[The Ludwigshafen Osteoporosis Screening Questionnaire (LOS Questionnaire): result of the evaluation of anamnestic risk factors in osteoporosis diagnostics]. / Ludwigshafener Osteoporosescreeningbogen (LOS-Bogen) : Resultat aus der Evaluation anamnestischer Risikofaktoren in der Osteoporosediagnostik.

BACKGROUND: Osteoporosis is a major health problem worldwide and is included in the WHO list of the top ten major diseases. However, it is often undiagnosed until the first fracture occurs, due to inadequate patient education and lack of insurance coverage for screening tests. METHODS AND MATERIAL: In our study of 78 patients with metaphyseal long bone fractures, we searched for a correlation between anamnestic risk factors, bone-specific laboratory values, and the bone morphogenic density (BMD). Each indicator was examined as a possible diagnostic instrument for osteoporosis. The secondary aim of this study was to demonstrate the high prevalence of osteoporosis in patients with metaphyseal fractures. RESULTS: Of our fracture patients 76.9% had decreased bone density and 43.6% showed manifest osteoporosis in DXA (densitometry) measurements. Our modified LOS Questionnaire, identifying anamnestic risk factors, correlated highly significantly (p=0.01) with reduced BMD, whereas seven bone-specific laboratory values (p=0.046) correlated significantly. CONCLUSION: Anamnestic risk factors correlate with pathological BMD more than bone-specific laboratory values. The LOS Questionnaire used in this study would therefore function as a cost-effective primary diagnostic instrument for identification of osteoporosis patients.

Characteristics of bone metabolism markers during the healing of osteoporotic versus nonosteoporotic metaphyseal long bone fractures: a matched pair analysis.

PURPOSE: The activity and metabolism of fracture healing can be monitored quantitatively by measuring bone turnover markers (BTMs) in serum or urine. However, in osteoporotic bone, the exact metabolism processes during the healing of metaphyseal fractures remain unknown. There is no diagnostic approach which currently allows dynamic insight into the fracture healing processes in order to monitor the progression of healing and to assist in therapeutic decision making. METHODS: Between March 2007 and February 2009, 30 patients over 50 years of age who suffered a metaphyseal fracture were included in our study. The levels of the osteoanabolic marker BAP (bone-specific alkaline phosphatase) and osteocatabolic marker ß-CTX [crosslinked C-(CTX)-telopeptide-of-type-I-collagen] were monitored during the fracture healing of osteoporotic and nonosteoporotic fractures for a duration of 8 weeks. RESULTS: After an initial decrease of BAP in the first week, the BAP level steadily increased through the fourth week in both groups. The levels of BAP in the osteoporotic group surpassed the healthy group. ß-CTX steadily increased in healthy bone up to the fourth week; in osteoporotic bone, ß-CTX first increased and, thereafter, decreased from the first week onwards. CONCLUSIONS: In this work, the first molecular biological aspects of osteoporotic fracture healing have been uncovered, helping to explain the mechanisms of delayed fracture healing in osteoporotic bone. The early decrease of reduced ß-CTX as well as elevated BAP during the healing process may be the first aspects within the delayed healing of osteoporotic bone. Further studies are necessary in order to achieve more detailed insight to fracture healing and to ascertain the progression of fracture healing as being essential (criteria) for therapeutic decision making.

Treatment of reduced bone density with ibandronate in dialysis patients.

Bisphosphonates inhibit bone resorption and are widely used to treat osteolytic metastases and osteoporosis. Renal osteodystrophy patients have continuous bone loss due to chronically elevated parathyroid hormone (PTH). In this open-label study, ibandronate was evaluated for the treatment of reduced bone density in renal osteodystrophy. Patients (n=16) with end-stage renal disease (ESRD) and regular hemodialysis schedules were recruited. All patients had low bone mineral density (BMD; lumbar spine T-score <-1.0) and elevated PTH levels (>2-fold higher than normal). Patients received ibandronate 2 mg every 4 weeks for 48 weeks. Serum levels of markers of bone turnover, calcium, phosphate and magnesium were determined (week 0 [prior to treatment] vs. at week 48). BMD (n=11) increased significantly from 88.94 +/- 31.68 mg/mL calcium hydroxylapatite (CaHA) to 93.51 +/- 35.36 mg/mL CaHA (p=0.032). T-scores increased significantly from -3.08 +/- 1.11 to -2.78 +/- 1.27 (p<0.01). The mean PTH level initially increased before dropping to 18.99 pmol/L at week 48 (7.99% decrease vs. week 0; not significant). Bone turnover markers decreased, whereas calcium and magnesium levels remained stable and within normal ranges. Phosphate levels were variable throughout the study. Two patients did not complete the study, and 3 patients died due to concomitant cardiovascular disease. Calcitriol dosage increased from 1.5 to 1.83 microg/week. In patients with renal osteodystrophy and ESRD, ibandronate significantly increased BMD and decreased bone turnover.

Comparison of bone scintigraphy with bone markers in the diagnosis of bone metastasis in lung carcinoma patients.

This study was designed to evaluate the utility of the bone markers total alkaline phosphatase (TAP), bone-specific alkaline phosphatase (BAP), aminoterminal propeptide of type I collagen (PINP), carboxyterminal propeptide of type I collagen (PICP), pyridinoline crosslinks (PYD), deoxypyridinoline crosslinks (DPD), cross-linked carboxyterminal telopeptide of type I collagen (ICTP), cross-linked carboxyterminal telopeptide of type I collagen (CTx, beta-CrossLaps) and tartrate-resistant acid phosphatase 5b (TRAP 5b) in comparison with bone scintigraphy for the diagnosis of bone metastasis in lung carcinoma patients. The study population consisted of 49 patients with bone metastasis confirmed by plain radiography and/or computed tomography, 89 patients without bone metastasis, 12 patients with benign lung diseases and 18 healthy persons. All patients were of male gender. The bone markers were measured using commercially available tests. Serum and urine were collected from fasting patients at the time of bone scan between 7.00 and 8.00 a.m. The sensitivity of bone scintigraphy was 100%, its specificity 76.4%, resulting in a diagnostic efficiency of 84.8%. The positive predictive value was calculated to be 70% and the negative one to be 100%. The concentrations of the bone markers TAP, BAP, PINP, PYD, DPD and ICTP were significantly higher in patients with bone metastasis than in those without bone metastasis (p<0.01). The levels of PICP and CTx only tended to be higher in the patients with bone metastasis compared to those without bone metastasis. There was no significant difference in the TRAP 5b levels between the two groups. There was also no difference in the marker levels between osteoblastic, osteolytic and mixed osteoblastic-osteolytic lesions. Contrary to BAP, PICP, CTx and TRAP 5b, the markers TAP, PINP, PYD, DPD and ICTP were found to be higher (p<0.01-0.05) in patients with bone metastasis than in patients with benign lung diseases. In addition, PYD, DPD and ICTP differentiated patients with benign lung diseases from the healthy controls. Based on cut-off values that correspond to 95% specificity in the group of healthy persons, the sensitivity of the marker assays were as follows (specificity in brackets): TAP 33.3% (97.5%), BAP 22% (100%), PINP 18.4% (97.5%), PICP 2.1% (95.2%), PYD 91.8% (24.1%), DPD 83.7% (34.5%), ICTP 75.5% (44.6%), CTx 45.8% (77.5%) and TRAP 5b 14% (84%). The corresponding data for the diagnostic efficiency were as follows: TAP 73.6%, BAP 77.1%, PINP 67.7%, PICP 61.1%, PYD 48.5%, DPD 55.2%, ICTP 56.1%, CTx 65.6% and TRAP 5b 58.7%, respectively. The positive predictive values ranged from 20% (PICP) to 100% (BAP) and the negative values from 62.7% (PICP) to 84% (PYD). In the ROC analysis, TAP, followed by RAP, PINP and PYD, showed the best performance. The levels of TAP, BAP, PINP, PYD, DPD and ICTP were found to be higher in the patients with bone metastasis compared to those with metastastic lesions in other sites (p<0.01, except for ICTP having a p value of < 0.05). The levels of TAP, BAP, PYD, DPD and ICTP increased significantly with the number of metastases. There was also a steady increase in T scores of the markers PINP, PYD, DPD and ICTP with the extent of the metastatic bone disease. It is concluded that the currently available bone markers cannot replace bone scintigraphy, either for screening or in the diagnosis of bone metastasis, in lung carcinoma patients. However, a panel consisting of TAP, BAP, PINP, PYD, DPD and ICTP may be of some value as an adjunct tool to bone scintigraphy for this purpose.

Risk factors in alcohol associated breast cancer: alcohol dehydrogenase polymorphism and estrogens.

Chronic alcohol consumption is associated with an increased risk for breast cancer, even if consumed in moderate doses. Since acetaldehyde is a carcinogenic factor associated with chronic alcohol consumption, individuals with the alcohol dehydrogenase 1C*1 allele (ADH1C*1 allele) seem to be at particular risk, since this allele encodes for a rapidly ethanol metabolizing enzyme leading to increased acetaldehyde levels. Since recent epidemiological studies demonstrated an increased risk for breast cancer for individuals with the ADH1C*1 allele, we have investigated here ADH1C genotypes in moderate alcohol consumers. Furthermore, estradiols are also known risk factors for breast cancer and acute alcohol ingestion in high doses results in increased serum estradiol concentrations. Thus, in the present study, we tested the effect of low ethanol doses on estrogen serum concentrations. We analyzed the ADH1C genotype in 117 moderate alcohol consumers with breast cancer and in 111 age-matched women with alcohol associated diseases without cancer (74 cirrhotics, 22 patients with pancreatitis and 15 alcohol dependent patients). In addition, 107 healthy controls were studied. Genotyping of the ADH1C-locus was performed using polymerase chain reaction-based restriction fragment length polymorphism methods on leukocyte DNA. To study the effects of ethanol on estradiol levels, ethanol in a dose of 0.225 g/kg body weight was given orally to 8 premenopausal women at various time points of their menstrual cycle. Thereafter estradiol serum concentrations were measured over time. The allele frequency of the ADH1C*1 allele was found to be significantly increased in moderate alcohol consumers with breast cancer as compared to age-matched alcoholic controls without cancer (62% vs. 41.9%, p=0.0035). Women with the ADH1C*1,1 genotype were found to be 1.8 times more at risk for breast cancer than those with another genotype (95% CI 1.431-2.330, p<0.001). Oral ethanol increased serum estradiol levels significantly by 27-38%. The data demonstrate that moderate alcohol consumers with the ADH1C*1 allele have an increased risk to develop breast cancer and even small amounts of alcohol increase serum estradiol levels significantly in premenopausal women especially in the midphase of the menstrual cycle.

Hormonal and biochemical normalization and tumor shrinkage induced by anti-parathyroid hormone immunotherapy in a patient with metastatic parathyroid carcinoma.

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism, and the efficacy of medical therapy and chemo- and radiotherapy is poor in recurrent or metastatic disease. We report the first case of PTH immunization in which tumor shrinkage accompanied hormonal, biochemical, and clinical improvements in a patient with metastatic parathyroid carcinoma.A 50-yr-old woman with refractory parathyroid carcinoma and pulmonary metastases was immunized eight times between February 2001 and December 2003 with bovine and modified human PTH fragments and intact human PTH, mixed with Freund's adjuvant. Total and ionized calcium and PTH levels were assayed weekly for 6 months and regularly thereafter. Thoracic computed tomography scans were performed regularly. Antibodies to all PTH fragments were detected after two immunizations. Baseline PTH and total calcium were 213.0 ng/liter and 13.96 mg/dl, respectively, and remained elevated during the first three immunizations. From the fourth immunization onward, PTH and calcium decreased, and the patient's clinical condition improved markedly. PTH and calcium levels have remained controlled for more than 24 months, and the sizes (surface area) of pulmonary metastases decreased from baseline by 39-71%. This is the first evidence that PTH immunization not only can improve clinical, hormonal, and biochemical measures in parathyroid carcinoma but also has an antitumor effect.

A case of neuroendocrine oncogenic osteomalacia associated with a PHEX and fibroblast growth factor-23 expressing sinusidal malignant schwannoma.

Oncogenic osteomalacia is a rare paraneoplastic syndrome that is characterized biochemically by hypophosphatemia and low plasma 1,25-dihydroxyvitamin D3, and clinically by osteomalacia, pseudofractures, bone pain, fatigue, and muscle weakness. We present a patient with a malignant schwannoma as the underlying cause of this disorder. A permanent cell line (HMS-97) derived from this tumor showed evidence of neuroendocrine differentiation by immunohistochemistry and of neurosecretory activity by electron microscopy. The cell line did express PHEX (phosphate-regulating gene with homologies to endopeptidases located on the X-chromosome) and FGF-23 (fibroblast growth factor-23) transcripts on northern hybridization; however, none of the known mutations from the related mendelian disorders of X-linked hypophosphatemic rickets or autosomal-dominant hypophosphatemic rickets could be detected. Tumor cell (HMS-97)-derived conditioned medium did not inhibit phosphate transport in a standard opossum kidney cell assay and in animal experiments. The medium also showed no PTH1- or PTH2-receptor-stimulating bioactivity. HMS-97 cells might be useful for further studies that aim to determine the genetic mechanism that leads to the observed PHEX and FGF-23 expression, both of which might have a direct role in the pathogenesis of oncogenic osteomalacia. In addition, these cells might be a useful tool for the investigation of neuroendocrine Schwann cell function and autoimmune peripheral nerve disease.

Detection of colorectal neoplasms by the highly sensitive hemoglobin-haptoglobin complex in feces.

Screening for fecal occult blood by means of guaiac tests has an unsatisfactory sensitivity for the detection of colorectal neoplasms. The immunological determination of human hemoglobin in feces has a higher sensitivity and specificity, but hemoglobin is degraded during its transport through the gastrointestinal tract. We compared the hemoglobin test to a newly developed immuno-chemiluminometric (ILMA) assay for quantifying the hemoglobin-haptoglobin complex in feces which shows high stability against degradation. From each of 621 patients with gastrointestinal complaints before scheduled colonoscopy we collected two 1-ml samples from a single stool; there were no dietary restrictions. The sensitivity for detecting colorectal carcinomas proved 87% with hemoglobin. With the hemoglobin-haptoglobin complex it was 87% at a cutoff level of 1.5 microg/g feces, 83% at 2.0 microg/g feces, and 78% at 2.5 and 3.0 microg/g feces. The sensitivity for detecting large adenomatous polyps was 54% with hemoglobin, 76% with the hemoglobin-haptoglobin complex at a cutoff point of 1.5 microg/g feces, 73% with the hemoglobin-haptoglobin complex at 2.0 and 2.5 microg/g feces, and 65% with the hemoglobin-haptoglobin complex at 3.0 microg/g feces. The optimal cutoff point for the hemoglobin-haptoglobin complex was estimated to be 2.0 microg/g stool. The specificity for hemoglobin (99%) was significantly higher than that for the hemoglobin-haptoglobin complex at 2.0 microg/g feces (96%). Immunological determination of the hemoglobin-haptoglobin complex in feces has a comparable sensitivity as the fecal hemoglobin assay for colorectal carcinomas and a significantly higher sensitivity for adenomatous polyps but a significantly lower specificity. Its use for colorectal cancer prevention is currently being evaluated in a screening study.

Screening for colorectal neoplasms with a new immunological human faecal haemoglobin and albumin test.

In Germany, screening for colorectal cancer shows low efficiency, which is partly due to demographic changes with a rising mean age of the population, a low participation rate and an unsatisfactory sensitivity of guaiac tests for detecting faecal occult-blood. Therefore, a pilot screening study with a new immunological faecal haemoglobin and albumin test was performed in Ostringen, Germany to assess its compliance, performance characteristics and cost-effectiveness. Two thousand, seven hundred and eighty-five persons (1,498 women and 1,287 men) collected 1 ml samples from two different sites of one stool. The upper limit of normal was 10 micrograms/g stool for haemoglobin and 100 micrograms/g stool for albumin. The compliance was 82%; 224 persons (8%) had a positive test result. Of these, 184 underwent full colonoscopy. We detected 14 colorectal cancers, 10 of which were Dukes' stage A carcinomas removed by endoscopic polypectomy, 34 large adenomas and 43 small adenomas. The detection rate for colorectal neoplasms was above the rate described for other immunological haemoglobin tests and for Haemoccult tests. The specificity of the test--defined with false-positive results if a normal colon mucosa and no other reasons for upper or lower gastrointestinal bleeding were found--was 99.5%. The cost-effectiveness was assessed by comparing the diagnostic costs with the savings resulting from prevention of colorectal carcinomas by endoscopic polypectomy of malignant polyps (Dukes' stage A). The savings in our screening study exceeded the diagnostic costs by approximately 2.3 times. The combined immunological faecal haemoglobin and albumin test should substitute the Haemoccult test in colorectal cancer screening because of its higher sensitivity and specificity combined with cost-effectiveness and good patient compliance.

Validity of new immunological human fecal hemoglobin and albumin tests in detecting colorectal neoplasms--an endoscopy-controlled study.

BACKGROUND: Screening for occult blood by means of guaiac tests has an unsatisfactory sensitivity for the detection of colorectal neoplasms. To increase sensitivity and specificity the immunological determination of human hemoglobin and albumin in feces has been developed. The validity of analyzing only two samples from one bowel movement of either test is not known. METHODS: An immunological determination of human fecal hemoglobin and albumin using luminescence immunoassays (LIA) was performed in 739 patients with gastrointestinal complaints before scheduled colonoscopy. Each patient collected two 1 ml samples from one stool. There were no dietary restrictions. RESULTS: The sensitivity for detecting colorectal carcinomas was 95.3% (95% confidence interval 84.2-99.4%) with hemoglobin and 67.4% (95% confidence interval 51.2-80.9%) with albumin. The sensitivity for detecting large adenomatous polyps was 62.9% (95% confidence interval 50.5-74.1%) with hemoglobin and 32.9% (95% confidence interval 22.1-45.1%) with albumin. The specificity was 97% for hemoglobin, 96% for albumin and 94% for the combined test. CONCLUSIONS: The immunological determination of fecal hemoglobin is superior to albumin and has a better sensitivity for the detection of colorectal neoplasms than that reported for guaiac tests, even if two samples from one bowel movement are examined. The immunological determination of fecal hemoglobin should therefore be evaluated for use in colorectal cancer screening.

[Effect of proctocolectomy on fluid balance--comparison of conventional ileostomy, ileorectal anastomosis and ileoanal pouch operation]. / Einfluss der Proktokolektomie auf die Flüssigkeitsbilanz--konventionelle Ileostomie, ileorektale Anastomose und ileoanale Pouch-Operation im Vergleich.

Total colectomy for ulcerative colitis (UC) and familiar adenomatous polyposis coli (FAP) is mainly performed as an ileoanal Pouch procedure (IAP). Alternatives are ileorectal anastomosis (IRA) and conventional proctocolectomy with Brooke ileostomy (CPS). The different surgical techniques may influence the excretion of water and electrolytes in stool and urine and may lead to a higher risk for urolithiasis. We investigated patients (12 IAP, 12 IRA and 8 CPS) several years after surgery and compared them to twelve normal controls. Total fecal and urinary output was collected at two consecutive days. Volume and electrolytes were determined in stool and urine. The risk for urinary stone formation was calculated by nomograms. Fecal volume and sodium (Na+) excretion was increased in all therapy groups compared to controls. IAP and IRA had significant less stool volume and Na+ excretion compared to CPS. Augmented fecal Na+ excretion was compensated by reduction of renal output after colectomy compared to controls. There were no significant differences in the daily urine volume between any groups. There was no urolithiasis in any groups. The nomograms showed a risk for all groups and controls to develop urinary stones.

Sequential changes of biochemical bone parameters after kidney transplantation.

BACKGROUND: Persistent hyperparathyroidism after renal transplantation (Rtx) has been reported in several studies. However these studies evaluated biochemical bone parameters either only during a short time period (up to 6 months) or for a longer time period, but with long intervals in between. Therefore, we prospectively evaluated biochemical bone parameters of kidney-transplant recipients at short intervals for 2 years after surgery. METHODS: Biochemical bone parameters were prospectively investigated in 129 patients 2, 3, 5, 8, 12, 18 and 24 months after Rtx. All patients received prednisone and cyclosporin A as immunosuppressive therapy, and 75 patients also received azathioprine. None of the patients was treated with calcium, phosphorus, or vitamin D preparations. RESULTS: Serum creatinine levels decreased from 166.8 +/- 5.4 mumol/l to 140.0 +/- 4.9 two years after Rtx; (data are expressed as mean +/- s.e.m.). Serum phosphorus levels increased slightly from 0.9 +/- 0.022 mmol/l to 0.98 +/- 0.025 (12 m), but remained within the lower normal range. We observed a rise in total and albumin adjusted calcium concentrations 3 months after Rtx. 52% of all patients had serum calcium levels above 2.62 mmol/l (upper normal limit in our laboratory) 3 months after renal transplantation with a gradual decrease thereafter. There was no correlation of calcium and PTH levels. We observed a significant rise in biochemical bone parameters from 2 to 5 months after renal transplantation (P < 0.001): alkaline phosphatase (AP) increased from 164.3 +/- 9.4 to 236 +/- 12.7 U/l (normal 50-180), bone specific alkaline phosphatase (BAP) rose from 17.7 +/- 1.36 to 23.2 +/- 1.7 ng/ml (normal:4-20) and osteocalcin (OC) increased from 20.2 +/- 1.5 to 26.7 +/- 1.9 ng/ml (normal 4-12). AP and BAP levels values normalized 12 months after renal transplantation, whereas OC was still above normal throughout the study period. Patients were subdivided into two groups: those with good and those with impaired graft functions. Patients with good graft function had stable serum creatinine levels (< or = 132 mumol/l or < or = 1.5 mg/dl) well below the mean serum creatinine concentration during the study period. The significant changes in AP, BAP, and OC occurred irrespective of renal function. However, patients with impaired graft function (n = 65) had significantly higher PTH-levels (70 pg/ml higher) than patients with good graft function (n = 64), P < 0.01. PTH was positively correlated with serum creatinine (r = 0.81, P < 0.001). Moreover, patients with low 25 (OH) vitamin D levels (n = 63) had significantly higher PTH concentrations (between 40 and 80 pg/ml, P < 0.01) throughout the study period compared to patients (n = 66) with a sufficient 25(OH)D supply irrespective of graft function. There was a negative correlation of 25 (OH)D levels and PTH; (r = -0.49, P < 0.001). 1,25(OH)2D3 (evaluated in 24 patients) levels increased from 46.5 +/- 6.6 to 76.9 +/- 7.6 pg/ml (normal:35-90) at 12 months. CONCLUSION: Hypercalcaemia is a common phenomenon in the early period after kidney transplantation and occurs in the presence of low normal phosphorus levels. It is most probably related to improved PTH action and 1-hydroxylation of vitamin D. The rise in biochemical bone parameters between 3 and 5 months occurs irrespective of graft function and normalization is only achieved 1 year after transplantation. PTH is constantly elevated for up to 2 years after kidney transplantation and is most probably related (a) to impaired graft function and (b) to suboptimal 25 OH vitamin D supply.

Solid phase competitive luminescence immunoassay for immunoglobulin A in faeces: development and clinical validation.

We describe a new simple solid-phase competitive luminescence immunoassay (LIA) for the determination of immunoglobulin A (IgA) in faeces. The assay utilizes an anti-alpha-chain IgA antibody which is coated to polystyrene beads and acridinium ester-labelled human IgA as tracer and, therefore, measures both monomeric and polymeric IgA. Dilution recovery of an internal standard was 96, 100 and 103%. Interassay and intra-assay coefficients of variation (C.V.) ranged from 4.5 to 12.9%. The upper limit of normal of faecal IgA in 122 healthy controls was found to be 300 mg/l IgA (mean 73 mg/l, specificity of 99.2%). Patients with inactive Crohn's disease (Crohn's disease activity index (CDAI < 150, n = 14) had faecal IgA values up to 3317 mg/l (mean 1073 mg/l; P < 0.0001). In the active group (CDAI > 150, n = 26) faecal IgA values ranged from 49 to 4094 mg/l (mean 1253 mg/l; P < 0.0001). Patients with ulcerative colitis were divided into a group with active disease (n = 18) and a remission group (n = 16) with values up to 1843 mg/l faecal IgA (man 486 mg/l; P < 0.0032) and up to 602 mg/l faecal IgA (mean 176 mg/l; P < 0.4833), respectively. We also studied patients with non-inflammatory diseases of the gut with this assay. This LIA has proved to be a reliable method for the determination of elevated faecal IgA concentrations and for the detection of pathological findings in the gastrointestinal tract, especially in Crohn's disease.

Prevalence of dialysis-related amyloidosis in diabetic patients. Diabetes Amyloid Study Group.

It has recently been shown that beta 2-microglobulin isolated from amyloid deposits in dialysis patients is modified by advanced glycation (AGE). In this context it appeared of interest to examine in a cross-sectional multicentre study whether dialysis-related amyloidosis, as evaluated by X-ray assessment of cysts in the metacarpal bones, was different in diabetic patients on maintenance haemodialysis for more than 5 years time compared with matched non-diabetic controls. We evaluated the hand skeleton of 75 diabetic patients (9 type I, 66 type II; 35 male, 40 female; median age 64 years, range 31-86; median duration of dialysis 7 years, range 5-17). They were compared with 150 patients without diabetes mellitus who were matched for age, gender and duration of dialysis. Hand X-rays were centrally evaluated by one radiologist unaware of the underlying clinical diagnosis. The overall frequency of amyloid cysts was 9/75 (12%) in diabetic patients (95% confidence interval 4.6-19.3%) and 28/150 (19%) in matched controls (95% confidence interval 12.4-24.9%). The results indicate that diabetes mellitus does not confer an increased risk of dialysis-related amyloid cysts. The results are of interest with respect to the mechanism of amyloid formation.

Immunoluminometric assay (ILMA) for intact human proinsulin and its conversion intermediates.

We describe an immunoluminometric assay (ILMA) for determination of intact proinsulin and its conversion intermediates. 32,33-split and 65,66-split proinsulin, in human serum. After incubation of the serum samples with the IgG fraction of a guinea pig antiserum against human insulin coated to the surface of polystyrene beads, a sandwich complex was formed using a monoclonal antibody against human C-peptide labelled with acridinium ester as second antibody, yielding a detection limit of 0.11 pmol/l. Mean proinsulin concentration in the serum of 38 healthy fasting subjects was 7.3 pmol/l (S.D. +/- 5 pmol/l, median 5 pmol/l, 95th percentile 15 pmol/l); maximum serum proinsulin after oral glucose stimulation never exceeded 40 pmol/l. Eighteen of 20 patients with confirmed insulinoma had proinsulin concentrations over 50 pmol/l (mean 261 pmol/l, S.D. +/- 248 pmol/l, median 170 pmol/l, 95th percentile 663 pmol/l); serum proinsulin in two patients with completely enucleated B-cell adenoma declined to normal values after surgery.

Efficient symptomatic control of carcinoid tumors with somatostatin in patients with disease progression under alpha-interferon therapy.

BACKGROUND/AIMS: We report--as a retrospective observation--on eight patients with malignant carcinoid tumors. MATERIALS AND METHODS: All patients were initially treated with alpha-interferon and received the longacting somatostatin analogue octreotide (SMS 201-995) after disease progression. Tumor growth was monitored by CT-scan or ultrasound. In addition, serum CgA and urinary 5-HIAA values were determined. RESULTS: All patients responded with relief of symptoms within a few days after the start of octreotide therapy. A regression of the tumor size did not occur, however four patients showed no significant progress over a period of nine to more than eighteen months. The endocrine parameter chromogranin A--determined by immunoluminometric assay (ILMA)--was elevated in all eight patients regardless of symptoms and showed a close correlation with the course of disease. The urinary 5-HIAA values were only elevated in seven patients. In addition, 123I-SMS 204-090 scintigraphy could be performed in six patients. Using this method most of the primary tumors and metastases could be detected. CONCLUSIONS: Only octreotide therapy showed a sufficient symptomatic control and has to be considered as progress in drug therapy for patients with malignant carcinoid tumors. In addition, chromogranin A is an interesting endocrine parameter for the follow-up of the secretory activity.