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Biomedical subjects

G Lindberg

Publications and source records attributed to G Lindberg.

At least 19 recordsLinked to original sources
PubMed2006

The nocturnal jejunal migrating motor complex: defining normal ranges by study of 51 healthy adult volunteers and meta-analysis.

Interdigestive human small bowel motility is characterized by the migrating motor complex (MMC). The aims of this study were to: (i) establish the normal range of variables of the nocturnal jejunal MMC and (ii) incorporate these data in a subsequent meta-analysis. Eighty-one recordings were performed by prolonged (24 h) ambulatory manometry in 51 subjects in two centres. Quantitative analysis was undertaken of 419 Phase III and 332 Phase II episodes. Adjusted mean values of seven variables were calculated using a mixed-effects model. Meta-analysis of pooled published data to generate a reliable 95% reference range was also performed. Adjusted mean values and confidence intervals are presented for all seven variables. Intrasubject variances were large in comparison with intersubject. Meta-analysis of 19 studies (356 pooled patients) meeting inclusion criteria produced wide reference ranges. At least five such ranges are useful for the detection of abnormality in the individual. This is the largest study of normal volunteers presented to date, with ranges for many variables produced using appropriate statistical methodology. A model for definition of abnormality has been proposed. We recommend that these data may be used by investigators in this field as a complement to other existing indicators of small bowel dysmotility.

Adolescent↗
PubMed2004

Deranged smooth muscle alpha-actin as a biomarker of intestinal pseudo-obstruction: a controlled multinational case series.

BACKGROUND AND AIMS: Chronic idiopathic intestinal pseudo-obstruction (CIIP) is a severe motility disorder associated with significant morbidity. Several histopathological (neuropathic and myopathic) phenotypes have been described but only a single adult with jejunal smooth (circular) muscle alpha-actin deficiency. We present a prospective multinational case series investigating smooth muscle alpha-actin deficiency as a biomarker of this disease. METHODS: A total of 115 fully clinically and physiologically (including prolonged (24 hour) ambulatory jejunal manometry) characterised CIIP patients from three European centres were studied. Immunohistochemical localisation of actins and other cytoskeletal proteins were performed on laparoscopic full thickness jejunal biopsies and compared with adult controls. Distribution of alpha-actin was also characterised in other gut regions and in the developing human alimentary tract. RESULTS: Twenty eight of 115 (24%) CIIP patient biopsies had absent (n = 22) or partial (n = 6) jejunal smooth muscle alpha-actin immunostaining in the circular muscle layer. In contrast, smooth muscle alpha-actin staining was preserved in the longitudinal muscle and in adult jejunal controls (n = 20). Comparative study of other adult alimentary tract regions and fetal small intestine, suggested significant spatial and temporal variations in smooth muscle alpha-actin expression. CONCLUSIONS: The ability to modulate alpha-smooth muscle actin expression, evident in development, is maintained in adult life and may be influenced by disease, rendering it a valuable biomarker even in the absence of other structural abnormalities.

Actins↗
PubMed2003

Distribution of genetic variants in preneoplastic areas of colorectal tumours.

AIMS: Loss of heterozygosity (LOH) may vary almost randomly within a colorectal tumour due to the heterogeneous morphologic character of these tumours. Despite this, as a rule, single biopsies are the source of genetic material used in studies of markers important for prognosis, clinical behaviour of the disease, or susceptibility of specific tumours to different treatment modalities. METHODS: To evaluate the importance of intratumoural variation for the results of analysis of LOH and point mutations in colorectal cancer and to determine the frequency of genetic alterations in different types of pre-neoplastic areas of the tumours, 36 consecutively operated patients with colorectal cancer were studied. After fixation, specimens were mounted on large slides containing the whole tumour. The specimens were sub classified into different areas defined as normal tissue, normal tissue closely adjacent the tumour mass, adenoma, dysplasia and invasive cancer cells. These areas were dissected and subjected to DNA extraction. RESULTS: The extracted genomic DNA was studied for LOH at chromosome 5q, 17p, and 18q and for k-ras mutations. Overall, a correlation between the intratumoural degree of neoplastic progression and the frequency of LOH and k-ras mutations was seen. These correlations were significant (p<0.008) except for dysplasia/adenomatous tissue versus invasive cancer. Microsatellite instability was found in 9% of the tumours, all except one in invasive parts of the tumours. CONCLUSIONS: This study demonstrates a statistical correlation between intratumoural differences in neoplastic degree of dedifferentiation and genetic instability in terms of LOH and point mutations of the k-ras gene in colorectal carcinoma. The importance of a careful dissection in order to localise the region with the highest probability of genetic aberrations and multiple biopsing must not be neglected. The observation that the prevalence of k-ras mutations and LOH are correlated to the degree of dedifferentiation within a colorectal tumour is in line with the concept that selected cell clones are responsible for the neoplastic progression of the tumour.

Adenoma↗
PubMed2003

The micro-flora of the small bowel in health and disease.

The micro-flora of the proximal jejunum in healthy volunteers was compared with the micro-flora in patients with gastrointestinal symptoms suggestive of spontaneous bacterial overgrowth in the small intestine. Biopsies were taken distally to the ligament of Treitz with a Watson capsule. The samples were diluted and inoculated on selective and non-selective agar plates that were incubated aerobically and anaerobically. No major differences were found in the small jejunum micro-flora in healthy persons or in a heterogenous group of patients with gastrointestinal disorders. Oropharyngeal micro-organisms dominated the micro-flora in all subjects and colonic micro-organisms were found in low numbers in a few subjects from both groups. Streptococcus intermedius and Haemophilus parahaemolyticus were only found in the micro-flora of healthy subjects while Lactobacillus spp. was more frequently found in the samples from patients. Eight of 20 healthy subjects and five of 18 patients met the criterion of small intestinal overgrowth. Emerging evidence suggests that other factors are involved in the pathogenesis of the irritable bowel syndrome complex. There is a need for better understanding of the complicated interactions between the host and the endogenous micro-flora.

Journal Article↗
PubMed2003

Pneumoperitoneum versus abdominal wall lift: effects on central haemodynamics and intrathoracic pressure during laparoscopic cholecystectomy.

BACKGROUND: It has been shown repeatedly that laparoscopic cholecystectomy using pneumoperitoneum (CO2 insufflation) may be associated with increased cardiac filling pressures and an increase in blood pressure and systemic vascular resistance. In the present study, the effects on the central circulation during abdominal wall lift (a gasless method of laparoscopic cholecystectomy) were compared with those during pneumoperitoneum. The study was also aimed at elucidating the relationships between the central filling pressures and the intrathoracic pressure. METHODS: Twenty patients (ASA I), scheduled for laparoscopic cholecystectomy, were randomised into two groups, pneumoperitoneum or abdominal wall lift. Measurements were made by arterial and pulmonary arterial catheterization before and during pneumoperitoneum or abdominal wall lift with the patient in the horizontal position. Measurements were repeated after head-up tilting the patients as well as after 30 min head-up tilt. The intrathoracic pressure was monitored in the horizontal position before and during intervention using an intraesophageal balloon. RESULTS: After pneumoperitoneum or abdominal wall lifting there were significant differences between the two groups regarding MAP, SVR, CVP, CI, and SV. Analogous to previous studies, in the pneumoperitoneum group CVP, PCWP, MPAP, and MAP as well as SVR were increased after CO2 insufflation (P < 0.01), while CI and SV were not affected. In contrast, in the abdominal wall lift group, CI and SV were significantly increased (P < 0.01), as was MAP (P < 0.01), while CVP, PCWP, MPAP, and SVR were not significantly affected. There was a significant difference in intraesophageal pressure between the two groups. In the pneumoperitoneum group, the intraesophageal pressure was increased by insufflation (P < 0.01) while, in the abdominal wall lift group, it was unaffected. In the pneumoperitoneum group the mean increases in cardiac filling pressures were of the same magnitude as the mean increase in the intraesophageal pressure. CONCLUSIONS: In healthy patients, abdominal wall lift increased cardiac index while pneumoperitoneum did not. Cardiac filling pressures and systemic vascular resistance were increased by pneumoperitoneum but unaffected by abdominal wall lift. The recorded elevated cardiac filling pressures during pneumoperitoneum may be only a reflection of the increased intra-abdominal pressure.

Abdominal Muscles↗
PubMed2003

No benefit from adding GM-CSF to induction chemotherapy in transforming myelodysplastic syndromes: better outcome in patients with less proliferative disease.

In this prospective randomized multicenter trial 93 patients, median age 72 years, with RAEB-t (n=25) and myelodysplastic syndrome (MDS)-AML (n=68) were allocated to a standard induction chemotherapy regimen (TAD 2+7) with or without addition of granulocyte-macrophage-CSF (GM-CSF). The overall complete remission (CR) rate was 43% with no difference between the arms. Median survival times for all patients, CR patients, and non-CR patients were 280, 550, and 100 days, respectively, with no difference between the arms. Response rates were significantly better in patients with serum lactate dehydrogenase (S-LDH) levels </=9.5 microkat/l, bone marrow cellularity </=70%, and WBC counts <4.0 x 10(9)/l, but S-LDH was the only variable independently associated with response by logistic regression analysis. Cox's regression analysis identified four significant prognostic factors for survival: bone marrow cellularity, S-LDH, cytogenetic risk group (International Prognostic Scoring System), and age. Only bone marrow cellularity (P=0.01) and S-LDH (P=0.0003) retained statistical significance in the log-rank test. Severe adverse events were significantly more common in the GM-TAD arm (P=0.01). Thus, addition of GM-CSF to chemotherapy showed no clinical benefit in terms of response but carried an increased risk for side effects. We present a clinically useful tool to predict response to chemotherapy and survival in elderly patients with transforming MDS, favoring patients with features of less proliferative disease.

Acute Disease↗
PubMed2002

The effect of hepatic inflow occlusion on laparoscopic radiofrequency ablation using simulated tumors.

BACKGROUND: The purpose of this study was to determine the effect of hepatic inflow occlusion (the Pringle maneuver) on laparoscopic radiofrequency (RF) ablation. METHODS: Using a previously validated agarose tissue-mimic model, 1-cm simulated hepatic tumors (three per animal) were laparoscopically ablated in five pigs with normal perfusion and then in five pigs with hepatic artery and portal vein occlusion. Energy was applied until tissue temperature reached 100 degrees C (warm-up) and thereafter for eight min. Specimens were examined immediately after treatment. RESULTS: Vascular occlusion was successful in all cases per color-flow Doppler ultrasound. Pringle time was 11.4 +/- 1.6 min. Warm-up time (2.7 +/- 1.4 vs 20.2 +/- 14.0 min) was significantly faster in the Pringle group. Ablation diameter (34.8 +/- 2.9 vs 24.7 +/- 3.1 mm), proportion of round/ovoid lesions (93% vs 20%), ablation symmetry (100% vs 40%), and margin distance (5.1 +/- 3.0 vs 1.1 +/- 1.2 mm) were significantly better for the Pringle group than the No Pringle group, respectively. CONCLUSION: Using a Pringle maneuver during laparoscopic RF ablation significantly enhances ablation geometry and results in larger margins.

Animals↗
PubMed2002

Electrogastrography before and after a high-caloric, liquid test meal in healthy volunteers and patients with severe functional dyspepsia.

BACKGROUND: The cutaneous recording of gastric electric rhythm, so-called electrogastrography (EGG), has been purported as a non-invasive method for studying patients with functional dyspepsia and unexplained nausea and vomiting. The aims of this study were to determine normal values for EGG characteristics before and after a liquid, high-caloric test meal and to investigate whether EGG could discriminate between patients with functional dyspepsia and normal controls. METHODS: In studying 20 healthy volunteers and 10 patients with functional dyspepsia, we recorded gastric electrical activity during the 30 min before and after a liquid 1.0-1.5 kcal/ml test meal. Satiety before and after the meal was estimated on a 10-point scale. EGG was analysed regarding dominant frequency, instability of the dominant frequency, power ratio and percentage activity in the normal frequency range. RESULTS: The mean (+/-s) caloric intake in patients with functional dyspepsia (286 +/- 160 kcal) was significantly lower (P < 0.001) than in healthy volunteers (610 +/- 211 kcal). The patients reported a more pronounced feeling of satiety before the test meal (5.6 +/- 3.2) compared to healthy volunteers (3.6 +/- 1.2, P < 0.05), but at the end of the test meal there was no difference in satiety (7.9 +/- 2.5 versus 7.7 +/- 1.0). However, none of the EGG parameters showed any difference between patients and healthy volunteers. CONCLUSIONS: EGG before and after a high-caloric test meal showed large variation in healthy subjects and seemed to be of little value for differentiating between healthy individuals and patients with functional dyspepsia.

Adolescent↗
PubMed2002

Differences in resting state regional cerebral blood flow assessed with 99mTc-HMPAO SPECT and brain atlas matching between depressed patients with and without tinnitus.

An increased occurrence of major depressive disorder has been reported in tinnitus patients, and of tinnitus in depressive patients. Involvement of several Brodmann areas (BAs) has been reported in tinnitus perception. The aim of this study was to assess the regional cerebral blood flow (rCBF) changes in depressed patients with and without tinnitus. The rCBF distribution at rest was compared among 45 patients with a lifetime prevalence of major depressive disorder, of whom 27 had severe tinnitus, and 26 normal healthy subjects. 99mTc-hexamethylenepropylene amine oxime (99mTc-HMPAO) single photon emission computed tomography (SPECT), using a three-headed gamma camera, was performed and the uptake in 34 functional sub-volumes of the brain bilaterally was assessed by a computerized brain atlas. Decreased rCBF in right frontal lobe BA 45 (P<0.05), the left parietal lobe BA 39 (P<0.00) and the left visual association cortex BA 18 (P<0.05) was found in tinnitus patients compared with non-tinnitus patients. The proportion of tinnitus patients with pronounced rCBF alterations in one or more of the temporal lobe BAs 41+21+22 was increased compared to gender matched controls (P<0.00) and patients without tinnitus (P<0.05). Positive correlations were found between trait anxiety scales from the Karolinska Scales of Personality and rCBF in tinnitus patients only in three limbic BAs (P<0.01), and inverse correlations in non-tinnitus patients only in five BAs subserving auditory perception and processing (P<0.05). rCBF differences between healthy controls and depressed patients with and without tinnitus were found in this study. The rCBF alterations were distributed in the cortex and were particularly specific in the auditory cortex. These findings suggest that taking audiological symptoms into account may yield more consistent results between rCBF studies of depression.

Age Factors↗
PubMed2001

Accuracy and effectiveness of laparoscopic vs open hepatic radiofrequency ablation.

BACKGROUND: The purpose of this study was to compare the accuracy (in terms of ultrasound-guided probe placement) and the effectiveness (in terms of pathologic tumor-free margin) of laparoscopic vs open radiofrequency (RF) ablation. METHODS: Using a previously validated tissue-mimic model, 1-cm simulated hepatic tumors were ablated in 10 pigs randomized to open or laparoscopic techniques. Energy was applied until tissue temperature reached 100 degrees C (warm-up) and thereafter for 8 min. A pathologist blinded to technique examined all specimens immediately after treatment. Analysis was by Fisher's exact test and the Mann-Whitney U test; p < 0.05 was considered significant. RESULTS: Off-center distance (3.5 +/- 1.6 vs 4.2 +/- 1.4 mm), size (24.7 +/- 3.1 vs 25.6 +/- 3.8 mm), symmetry (40% vs 73%), margin positivity (33% vs 9%), and margin distance (1.1 +/- 1.2 vs 2.2 +/- 1.6 mm) were not significantly different between laparoscopic (n = 15) and open (n = 11) ablations, respectively. The proportion of round/ovoid lesions (20% vs 64%) was lower (p = 0.043), and warm-up time (20.2 +/- 14.0 vs 10.7 +/- 7.5) was longer (p = 0.049) for the laparoscopic than for the open groups, respectively. CONCLUSION: Accurate probe placement can be achieved using laparoscopic and open RF ablation techniques. The physiologic effects of laparoscopy may alter ablation shape and warm-up time. Additional studies are needed to establish effective ways of achieving complete tumor destruction.

Animals↗
PubMed2001

The utility of transbronchial (Wang) fine needle aspiration in lung cancer diagnosis.

We evaluated our experience with transbronchial fine needle aspiration (TBNA) in cancer diagnosis over a period of 1 year. A total of 51 aspirates were performed by specialist chest physicians in the presence of a cytopathologist who made on spot evaluation of Diff-Quik smears for adequacy and guided the aspirator for additional sampling if necessary. Two clusters of at least 10 malignant cells were required on the Diff-Quik smears to render an on the spot positive diagnosis of malignancy. Aspirates showing atypical cells or few malignant cells not fulfilling the above criteria were placed in a suspicious category and additional material was requested. The TBNA results were correlated with the transbronchial biopsy when available.

Biopsy, Needle↗
PubMed2001

Differences in pharmacotherapy and in glucose control of type 2 diabetes patients in two neighbouring towns: a longitudinal population-based study.

AIM: To compare prescribing, dosage and blood glucose levels in patients with type 2 diabetes in two communities with differences in anti-hyperglycaemic drug utilization. METHODS: A retrospective longitudinal (1984-1994) population-based study in two neighbour towns in southern Sweden. The mean prescribed daily dose was expressed as a fraction of the Defined Daily Dose (DDD) for each drug. RESULTS: In town A, prescribing of oral agents and insulin was predominantly made by one specialized diabetes clinician, while in town B it was spread among several different general practitioners and one specialist. Altogether 44 636 medical visits by 2348 patients were identified. In each town, about 40% of the patients were treated without anti-hyperglycaemic drugs, about 40% with oral agents and about 20% with insulin. However, there were pronounced between-town differences in dosage and glucose control. The mean prescribed daily dose of sulphonylurea monotherapy decreased gradually from approximately 0.7 to approximately 0.5 DDD in town B but remained approximately 0.8 DDD in town A. The proportion of patients on both sulphonylurea and metformin increased substantially in town A but not in town B. In these patients, the mean prescribed daily dose of sulphonylurea exceeded 1.0 DDD in both towns, although it decreased with time in town B. The mean prescribed daily dose of insulin increased from 1.05 to 1.2 DDD in town A but remained virtually unchanged at 0.95 DDD in town B. The mean fasting blood glucose was lower in town A than in town B both overall (7.7 vs. 8.8 mmol/l), in those treated without any anti-hyperglycaemic drugs (7.2 vs. 8.1 mmol/l), in those on sulphonylurea monotherapy (8.3 vs. 9.7 mmol/l) and in those treated with insulin (8.1 vs. 10.2 mmol/l). CONCLUSIONS: Glucose control in routine care was better when most patients were treated by a diabetes specialist and were exposed to more intense pharmacotherapy.

Aged↗
PubMed2001

Conceptions of depressive disorder and its treatment among 17 Swedish GPs. A qualitative interview study.

BACKGROUND: Making clinical decisions for psychiatric patients in general practice is a complicated issue. A marked variation in the prescribing rates for antidepressant drugs in general as well as between geographical regions has been reported. Also, GPs tend to underestimate and undertreat depressive disorders. OBJECTIVES: The aim of this study was to explore GPs' conceptions of depressive disorder and its treatment. METHOD: A qualitative semi-structured interview was carried out on 17 GPs, selected to ensure variation of pre-conditions, in the county of Orebro, Sweden. Informants' conceptions about four depression-related issues were determined: the depressive disorder, antidepressant drugs, the treatment decision and psychotherapy. RESULTS: Conceptions of the four themes varied widely among informants in the interviews. However, the informants shared certain conceptions concerning the selection of drugs and drug treatment of major depression as well as the patient's role in deciding whether or not to treat pharmacologically. CONCLUSIONS: The study adds knowledge of GPs' thoughts about depressive disorder and their diagnostic and treatment preferences. Utilizing the concepts discussed herein, a quantitative study will be conducted to analyse how GPs' conceptions of depression are inter-related.

Adult↗
PubMed2001

Nasopharyngeal gangliocytic paraganglioma.

Gangliocytic paraganglioma (GP) is a rare neoplasm described almost exclusively in the gastrointestinal tract, especially the periampullary region. However, several examples have been reported at various sites, including the stomach, jejunum, and appendix. Herein we report a case of GP involving the nasopharynx. To our knowledge, this is the first report of GP at this site. A 44-year-old woman presented with headaches and symptoms of fullness and pressure related to mass effect. An initial endoscopic biopsy was followed by surgical excision of the nasopharyngeal mass. The triphasic tumor fulfilled the morphologic and immunohistochemical criteria for GP. The histogenesis of GP is uncertain, and the current belief is that it arises from the embryonic ventral pancreas. This concept is based largely on the location of most cases, which is along the embryologic migration route of the ventral pancreas, as well as the expression of pancreatic polypeptide by the tumor. The nasopharyngeal location of our case clearly refutes the pancreatic origin of GP. We propose that the tumor probably arises from totipotential adult stem cells, which in the right microenvironment differentiate along nonnative cell lineages.

Adult↗
PubMed2001

Laparoscopic radiofrequency thermal ablation of renal tissue with and without hilar occlusion.

PURPOSE: Few studies have evaluated the effect of radiofrequency thermal ablation on renal tissue, although it has been used clinically to treat small renal masses. We studied the size and histology of lesions created with radiofrequency thermal ablation administered via the laparoscopic approach with and without hilar occlusion in a porcine model. MATERIALS AND METHODS: The lower pole of each kidney was exposed laparoscopically in 11 farm pigs. In each kidney a 7-electrode dry radiofrequency thermal ablation probe was inserted at an identical location and deployed to a diameter of 2 cm. Energy was applied for 8 minutes at an average temperature of 100C. The left renal hilum of each pig was clamped during radiofrequency thermal ablation. Two pigs were sacrificed immediately, and 3 each were sacrificed at 24 hours, 2 and 4 weeks. The size and shape of the lesions created were measured and examined histologically. RESULTS: There were no intraoperative or postoperative complications. Laparoscopic ultrasound confirmed probe placement but did not monitor lesion progression. Acutely lesions were firm and white with a small adjacent hemorrhagic zone. Histological evaluation revealed preserved renal architecture but the loss of distinct cytoplasmic features. Nicotinamide adenine dinucleotide staining demonstrated no viable cells within the lesions. In surviving animals pelvicaliceal integrity was preserved. In the 2 and 4-week survival groups kidneys treated with hilar occlusion had larger lesions than nonoccluded kidneys but the differences were not significant at 4 weeks (3.2 x 2.7 x 2.5 cm. and 3.5 x 1.7 x 2.0, respectively, p >0.05). Histologically untreated parenchyma of hilar occluded kidneys demonstrated changes consistent with chronic pyelonephritis. In 1 kidney radiofrequency thermal ablation with hilar occlusion resulted in complete lower pole loss at 4 weeks. CONCLUSIONS: In the porcine model renal radiofrequency thermal ablation creates rapid and completely devitalized lesions of consistent size and shape. Hilar occlusion may result in slightly larger lesions but risks damage to the whole renal unit.

Animals↗
PubMed2001

Correlation of gene expression of ten drug efflux proteins of the ATP-binding cassette transporter family in normal human jejunum and in human intestinal epithelial Caco-2 cell monolayers.

This investigation describes the expression and interindividual variability in transcript levels of multiple drug efflux systems in the human jejunum and compares the expression profiles in these cells with that of the commonly used Caco-2 cell drug absorption model. Transcript levels of ten-drug efflux proteins of the ATP-binding cassette (ABC) transporter family [MDR1, MDR3, ABCB5, MRP1-6, and breast cancer resistance protein (BCRP)], lung resistance-related protein (LRP), and CYP3A4 were determined using quantitative polymerase chain reaction in jejunal biopsies from 13 healthy human subjects and in Caco-2 cells. All genes except ABCB5 were expressed, and transcript levels varied between individuals only by a factor of 2 to 3. Surprisingly, BCRP and MRP2 transcripts were more abundant in jejunum than MDR1 transcripts. Jejunal transcript levels of the different ABC transporters spanned a range of three log units with the rank order: BCRP approximately MRP2 > MDR1 approximately MRP3 approximately MRP6 approximately MRP5 approximately MRP1 > MRP4 > MDR3. Furthermore, transcript levels of 9 of 10 ABC transporters correlated well between jejunum and Caco-2 cells (r2 = 0.90). However, BCRP exhibited a 100-fold lower transcript level in Caco-2 cells compared with jejunum. Thus, the expression of a number of efflux protein transcripts in jejunum are equal to, or even higher than, that of MDR1, suggesting that the roles of these proteins (in particular BCRP and MRP2) in intestinal drug efflux have been underestimated. Also, we tentatively conclude that the Caco-2 cell line is a useful model of jejunal drug efflux, if the low expression of BCRP is taken into account.

ATP-Binding Cassette Transporters↗