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L Svensson

Publications and source records attributed to L Svensson.

At least 19 recordsLinked to original sources

Association between interval between call for ambulance and return of spontaneous circulation and survival in out-of-hospital cardiac arrest.

AIM: To describe the association between the interval between the call for ambulance and return of spontaneous circulation (ROSC) and survival in out-of-hospital cardiac arrest. PATIENTS: All patients suffering an out-of-hospital cardiac arrest in whom cardiopulmonary resuscitation (CPR) was started, included in the Swedish Cardiac Arrest Registry (SCAR) for whom information about the time of calling for an ambulance and the time of ROSC was available. RESULTS: Among 26,192 patients who were included in SCAR and were not witnessed by the ambulance crew, information about the time of call for an ambulance and the time of ROSC was available in 4847 patients (19%). There was a very strong relationship between the interval between call for an ambulance and ROSC and survival to one month. If the interval was less than or equal to 5 min, 47% survived to one month. If the interval exceeded 30 min, only 5% (n = 35) survived to one month. The vast majority of the latter survivors had a shockable rhythm either on admission of the rescue team or at some time during resuscitation. CONCLUSION: Among patients who have ROSC after an out-of-hospital cardiac arrest, there is a very strong association between the interval between the call for ambulance and ROSC and survival to one month. However, even if this delay is very long (> 30 min after calling for an ambulance), a small percentage will ultimately survive; they are mainly patients who at some time during resuscitation have a shockable rhythm. The overall percentage of patients for whom CPR continued for more than 30 min who are alive one month later can be assumed to be extremely low.

Aged↗

Major differences in 1-month survival between hospitals in Sweden among initial survivors of out-of-hospital cardiac arrest.

AIM: To explore the rate of survival to hospital discharge among patients who were brought to hospital alive after an out-of-hospital cardiac arrest in different hospitals in Sweden. PATIENTS AND METHODS: All patients who had suffered an out-of-hospital cardiac arrest which was not witnessed by the ambulance crew, in whom cardiopulmonary resuscitation (CPR) was started and who had a palpable pulse on admission to hospital were evaluated for inclusion. Each participating ambulance organisation and its corresponding hospital(s) required at least 50 patients fulfilling these criteria. RESULTS: Three thousand eight hundred and fifty three patients who were brought to hospital by 21 different ambulance organisations fulfilled the inclusion criteria. The number of patients rescued by each ambulance organisation varied between 55 and 900. The survival rate, defined as alive 1 month after cardiac arrest, varied from 14% to 42%. When correcting for dissimilarities in characteristics and factors of the resuscitation, the adjusted odds ratio for survival to 1 month among patients brought to hospital alive in the three ambulance organisations with the highest survival versus the three with the lowest survival was 2.63 (95% CI: 1.77-3.88). CONCLUSION: There is a marked variability between hospitals in the rate of 1-month survival among patients who were alive on hospital admission after an out-of-hospital cardiac arrest. One possible contributory factor is the standard of post-resuscitation care.

Aged↗

Reduction in morbidity of rotavirus induced diarrhoea in mice by yeast produced monovalent llama-derived antibody fragments.

Apart from the use of oral rehydration solution, there are currently no treatment modalities for rotavirus induced diarrhoea, which is particularly relevant to developing countries. Fragments derived from llama heavy chain antibodies were previously shown to be highly stable, efficiently produced in yeast and exhibiting high epitope specific affinity. We now aim to demonstrate that these antibody fragments are capable of reducing morbidity of rotavirus induced diarrhoea. Here we show the isolation of rotavirus specific antibody fragments and their capability of reducing the morbidity of rotavirus induced diarrhoea in vivo in mice. They could provide a treatment modality for the moderation of human rotavirus infections having a significant impact on the course of an often fatal childhood disease.

Animals↗

Reduced cholesterol accumulation by leptin deficient (ob/ob) mouse macrophages.

OBJECTIVE: Although presenting many aspects of the metabolic syndrome, leptin deficient (ob/ob) mice do not spontaneously develop atherosclerosis. To examine the role of leptin in foam cell formation we analyzed ob/ob leukocyte inflammation markers and macrophage cholesterol accumulation. METHODS: Resident and thioglycollate (TG) elicited peritoneal cells of ob/ob and wildtype mice were studied. Activation markers, scavenger receptors (SR) and cholesterol accumulation were analyzed using flow cytometry and Taqman analysis. Cytokines, haptoglobin, adiponectin and amyloid A levels were analyzed with ELISA. RESULTS: Macrophages of ob/ob mice had reduced expression of MHC class II, CD11b, CD40, SR-A and CD36 and reduced cholesterol accumulation in vitro. Plasma haptoglobin was increased and T-cell IFNgamma was reduced in ob/ob mice. Peritoneal TG instillation induced an unexpectedly weak inflammatory response in ob/ob mice. CONCLUSIONS: The ob/ob mice had a reduced inflammatory response and reduced macrophage cholesterol accumulation in vitro. The data suggest decreased foam cell formation and atherosclerosis development in ob/ob mice.

Adiponectin↗

Steroid-free immunosuppression in kidney transplant recipients and prograf monotherapy: an interim analysis of a prospective multicenter trial.

This report described an interim analysis of a investigator-driven multicenter trial in renal transplant recipients: the Prospective Quality of life Renal Transplantation Switch Study; Tacrolimus-based immunosuppression ("PQRST study"). Patients included in the trial initially treated with cyclosporine-based immunosuppression after renal transplantation who experienced side effects, such as hypertension, hyperlipidemia, hypertrichosis, or other adverse reactions, were converted to a tacrolimus-based immunosuppressive regimen (n = 31). Steroids were subsequently discontinued between 3 and 6 months after the conversion. As of today 19/31 (50%) patients have been successfully weaned off steroids with the remaining patients in this process. In this interim analysis, with a follow-up ranging from 1 to 18 months both patient and graft survivals were 100%. No patient experienced an acute rejection episode; none of the grafts were lost. Blood pressure decreased in 22/31 (71%) of the patients. No patient developed de novo diabetes or other serious side effect related to the conversion. Three patients were withdrawn from the trial because of side effects: bleeding, depression, and proteinuria. However, none of these adverse events were felt to be directly related to the change of the immunosuppressive regimen to tacrolimus monotherapy. In conclusion, conversion from cyclosporine to tacrolimus-based therapy was safe and well tolerated; it may improve the cardiovascular risk profile after kidney transplantation.

Adult↗

Can dynamic susceptibility contrast magnetic resonance imaging replace single-photon emission computed tomography in the diagnosis of patients with Alzheimer's disease? A pilot study.

PURPOSE: To compare single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) in a cohort of patients examined for suspected dementia, including patients with no objective cognitive impairment (control group), mild cognitive impairment (MCI), and Alzheimer's disease (AD). MATERIAL AND METHODS: Twenty-four patients, eight with AD, 10 with MCI, and six controls were investigated with SPECT using 99mTc-hexamethylpropyleneamine oxime (HMPAO) and dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with gadobutrol. Three observers performed a visual interpretation of the SPECT and MR images using a four-point visual scale. RESULTS: SPECT was superior to DSC-MRI in differentiating normal from pathological. All three observers showed statistically significant results in discriminating between the control group, AD, and MCI by SPECT, with a P value of 0.0006, 0.04, and 0.01 for each observer. The statistical results were not significant for MR (P values 0.8, 0.1, and 0.2, respectively). CONCLUSION: DSC-MRI could not replace SPECT in the diagnosis of patients with Alzheimer's disease. Several patient- and method-related improvements should be made before this method can be recommended for clinical practice.

Aged↗

Characteristics and outcome amongst young adults suffering from out-of-hospital cardiac arrest in whom cardiopulmonary resuscitation is attempted.

OBJECTIVES: Amongst patients suffering from out-of-hospital cardiac arrest, young adults represent a minority. However, these victims suffer from the catastrophe when they are in a very active phase of life and have a long life expectancy. This survey aims to describe young adults in Sweden who suffer from out-of-hospital cardiac arrest and in whom cardiopulmonary resuscitation (CPR) is attempted in terms of characteristics and outcome. DESIGN: Prospective and descriptive design. SUBJECTS AND METHODS: Young adults (18-35 years) who suffered from out-of-hospital cardiac arrest in whom CPR was attempted and who were included in the Swedish Cardiac Arrest Registry between 1990 and 2004. MAIN OUTCOME MEASURES: Survival to 1 month. RESULTS: In all, 1105 young adults (3.1% of all the patients in the registry) were included, of which 29% were females, 51% were nonwitnessed and 15% had a cardiac aetiology. Only 17% were found in ventricular fibrillation, 53% received bystander CPR. The overall survival to 1 month was 6.3%. High survival was found amongst patients found in ventricular fibrillation (20.8%) and those with a cardiac aetiology (14.8%). Ventricular fibrillation at the arrival of the rescue team remained an independent predictor of an increased chance of survival (odds ratio: 7.43; 95% confidence interval: 3.44-16.65). CONCLUSION: Amongst young adults suffering from out-of-hospital cardiac arrest and in whom CPR was attempted, a minority survived to 1 month. Subgroups with a higher survival could be defined (patients found in ventricular fibrillation and patients in whom there was a cardiac aetiology). However, only one independent predictor of an increased chance of survival could be demonstrated, i.e. ventricular fibrillation at the arrival of the rescue team.

Adolescent↗

Minimized weight gain between hemodialysis contributes to a reduced risk of death.

UNLABELLED: The risk of death is higher in dialysis patients compared to age matched healthy subjects, the main reason being cardiovascular. This prospective study investigated if the extent of ultrafiltration was of importance for the outcome. MATERIAL AND METHODS: 88 hemodialysis patients were included and followed prospectively. The outcome was registered in regard to death, acute myocardial infarction or coronary vascular intervention. The extent of ultrafiltration needed at dialysis was calculated as a mean during the observation period as were other variables. The mean extent of ultrafiltration was compared for patients who had survived without end-points (group 1, n=53) versus those who reached any end-point during the period (group 2, n=35). RESULTS: In total, 40% of the patients reached end-point during the observation period. There was no difference at baseline between the groups in regard to age, prevalence of diabetes mellitus or history of previous cardiovascular disease, KT/V, residual renal function ultrafiltration need, C-reactive protein, s-albumin, cholesterol, LDL-cholesterol, HDL-cholesterol, appetite or wellbeing, while triglyceride was lower in group 2 (p=0.035). The observation period for group 1 was at a mean 24.7 months (SD13.1) and for those in group 2 at a mean 13.8 (+/-11.7 months, p<0.001). Patients representing group 1 at 24 and 30 months had less need of ultrafiltration than those in group 2. Thus, the need of ultrafiltration was about 27% lower at 24 months (for 29 persons in group 1: 3.63+/-1.93 weight% versus 4.97+/-1.70 weight% for 9 patients from group 2, p=0.046) and 46% at 30 months (for 18 from group 1: 3.48+/-1.95 versus 6.45+/-1.55 for 3 from group 2, p=0.030). C-reactive protein did not differ significantly between the groups during the period. CONCLUSION: After a prolonged period of 24 months the extent of ultrafiltration need seems to be important for the outcome of the patients. Thereby those with higher need of ultrafiltration had worse prognosis. It seems important to motivate patients to reduce the extent of fluid intake between dialysis to prolong survival.

Adult↗

Lymph circulation in the breast after radiotherapy and breast conservation.

The aim of this study was to investigate the breast lymph circulation and skin blood circulation after radiotherapy and breast conservation. In 23 patients who had undergone lumpectomy for breast cancer (mean age 58 years, range 44-75) and 12 patients with lumpectomy for benign lesions (mean age 51 years, range 33-72), lymph circulation in the breast was measured by 99mTc-nanocolloid clearance and skin circulation by Laser Doppler Fluxmetry (LDF). Measurements were made 2-5 years after radiotherapy (50 Gy) in the former group and at a corresponding time in the latter. The lymph circulation was measured 2 cm above and medial or lateral to the areolar border in the quadrant not operated on for carcinoma. Skin circulation was measured at corresponding sites. The lymph circulation expressed as the ratio of 99mTc-nanocolloid clearance in the operated irradiated to that in the non-operated (radiation 2-4 Gy) breast was 2.33 (2.66) (median, interquartile range) (p value 0.01) and the skin circulation ratio over the corresponding area was 0.92 (0.21). Corresponding ratios in the non-radiotherapy group were 2.07 (1.96) (p value 0.03) and 1.04 (0.18) respectively. Compared with the control breast (i.e., the non-operated non-irradiated breast), there was a 4-fold increase in lymph flow in the operated, irradiated breast, a 2.5-fold increase in the contralateral non-operated (2-4 Gy) breast and a 1.5-fold increase in the operated non-irradiated breast. Radiotherapy after breast conservation surgery leads to increased long-term changes in basal lymph circulation and smaller increases in lymph flow in the contralateral breast receiving 2-4 Gy and after surgery. If maximal lymph transport capacity is unchanged, edema may be more likely in this circumstance of reduced lymphatic transport reserve.

Adult↗

Are predictors for myocardial infarction the same for women and men when evaluated prior to hospital admission?

AIM: To describe predictors of myocardial infarction prior to hospital admission in women and men among patients with a suspected acute coronary syndrome without ST-elevation. DESIGN: Prospective observational study in Stockholm and Göteborg, Sweden. RESULTS: Of 433 patients who did fulfill the inclusion criteria 45% were women. Fewer women (17%) than men (26%) developed acute myocardial infarction (AMI) (p=0.054), particularly among patients with initial ST-depression, in whom AMI was developed in 22% of women and 54% of men (p = 0.001). Predictors for infarct development in women were: a history of AMI and advanced age. Among men they were: initial ST-depression or a Q-wave on ECG and elevation of biochemical markers (both recorded on admission of the ambulance crew). There was a significant interaction between gender and the influence of ST-depression on the risk for development of myocardial infarction (p < 0.05). CONCLUSION: Among patients transported with ambulance due to a suspected acute coronary syndrome and no ST-elevation fewer women than men seem to develop AMI particularly among patients with ST-depression. These results suggest that early prediction of myocardial infarction might differ between women and men with acute chest pain.

Aged↗

Characteristics and outcome among children suffering from out of hospital cardiac arrest in Sweden.

AIM: To evaluate the characteristics, outcome and prognostic factors among children suffering from out of hospital cardiac arrest in Sweden. METHODS: Patients aged below 18 years suffering from out of hospital cardiac arrest which were not crew witnessed and included in the Swedish cardiac arrest registry were included in the survey. This survey included the period 1990-2001 and 60 ambulance organisations covering 85% of the Swedish population (8 million inhabitants). RESULTS: In all 457 children participated in the survey of which 32% were bystander witnessed and 68% received bystander CPR. Ventricular fibrillation was found in 6% of the cases. The overall survival to 1 month was 4%. The aetiology was sudden infant death syndrome in 34% and cardiac in 11%. When in a multivariate analysis considering age, sex, witnessed status, bystander CPR, initial rhythm, aetiology and the interval between call for, and arrival of, the ambulance and place of arrest only one appeared as an independent predictor of an increased chance of surviving cardiac arrest occurring outside home (adjusted odds ratio 8.7; 95% CL 2.2-58.1). CONCLUSION: Among children suffering from out of hospital cardiac arrest in Sweden that were not crew witnessed, the overall survival is low (4%). The chance of survival appears to be markedly increased if the arrest occurs outside the patients home compared with at home. No other strong predictors for an increased chance of survival could be demonstrated.

Child↗

Standard orientation of the pelvis: validation on a model and ten patients.

PURPOSE: To validate an image post-processing method for re-orienting the pelvis in CT volumes to a standardized orientation in a model and in 10 patients. MATERIAL AND METHODS: Twenty-four CT volumes of a pelvic model and 10 pairs of postoperative total hip arthroplasty (THA) patient CT scans were rotated to a defined pelvic standard orientation and the rotation was recorded. For precision, a test-retest procedure was used. For accuracy, three exactly represented coordinate points were used. For clinical application, the standard orientation was used for calculating the direction of acetabular cup migration from a previous model study. RESULTS: Precision of pelvic standard orientation, calculated as maximal directional error, was better than 1 degrees in the model study and better than 1.5 degrees in the patient study. Accuracy, expressed as angle between ideal and measured coordinate axes, was 0.1 degrees for x, y, z axes. No measurable systematic errors were found. When applied to acetabular cup migration in the model, standardization of pelvic orientation had no significant effect on the measurements. CONCLUSION: Reorienting the pelvis during image post-processing was shown to be accurate. It enables measurements relative to the pelvis and minimizes the dependency of patient positioning.

Adult↗

Difference in survival after out-of-hospital cardiac arrest between the two largest cities in Sweden: a matter of time?

BACKGROUND: Dramatic differences in survival after out-of-hospital cardiac arrests (OHCA) reported from different geographical locations require analysis. We therefore compared patients with OHCA in the two largest cities in Sweden with regard to various factors at resuscitation and outcome. SETTING: All patients suffering an OHCA in Stockholm and Goteborg between 1 January 2000 and 30 June 2001, in whom cardiopulmonary resuscitation (CPR) was attempted were included in this retrospective analysis. RESULTS: All together, 969 OHCA in Stockholm and 398 in Goteborg were registered during the 18-month study period. There were no differences in terms of age, gender, and percentage of witnessed cases or percentage of patients who had received bystander CPR. However, the percentage of patients with ventricular fibrillation (VF) at arrival of the ambulance crew was 18% in Stockholm versus 31% in Goteborg (P <0.0001). The percentage of patients who were alive 1 month after cardiac arrest was 2.5% in Stockholm versus 6.8% in Goteborg (P=0.0008). Various time intervals such as cardiac arrest to calling for an ambulance, cardiac arrest to the start of CPR and calling for an ambulance to its arrival were all significantly longer in Stockholm than in Goteborg. CONCLUSION: Survival was almost three times higher in Goteborg than in Stockholm amongst patients suffering an OHCA. This is primarily explained by a higher occurrence of VF at the time of arrival of the ambulance crew, which in turn probably is explained by shorter delays in Goteborg. The reason for the difference in time intervals is most likely multifactorial, with a significantly higher ambulance density in Goteborg as one possible explanation.

Age Distribution↗

Novel glycolipid variations revealed by monoclonal antibody immunochemical analysis of weak ABO subgroups of A.

BACKGROUND AND OBJECTIVES: The chemical basis of the subgroups of A is largely unknown. We used thin-layer chromatography immunochemical staining techniques together with a range of characterized monoclonal reagents to analyse glycolipids isolated from a variety of weak subgroups. MATERIALS AND METHODS: Glycolipids isolated from red cells collected from nine genetically defined individuals of the rare subgroups of A, including a novel A(3) allele (A(2) 539G>A) not described previously, were subjected to a highly sensitive thin-layer chromatographic immunochemical analysis. RESULTS: Semicharacterized monoclonal antibodies revealed that, in addition to the expected quantitative differences between common phenotypes and the weak subgroups, qualitative glycolipid differences (or at least an apparent qualitative basis), caused by major changes in the ratios of different structures exist. Specifically it was found that the weakest A-expressing samples (A(el) phenotype) appeared to express an unusual A structure in the 8-12 sugar region. Variable expression of several structures in one of the A weak samples were suggestive of novel blood group A structures. CONCLUSIONS: Although no structural characterization could be undertaken, the results are clearly indicative that the variant glycosyltransferases of the rare ABO subgroups are not only inefficient, but they may potentially synthesize novel ABO structures.

ABO Blood-Group System↗

Acute glomerulonephritis associated with streptococcus pyogenes with concomitant spread of streptococcus constellatus in four rural families.

We studied history, renal histopathology and microbiology of an epidemic of acute glomerulonephritis associated with throat infections and uncommon culture results in four neighbour families. A 40-year-old man (index patient) was referred to a university hospital for dialysis and kidney biopsy due to a suspected acute glomerulonephritis. An acute tonsillitis had preceded the condition. Penicillin treatment had been started four days before the discovery of renal failure. Throat swabs were positive for beta-hemolytic streptococci, group C (GCS). GCS were also found in throat cultures from his wife and two of their children. The bacteria were typed as Streptococcus constellatus. A third child had S. constellatus expressing Lancefield antigen group G. A neighbour and two of his children fell ill the following week with renal involvement. Throat swabs from both these children were positive for S. constellatus. His third child had erythema multiforme and S. constellatus in the throat while a fourth child had beta-hemolytic streptococci group A; Streptococcus pyogenes. Kidney biopsies on the index patient and his neighbour showed an acute diffuse prolipherative glomerulonephritis compatible with acute post-streptococcal nephritis and microbiological analysis of renal tissue revealed in both cases S. pyogenes and S. constellatus. The families had had much contact and had consumed unpasteurized milk from our index patient's farm. In four of seven persons in two additional neighbouring families S. constellatus was found in throat swabs during the same month while two persons carried Streptococcus anginosus expressing the Lancefield C antigen. In conclusion spread of S. constellatus coincided with the occurrence of four cases of acute glomerulonephritis. The two biopsied patients had both S. pyogenes and S. constellatus present in renal tissue. The epidemic either suggested that the outbreak of glomerulonephritis was due to S. pyogenes but coincided with the transmission and colonization of S. constellatus or that the S. constellatus strains were highly pathogenic or nephritogenic and that this organism can be transmitted in such cases.

Acute Disease↗

Prognostic value of biochemical markers, 12-lead ECG and patient characteristics amongst patients calling for an ambulance due to a suspected acute coronary syndrome.

OBJECTIVES: To evaluate whether a 12-lead ECG, together with a multi-marker strategy that used point-of-care measurements of myoglobin, creatine kinase (CK-MB) and troponin I, was able to predict patients at short- and long-term risk of death, when simultaneously considering age, gender, previous history, symptoms and clinical findings on arrival of the ambulance. DESIGN: Prospective observational study. SETTING AND SUBJECTS: Consecutive patients (n=511) in ambulances in Stockholm and Göteborg in Sweden who called for an ambulance due to chest pain or other symptoms raising a suspicion of acute coronary syndrome. INTERVENTION: In almost all patients, a diagnostic ECG, patient baseline characteristics and measurements of CK-MB, troponin I and myoglobin were recorded. RESULTS: In univariate analysis, the highest 30-day mortality (17%) was found amongst patients with the combination of ECG signs of myocardial ischaemia and the elevation of any biochemical marker. The highest 1-year mortality (20%) was found amongst patients with ECG signs of myocardial ischaemia and the elevation of any biochemical marker. Increasing age (RR 1.07; 95 CI 1.02-1.13) lack of symptoms of chest pain and a previous history of hypertension (3.02; 1.08-8.79) were independent predictors of 30-day mortality. Myoglobin was the only biochemical marker independently associated with 30-day mortality (6.66; 1.83-22.3). Increasing age (1.11; 1.06-1.16), previous history of diabetes (3.42; 1.41-8.25) heart failure (2.64; 1.26-5.52) and other symptoms than chest pain and dyspnoea (5.23; 2.14-12.76) were independent predictors of 1-year mortality. In many of the variables the confidence limits were wide. CONCLUSION: Amongst patients with a clinical suspicion of acute coronary syndrome, those with the combination of ECG signs of myocardial ischaemia and the elevation of any biochemical marker on arrival of the ambulance form a group with a particularly high risk of death. However, age as well as aspects of clinical history and type of symptoms independently contribute to prognostic information.

Acute Disease↗

Tendon injury and repair after core biopsies in chronic Achilles tendinosis evaluated by serial magnetic resonance imaging.

OBJECTIVE: To evaluate the morphological response and healing process after transverse ultrasound guided core biopsies in chronic Achilles tendinosis using serial magnetic resonance imaging (MRI) over a period of one year. METHODS: The study included 10 patients. Six had five transverse core biopsies and were longitudinally evaluated by MRI before the biopsies and then after one week, three months, seven months, and one year. These patients started a three month eccentric training programme one to two weeks after the biopsy. Four "non-biopsied" and untreated patients were used for comparison. The clinical outcome was categorised according to the level of pain and performance. RESULTS: The MRI one week after the biopsies showed an increase in tendon volume (T1-WI) and mean signal intensity (PD-WI) of 29% and 30% (p = 0.04). During follow up, tendon volume and mean signal intensity gradually decreased. One year after the biopsy, the tendon volume had decreased by 20% and the intratendinous signal by 28% compared with the index MRI (p = 0.04). The untreated patients showed an increase in both tendon volume (39%, p = 0.06) and intratendinous signal (37%, p = 0.14) at the one year follow up. After one year, pain and performance had improved in the treated patients but not the untreated patients. CONCLUSION: Five transverse ultrasound guided core biopsies induced a lesion in the diseased Achilles tendon. Alterations during healing such as tendon size and intratendinous signal intensity could be evaluated by MRI. The tendon alterations had decreased one year after the core biopsies.

Achilles Tendon↗

Serotonin and vasoactive intestinal peptide antagonists attenuate rotavirus diarrhoea.

BACKGROUND AND AIMS: The mechanisms underlying intestinal secretion in rotavirus diarrhoea remain to be established. We previously reported that rotavirus evokes intestinal fluid and electrolyte secretion by activation of the enteric nervous system. We now report that antagonists for the 5-hydroxytryptamine 3 receptor (5-HT(3)) and vasoactive intestinal peptide (VIP) receptor, but not antagonists for 5-hydroxytryptamine 4 receptor or the muscarinic receptor, attenuate rotavirus induced diarrhoea. METHODS: Neurotransmitter antagonists were administered to wild-type or neurokinin 1 receptor knockout mice infected with homologous (EDIM) or heterologous (RRV) rotavirus. RESULTS: While RRV infected mice had diarrhoea for 3.3 (0.2) days (95% confidence interval (CI) 3.04-3.56), the 5-HT(3) receptor antagonist (granisetron) and the VIP receptor antagonist (4Cl-D-Phe(6),Leu(17))-VIP both reduced the total number of days of RRV induced diarrhoea to 2.1 (0.3) (95% CI 1.31-2.9) (p<0.01). EDIM infected mice treated with granisetron had a significantly shorter duration of diarrhoea (5.6 (0.4) days) compared with untreated mice (8.0 (0.4) days; p<0.01). Experiments with neurokinin 1 receptor antagonists suggest that this receptor may possibly be involved in the secretory response to rotavirus. On the other hand, rotavirus diarrhoea was not attenuated in the neurokinin 1 receptor knockout mice. CONCLUSIONS: Our results suggest that the neurotransmitters serotonin and VIP are involved in rotavirus diarrhoea; observations that could imply new principles for treatment of this disease with significant global impact.

Animals↗