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Biomedical subjects

G Sundkvist

Publications and source records attributed to G Sundkvist.

At least 73 records · Page 4Linked to original sources

Persistent postoperative complaints after whole sural nerve biopsies in diabetic and non-diabetic subjects.

The postoperative effects of a whole sural nerve biopsy in diabetic (11) and non-diabetic (10 healthy controls, 10 patients with impaired glucose tolerance and 2 patients with polyneuropathy) subjects were investigated by a mailed questionnaire 20-44 months after the surgical procedure (10/11 vs 21/22 answers received). Pain in the biopsy area at follow-up was reported in 4/10 of the diabetic patients (p = 0.01) but in none of the non-diabetic subjects (0/21). An increased number (p = 0.01) of diabetic patients (5/10 vs 1/21) had cold intolerance in their foot or leg whereas 11/31 of all patients had dysaesthesia in the affected skin. Overall 6/31 patients described serious problems at the time of the questionnaire, and 4 of this 6 having diabetes. Loss of sensation was reported in almost all subjects irrespective of diabetes or not; however, a decrease in the area of loss of sensation was reported most often in diabetic patients (8/10 vs 8/21, p = 0.02). It is concluded that whole surval nerve biopsies give rise to persistent problems both in diabetic and non-diabetic subjects. The reason for a sural nerve biopsy has always to be carefully considered before being conducted.

Adult↗

Skin temperature changes and changes in skin blood flow monitored with laser Doppler flowmetry and imaging: a methodological study in normal humans.

The aim of the present study was to elucidate the interrelation between changes in skin temperature and changes in skin blood flow, as measured by laser Doppler techniques. Therefore, 17 healthy volunteers were studied upon immersion of both feet in water of 15 degrees C for 10 min followed by body warming for 30 min. Measurements using laser Doppler flowmetery (LDF) were performed from the nailfold of the big toe, while measurements using laser Doppler imaging (LDI) were performed from the dorsum of the foot. Temperatures were recorded simultaneously from the toe tip and the dorsal foot skin. Temperatures at the toe tip were significantly lower than at the dorsal foot skin. Cooling caused decreased values in all parameters, with restitution during indirect heating. There was an exponential interrelation between LDF and temperature readings from the toe owing to very high LDF values at the end of indirect heating. On the dorsum of the foot, relative changes in LDI and temperature showed a linear relationship (rs = 0.65), although LDI values were consistently higher than temperatures. It is concluded that temperature readings constitute an ambiguous measure of skin blood flow. On the toe tip, blood flow through opened arteriovenous shunts during indirect heating does not correlate with temperature. Cooling of the foot decreases skin temperature, mainly by heat conduction, whereas skin blood flow is only slightly reduced.

Adult↗

Disturbances of autonomic nervous function in primary Sjögren's syndrome.

Autonomic nervous function was evaluated by deep breathing [expiration/inspiration (E/I) ratio] and tilt table tests [acceleration (AI) and brake indices (BI)] in 19 patients with primary Sjögren's syndrome (pSS) and in 56 age matched controls. The E/I-ratio and systolic blood pressure (at rest, 1, and 8 min after tilt) were found to be significantly reduced (p < 0.001, p < 0.05, p < 0.01, p < 0.01 respectively) in patients with pSS whereas neither AI, BI nor diastolic blood pressure did differ significantly between patients and controls (NS). The van Bijsterveld's score correlated negatively with the AI (r = -0.77, p< 0.001) as well as the BI (r = -0.60, p < 0.01). No correlations were found between the 3 autonomic nerve function parameters (E/I-ratio, AI, BI) and unstimulated whole sialometry or salivary gland scintigraphy. We conclude that autonomic disturbances, mainly affecting the parasympathetic nerves are associated with pSS.

Adolescent↗

Disturbances of autonomic nervous function in primary Sjögren's syndrome.

Autonomic nervous function was evaluated by deep breathing [expiration/inspiration (E/I) ratio] and tilt table tests [acceleration (AI) and brake indices (BI)] in 19 patients with primary Sjögren's syndrome (pSS) and in 56 age matched controls. The E/I-ratio and systolic blood pressure (at rest, 1, and 8 min after tilt) were found to be significantly reduced (p < 0.001, p < 0.05, p < 0.01, p < 0.01 respectively) in patients with pSS whereas neither AI, BI nor diastolic blood pressure did differ significantly between patients and controls (NS). The van Bijsterveld's score correlated negatively with the AI (r = -0.77, p < 0.001) as well as the BI (r = -0.60, p < 0.01). No correlations were found between the 3 autonomic nerve function parameters (E/I-ratio, AI, BI) and unstimulated whole sialometry or salivary gland scintigraphy. We conclude that autonomic disturbances, mainly affecting the parasympathetic nerves are associated with pSS.

Adolescent↗

Glutamate decarboxylase antibodies in non-diabetic pregnancy precedes insulin-dependent diabetes in the mother but not necessarily in the offspring.

We studied the risk for diabetes of glutamate decarboxylase (GAD65Ab) and islet cell (ICA) autoantibodies in non-diabetic pregnant mothers and their children. Pregnancy and cord blood sera were collected in 1970-87 from about 35,000 mothers who delivered a child in the city of Malmö, Sweden. A total of 42 mothers were identified in 1988 who, 1-18 years after their pregnancies, had developed either insulin-dependent (n = 22) or non-insulin dependent (n = 20) diabetes mellitus. First, in 123 pregnant mothers selected as controls, 0.8% had GAD65Ab and 0.8% ICA. Second, among the mothers with non-insulin dependent diabetes, 7/20 (35%) had GAD65Ab eight months to 13 years, 10 months before clinical diagnosis. Third, in mothers who later developed insulin-dependent diabetes, 12/22 (55%) had GAD65Ab and 10/22 (45%) had ICA in pregnancies preceding the clinical diagnosis by 13 months to 9 years, 4 months. In 1996, none of the children born to the 42 mothers have developed diabetes. GAD65Ab and ICA in non-diabetic pregnancies may predict insulin-dependent diabetes in the mother but not necessarily in the offspring.

Adolescent↗

Measurement of antibodies against glutamic acid decarboxylase 65 (GADA): two new 125I assays compared with [35S]GAD 65-ligand binding assay.

Recently, 65-kDa glutamic acid decarboxylase (GAD 65) antibodies (GADA) have been introduced as autoimmune markers in blood to confirm the diagnosis of insulin-dependent diabetes mellitus (IDDM). In this study, to evaluate two new assays that use 125I-labeled GAD 65, we assayed samples from 100 children with recent onset of diabetes and 100 control children, the results were compared with those of a [35S]GADA assay and with results for islet cell antibodies (ICA), the conventional autoimmune marker. Receiver operating characteristic (ROC) curve analysis showed one of the new assays (from RSR) to be more sensitive (P = 0.01) than the comparison ([35S]GADA) assay, whereas the second new assay (from Elias) was less sensitive (P < 0.001). The GADA frequency at 97.5% specificity was greatest in the comparison assay: 63 of 100 vs 41 of 100 (P < 0.01) and 53 of 100 (P = 0.16) in the RSR and Elias assays, respectively. Almost all GADA-positive patients had ICA, but one-third of the ICA-positive patients was GADA-negative. Accordingly, adding GADA analysis results to ICA testing increased the frequency of detection of autoimmune markers only slightly (from 81% to 85%). In conclusion, at 97.5% specificity the [35S]GADA assay seemed to be more efficient than the 125I assays, although the difference was significant only for the Elias 125I assay. Antigen-specific antibodies other than GADA may explain the difference in GADA and ICA frequencies.

Adolescent↗

Protein tyrosine phosphatase-like protein IA2-antibodies plus glutamic acid decarboxylase 65 antibodies (GADA) indicates autoimmunity as frequently as islet cell antibodies assay in children with recently diagnosed diabetes mellitus.

Islet cell antibodies (ICA), the classical autoimmunity marker for insulin-dependent diabetes mellitus (IDDM), are detected in approximately 85% of children with recently diagnosed diabetes. Because the ICA assay is semiquantitative and difficult to standardize, alternative assays are needed. When glutamic acid decarboxylase 65 (GAD 65) was discovered as a major islet antigen, the measurement of antibodies to GAD 65 (GADA) was considered a good alternative to ICA. Recently, however, we showed that 1 in 3 ICA-positive diabetic patients do not have GADA. Now, antibodies against the protein tyrosine phosphatase-like protein IA2 (IA2-ab) have been detected in IDDM. To find out whether measurements of IA2-ab combined with those of GADA could detect autoimmunity to the same extent as ICA, we have measured all three kinds of antibodies (using radioligand binding assays for IA2-ab and GADA) in 100 recently diagnosed diabetic and 100 control children: ICA were found in 87, IA2-ab in 69, and GADA in 66 of the 100 diabetic patients, whereas in the 100 control children ICA were found in 2, IA2-ab in 1, and GADA in 3. Among the 87 ICA-positive patients, 45 (52%) had both IA2-ab and GADA, 21 (24%) had only IA2-ab, and 16 (18%) had only GADA, whereas 5 (6%) lacked both IA2-ab and GADA. Among the 13 ICA-negative patients, 1 (8%) had both IA2-ab and GADA, 2 (15%) had only IA2-ab, and 4 (31%) had only GADA. Thus, 6 of the 100 patients had neither ICA, IA2-ab, nor GADA. Combining the IA2-ab and GADA assays gave positive results for autoimmunity in 89 of the 100 patients, compared with 87 by the ICA assay. The combination of the IA2-ab and GADA assays appears to be an effective alternative to the ICA assay.

Autoantibodies↗

Blockade of muscarinic transmission increases the frequency of diabetes after low-dose alloxan challenge in the mouse.

The diabetogenic action of the beta-cell toxin, alloxan, is transient when administered to mice at a dosage of 50 mg/kg. We examined whether increased cholinergic activity is involved in the compensatory mechanisms. Therefore, following administration of alloxan, methylatropine (32 mumol/kg) was given intraperitoneally once daily for 5 consecutive days. Methyl atropine worsened the degree of hyperglycaemia during the first week after alloxan administration. Recovery from the diabetes mellitus was observed in a substantial number of animals given alloxan without methyl atropine, whereas the risk of developing manifest diabetes was markedly enhanced by methyl atropine. At 35 days after alloxan administration, 33% of the animals, which were given alloxan alone and were diabetic after 4 days, still had diabetes. In contrast, of the animals rendered diabetic by alloxan with concomitant atropinization, 92% remained diabetic throughout the study (p = 0.0145 vs alloxan alone). Glucose-stimulated insulin secretion and pancreatic insulin content were markedly reduced in animals with diabetes while being less reduced in alloxan-injected animals without diabetes. Moreover, in situ hybridization and immunocytochemistry revealed markedly decreased levels of insulin mRNA and number of insulin cells in alloxan-treated animals. With regard to insulin secretion, pancreatic insulin content, insulin mRNA and insulin cell number, the reduction was the same irrespective of whether methyl atropine had been given. Thus, 5 days of atropinization increases the incidence of diabetes following alloxan at 50 mg/kg in mice. We suggest that cholinergic activity protects insulin cells from glucotoxicity during the first week after alloxan administration and therefore, reduces the frequency of diabetes.

Alloxan↗

Patient administrative system as a tool to validate the ascertainment in the diabetes incidence study in Sweden (DISS).

The aim of this study was to evaluate the degree of ascertainment in a nationwide prospective registration of incident cases of diabetes mellitus in the age group 15-34 years (The Diabetes Incidence Study in Sweden (DISS)). Incident cases of diabetes mellitus in DISS during a five year period were compared with inpatients, with the diagnosis of diabetes mellitus, registered in a routine computer-based administrative register. The Patient Administrative System-Inpatient Care (PAS-IC). To clarify this issue the two-sample capture-recapture phenomena was employed in the two southernmost counties in Sweden, Malmöhus and Kristianstad, covering 9.2% of the total of 2.3 million people aged 15-34 years in Sweden. The results showed that the ascertainment level in DISS was 0.86 for insulin dependent diabetes mellitus (IDDM). Hence, the DISS registry is a valid tool to monitor the incidence of IDDM in young (15-34 years) adult subjects.

Adolescent↗

Islet cell and glutamic acid decarboxylase antibodies in hyperthyroid patients: at diagnosis and following treatment.

OBJECTIVES: To study the frequency of islet cell (ICA) and glutamic acid decarboxylase (GAD-Ab) antibodies in patients with hyperthyroidism of different types at diagnosis before treatment and in the euthyroid state following treatment. SETTING: Department of Endocrinology, Malmö University Hospital, Malmö, Sweden. SUBJECTS AND DESIGN: Blood samples were collected at diagnosis from 129 hyperthyroid patients, and about 6 months later, from 78 of the patients (euthyroid state). Ninety-two patients had Graves' disease (69 females and 23 males, median age 49 years, range 17-85 years), and 37 patients had toxic nodular goitre/solitary toxic adenoma (34 females and three males, median age 69 years, range 24-86 years). INTERVENTIONS: Most patients were treated by radioactive iodine following the first blood sample. MAIN OUTCOME MEASURES: ICA and GAD-Ab in serum. RESULTS: At diagnosis of Graves' disease, ICA were detected in two out of 92 (2.2%) patients, two out of 85 (2.4%) without diabetes mellitus and in the euthyroid state in one patient. None of the patients with toxic nodular goitre/solitary toxic adenoma had detectable ICA. At diagnosis of Graves' disease, GAD65-Ab as well as GAD67-Ab were detected in 11 out of 85 (13%) patients without diabetes. As many as six out of 11 GAD67-Ab-positive patients were GAD65-Ab negative. In the euthyroid state, GAD65-Ab were found in six out of 51 (12%) and GAD67-Ab in eight out of 51 (16%) of the non-diabetic Graves' disease patients. The frequencies of GAD65-Ab and GAD67-Ab in toxic nodular goitre/solitary toxic adenoma, diabetes excluded, were 3 and 0%, respectively, in the hyperthyroid state. CONCLUSION: The frequency of ICA in patients with hyperthyroidism is not increased as compared to the background population. GAD-Ab seems to be associated with Graves' disease and not with hyperthyroidism. The presence of GAD67-Ab in GAD65-Ab negative sera from patients with Graves' disease indicates autoreactivity against a specific GAD67 epitope.

Adolescent↗

Autoantibodies against adrenal medulla in type 1 and type 2 diabetes mellitus: no evidence for an association with autonomic neuropathy.

OBJECTIVE: To examine the role of autoimmunity in the development of autonomic neuropathy in diabetes mellitus. DESIGN: Retrospective cross-sectional study. SETTING: The Department of Medicine, University Hospital, Uppsala, and the Department of Endocrinology, University of Lund, Malmö General Hospital, Malmö, Sweden. SUBJECTS AND MAIN OUTCOME MEASURES: We examined 135 patients with type 1 (n = 96) or type 2 (n = 39) diabetes mellitus. Tests for cardiovascular autonomic functions were performed, and patient sera were analysed for the presence of autoantibodies against the adrenal medulla by indirect immunofluorescence, Western blot and immunoprecipitation techniques. RESULTS: Sera from 13% (12/96) of the type 1 and 20% (8/39) of the type 2 patients showed a positive cytoplasmic immunofluorescence (IF) staining of the adrenal medullary cells, as did 20% (30/151) of sera from healthy controls. Fifty-eight and 64% of type 1 and type 2 patients, respectively, had cardiovascular autonomic neuropathy, but no correlation between autonomic neuropathy and positive IF against the adrenal medulla was observed, with the exception of significant drops in diastolic blood pressure 8 min after tilt (P < 0.005) in type 1 patients. The various IF-positive sera reacted with several different proteins when analysed with Western blot technique using a total homogenate of the bovine adrenal medulla. These did not correspond to any of the proteins involved in the synthesis or storage of catecholamines which were considered as putative autoantigens. CONCLUSION: The finding of similar frequencies of immunoglobulins binding to adrenal medulla in both type 1 and 2 diabetic patients as well as in normal controls, argues against a role of anti-adreno-medullary antibodies in the pathogenesis of autonomic diabetic neuropathy.

Adrenal Medulla↗

Genetic and immunological findings in patients with newly diagnosed insulin-dependent diabetes mellitus. The Swedish Childhood Diabetes Study Group and The Diabetes Incidence in Sweden Study (DISS) Group.

Two large population-based case-control studies are reviewed. The aim is to determine the effects of HLA, other genetic factors and immune markers (ICA, IAA and GAD65Ab) on the age at onset of insulin-dependent diabetes mellitus (IDDM) in 0-34 year olds. The primary HLA risk gene sequence for IDDM was difficult to identify because of the low recombination frequency within the HLA region. The frequency of the DR3-DQA1*0501-DQB1*0201 haplotype and the DR3-DQA1*0501-DQB1*0201 (DQ2)/DR4-DQA1*0301-DQB1*0302 (DQ8) genotype were higher among patients diagnosed before the age of 10 compared with those diagnosed after the age of 30. The negatively associated haplotype, DR15-DQA1*0102-DQB1*0602 was absent before the age of 10, but the frequency increased with increasing age at onset. The IDDM2 gene representing the variable number of tandem repeat (VNTR) sequences and 5' of the insulin gene on chromosome 11 were associated with IDDM since homozygous short VNTR was positive but not homozygous, and heterozygous long VNTR was negatively associated with the disease. The diagnostic sensitivity and specificity of GAD65 (GA65Ab) and insulin (IAA) autoantibodies varied with the age at onset and gender. GAD65Ab had the highest sensitivity (> 80%) in patients older than 20 years of age with no difference in gender. The lowest sensitivity (54%) was in 0-10 year old boys, while age did not affect the sensitivity in girls. In contrast, the sensitivity of IAA was highest (46%) before the age of 15 but decreased thereafter as did the sensitivity for ICA. Classification of patients who develop IDDM above 20-25 years of age was inadequate since many patients classified with NIDDM either had GAD65Ab or ICA or developed these antibodies after 1-2 years of NIDDM. We conclude that not only age but also gender affect the risk for IDDM associated with HLA, other IDDM genes as well as commonly used immunological markers for IDDM.

Age Factors↗

Islet cell antibodies at diagnosis, but not leanness, relate to a better cardiovascular risk factor profile 5 years after diagnosis of NIDDM.

OBJECTIVE: To evaluate the relationship between islet cell antibodies (ICAs) and the cardiovascular risk profile 5 years after clinical diagnosis of NIDDM. RESEARCH DESIGN AND METHODS: Five years after clinical diagnosis, we evaluated blood pressure (BP) and lipids in 17 NIDDM patients with ICA at diagnosis (age 60 +/- 4 years) and 133 NIDDM patients without ICA at diagnosis (age 61 +/- 1 year). Urinary albumin excretion was evaluated in a subset of 12 NIDDM patients with ICA at diagnosis (age 60 +/- 4 years) and 82 NIDDM patients without ICA at diagnosis (age 61 +/- 1 year). RESULTS: NIDDM patients without ICA showed higher BP (140/86 +/- 2/1 mmHg vs. 128/79 +/- 3/2 mmHg; P < 0.05), total cholesterol (6.10 +/- 0.11 vs. 5.09 +/- 0.29 mmol/l; P < 0.01), LDL-to-HDL ratio (3.85 +/- 0.14 vs. 2.49 +/- 0.18; P < 0.001), and triglycerides (2.58 +/- 0.24 vs. 0.90 +/- 0.06 mmol/l; P < 0.001), lower HDL cholesterol (1.08 +/- 0.03 vs. 1.40 +/- 0.08 mmol/l; P < 0.001), and higher urinary albumin excretion (0.16 +/- 0.06 vs. 0.01 +/- 0.01 g/24 h; P < 0.05) than NIDDM patients with ICA. Among NIDDM patients without ICA, no differences concerning BP or lipids were found between obese and nonobese patients. CONCLUSIONS: ICA at diagnosis of NIDDM is a marker of more favorable cardiovascular risk profile 5 years after clinical diagnosis.

Adult↗

Capillary blood on filter paper for determination of HbA1c by ion exchange chromatography.

OBJECTIVE: To facilitate HbA1c determination, we evaluated an HbA1c filter paper system enabling capillary blood sampling at home by the patients. RESEARCH DESIGN AND METHODS: Capillary blood (two drops) was applied to a filter paper (HbA1c Via Post) and sent to the laboratory where a small disc was punched out on the filter paper. Hemoglobin was eluted from the disc in a buffer containing cysteine to eliminate the interfering glutathione adduct (HbA3) formed during storage. Analysis was performed by ion-exchange chromatography (Mono S, high-performance liquid chromatography), and the eluate was compared with hemolysate of venous blood from 41 patients. The stability of blood impregnated on filter paper was checked at different temperatures over different periods of time. RESULTS: There was an excellent agreement (r = 0.99) between HbA1c values from capillary blood on filter paper and HbA1c values from venous blood. HbA1c values were constant when stored on filter paper for 5-7 days at 20-21 degrees C (room temperature) or at 4-6 degrees C (refrigerator) for 10 days as well as at -70 degrees C for several months after blood sampling. A new chromatographic-interfering hemoglobin fraction both from venous and capillary samples was identified as free alpha-chain of hemoglobin. CONCLUSIONS: The HbA1c filter paper system enables capillary blood sampling at home, eliminates the need of vein puncture in children and adults, and provides the diabetologist with an HbA1c value when the patient visits the clinic without a need for a previsit phlebotomy.

Blood Specimen Collection↗

Proinsulin secretion during the first 3 years after diagnosis in diabetic patients with and without islet cell antibodies.

OBJECTIVE: To evaluate proinsulin secretion in different types of NIDDM. RESEARCH DESIGN AND METHODS: Proinsulin and insulin were evaluated at diagnosis of diabetes and 3 years later (fasting and after stimulation with intravenous glucose and glucagon) in 10 NIDDM patients without islet cell antibodies (ICAs) at diagnosis (age 52 +/- 4 years), 11 NIDDM patients with ICAs at diagnosis (age 50 +/- 5 years), and 21 healthy control subjects (age 53 +/- 4 years). RESULTS: At diagnosis, fasting proinsulin was higher in NIDDM patients without ICAs than in control subjects (39.6 +/- 10.0 vs. 12.8 +/- 1.6 pmol/l, P < 0.01). Proinsulin response to intravenous glucose decreased in NIDDM patients with ICAs (from 35.6 +/- 6.2 to 13.5 +/- 5.4 pmol/l, P < 0.05), but remained unchanged in those without ICAs. At 3 years after diagnosis, fasting proinsulin (10.0 +/- 3.7 vs. 59.1 +/- 17.0 pmol/l) and proinsulin responses to intravenous glucose (13.5 +/- 5.4 vs. 103.9 +/- 35.1 pmol/l) and to intravenous glucagon (7.4 +/- 3.9 vs. 36.0 +/- 7.7 pmol/l) were much lower (P < 0.01) in NIDDM patients with ICAs than in those without ICAs. CONCLUSIONS: After diagnosis of diabetes, proinsulin secretion decreases significantly in NIDDM patients with ICAs and remains constant in those without.

Autoantibodies↗