tryptophan 4369 in the carboxyl tail of apoB100. W4369Y LDL and R3500Q LDL isolated from transgenic mice had identically defective LDL binding and a higher affinity for the monoclonal antibody MB47, which has an epitope flanking residue 3500. We conclude that arginine 3500 interacts with tryptophan 4369 and facilitates the conformation of apoB100 required for normal receptor binding of LDL. From our findings, we developed a model that explains how the carboxyl terminus of apoB100 interacts with the backbone of apoB100 that enwraps the LDL particle. Our model also explains how all known ligand-defective mutations in apoB100, including a newly discovered R3480W mutation in apoB100, cause defective receptor binding.

Leukocyte migration in acute colonic inflammatory bowel disease: comparison of histological assessment and Tc-99m-HMPAO labeled leukocyte scan.

UNLABELLED: Noninvasive leukocyte scintigraphy for assessment of localization, extent, and degree of active inflammation in acute colonic inflammatory bowel disease have been shown to correlate well with endoscopy. This study compared findings of mucosal leukocyte migration assessed histologically with those of technetium 99m hexamethylpropylene-amineoxime-labeled leukocyte scintigraphy. PATIENTS AND METHODS: Twenty-one patients hospitalized because of a first attack or a relapse of known inflammatory bowel disease were investigated using leukocyte scintigraphy followed by total colonoscopy with multiple biopsies within 24 h. Histological interpretation focused on the degree of segmental mucosal leukocyte infiltration. RESULTS: Fourteen patients with ulcerative colitis (UC) and seven with colonic Crohn's disease (CD) were included. With the use of histology as the reference method, maximal proximal disease extent was correctly assessed by the leukocyte scan in 11 patients (8 with UC, 3 with CD), although the rectal involvement was not visualized in 5. In seven patients, the extent assessments almost matched (+/- one segment), and in the remaining three patients (two UC, one CD) the scan grossly misinterpreted active histological inflammation (> or = +/- two segments). In patients with UC, the sensitivity, specificity, and diagnostic accuracy concerning the extent of inflammation were 0.84, 0.79, and 0.83, respectively. In patients with CD, the sensitivity was 0.79, and the diagnostic accuracy was 0.78. The relative leukocyte scan activity score was less concordant with the degree of mucosal leukocyte infiltration but still significantly correlated (r = 0.616, p < 0.0001 in UC patients and r = 0.441, p < 0.003 in CD patients). CONCLUSION: Images created by the technetium 99m hexamethylpropylene-amineoxime-labeled leukocyte scan in acute colonic inflammatory bowel disease correlate to mucosal leukocyte migration in terms of proximal disease extent and, to a lesser degree, also to the intensity of mucosal inflammatory infiltration.

Radiography and bone scintigraphy in bone marrow transplant multiple myeloma patients.

PURPOSE: To compare conventional radiography and bone scintigraphy in relation to clinical outcome in bone marrow transplant multiple myeloma patients. MATERIAL AND METHODS: A total of 70 radiographies and 70 bone scintigraphies were compared in 35 patients. RESULTS: The skull, the extremities, the iliac and public bones were better assessed with radiography. For new vertebral lesions and for lesions in the ribs and sternum, bone scintigraphy proved superior. For the sacrum, the methods were equal. When bone scintigraphy was used as a complement to radiography, 4% more pathological sites were found. No patient had both a normal radiography and a pathological bone scintigraphy, but 5 patients had both a normal bone scintigraphy and a pathological radiography. The results of the radiological examinations did not always correlate with the clinician's grading of the patient's disease. The radiological examinations had no prognostic value for the 7 patients examined on several occasions. CONCLUSION: The ability of conventional radiography and bone scintigraphy to disclose myeloma lesions varies, depending on location and size of the lesions. Radiography should remain the primary examination modality also for bone marrow transplant multiple myeloma patients. Bone scintigraphy can serve as a complement for investigating unexplained pain, e.g. caused by lesions in vertebrae or ribs.