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Christoph Schmid

Publications and source records attributed to Christoph Schmid.

At least 37 records · Page 2Linked to original sources
PubMed2005

Mini-Mental State Examination is superior to plasma glucose concentrations in monitoring patients with suspected hypoglycaemic disorders during the 72-hour fast.

OBJECTIVE: To determine whether systematic evaluation of cognitive function by the Mini-Mental State Examination (MMSE) allows the objective detection and documentation of cognitive deterioration in patients referred for evaluation of suspected hypoglycaemic disorders by the 72-h fast. DESIGN: Prospective case series. METHODS: In 50 patients referred for evaluation of suspected hypoglycaemic disorders, the MMSE score (maximum 30 points) was assessed at the start and at the end of the fast. RESULTS: The fast was terminated before 72 h in 14 patients because they developed neuroglycopenic symptoms due to hypoglycaemic disorders. Their MMSE score fell from a median of 29 points (range 20-30) at the beginning to 17 points (range 0-24) at the termination of the fast. The score dropped by > or =6 points in all patients with hypoglycaemic disorders. Median (range) plasma glucose concentration at the end of the fast was 2.1 (1.1-2.5) mmol/l. Thirty-six individuals developed no neuroglycopenic symptoms throughout the 72-h fast, their MMSE score remained between 27 and 30 throughout the fast and their median plasma glucose concentration dropped to 2.9 (2-3.6) mmol/l. CONCLUSIONS: Systematic evaluation of cognitive function by the MMSE at the beginning and at the termination of the fast allows objective determination and documentation of the deterioration of the cognitive state in patients with hypoglycaemic disorders. A decline in the cognitive performance by > or =6 points in the MMSE score rather than a distinct plasma glucose concentration should be used as the criterion to terminate the prolonged fast before 72 h.

Adolescent↗
PubMed2005

Acute psychological stress affects glucose concentrations in patients with type 1 diabetes following food intake but not in the fasting state.

OBJECTIVE: To compare the effect of acute psychosocial stress on glucose concentrations in the fasting state and following food intake in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: In study 1, 20 patients were exposed to moderate psychosocial stress by means of the Trier Social Stress Test (TSST) in the fasting state. In study 2, the TSST was applied to 20 additional patients 75 min after intake of a standard meal. Glucose concentrations (by continuous glucose monitoring system), blood pressure, and heart rate were monitored on the control day and on the stress testing day. RESULTS: In both studies, blood pressure increased in response to TSST from 122/77 +/- 14/9 mmHg at baseline to a maximum of 152/93 +/- 21/13 mmHg (P < 0.001), and heart rate increased from 80 +/- 11 to 99 +/- 19 bpm (P < 0.001). In the fasting state (study 1), glucose concentrations remained unchanged during the control day as well as during the stress testing day. In study 2, glucose concentrations were similar on both days before and up to 75 min after the intake of the standard meal. However, a significant delay (of 45 min) in the decrease of glucose concentrations was induced by psychological stress. A two-factor repeated-measures ANOVA revealed a significant difference of glucose concentrations over time (F = 646.65/P < 0.001). CONCLUSIONS: In the postprandial period, acute psychological stress induced a significantly delayed decrease of glucose concentrations, whereas in the fasting state, no effect on poststress glucose concentrations was observed.

Adult↗
PubMed2004

Islets secretory capacity determines glucose homoeostasis in the face of insulin resistance.

BACKGROUND: Debate surrounds the relative importance of impaired beta-cell secretory function versus insulin resistance in type 2 diabetes. We therefore defined insulin secretion and sensitivity in patients with impaired glucose homoeostasis of varying aetiology and duration. METHODS: 126 consecutive patients undergoing an oral glucose tolerance test (OGTT) between 1999 and 2003 were included. Whole-body insulin sensitivity index (ISI) and insulinogenic index derived from the OGTT were determined in 32 healthy controls, 65 type 2 diabetic patients, 15 patients with acromegaly, 10 patients with insulinoma, and 4 patients with HAIRAN syndrome. RESULTS: Median ISI (quartiles Q25-Q75) of healthy controls and of patients with insulinoma were similar (3.5 [2.8-5.6] and 3.2 [1.7-4.2] respectively) but significantly decreased in patients with acromegaly, type 2 diabetes, and HAIRAN syndrome (2.8 [1.8-3.3], 1.9 [1.4-3], and 0.8 [0.6-1.3] respectively). Despite the decrease in ISI, patients with HAIRAN syndrome and acromegaly maintained normal glucose tolerance by adapting insulin secretion as reflected in the insulinogenic index (106.5 [90.4-127.5] and 49 [24.4-89] in HAIRAN and acromegaly respectively, versus 46.9 [27.3-66.7] in controls). In contrast, type 2 diabetic patients failed to adapt and displayed severely hampered insulin secretion (insulinogenic index of 7.6 [3.8-14.7]). Furthermore, the level of the insulinogenic index correlated significantly with duration of diabetes and HbA1c, which was not the case for the ISI. Insulinoma patients had a decreased insulinogenic index (38.7 [32-83.8]), leading to impaired glucose tolerance despite normal ISI. CONCLUSIONS: The data are compatible with the notion that beta-cell function rather than insulin sensitivity determines the evolution of hyperglycaemia.

Acanthosis Nigricans↗
PubMed2004

In-vivo generation of leukaemia-derived dendritic cells.

Adoptive immunotherapy with transfusion of donor lymphocytes in allogeneic stem cell chimeras has been successful in the treatment of recurrent chronic myelogenous leukaemia (CML) and some patients with acute myeloid leukaemia (AML). The hypothesis that the graft-vs-leukaemia effect (GVL) is promoted by leukaemia-derived dendritic cells has been supported by the concurrent treatment of patients with cytokines that are known to induce differentiation of leukaemia cells towards dendritic cells. In combination with donor lymphocyte transfusions, treatment with interferon-alpha and granulocyte-macrophage colony-stimulating factor has been studied in patients with recurrent CML and AML, and pre-emptively in patients with high-risk AML. Long-term remissions have been observed in cytokine-treated patients, indicating the beneficial effect of cytokine stimulation of GVL reactions. This is likely to be due to differentiation of leukaemia progenitor cells towards dendritic cells in vivo.

Cell Lineage↗
PubMed2004

Assessment of hyperinsulinaemia at the termination of the prolonged fast.

BACKGROUND: Traditional criteria to diagnose hyperinsulinaemic hypoglycaemia are based on insulin measurements by unspecific insulin assays. This study was performed to test whether these traditional criteria can be applied when insulin is measured by specific immunoassays. METHODS: 29 consecutive patients undergoing a prolonged fast were included; 11 patients with insulinoma and 18 healthy individuals. We determined plasma glucose, insulin, C-peptide, proinsulin, and beta-hydroxybutyrate concentrations at the termination of the fast. Insulin was measured by an unspecific radioimmunoassay (RIA) and a specific enzyme-linked immunosorbent assay (ELISA). RESULTS: In 11 insulinoma patients, insulin concentrations at median plasma glucose concentration of 2.1 (range 1.3-2.5) mmol/l were 170 (76-340) pmol/l measured by RIA and 61 (11-156) pmol/l by ELISA. Insulin concentrations measured by RIA confirmed hyperinsulinaemia (i.e., >36 pmol/l, the proposed cut-off value for traditional insulin assays) in all insulinoma patients, whereas insulin concentrations measured by ELISA were <36 pmol/l in four patients. In three insulinoma patients, insulin concentrations measured by ELISA were <18 pmol/l, a proposed cut-off level to diagnose hyperinsulinaemia for specific insulin assays. CONCLUSION: When insulin concentrations are measured by specific immunoassays in patients evaluated for fasting hypoglycaemia, traditional reference values cannot be applied.

3-Hydroxybutyric Acid↗
PubMed2004

Cellular immunotherapy after allogeneic stem cell transplantation in hematologic malignancies.

PURPOSE OF REVIEW: The chimeric state after allogeneic stem cell transplantation provides an ideal platform for adoptive immunotherapy of hematologic malignancies using donor-derived cells. The present review aims to summarize recent results of the transfusion of donor-derived cells with regard to the diseases treated, the cells used for treatment, and the origin of these cells. RECENT FINDINGS: The transfusion of donor lymphocytes has been studied widely, not only in patients with recurrent disease, persistent disease, and mixed chimerism but also in a variety of hematologic malignancies. Donors of lymphocytes and hematopoietic stem cells have been HLA-identical siblings, HLA-matched unrelated donors, and HLA-different haploidentical family members. A variety of cells have been used for adoptive immunotherapy, including plain lymphocytes, selected T cells, T cell lines, and T cell clones. The possible therapies have been expanded by natural killer cells and natural killer T cells as well as antibodies directing the effector cells toward the malignancy. SUMMARY: Adoptive immunotherapy in chimeras has become not only a routine form of treatment of recurrent hematologic malignancy but also a prophylactic measure in high-risk leukemia and lymphoma.

Hematologic Neoplasms↗
PubMed2004

Selective arterial calcium stimulation and hepatic venous sampling in the evaluation of hyperinsulinemic hypoglycemia: potential and limitations.

PURPOSE: To describe the potential and limitations of selective arterial calcium stimulation and hepatic venous sampling (ASVS) in the evaluation of patients with hyperinsulinemic hypoglycemia. MATERIALS AND METHODS: Twenty-seven consecutive adult patients with documented hyperinsulinemic hypoglycemia undergoing an ASVS test and histologically confirmed diagnosis were included. RESULTS: By histology, 24 patients were found to have an insulinoma, two had islet cell hyperplasia, and one had insulin-secreting neuroendocrine carcinoma of the liver. ASVS correctly predicted the source of excessive insulin secretion in 26 of 27 (sensitivity, 96%) patients. In two patients with an insulinoma, ASVS had to be repeated for correct diagnosis; in one patient with a glucose-sensitive insulinoma, ASVS was falsely negative. In one patient, a falsely negative ASVS test was caused by diazoxide treatment; in another patient a falsely negative ASVS test occurred because of extraordinarily high baseline insulin levels when the calcium stimulation was performed. CT and/or MR imaging correctly predicted the source of excessive insulin secretion in 59% of patients, the sensitivity of the intraoperative exploration was 88%. CONCLUSIONS: In the authors' experience, the ASVS test is superior to CT/MR imaging and even the intraoperative exploration in identifying the source of excessive insulin secretion in patients with hyperinsulinemic hypoglycemia. To prevent false negative ASVS tests, medications with an influence on insulin secretion have to be discontinued prior to ASVS and two baseline blood samples should be obtained before the calcium stimulation is performed.

Adult↗
PubMed2004

Abnormalities of proinsulin processing in functioning insulinomas: clinical implications.

OBJECTIVE: Abnormal proinsulin processing in insulinomas may result in secretory granules containing both insulin and proinsulin, a finding not encountered in healthy beta-cells. The aim of this study was to test whether such abnormalities in the proinsulin to insulin conversion have clinical implications in patients with hypoglycaemic disorders. DESIGN: Case-series. PATIENTS AND METHODS: Fifteen patients with histologically confirmed insulinoma and two patients with islet cell hyperplasia were included. The immunohistochemical distribution pattern of proinsulin within the tumour cells was classified as Golgi pattern (predominantly perinuclear immunolabelling) or diffuse pattern (immunolabelling in the periphery of the cells, indicating the presence of proinsulin in secretory granules). Data obtained from the 72-h fast and arterial calcium stimulation and hepatic venous sampling (ASVS) test were related to the morphological classification. RESULTS: Six insulinomas exhibited a diffuse proinsulin distribution pattern, while nine insulinomas and two islet cell hyperplasias disclosed a Golgi pattern. Median proinsulin concentrations at the termination of the fast tended to be higher in patients with the diffuse proinsulin distribution pattern than in patients with the Golgi pattern (86.9 vs. 18.8 pmol/l, P = 0.07). Higher insulin (P < 0.005) and proinsulin (P < 0.05) concentrations were significantly correlated with earlier occurrence of hypoglycaemia during the prolonged fast. During the ASVS test, tumours with the diffuse proinsulin distribution pattern exhibited a higher increase in both insulin (median, 37.3- vs. 10.5-fold, P < 0.05) and proinsulin (6.3- vs. 1.6 fold, P < 0.005) concentrations following calcium stimulation than the tumours with the Golgi pattern. CONCLUSIONS: Abnormalities in the proinsulin to insulin conversion in patients with insulinomas and islet cell hyperplasia correlate with impaired regulation of both insulin and proinsulin secretion during the prolonged fast as well as the ASVS test.

Adult↗
PubMed2004

A novel succinate dehydrogenase subunit B gene mutation, H132P, causes familial malignant sympathetic extraadrenal paragangliomas.

We report a family with malignant sympathetic paragangliomas (PGL) exhibiting a new type of germline mutation in the succinate dehydrogenase subunit B (SDHB) gene. Two affected brothers, presenting with symptoms at the ages of 25 and 52 yr, suffered from malignant abdominal extraadrenal sympathetic PGL. They died of their disease at ages 43 and 61 yr. Their mother had the same history of signs and symptoms, suggesting a catecholamine-producing tumor at the age of 55 yr. Analysis of the germline DNA from these three patients revealed a novel mutation in exon 4 (H132P) of the SDHB gene. This mutation was absent in 160 control chromosomes. Loss of heterozygosity analysis of the tumors showed a loss of one SDHB allele, and RT-PCR-based expression analysis confirmed the exclusive expression of the mutated allele in both tumors. A review of the published PGL families revealed malignant tumors in seven of 12 well-documented families with SDHB mutation-associated extraadrenal PGL. These findings, as well as findings of the family reported here, suggest a strong causal relationship of SDHB germline mutations with malignant extraadrenal abdominal PGL and imply the necessity of a close follow-up of affected individuals and family members.

Abdominal Neoplasms↗
PubMed2004

Insulin determination by specific and unspecific immunoassays in patients with insulinoma evaluated by the arterial stimulation and venous sampling test.

OBJECTIVE: The aim of this study was to compare insulin concentrations measured by a traditional radioimmunoassay (RIA) and a more specific enzyme-linked immunosorbent assay (ELISA) in blood samples obtained during the arterial stimulation and venous sampling (ASVS) test in patients with insulinoma. DESIGN: Prospective case series. METHODS: In 14 patients with an insulinoma undergoing an ASVS test, blood samples were obtained from the hepatic vein at baseline and 60 s after calcium injection into an artery supplying the tumour and a control artery (supplying pancreatic tissue without tumour). A selective arterial calcium stimulation was performed in five additional patients without evidence for an insulinoma. We measured insulin by a traditional RIA and a specific immunoassay. RESULTS: In patients with insulinoma, insulin concentrations increased between 2.3- and 24.2-fold (median 8.2-fold) when measured by RIA and between 7.3- and 59.4-fold (median 16) when measured by ELISA following calcium injection into the artery supplying the tumour. Following calcium injection into the control artery, insulin concentrations were 0.6 to 1.3 times (median 1.0) the baseline values by RIA and 0.5 to 2.5 times (median 1.1) the baseline values by ELISA. In patients without insulinoma, insulin concentrations increased following calcium stimulation between 0.7- and 2.1-fold (median 1.3-fold) when measured by RIA and between 0.6- and 4.7-fold (median 1.3-fold) when measured by ELISA. CONCLUSIONS: When insulin is measured by specific immunoassays, a higher cut-off (i.e. five- to sixfold increase) rather than the traditional criterion of a twofold increase should be used to localise an insulinoma during the ASVS test. The increase in insulin concentrations following calcium stimulation is significantly higher when insulin is measured by a specific assay compared with results obtained with traditional RIAs.

Adult↗
PubMed2003

Graft-versus-leukemia reactions in allogeneic chimeras.

There is a strong graft-versus-leukemia (GVL) effect of allogeneic stem cell transplantation (SCT) due to elimination of tumor cells by alloimmune effector lymphocytes. When leukemia relapses after allogeneic SCT, donor lymphocyte transfusions (DLTs) can induce sustained remissions in some patients. This review summarizes the current status on clinical use of DLT, the basis of GVL reactions, problems associated with this therapy, and new strategies to improve DLT. Several multicenter surveys demonstrated that the GVL effect of DLT is most effective in chronic myelogenous leukemia (CML), whereas it is less pronounced in acute leukemia and myeloma. Cytokine stimulation to induce differentiation of myeloid progenitor cells or to up-regulate costimulatory molecules on tumor cells may improve the efficacy of DLT. Infections and graft-versus-host disease (GVHD) are major complications of DLT. Control of GVHD may be improved using suicide gene-modified T cells for DLT, allowing T-cell elimination if severe GVHD develops. Hopefully, in the future, GVL effect can be separated from GVHD through adoptive transfer of selected T cells that recognize leukemia-specific antigens or minor histocompatibility antigens, which are expressed predominantly on hematopoietic cells, thereby precluding attack of normal tissues. In patients with leukemia and lymphomas with fast progression, tumor growth may outpace development of effector T cells. Here it may be preferable to select stem cell transplant donors with HLA-mismatches that allow alloreactive natural killer cells, which appear early after transplantation, to retain their cytolytic function. New approaches for adoptive immune therapy of leukemia, which promise a better prognosis for these patients, are being developed.

Animals↗
PubMed2003

Serum cystatin C is sensitive to small changes in thyroid function.

BACKGROUND: Serum cystatin C (CysC) is a novel marker for kidney function. The impact of mild thyroid dysfunction on CysC has never been investigated. METHODS: CysC was determined at the time of diagnosis of subclinical hypo- and hyperthyroidism, and when TSH returned into the normal range in 40 consecutive patients with mild thyroid dysfunction. RESULTS: Twenty-six patients with subclinical hypothyroidism and 14 patients with subclinical hyperthyroidism were included. In patients with subclinical hypothyroidism median (range) TSH was 7.8 (4.3-26.7) mU/l (reference 0.27-4.2) at diagnosis and decreased to 2.3 (0.36-4.0) mU/l following treatment with levothyroxine. Mean (+/-S.D.) CysC increased from 0.88+/-0.23 mg/l (reference 0.63-1.33) in the hypothyroid state to 1.01+/-0.21 mg/l when TSH normalized (p<0.001). In patients with subclinical hyperthyroidism, median TSH at diagnosis was 0.08 (0.001-0.26) mU/l and increased to 1.6 (0.28-4.0) mU/l in the euthyroid state. CysC declined from 1.04+/-0.29 mg/l at diagnosis of subclinical hyperthyroidism to 0.91+/-0.25 mg/l when TSH normalized (p<0.05). CONCLUSIONS: Mild thyroid dysfunction significantly alters CysC levels. Therefore, thyroid function has to be considered when CysC is used as a marker of kidney function.

Adolescent↗
PubMed2003

Impact of thyroid dysfunction on serum cystatin C.

BACKGROUND: Serum cystatin C (CysC) is a novel marker for kidney function that has been claimed to be superior to serum creatinine. Thyroid dysfunction may alter creatinine, which has been found to be increased in hypothyroidism and decreased in hyperthyroidism. This study was performed to evaluate whether changes in CysC and creatinine are parallel during the treatment of hypo- and hyperthyroidism, respectively. METHODS: Prospective case series of 22 consecutively referred patients with thyroid dysfunction. Creatinine and CysC were determined at the time of diagnosis of hypo- and hyperthyroidism, and when free thyroxine (fT4) returned into the normal range. Hypothyroid patients were treated with levothyroxine. Hyperthyroid patients were treated with antithyroid drugs, surgery, or radioiodine. RESULTS: Nine patients with hypothyroidism and 13 patients with hyperthyroidism were included. In patients with hypothyroidism mean fT4 (+/-SD) was 4.9 +/- 2.5 pmol/L (reference, 12 to 22) at diagnosis and increased to 16.6 +/- 3.6 pmol/L when patients were treated with levothyroxine. Creatinine decreased from 86 +/- 13 micromol/L (reference, 70 to 105) in the hypothyroid state to 76 +/- 16 micromol/L when fT4 normalized (P = 0.062), whereas CysC increased from 0.84 +/- 0.17 mg/L (reference, 0.63 to 1.33) to 1.1 +/- 0.28 mg/L (P < 0.001). In patients with hyperthyroidism, mean fT4 was 54.6 +/- 22.7 pmol/L (reference, 12 to 22) at diagnosis and decreased to 15.8 +/- 3.6 pmol/L following treatment with antithyroid drugs, thyroid surgery, or radioiodine. Creatinine increased from 67 +/- 15 micromol/L at diagnosis of hyperthyroidism to 75 +/- 9 micromol/L when fT4 normalized (P = 0.004), whereas CysC declined from 1.32 +/- 0.17 mg/L to 0.95 +/- 0.19 mg/L (P < 0.001). CONCLUSION: Thyroid dysfunction has a major impact on CysC levels. Therefore, thyroid function has to be considered when CysC is used as a marker of kidney function. In contrast to creatinine concentrations, CysC levels are lower in the hypothyroid and higher in the hyperthyroid state as compared with the euthyroid state.

Adolescent↗