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Biomedical subjects

P Petersen

Publications and source records attributed to P Petersen.

At least 19 recordsLinked to original sources
PubMed2005

Encapsulation of islets in rough surface, hydroxymethylated polysulfone capillaries stimulates VEGF release and promotes vascularization after transplantation.

The transplantation of encapsulated islets of Langerhans is one approach to treat type 1 diabetes without the need of lifelong immunosuppression. Capillaries have been used for macroencapsulation because they have a favorable surface-to-volume ratio and because they can be refilled. It is unclear at present whether the outer surface of such capillaries should be smooth to prevent, or rough to promote, cell adhesions. In this study we tested a new capillary made of modified polysulfone (MWCO: 50 kDa) with a rough, open-porous outer surface for islet transplantation. Compared with free-floating islets, encapsulation of freshly isolated rat islets affected neither the kinetics nor the efficiency of glucose-induced insulin release in perifusion experiments. Free-floating islets maintained insulin secretion during cell culture but encapsulated islets gradually lost their glucose responsiveness and released VEGF. This indicated hypoxia in the capillary lumen. Transplantation of encapsulated rat islets into diabetic rats significantly reduced blood glucose concentrations from the first week of implantation. This hypoglycaemic effect persisted until explantation 4 weeks later. Transplantation of encapsulated porcine islets into diabetic rats reduced blood glucose concentrations depending on the islet purity. With semipurified islets a transient reduction of blood glucose concentrations was observed (2, 8, 18, 18 days) whereas with highly purified islets a sustained normoglycaemia was achieved (more than 28 days). Explanted capillaries containing rat islets were covered with blood vessels. Vascularization was also observed on capillaries containing porcine islets that were explanted from normoglycaemic rats. In contrast, on capillaries containing porcine islets that were explanted from hyperglycemic rats a fibrous capsule and lymphocyte accumulations were observed. No vascularization on the surface of transplanted capillaries was observed in the absence of islets. In conclusion, encapsulated islets can release VEGF, which appears to be an important signal for the vascularization of the capillary material. The rough, open-porous outer surface of the polysulfone capillary provides a site well suited for vascular tissue formation and may allow a prolonged islet function after transplantation.

Animals↗
PubMed2003

Areal density measurement is a convenient method for the determination of porcine islet equivalents without counting and sizing individual islets.

The determination of islet mass is important for the normalization of islet experiments in the laboratory and for the precise dosing of islets for transplantation. The common microscopical analysis is based on individual islet sizing, calculation of the frequency distribution, and conversion into islet equivalents (IEQ), which is the volume of a spherical islet with a diameter of 150 microm. However, islets are of irregular form, which makes this determination user dependent, and the analysis is irreproducible once the original sample is discarded. This routine technique of islet quantification was compared with the analysis of areal density measurements. It was assumed that the entire area occupied by islets can be expressed in IEQ without sizing and counting individual islets. Porcine islets were isolated by continuous digestion/filtration and purified by gradient centrifugation. Purified islets were stained with dithizone and were repeatedly pictured under the microscope with random area selection. A total of 51 pictures was taken from 11 different purifications and stained islets were detected by digital image analysis. The correlation coefficient (r) between bothanalyses was 0.977 with an underestimation of islet yield by areal density detection (slope: 0.75 +/- 0.03). Areal density analysis per picture took about 1 min, which is about 10 times faster than the traditional method without increasing the method error (CV 2.1% vs. 2.7%). In summary, areal density measurements allow a rapid and reproducible estimation of IEQ without counting individual islets. It can be performed in a single step analysis without computer programming and is valuable for online determinations of islet yield preceding transplantation.

Animals↗
PubMed2002

Sensory-motor responses to volume-controlled duodenal distension.

Abstract Visceral perception and secondary peristalsis evoked by distension of the duodenum were studied in 10 healthy volunteers. An impedance planimetric probe for cross-sectional area (CSA) measurements inside a balloon and with three pressure channels was used. Balloon distensions were performed in the fed state with or without the administration of the antimuscarinic drug butylscopolamine. A modified questionnaire was used to assess the nonpainful and painful sensations. The total tension (T(total)) and the passive tension (T(passive)) were determined from the distensions without and with the administration of butylscopolamine, respectively. The active tension (T(active)) was T(total) - T(passive). The stepwise balloon distensions induced the first sensation at a volume of 33 +/- 3 mL. After administration of butylscopolamine the first sensation appeared at 42 +/- 1 mL. The perception score (PS) revealed an approximately linear increase as function of volume, CSA, pressure and tension after the first sensation. Butylscopolamine resulted in significant changes in PS score as function of volume, CSA and strain, but not as a function of pressure and tension. The frequency of the secondary peristalsis increased to the highest value (8.2 +/- 0.8 contractions min(-1)) at a volume of 21 mL. Butylscopolamine almost abolished the distension-evoked motility. T(total) and T(passive) increased nonlinearly as a function of volume, whereas T(active) increased up to a distension volume of 33 mL and then decreased at higher volumes. Hence, the conventional length-tension diagrams as known from studies of smooth muscle strips in vitro can be reproduced in the human duodenum in vivo. This new way of studying intestinal sensation and motility may prove to have both basic and clinical importance as both passive tissue structures and the sensorimotor function are tested.

Adult↗
PubMed2001

Prevalence of hereditary haemochromatosis in late-onset type 1 diabetes mellitus: a retrospective study.

BACKGROUND: Although genotyping studies suggest that hereditary haemochromatosis is one of the most common genetic disorders in white people, it is still thought of as an uncommon disease. Our aim was to test the hypothesis that hereditary haemochromatosis is a disease often overlooked in patients with late-onset type 1 diabetes mellitus, a late manifestation of untreated iron overload. METHODS: We did a retrospective study in which we genotyped for the C282Y and H63D mutations in the haemochromatosis gene in 716 unselected Danish patients who developed type 1 diabetes mellitus after age 30 years and 9174 controls from the general Danish population. We also screened for hereditary haemochromatosis by assessment of transferrin saturation. FINDINGS: More patients with diabetes (n=9, relative frequency 1.26%, 95% CI 0.58-2.37) than controls (23, 0.25%, 0.16-0.38) were homozygous for C282Y (odds ratio 4.6, 2.0-10.1, p=0.0001). These patients had unrecognised signs of haemochromatosis. Transferrin saturation and ferritin concentrations ranged from 57% to 102% and 17 microg/L to 8125 microg/L, respectively. Frequency of compound heterozygosity (C282Y/H63D) did not differ between patients with diabetes (eight) and controls (131) (odds ratio 0.8, 95% CI 0.4-1.7). Positive and negative predictive values of transferrin saturation greater than 50%, in identification of C282Y homozygosity, were 0.26 and 1.00, respectively. A saturation of less than 50% therefore excluded C282Y homozygosity, whereas a saturation of more than 50% suggested C282Y homozygosity. INTERPRETATION: Measurement of transferrin saturation followed by genetic testing could prevent liver and heart problems and improve life expectancy in patients with diabetes. Population screening before the onset of diabetes might improve the outlook of patients even further, but will be less cost effective.

Adult↗
PubMed2001

Macroencapsulation of rat islets without alteration of insulin secretion kinetics.

Transplantation of encapsulated islets may restore endogenous insulin secretion in type 1 diabetics with no need of lifetime immunosuppression of the recipient. A biomaterial should be developed which combined immunoisolation with rapid and efficient diffusion of glucose and insulin. Rat islets were macroencapsulated in capillaries (molecular cut off 50 kD) of differently modified polysulphone. Macroencapsulated islets were perifused to study the kinetics of glucose induced insulin secretion into the perifusion medium. Blending polysulphone (PSU) with poly vinyl pyrrolidone or sodium dodecyl sulphate was not suited for islet macroencapsulation since glucose induced insulin release was absent after encapsulation. Hydroxy methylation (CH2OH) of PSU improved the secretory behaviour of macroencapsulated islets depending on the degree of substitution (DS). At 0.8 DS glucose induced insulin secretion was delayed and inefficient. At maximal degrees of PSU-substitution (1.8) the kinetics of insulin release and the efficiency of insulin release were very similar to that observed of free floating islets. In conclusion, highly substituted hydroxy methylated polysulphone allows a rapid and efficient insulin release after macroencapsulation and is suited for the further development of a bioartificial pancreas.

Animals↗
PubMed2001

Sensitivity and distensibility of the rectum and sigmoid colon in patients with irritable bowel syndrome.

BACKGROUND: Hyperalgesia to visceral stimuli is a biological marker of the irritable bowel syndrome (IBS). Abnormal pain processing is probably of most importance, but biomechanical abnormalities of the gut wall may also contribute to the findings. In the current study, we investigated the sensation of the gut to electrical stimuli as well as the distensibility of the rectum and sigmoid colon in IBS patients and a control group. METHODS: Nine patients with IBS and 11 controls entered the study. The pain threshold to electrical stimuli at the rectosigmoid junction was determined with bipolar electrodes integrated on the biopsy forceps for the endoscope. Subsequently, controlled distensions of the sigmoid colon and rectum were performed with a balloon integrated on a probe for impedance planimetry, providing the possibility to measure the cross-sectional area (CSA), wall tension and strain to different pressures together with the sensation ratings. RESULTS: The pain detection thresholds to electrical stimuli at the rectosigmoid junction were 12.5 (range 7-39) mA in controls and 7.5 (range 0.75-12) mA in IBS patients (P = 0.03). The calculated pressures at the pain detection threshold in the sigmoid colon were lower in the IBS patients (31.5 (range 5-58) versus 5 cm (range 5-25) water; P = 0.03), otherwise no differences were seen in sensation rating to the different distension pressures. The CSA was slightly higher in controls to the different pressures, whereas no differences between the groups were seen in strain and tension of the rectum and sigmoid colon. CONCLUSION: The visceral hypersensitivity in IBS seems to be related to alterations in the nervous system rather than biomechanical parameters such as the tension and strain of the gut wall. Treatment of pain in IBS should therefore be based on drugs with documented action on the nociceptive pathways in the central nervous system.

Adult↗
PubMed2001

In vitro test of new biomaterials for the development of a bioartificial pancreas.

The implantation of macroencapsulated islets has the potential to restore endogenous insulin secretion in type 1 diabetics, with no need for lifetime immunosuppression. To match the physiological fluctuations of blood glucose concentrations with appropriate insulin release, the macroencapsulation material must combine immunoprotection with optimal diffusion properties for glucose and insulin. The impact of chemical modifications of polysulphone (PSU) capillary polymers with a cutoff of 50 kD on glucose-induced insulin secretion of macroencapsulated rat islets was studied in perifusion experiments. The insulin release of free-floating islets showed the typical rapid response to glucose stimulation. Total insulin release (AUC between minute 30 and 120 of perifusion) reached 117+/-22 ng/ml. Blending PSU with polyvinylpyrrolidone or sodium-dodecyl-sulfate was not suitable for islet macroencapsulation, since glucose-induced insulin release was absent or disturbed. Hydroxy-methylation (CH2OH) of PSU improved the secretory behavior of macroencapsulated islets depending on the degree of PSU substitution (DS 0.8, AUC 62+/-15 ng/ml; DS 1.8, 111+/-24 ng/ml). In highly substituted PSU-capillaries the kinetics of glucose-induced insulin release was very similar to that observed in free-floating islets. Two consecutive glucose stimulations potentiated insulin release of free-floating islets during the second period of stimulation. Furthermore, freshly isolated macroencapsulated islets responded with more efficient insulin secretion after the initial priming. In conclusion, in vitro membrane screening identified highly substituted hydroxy-methylated PSU as the material of choice for islet encapsulation in a bioartificial pancreas.

Animals↗
PubMed2001

Sensory and biomechanical responses to distension of the normal human rectum and sigmoid colon.

BACKGROUND: Visceral pain is a major clinical problem. The aim of the present study was to compare the pain and biomechanical responses to standardized distension of the human colon. METHODS: The relation between pain intensity and pressure, cross-sectional area (CSA) and tension-strain relations of the rectum and sigmoid colon were studied in 11 normal subjects following standardized distension using impedance planimetry. The bag was inflated stepwise with pressures up to 6 kPa. The subjects, who were blinded for the distension procedure, rated their pain intensity using an aggregate visual analogue score (VAS) combining the intensity of the feeling of air, urge to defecate and pain. RESULTS: The distensions produced an initial rapid increase in CSA followed by a phase of slow increase until a steady state CSA was reached after 0.5-1 min. Several phasic contractions (observed as short-term decreases in the CSA) were recorded in the rectum from the end of the rapid phase to the end of distension at pressures from 1 to 5 kPa. The CSA in the rectum and sigmoid colon was 3,706 +/- 426 mm(2) and 2,305 +/- 426 mm(2) at the maximum bag pressure of 6 kPa (F = 52.4, p < 0.001). The tension-strain relation did not differ between the normal rectum and sigmoid colon. The VAS score for every modality (air, defecation and pain) revealed an increase in intensity as a function of pressure. The VAS score in the rectum and the sigmoid colon as a function of tension and strain did not show any differences. CONCLUSIONS: The biomechanical properties in the sigmoid colon and rectum were alike. For a given wall tension and circumferential strain the sensibility seems equal in the rectum and the sigmoid colon. The observed difference in perception between the two segments was related to the greater CSA in the rectum.

Abdominal Pain↗
PubMed2000

[Treatment needs of alcoholics with parental alcoholism].

The present study covers 375 consecutive patients referred to the three outpatient clinics at the Psychiatric department of Odense University Hospital from November 1995 to February 1997. The aim of the study was to describe differences in problem profiles for alcoholics with or without parental alcoholism. All patients were assessed by means of the Addiction Severity Index at admission. There was a tendency towards alcoholics with parental alcoholism having more severe alcohol problems than alcoholics without such a family history. Furthermore, alcoholics with parental alcoholism had a more complex problem profile, i.e. more legal problems, psychological problems and work-related problems, especially among the males. In sum, male alcoholics with a family history of alcoholism showed a problem profile almost as complex as that of female alcoholics in general.

Adult↗
PubMed2000

[Homeless persons residing in shelters in the county of Funen I. Psychosocial characteristics and need of treatment].

In the County of Funen (population 460,000) 120 homeless people resided in shelters for homeless people during week 49, 1996. Of these homeless persons, 94 (or 78%) were examined using ICD-10 and the Addiction Severity Index. Ninety percent were men, 90% were aged 20-59 years, 98% were unmarried or separated/divorced. Seventy-one percent had lived alone during the past three years, only 2% were employed, and sources of income for 83% were public assistance or disability pensions. The population of homeless people was divided into three groups: 1) Psychoses were found in 13 cases or 14%--schizophrenia (4%), paranoid psychosis (4%) and affective disorder (5%). About 2/3 had double disorder, psychosis plus substance abuse. 2) Sixty-four or 68% were non-psychotic homeless people, who had alcohol/substance abuse (53 or 83%) and/or personality disorder (57 or 89%). 3) Seventeen or 18% had no mental illness. About 60% had been sentenced to prison at least once. About 20% needed psychiatric treatment.

Adolescent↗
PubMed2000

[Homeless persons residing in shelters in the county of Funen II. Comparison between 1990 and 1996 and occurrence of mental disease].

The question has been raised whether the change from hospital to community psychiatry is accompanied by an increasing number of the mentally ill in institutions for homeless people. During week 49, 1996, the residents in institutions for homeless people in the County of Funen were interviewed and diagnosed according to ICD-8, and the results were compared with a similar study from week 47, 1990. The prevalence of psychoses was 11% in 1990 and 14% in 1996. This difference was not significant. Significantly fewer psychotic homeless people were treated for their psychotic disorders in 1996 compared with 1990. The prevalence of alcoholics had fallen by 35%, while the prevalence of narcotics and cannabis addicts had risen by 78% and 110%, respectively. These changes were statistically significant. There was still a high prevalence of personality disorders, 70% in 1990 and 60% in 1996. Even though the deinstitutionalization of the psychiatric service has not been accompanied by more psychotic patients in institutions for the homeless, the clientele is still heavily strained with psychosis, personality disorder and substance abuse.

Adolescent↗
PubMed2000

[Injury profile in modern competitive karate--analysis of 1999 WKC-Karate World Championship Games in Bochum].

Competitions in Karate are either carried out as Shobu sanbon (with fist padding) or Shobu Ippon (without fist padding). Aim of this study was to gain current data on injuries in modern competitive Karate and to compare the two different competitive systems. During the WKC-Karate-World-Championships held from June 12-13 1999 at Bochum, 392 bouts were carried out. Every injury that was seen by the tournament doctor was registered. 142 competitors sustained 168 injuries: 141 mostly minor contusions of the head and throat, 12 facial lacerations, 3 knock-outs (mild brain injury), 3 thoracal contusions, 1 midfoot fracture and 9 other blunt injuries. We saw more injuries in Shobu Sanbon (146/302 bouts) than in Shobu Ippon (23/90). Most of the injuries (152) were caused by punches. In Shobu Sanbon, kicking techniques led to 17 injuries only. The injury pattern shown here is comparable to earlier studies. Severe injuries in competitive Karate are rare. The higher number of injuries in Shobu sanbon may be due to the longer fighting time and higher scoring. Fist pads used in Shobu Sanbon might also lead to a loss of control. Therefore, prophylactic fist padding to avoid injuries in competitive Karate has to be seen critically.

Adolescent↗
PubMed2000

The postoperative course of gamma-glutamyl transpeptidase--a marker of cytomegalovirus (CMV) replication risk?

Cytomegalovirus (CMV) infection is a common complication in the postoperative course of liver transplantation. In order to start early prophylactic therapy, but to avoid unnecessary treatment, or expensive screening, a desirable goal in post-transplant monitoring is to find appropriate markers in standard laboratory diagnostics. In the present study, the results of a 6-week CMV replication monitoring schedule by the pp65 antigenemia assay in 100 liver graft recipients were included. The activities of transaminases, glutamate dehydrogenase and gamma-glutamyl transpeptidase (gamma-GT) were measured by routine laboratory methods. In contrast to the transaminases, the serum activity of gamma-GT increased during the first postoperative week. The maximum levels were 246 +/- 211 U/l in patients without (n = 46) and 140 +/- 89 U/l in patients with early CMV replication (n = 54; p = 0.02). Patients with gamma-GT levels below 200 U/l on the 5th postoperative day (n = 72) had a CMV replication risk of 65%, whereas those patients with gamma-GT levels above this threshold had a risk of 30% (n = 28; p = 0.0007; relative risk = 2.9). These findings provide a routinely usable marker for the identification of patients at an increased risk of CMV replication. It can be considered that these phenomena may be caused by an additional immunosuppressive effect of the CMV virus.

Biomarkers↗