Search PubMedSearch

Biomedical subjects

J Møller

Publications and source records attributed to J Møller.

At least 19 recordsLinked to original sources

An outbreak of Pontiac fever among children following use of a whirlpool.

We investigated an outbreak of fever, most likely due to a contaminated whirlpool, among nine adults and six children residing in a summerhouse. The outbreak was characterized by a high attack rate, short incubation periods, influenza-like symptoms, and rapid recoveries, all features typical of Pontiac fever. However, the children had less-characteristic symptoms than the adults, and they did not have any sequelae. Findings on the children's chest radiographs were unremarkable, and none of the children had leukocytosis. Evidence of Legionella pneumophila infection was found in six cases: in one case by isolation of L. pneumophila serogroup 1 and detection of legionellae by PCR, and in five cases by seroconversion to the clinical isolate. Six additional cases had presumptive evidence of legionella infection, with seroconversion to Legionella micdadei antigen; a PCR assay was also positive for legionellae for one of these cases. In contrast, two adult nonusers of the whirlpool had no symptoms and no serological evidence of infection. Serological testing and cultures for other pathogens, as well as cultures of all environmental samples, were negative. This investigation demonstrates the differences between adults and children with respect to the clinical picture of Pontiac fever; furthermore, it shows that culture and PCR assay of tracheal aspirates for legionellae can be performed in a hospital setting for rapid diagnosis, although the sensitivities of these methods are low.

Adult

Percutaneous dilatational tracheostomy versus conventional surgical tracheostomy. A clinical randomised study.

BACKGROUND: As no clinical randomised studies have previously been performed comparing complications with the Ciaglia Percutaneous Dilatational Tracheostomy Introducer Set (PDT) and conventional surgical tracheostomy (TR), we designed a study with the aim of comparing the efficacy and safety of the two techniques. METHODS: Sixty patients selected for elective tracheostomy were randomised for either PDT (30 patients) or TR (30 patients). All patients had general anaesthesia and were ventilated with 100% oxygen. Furthermore, lidocaine with epinephrine 1% (3-5 ml) was used for local analgesia and to minimise bleeding during the procedure. RESULTS: The median time for insertion of the tracheostomy tube was 11.5 min (range 7-24 min) in the PDT group and 15 min (range 5-47 min) in the TR group (P<0.01). Complications during the procedure were cuff puncture of the endotracheal tube in 5 cases in the PDT group. Minor bleeding was encountered in 6 cases in the PDT group as opposed to 24 cases in the TR group (P<0.01), major bleeding in none versus 2 cases, respectively. In 8 cases in the PDT group, increased resistance to insertion of the tracheostomy tube was met by further dilatation. During the post-tracheostomy period, complications occurred with minor bleeding in 2 cases in the PDT group as opposed to 9 cases in the TR group (P<0.05), and major bleeding was encountered in 1 case in each group. Minor infections were encountered in 3 cases in the PDT group as opposed to 11 cases in the TR group (P<0.01). Major infection was encountered in none versus 8 cases, respectively (P<0.01). CONCLUSION: Our results indicate that the percutaneous dilatational tracheostomy technique performed with the Ciaglia Introducer Set is effective, safe and superior to conventional surgical tracheostomy as immediate complications as well as complications with the tracheostomy tube in situ are fewer and of less severity.

Adolescent

No effect of growth hormone on serum insulin-like growth factor binding protein-3 proteolysis.

Increased proteolysis of insulin-like growth factor binding protein (IGFBP)-3 is seen in several pathophysiological conditions and may represent an important mechanism for the regulation of insulin-like growth factor bioavailability. It has previously been suggested that proteolysis of IGFBP-3 is dependent on the GH status. To investigate this, IGFBP-3 proteolysis was measured in three groups of subjects: 1) GH-deficient patients before and after GH replacement (n = 14); 2) healthy subjects before and after 14 days of GH administration (n = 7); and 3) acromegalic patients before and after treatment with a long-acting SRIH analogue (octreotide; n = 14). In vivo IGFBP-3 proteolysis was investigated by Western immunoblotting. No difference was detected in pretreatment samples, and GH treatment in GH-deficient subjects or octreotide treatment in acromegalic subjects had no impact on in vivo proteolysis. In contrast, GH administration to healthy subjects caused a 21% increase in in vivo proteolysis (P = 0.0008). In vitro IGFBP-3 proteolysis was investigated by incubation of serum with 125I-rhIGFBP-3, followed by SDS-PAGE. In pretreatment samples, the percentage of proteolyzed 125I-rhIGFBP-3 was 13 +/- 1% (acromegalic subjects), 11 +/- 1% (healthy subjects), and 9 +/- 1% (GH-deficient subjects) (P < 0.009, GH-deficient vs. acromegalic subjects). Treatment had no effect on in vitro proteolysis. We conclude that GH status has no major impact on IGFBP-3 protease activity in serum.

Acromegaly

Fish consumption, n-3 fatty acids in cell membranes, and heart rate variability in survivors of myocardial infarction with left ventricular dysfunction.

To elucidate a possible antiarrhythmic effect of long-chained n-3 polyunsaturated fatty acids, heart rate variability was assessed in 52 patients with a previous myocardial infarction and left ventricular dysfunction. The content of n-3 polyunsaturated fatty acids in platelets was closely associated with the patient's fish-consuming habits, and a significant positive correlation was observed between the n-3 fatty acid docosahexaenoic acid and heart rate variability.

Aged

Blockade of the renin-angiotensin-aldosterone system prevents growth hormone-induced fluid retention in humans.

To test if the renin-angiotensin-aldosterone system (RAAS) is involved in growth hormone (GH)-associated fluid retention, we examined the effect of GH administration in the presence or absence of RAAS blockade at different levels on body fluid homeostasis. Eight subjects were examined in a controlled, randomized double-blinded trial. During four 6-day periods they received subcutaneous GH (6 IU-m-2) or placebo injections and tablets as follows: 1) placebo and placebo, 2) GH and placebo, 3) GH and captopril, and 4) GH and spironolactone. GH increased extracellular volume (liters; placebo 18.87 +/- 0.85; GH + placebo 20.43 +/- 1.01) but this effect was abolished by captopril (GH + captopril 18.82 +/- 0.67) and spironolactone (GH + spironolactone 18.99 +/- 0.85). Correspondingly, the GH-induced reduction in bioimpedance was blocked by captopril and spironolactone. Plasma renin and angiotensin II concentrations increased during all three GH treatment regimens, whereas plasma aldosterone was increased only after GH plus spironolactone. The data demonstrate that GH activates the RAAS and that blockade of the RAAS by two separate mechanisms prevents fluid retention normally encountered after GH exposure. These observations suggest that the RAAS plays a key role in GH-induced regulation of fluid homeostasis.

Adult

An external quality assessment study on the analysis of methylmalonic acid and total homocysteine in plasma.

In spite of the increasing interest in the analysis of methylmalonic acid and total homocysteine in plasma, data on interlaboratory variation is lacking. We report the results of an external quality assessment study with the participation of 15 laboratories in the Scandinavian countries performing these analyses on a regular basis. For methylmalonic acid, using serum, heparin fluoride plasma and an aqueous sample, CVs were found in the range of 11-17%. For total homocysteine using EDTA plasma, heparin fluoride plasma and an aqueous sample, CVs were in the range of 6-12%. For both analytes, a significant correlation between the individual recoveries of added analyte and the results for the aqueous sample was found, suggesting that the use of inconsistent calibrations in the participating laboratories are contributing to the interlaboratory variation. An acceptable range for results from the individual laboratory was calculated using data on the biological within-subject and between-subject variations reported in the literature. These ranges were violated by several laboratories when using the consensus mean or median as target values. Even if the results of the present study document a reasonable standard in the measurement of methylmalonic acid and total homocysteine in plasma in the participating laboratories there is room for improvement and a permanent scheme of external quality assessment using relevant samples is essential. From 1997, a regular scheme has been available from our laboratory.

Anticoagulants

The immunodeficiency after allogeneic bone marrow transplantation in man: role of cytokines.

The effect of various cytokines including rIL-1, rIL-2, rIL-3, rIL-4, rIL-6, and growth factors including rNGF, rILGF and rEPGF on the post transplant immunodeficiency after allogeneic bone marrow transplantation was explored in 8 patients. The results show that neither cytokine alone was able to increase the proliferative capability in post transplant lymphocytes, however, when added in conjunction a significant increase in PHA driven proliferation was noted. Any significant lack of growth factors is probably not the only cause of immunodeficiency post transplant, since addition of any of these compounds did not have any influence on the lymphocyte proliferation, and so the data presented here suggest that therapeutic application of any of the investigated cytokines or growth factors to such patients is unlikely to be successful in overcoming the defects of T cell function post grafting.

Acquired Immunodeficiency Syndrome

GLP-1 does not not acutely affect insulin sensitivity in healthy man.

Previous studies have suggested that glucagon-like peptide-1 (GLP-1) (7-36 amide) may have the direct effect of increasing insulin sensitivity in healthy man. To evaluate this hypothesis we infused GLP-1 in seven lean healthy men during a hyper insulinaemic (0.8 mU.kg-1.min-1), euglycaemic (5 mmol/l) clamp. Somatostatin (450 micrograms/h was infused to suppress endogenous insulin secretion, and growth hormone (3 ng.kg-1.min-1) and glucagon (0.8 ng.kg-1.min-1) were infused to maintain basal levels. GLP-1 (50 pmol.kg-1.h-1) or 154 mmol/l NaCl (placebo) was infused after 3 h of equilibration, i.e. from 180-360 min. GLP-1 infusion resulted in GLP-1 levels of approximately 40 pmol/l. Plasma glucose, insulin, growth hormone, and glucagon levels were similar throughout the clamps. The rate of glucose infusion required to maintain euglycaemia was similar with or without GLP-1 infusion (7.69 +/- 1.17 vs 7.76 +/- 0.95 mg kg-1.min-1 at 150-180 min and 8.56 +/- 1.13 vs 8.55 +/- 0.68 mg.kg-1.min-1 at 330-360 min) and there was no difference in isotopically determined hepatic glucose production rates (-0.30 +/- 0.23 vs -0.16 +/- 0.22 mg.kg-1.min-1 at 330-360 min). Furthermore, arteriovenous glucose differences across the forearm were similar with or without GLP-1 infusion (1.43 +/- 0.23 vs 1.8 +/- 0.29 mmol/l), (ANOVA; p > 0.60, in all instances). In conclusion, GLP-1 (7-36 amide) administered for 3 h, leading to circulating levels within the physiological range, does not affect insulin sensitivity in healthy man.

3-Hydroxybutyric Acid

Bioavailability and bioactivity of intravenous vs subcutaneous infusion of growth hormone in GH-deficient patients.

OBJECTIVE: The bioavailability of GH immunoreactive serum concentrations is reduced following subcutaneous (s.c.) as compared with intravenous (i.v.) administration. Whether this difference also translates into a different biological activity remains to be investigated. The aim of the present study was to evaluate the short-term metabolic effects of GH following i.v. and s.c. delivery. DESIGN AND MEASUREMENTS: In a cross-over design 10 GH-deficient patients were randomized to receive GH (0.03 microgram (0.1 mU/kg/min) as a continuous i.v. or s.c. infusion for 39 hours on two different occasions. Preceding each study GH therapy was discontinued for 5 days. Serum profiles of GH, IGF-I, IGF-II, IGF binding protein 3 (IGFBP-3), insulin, glucose and non-esterified fatty acids (NEFA) were recorded during the studies. Serum GH was measured by a polyclonal radio-immunoassay (RIA) and by a double monoclonal immunofluorimetric assay (DELFIA). RESULTS: Higher mean integrated values (AUC) of serum GH (mU/l) were obtained with i.v. GH delivery [47.4 +/- 5.1 (i.v.), 33.3 +/- 3.0 (s.c.), P < 0.05]. The two GH assays showed qualitatively similar results, but higher mean GH concentrations were measured by RIA following both s.c. (P < 0.001) and i.v. infusion (P < 0.001). Serum IGF-I levels displayed different patterns following i.v. and s.c. GH infusion (P < 0.05 by ANOVA) and mean IGF-I levels (micrograms/l) were lower following s.c. GH infusion [159.5 +/- 21.8 (s.c.), 185.2 +/- 27.7 (i.v.), P = 0.002]. Serum IGF-II levels were unaffected by short-term GH treatment and by the route of GH administration. Serum IGFBP-3 levels increased in response to GH administration (P < 0.001), irrespective of route (P = 0.76). The IGF-I/IGFBP-3 molar ratio increased significantly following GH administration (P < 0.001), and a higher ratio was obtained following i.v. infusion (P < 0.005). Subcutaneous GH infusion resulted in significantly lower mean levels of serum NEFA (P < 0.02), whereas similar mean levels of serum insulin (P = 0.54), blood glucose (P = 0.24), energy expenditure (P = 0.13), and respiratory exchange ratio (P = 0.09) were observed on the two occasions. CONCLUSIONS: A reduced bioavailability of s.c. as compared with i.v. administered GH has been recorded with two independent GH assays, and this was also accompanied by a significant, albeit modest, reduction in biological activity.

Adult

Decreased plasma and extracellular volume in growth hormone deficient adults and the acute and prolonged effects of GH administration: a controlled experimental study.

OBJECTIVE: There are few data on the endocrine mechanisms underlying the body fluid changes in GH deficiency and their subsequent alteration following GH replacement. We have therefore investigated the time effects of GH on body fluid distribution and fluid regulating hormones in GH deficient adults. DESIGN: The patients underwent in random order four study periods: (1) saline, a 42-hour infusion following 3 weeks without GH, (2) acute GH, a 42-hour GH infusion following 3 weeks without GH, (3) 3 days GH, a 42-hour GH infusion preceded by 3 weeks without GH and 3 days pretreatment with subcutaneous GH injections, (4) 3 weeks GH, a 42-hour GH infusion after at least 3 weeks GH therapy. SUBJECTS: Seven GH deficient adult males and 8 healthy control subjects. MEASUREMENTS: During each infusion period 24-hour blood pressure was recorded, bioimpedance was repeatedly measured and blood samples were obtained every 6 hours. After 41 hours extracellular and plasma volumes were determined isotopically. Extracellular volume, plasma volume and bioimpedance were measured in the control group. RESULTS: GH increased extracellular volume (saline 16.45 +/- 0.79 vs acute GH 16.83 +/- 0.87; vs 3 days GH 17.58 +/- 0.71; vs 3 weeks GH 17.92 +/- 0.88 l, P = 0.01). After 3 weeks of GH, extracellular volumes in the patients and in the control group were identical (control 17.94 +/- 0.32). Plasma volume was increased only after 3 weeks GH treatment (saline 2.93 +/- 0.16 vs acute GH 3.04 +/- 0.22; vs 3 days GH 3.06 +/- 0.07; vs 3 weeks GH 3.37 +/- 0.18 l, P = 0.03), and was decreased compared to the control group (control 3.56 +/- 0.03 l, P < 0.01). Bioimpedance decreased significantly in all treatment periods and was significantly increased compared to the control group. Plasma renin increased during GH administration (saline 16.2 +/- 1.9 vs acute 19.0 +/- 1.9; vs 3 days GH 30.8 +/- 3.0; vs 3 weeks GH 27.0 +/- 3.0 mU/l, P = 0.03), whereas aldosterone and atrial natriuretic factor (ANF) levels remained unaffected by GH. GH caused an increase in systolic blood pressure (BP) and heart rate, whereas diastolic BP remained unaffected. CONCLUSIONS: The present data show that GH deficiency is associated with decreased plasma volume and extracellular volume. GH exposure acutely increases extracellular volume, whereas substitution for a longer time was required to normalize both extracellular and plasma volumes. Renin seems to be involved in these fluid volume regulating effects of GH.

Adult

Sarcoidosis causes abnormal seasonal variation in 1,25-dihydroxy-cholecalciferol.

OBJECTIVES: The spontaneous seasonal variations in the calcium regulating hormones 1,25-dihydroxy-cholecalciferol (1,25-DHCC) and parathyroid hormone (PTH) were investigated in patients with sarcoidosis. DESIGN: Controlled, prospective observational study with measurements in the winter and summer seasons, respectively. SUBJECTS: Twelve patients (age: median 33, range 21-54 years) with biopsy-verified (n = 8) sarcoidosis were included as well as 11 age-matched healthy control subjects. MAIN OUTCOME MEASURES: Serum values of calcium, ionized calcium, phosphate, chloride, bicarbonate, creatinine, albumin, angiotensin-converting enzyme, alkaline phosphatase, 1,25-DHCC, and PTH. Also, 24-h whole body retention of 99mTc methylene-diphosphonate was assessed. RESULTS: The patient group showed an increased level of 1,25-DHCC in the summer season (w:146 +/- 67, s:198 +/- 73 pmol L-1; P < 0.01) in contrast to the opposite finding among controls (w:161 +/- 34, s:144 +/- 43 pmol L-1; P < 0.05). Comparing the individual seasonal changes between the two groups, the difference was marked (P < 0.001). Compared with controls, total serum calcium was elevated in the summer season in the patient group (P < 0.05), in which the same parameter correlated positively with 1,25-DHCC (r = 0.658; P < 0.01). PTH was increased two to three times above the control values throughout the year (patients: w:0.37 +/- 0.13, s:0.24 +/- 0.08 micrograms L-1; controls: w:0.14 +/- 0.09, s:0.10 +/- 0.04 micrograms L-1; P < 0.001); although, the level of this hormone was still found within the reference interval. 24-h whole body bone scintigraphy failed to show any seasonal variation in bone metabolism. In contrast, serum alkaline phosphatase was found to be increased during the summer season compared with the control group (P < 0.001). Angiotensin-converting enzyme showed no seasonal variation. CONCLUSIONS: In sarcoidosis, 1,25-DHCC is abnormally regulated throughout the year, with a significantly higher serum level in the summer season. Uncontrolled production of 1,25-DHCC in sarcoid pulmonary alveolary macrophages is possibly responsible for hypercalcaemic episodes, and this parameter should be used as a marker of disease activity.

Adult

Dose-dependent effects of recombinant human growth hormone on biochemical markers of bone and collagen metabolism in adult growth hormone deficiency.

Administration of growth hormone (GH) to patients with growth hormone deficiency (GHD) has beneficial effects, but so far has been employed only empirically. We have, therefore, investigated the dose-dependent effect of GH on target tissue by studying biochemical markers of bone and collagen turnover in GHD. Then patients with GHD (nine males and one female aged 21-43 years, mean age 28 years) participated in the study. Growth hormone deficiency was defined as a peak serum GH response of less than 15 mU/l in two provocation tests. After a 4-week run-in period, the study population received increasing doses of GH at 4-week intervals (1, 2 and 4 U/m2). Blood samples were collected in the fasting state at 7.00 h on the last day of each period and assayed for serum levels of osteocalcin (S-BGP), bone alkaline phosphatase (B-ALP), C-terminal propeptide of type I collagen (S-PICP), carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (S-ICTP) and N-terminal propeptide of type III collagen (S-PIIINP). Following replacement therapy, serum insulin-like growth factor I and insulin-like growth factor binding protein 3 increased sequentially with time (p < 0.001 and p < 0.001, MANOVA) and the values were elevated significantly over baseline levels after treatment with 1 U/m2. Serum BGP values were below normal at the start of the study and increased gradually following GH treatment to levels in the low-normal range. Baseline values for serum bone alkaline phosphatase (B-ALP), PICP and PIIINP were within the normal range. The collagen parameters increased with GH replacement (p < 0.001, MANOVA) to levels above normal, whereas B-ALP stayed within normal limits. Serum ICTP values were elevated above the normal range at baseline, indicating increased bone resorption in GHD. A linear increase in values was observed with GH treatment (p < 0.001, MANOVA). Serum ICTP did not correlate significantly with the bone formative parameters but was correlated positively to PIIINP. The sensitivity of S-ICTP as a bone resorptive marker is thus questioned. In conclusion, a dose-dependent increase in markers of growth hormone metabolism and in biochemical markers of both bone and non-bone collagen synthesis was seen following incremental doses of GH in GHD.

Adult

Free and total insulin-like growth factors and insulin-like growth factor binding proteins during 14 days of growth hormone administration in healthy adults.

The objective was to investigate the effect of growth hormone (GH) administration on circulating levels of free insulin-like growth factors (IGFs) in healthy adults. Eight healthy male subjects were given placebo and two doses of GH (3 and 6 IU/m2 per day) for 14 days in a double-blind crossover study. Fasting blood samples were obtained every second day. Free IGF-I and IGF-II were determined by ultrafiltration of serum. Total IGF-I and IGF-II were measured after acid-ethanol extraction. In addition, GH, insulin, IGF binding protein 1 (IGFBP-1) and IGFBP-3 were measured. Serum-free and total IGF-I increased in a dose-dependent manner during the 14 days of GH administration. After 14 days, serum-free IGF-I values were 610 +/- 100 ng/l (mean +/- SEM) (placebo), 2760 +/- 190 ng/l (3 IU/ m2) and 3720 +/- 240 ng/l (6 IU/m2) (p = 0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.004 for 3 IU/m2 vs 6 IU/m2). Total IGF-I values were 190 +/- 10 micrograms/l (placebo), 525 +/- 10 (3 IU/m2), and 655 +/- 40 micrograms/l (6 IU/m2) (p < 0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.04 for 3 IU/m2). There were no differences in the levels of free or total IGF-II during the three study periods. Insulin-like growth factor binding protein 1 was decreased during GH administration (p = 0.04 for placebo vs 3 IU/m2; p = 0.006 for placebo vs 6 IU/m2). In conclusion, fasting serum free IGF-I increased dose dependently during GH administration and free IGF-I increased relatively more than total IGF-I. This may partly be due to the decrease in IGFBP-1.

Adult

Calibration of the Ektachem Amylase method using human reference materials and the Phadebas Blue Starch method as an interim reference method.

In a multilaboratory study a consensus was established to calibrate the Ektachem Amylase method to reproduce the results of the Phadebas Blue Starch method. The calibration graph has a slope = 3.39 and intercept = 25. For the Ektachem Amylase method the reaction-rate ratio between salivary and pancreatic amylase was calculated to be 0.89, relative to that of the Phadebas Blue Starch method. A calibration value for the Nordic Amylase Calibrator to be used on Ektachem analysers was determined to be close to 469 U l-1 for the current batch. However, since the difference from the stated value of 460 U l-1 is negligible, the authors recommend the use of the stated value for this and future batches of the Nordic Amylase Calibrator. An error of around 10% introduced by the presence of salivary amylase is comparable to the methods accepted by the Scandinavian Committee on Enzymes. Introduction of a consensus calibration reduced the interlaboratory variation by up to 40% at all levels.

Amylases

Age- and gender-specific reference intervals for total homocysteine and methylmalonic acid in plasma before and after vitamin supplementation.

We present reference intervals for total homocysteine and methylmalonic acid in plasma based on samples from 126 women (ages 20-85 years, median 49 years) and 109 men (ages 20-84 years, median 50 years). The central 0.95 interval for methylmalonic acid was 0.08-0.28 micromol/L. Supplementation with cyanocobalamin caused a nonsignificant decrease in methylmalonic acid. Supplementation with folic acid caused a decrease in homocysteine concentrations, with data analysis identifying two significantly different clusters: 182 subjects with the lowest initial concentrations (7.76 +/- 1.54 micromol/L, mean +/- SD) and the smallest decrease (1.26 +/- 0.96 micromol/L), and 53 subjects with the highest initial concentrations (12.33 +/- 2.04 micromol/L) and greatest decrease (4.14 +/- 1.32 micromol/L). We argue in favor of the age- and gender-specific central 0.95 intervals obtained for the 182 subjects before being supplemented with folic acid: 4.6-8.1 micromol/L for subjects at <30 years; 4.5-7.9 micromol/L for women, ages 30-59 years; 6.3-11.2 micromol/L for men, ages 30-59 years; and 5.8-11.9 micromol/L for subjects at >60 years.

Adult

Immunodeficiency after allogeneic bone marrow transplantation in man: the role of antigen presenting cells.

We investigated the proliferative response of donor T cells to phytohemagglutinin (PHA) presented by donor non-T cells in 7 patients after allogeneic bone marrow transplantation. Compared with the cellular response in the healthy marrow donors, T cell proliferation was found to be deficient in every recipient, from 130 to 739 days after grafting. Results of cell mixing experiments showed that the non-T cells of the patients were as capable as healthy donor non-T cells in presenting PHA to normal donor T cells. However, T cells from patients did not proliferate after substituting donor non-T cells for non-T cells from patients. This inability of T cells to proliferate was most likely the result of ineffective interactions among T cell subsets in patients after allogeneic bone marrow transplantation.

Adolescent

Cytotoxic T cell activity after HLA-mismatch bone marrow transplantation.

Six patients with various hematologic diseases were treated with HLA-haploidentical bone marrow mismatched for 1-2 loci at the disparate chromosome with a relative response in the mixed lymphocyte reaction (MLR) ranging between 0.04 and 0.96 (median 0.27). Thirty to 371 days after bone marrow grafting, patient lymphocytes (of donor origin) were tested for reactivity in mixed lymphocyte culture (MLC) and cell mediated lympholysis (CMLy) to lymphocytes from the host (cryopreserved before grafting), the marrow donor, and unrelated individuals. After grafting, Lymphocytes from the patients showed a host-specific decrease in proliferation and in cytotoxic response (%51Cr release in a standard chromium release assay), when compared to the pretransplant host-specific donor response, whereas the responses towards third party cells were unaffected. This host-specific unresponsiveness after HLA-mismatch bone marrow transplantation is compatible with a clonal deletion theory and might be the reason that this procedure is at all possible.

Adolescent