Real-world accuracy of computed tomography in patients admitted with small bowel obstruction: a multicentre prospective cohort study.

PURPOSE: Small bowel obstruction (SBO) is a common surgical emergency. Previous studies have shown the value computed tomography (CT) scanning in both confirming this diagnosis and identifying indications for urgent surgical intervention, such as strangulated bowel or closed loop obstructions. However, most of the literature is based on retrospective expert review of previous imaging and little data regarding the real-time accuracy of CT reporting is available. Here, we investigated the real-world accuracy of CT reporting in patients admitted with SBO. METHODS: This was a multicentre prospective study including consecutive patients admitted with SBO. The primary outcomes were the sensitivity and specificity of CT scanning for bowel obstruction with ischaemia and closed loop obstruction. Data were retrieved from the original CT reports written by on-call radiologists and compared with operative findings. RESULTS: One hundred seventy-six patients were included, all of whom underwent CT scanning with intravenous contrast followed by operative management of SBO. Bowel obstruction with ischaemia was noted in 20 patients, with a sensitivity and specificity of CT scanning of 40.0% and 85.5%, respectively. Closed loop obstructions were noted in 26 patients, with a sensitivity and specificity of CT scanning of 23.1% and 98.0%, respectively. CONCLUSIONS: The real-world accuracy of CT scanning appears to be lower than previously reported in the literature. Strategies to address this could include the development of standardised reporting schemas and to increase the surgeon's own familiarity with relevant CT features in patients admitted with SBO.

Management and short-term outcomes of patients with small bowel obstruction in Denmark: a multicentre prospective cohort study.

AIMS: The optimal management of small bowel obstruction (SBO) remains a matter of debate and treatment varies internationally. In Denmark, a more surgically aggressive strategy has traditionally been used, but to what extent patient outcomes differ from international reports is unknown. This study aimed to describe the current management and outcomes of patients admitted with SBO in Denmark. METHODS: This was a prospective cohort study conducted at six acute hospitals in Denmark over a 4-month period. Patients aged ≥ 18 years with a clinical or radiological diagnosis of SBO were eligible. Primary outcomes were 30 day morbidity and mortality rates. RESULTS: 316 patients were included during the study period. The median age was 72 years and 56% were female. Diagnosis was made by computed tomography (CT) in 313 patients (99.1%), with the remaining three diagnosed clinically. Non-operative management was the initial strategy in 152 patients (48.1%) and successful in 119 (78.3%). Urgent surgery was performed in the remaining 164 (51.9%), with a laparoscopic approach used in 84 patients (51.2%). The entire cohort had a 30 day mortality rate of 7.3% and a 30 day morbidity rate of 17.1%. CONCLUSIONS: The management of SBO in Denmark differs markedly to previous international reports, with an almost ubiquitous use of CT for diagnosis and a high proportion of patients undergoing urgent surgery. Despite higher rates of surgery, patient outcomes are broadly similar to reports of more conservative strategies, perhaps due to a reduction in delayed operations. TRIAL REGISTRATION: Trial registration number: NCT04750811. Trial registration date: 11/02/2021.

Natural killer cells determine development of allergen-induced eosinophilic airway inflammation in mice.

The earliest contact between antigen and the innate immune system is thought to direct the subsequent antigen-specific T cell response. We hypothesized that cells of the innate immune system, such as natural killer (NK) cells, NK1.1(+) T cells (NKT cells), and gamma/delta T cells, may regulate the development of allergic airway disease. We demonstrate here that depletion of NK1.1(+) cells (NK cells and NKT cells) before immunization inhibits pulmonary eosinophil and CD3(+) T cell infiltration as well as increased levels of interleukin (IL)-4, IL-5, and IL-12 in bronchoalveolar lavage fluid in a murine model of allergic asthma. Moreover, systemic allergen-specific immunoglobulin (Ig)E and IgG2a levels and the number of IL-4 and interferon gamma-producing splenic cells were diminished in mice depleted of NK1.1(+) cells before the priming regime. Depletion of NK1.1(+) cells during the challenge period only did not influence pulmonary eosinophilic inflammation. CD1d1 mutant mice, deficient in NKT cells but with normal NK cells, developed lung tissue eosinophilia and allergen-specific IgE levels not different from those observed in wild-type mice. Mice deficient in gamma/delta T cells showed a mild attenuation of lung tissue eosinophilia in this model. Taken together, these findings suggest a critical role of NK cells, but not of NKT cells, for the development of allergen-induced airway inflammation, and that this effect of NK cells is exerted during the immunization. If translatable to humans, these data suggest that NK cells may be critically important for deciding whether allergic eosinophilic airway disease will develop. These observations are also compatible with a pathogenic role for the increased NK cell activity observed in human asthma.

The coordinated action of CC chemokines in the lung orchestrates allergic inflammation and airway hyperresponsiveness.

The complex pathophysiology of lung allergic inflammation and bronchial hyperresponsiveness (BHR) that characterize asthma is achieved by the regulated accumulation and activation of different leukocyte subsets in the lung. The development and maintenance of these processes correlate with the coordinated production of chemokines. Here, we have assessed the role that different chemokines play in lung allergic inflammation and BHR by blocking their activities in vivo. Our results show that blockage of each one of these chemokines reduces both lung leukocyte infiltration and BHR in a substantially different way. Thus, eotaxin neutralization reduces specifically BHR and lung eosinophilia transiently after each antigen exposure. Monocyte chemoattractant protein (MCP)-5 neutralization abolishes BHR not by affecting the accumulation of inflammatory leukocytes in the airways, but rather by altering the trafficking of the eosinophils and other leukocytes through the lung interstitium. Neutralization of RANTES (regulated upon activation, normal T cell expressed and secreted) receptor(s) with a receptor antagonist decreases significantly lymphocyte and eosinophil infiltration as well as mRNA expression of eotaxin and RANTES. In contrast, neutralization of one of the ligands for RANTES receptors, macrophage-inflammatory protein 1alpha, reduces only slightly lung eosinophilia and BHR. Finally, MCP-1 neutralization diminishes drastically BHR and inflammation, and this correlates with a pronounced decrease in monocyte- and lymphocyte-derived inflammatory mediators. These results suggest that different chemokines activate different cellular and molecular pathways that in a coordinated fashion contribute to the complex pathophysiology of asthma, and that their individual blockage results in intervention at different levels of these processes.

Crucial role of the interleukin 1 receptor family member T1/ST2 in T helper cell type 2-mediated lung mucosal immune responses.

T1/ST2 is an orphan receptor of unknown function that is expressed on the surface of murine T helper cell type 2 (Th2), but not Th1 effector cells. In vitro blockade of T1/ST2 signaling with an immunoglobulin (Ig) fusion protein suppresses both differentiation to and activation of Th2, but not Th1 effector populations. In a nascent Th2-dominated response, anti-T1/ST2 monoclonal antibody (mAb) inhibited eosinophil infiltration, interleukin 5 secretion, and IgE production. To determine if these effects were mediated by a direct effect on Th2 cells, we next used a murine adoptive transfer model of Th1- and Th2-mediated lung mucosal immune responses. Administration of either T1/ST2 mAb or T1/ST2-Ig abrogated Th2 cytokine production in vivo and the induction of an eosinophilic inflammatory response, but failed to modify Th1-mediated inflammation. Taken together, our data demonstrate an important role of T1/ST2 in Th2-mediated inflammatory responses and suggest that T1/ST2 may prove to be a novel target for the selective suppression of Th2 immune responses.

Allergic rhinitis--a total genome-scan for susceptibility genes suggests a locus on chromosome 4q24-q27.

Allergic rhinitis is a common disease of complex inheritance and is characterised by mucosal inflammation caused by allergen exposure. The genetics of closely related phenotypes such as asthma, atopy and to some extend atopic dermatitis has attracted attention in recent years. Genetic reports of allergic rhinitis on the contrary have as yet been most sparse. To identify candidate regions holding genes for allergic rhinitis we performed a total genome-scan on affected sib-pair families. From 100 Danish sib-pair families selected for allergy, families containing sib-pairs matching a phenotype definition of both clinical allergic rhinitis and confirmed specific allergy were chosen. Thirty-three affected sib-pair families qualified for the scan that was undertaken using 446 microsatellite markers. Non-parametric linkage results were obtained from MAPMAKER/SIBS computer program. The study revealed one major candidate region on chromosome 4q24-q27 (LOD=2.83) and eight minor candidate regions 2q12-q33, 3q13, 4p15-q12, 5q13-q15, 6p24-p23, 12p13, 22q13, and Xp21 (LOD=1.04-1.63) likely to contain susceptibility genes for allergic rhinitis. Our findings did not support a previous report of linkage of allergic rhinitis to chromosome 12q14-q24 but they added positive evidence to the asthma and atopy candidate regions 2q33 and 6p23. Further identification of the specific genes involved in allergic rhinitis will give opportunities for improved diagnosis and treatment.

Purification of human blood basophils by negative selection using immunomagnetic beads.

A simple and rapid method for isolating highly purified and functionally intact basophils from normal human blood is described. Blood from healthy volunteers was centrifuged through a two layer Percoll density gradient. The majority of the basophils were recovered between Percoll layers with densities of 1.070 and 1.080, constituting 45.6% of total leukocytes. Lymphocytes, monocytes and neutrophils were extracted from this fraction using a panel of mabs in a direct or indirect selection procedure using immunomagnetic beads (Dynabeads) coated with sheep anti-mouse IgG. These negative immunoselection procedures produced a high yield of basophils with a mean purity of 97.8% (range 93.0-99.5%) and 97.0% (range 96.2-99.0%) using the direct and indirect method, respectively. The cells isolated by this method are viable, release histamine to various stimuli in a normal manner, and appear morphologically normal in transmission electron microscopy.

Relation between attempted suicide and suicide rates among young people in Europe.

STUDY OBJECTIVE: To determine if there are associations between rates of suicide and attempted suicide in 15-24 year olds in different countries in Europe. DESIGN: Attempted suicide rates were based on data collected in centres in Europe between 1989 and 1992 as part of the WHO/EURO Multicentre Study of Parasuicide. Comparison was made with both national suicide rates and local suicide rates for the areas in which the attempted suicide monitoring centres are based. SETTING: 15 centres in 13 European countries. PATIENTS: Young people aged 15-24 years who had taken overdoses or deliberately injured themselves and been identified in health care facilities. MAIN RESULTS: There were positive correlations (Spearman rank order) between rates of attempted suicide and suicide rates in both sexes. The correlations only reached statistical significance for male subjects: regional suicide rates, r = 0.65, p < 0.02; national suicide rates, r = 0.55, p < 0.02. CONCLUSIONS: Rates of attempted suicide and suicide in the young covary. The recent increase in attempted suicide rates in young male subjects in several European countries could herald a further increase in suicide rates.

Human blood eosinophils produce and secrete interleukin 4.

Interleukin 4 (Il-4) is an immunoregulatory cytokine which induces T-cell proliferation and differentiation into a Th2 phenotype, and is of particular importance for the induction of IgE synthesis. In the present study, the capability of human peripheral blood eosinophils from allergic and non-allergic donors to produce Il-4 was examined. Using reverse transcribed polymerase chain reaction (RT-PCR), it was shown that highly purified eosinophils from allergic patients express mRNA for Il-4. Resting eosinophils also gave specific immunoreactivity with anti-Il-4 antibodies, consistent with translation of Il-4 mRNA. Light and electron microscopic immunocytochemistry revealed that Il-4 was prestored in the eosinophilic granules. These results were confirmed by Il-4 specific ELISA which showed that Il-4 production could be upregulated in the eosinophils and released from the eosinophils following stimulation with the calcium ionophore A23187. These data indicate that eosinophils may be an important source of Il-4 at sites of allergic inflammation. Thus, eosinophils may act as immunomodulatory cells enhancing the allergic response through formation of Th2-cells and inducing the isotype switching to IgE in human B-cells.

The WHO-EURO Multicentre Study: risk of parasuicide and the comparability of the areas under study.

The 15 areas under study in the WHO/Euro Multicentre Study on Parasuicide vary considerably with regard to socio-economic factors, culture, life-styles, etc. In this paper, the authors discuss whether the traditional high risk factors for suicidal behavior (such as unemployment, abuse, divorce, etc.) take on different weights depending on local societal and cultural settings. Results from analyzing covariations between various background factors characteristic of the different areas under study and the frequency of attempted suicide showed weak or insignificant correlations, indicating that high-risk factors can only be identified from international pooled data with great care.

Pediatric pain management: a research-based clinical pathway.

Nurses want to provide pain management for pediatric patients, but different approaches lead to inconsistent pain management. This article presents a pediatric pain management clinical pathways developed as a result of research in the pediatric intensive care unit and based on pain management research. Using this pathway can help nurses deliver consistent pain management to pediatric patients.

Locus of control and attitudes toward large carnivores.

It has been hypothesized tha the negative attitudes toward carnivores found among rural groups is only one element embedded in a larger sociopolitical complex of disputes over resource use and rural development. Negative attitudes may reflect a protest against increased control of land use by central political authorities. In a survey among sheep farmers, wildlife managers, and research biologists in Norway we found that the sheep farmers expressed an external locus of control, indicating a belief that external forces control events, relative to the two other groups. Among sheep farmers and research biologists a positive association was found between an external locus of control and negative attitudes toward large carnivores.

Parasuicide in the county of Sør-Trøndelag, Norway. General epidemiology and psychological factors.

During the period 1 October 1988 to 31 December 1993, 2068 episodes of parasuicide involving 1543 persons were registered in the county of Sør-Trøndelag, Norway. Parasuicide rates decreased in the area compared with 1987, more for females than for males. Rates were higher for divorced females and separated males than for those of other marital statuses, but these rates were lower than previously found in the same area. The proportion of unemployed patients remained fairly stable, while the rate of unemployment increased in the general population. Compared to males, female parasuicide patients more often reported family problems and economic inactivity, and more often had been victims of violence or sexual abuse. Male parasuicide patients more often than females were living alone, were unemployed, abused alcohol, had financial problems, and had been engaged in criminal activity. Compared with older parasuicide patients, the young of both sexes were more often unemployed and abused drugs, but had less often been in contact with the health or social services. In addition, young female parasuicide patients more often had experienced family problems and suicidal behaviour among family or friends. The results were generally considered to be consistent with theories of sex role stereotypes, which emphasize expressive traits in an affiliative context for females and instrumental traits in a public or economic context for men.

Renal tubular uptake of protein: effect of pH.

The present study was performed to determine to what extent pH influences protein reabsorption in renal proximal tubule cells. Rat surface proximal tubules were microinfused in vivo with 125I-labelled albumin in buffer solutions at different pHs. Tubular uptake was determined as the difference between microinfused and urinary trichloroacetic acid-precipitable radioactivity. In separate experiments the tubular uptake was followed by electron microscope autoradiography. The results showed that the uptake at pH 4.5 and 6.0 was about 15% higher as compared to uptake at pH 7.4. Furthermore, the electron microscope autoradiography demonstrated that albumin is taken up by endocytosis at acid pH as under normal conditions.

The effects of clinical pathways for renal transplant on patient outcomes and length of stay.

OBJECTIVES: Clinical pathways have been implemented nationwide but little is understood about their effects on efficiency of care and patient outcomes. The present study examined the effects of both development and implementation of two renal transplant pathways. METHODS: Cohorts of patients at a university hospital were compared before, during, and after the development and implementation of two renal transplant clinical pathways: isolated renal transplant from cadaveric donors (n = 170) or from living donors (n = 178). Clinical pathways for cadaveric and living related donor renal transplants were developed and implemented. Hospital length of stay and complications and infections after renal transplant were determined. RESULTS: Mean length of hospital stay decreased after development and implementation of the cadaveric donor pathway (11.8 days after implementation versus 17.5 days before development). Cadaveric kidney recipients also had statistically fewer complications and infections after both guideline development and guideline implementation (57.1% before, 24.5% during, 18.5% after), but the greatest effect occurred during development. All of these findings persisted after control for demographic and comorbid factors. There were no changes in hospital stay, complications, or infections in the patients who received kidneys from living donors. CONCLUSIONS: The development and use of a clinical pathway for cadaveric donor renal transplant patients was associated with a significant decline in length of stay, complications, and infections, but much of the effect was seen during development rather than during implementation, and a closely related pathway for living related donor patients had no effect. Further understanding of what factors predict an effective pathway and what elements (ie, development or implementation) have an effect should be undertaken.

[Parasuicide in Sør-Trøndelag 1989-1992--clinical and psychological characteristics]. / Parasuicid i Sør-Trøndelag 1989-92--kliniske og psykologiske karakteristika.

The present study is based on interviews with 953 patients (572 females and 381 males) from the county of Sør-Trøndelag who came in contact with the health services after a parasuicide during the period 1 October 1988 to 31 December 1992. Almost half of the patients had a history of earlier parasuicide, and almost half reported that the intention of the last parasuicide was to kill themselves. The parasuicides were regarded as serious by the medical staff in 26% of the cases. There was a significant association between suicidal intention and seriousness. The patients often reported alcohol, drug, family and psychiatric problems, and had often been in contact with health services during the month preceding the parasuicide. 3% of the females and 23% of the males had been sentenced to jail. 24% had experienced a parasuicide and 17% a suicide among family members or friends. 33% of the females and 18% of the males reported having been physically abused, and 14% of the females and 6% of the males reported sexual abuse. The results are discussed in light of previous Norwegian studies.

Tubular handling of neurotensin in the rat kidney as studied by micropuncture and HPLC.

Micropuncture studies were performed to assess the reabsorption and metabolism of the vasoactive peptide neurotensin (NT) in individual nephron segments and compare it to the handling of the closely related peptide bradykinin (BK). Rat proximal and distal convoluted tubules were microinfused with [3H]NT or [3H]BK. In a second set of experiments, [3H]NT and its metabolites in the ureteral urine were separated and characterized using high-performance liquid chromatography (HPLC) technique. The urinary recovery of 3H-labeled material was 31% when proximal tubules were microinfused with [3H]NT and 94% when distal tubules were infused. For proximal tubules the label recovered in the ureteral urine consisted exclusively of metabolites of NT and appeared as tyrosine, NT1-11, probably NT9-13, and two uncharacterized products. For distal tubules, 9% chromatographed as intact NT in the urine and except for the proportion the metabolites were almost identical to those found when proximal tubules were microinfused. Following microinfusion of [3H]BK into proximal tubules, the urinary recovery of 3H-labeled material was 19%. There was no correlation between fractional reabsorption of 3H-labeled material and proximal tubular length when [3H]NT or [3H]BK was microinfused. In vitro incubation studies with rat ureteral urine showed extensive degradation of NT yielding tyrosine, NT1-6, probably NT9-13, NT, and two uncharacterized products. In contrast, there was no detectable breakdown of BK over a 32-min period. Finally, [3H]NT was incubated in rat serum, and these experiments also showed degradation of the peptide but not to the extent as when incubated in ureteral urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Transcellular transport of ferritin in rabbit renal proximal tubules.

The purposes of this study were (1) to determine whether or not transcytosis of protein takes place in vivo in rabbit proximal tubules, using ferritin as a marker, (2) to follow the time course of intracellular transport of ferritin, (3) to study the organelles involved in the sequential intracellular transport of the protein, (4) to compare the intracellular transport in vivo and in vitro, and (5) to compare the intracellular transport in rabbit proximal tubules with transport in rat proximal tubules. Female albino rabbits were prepared for micropuncture, and individual proximal tubules were microinfused with a bolus of cationic ferritin for 2-3 min. The tubules were fixed by perfusion with glutaraldehyde at different time intervals after exposure to ferritin. Ferritin was located in the endocytic vesicles, vacuoles, dense apical tubules and lysosomes including multivesicular bodies, initially in the apical part of the cells, then progressively with time transported to the basal part of the cells. An organelle not previously described represented by small tubulovesicular structures (< 0.05 microns in diameter) also contained ferritin. This organelle was observed either close to large ferritin-loaded vacuoles and sometimes connected to the latter, or scattered throughout the cytoplasm, initially in the apical part of the cell but later found increasingly in the basal part. Small clusters of ferritin particles were found in the basolateral intercellular spaces. After 15 min, only small amounts were observed but the number of clusters increased with time after ferritin infusion. No ferritin particles were observed in the Golgi region.(ABSTRACT TRUNCATED AT 250 WORDS)

Stepwise degradation of NT in pars convoluta and recta of rabbit proximal tubules: evidence of axial heterogeneity.

Reabsorption and degradation of the neuropeptide neurotensin (NT) in rabbit proximal pars convoluta (PC) and pars recta (PR) nephron segments were characterized. Brush-border membrane vesicle fractions (PC or PR) were incubated with [3H]NT, and the extent and pattern of peptide hydrolysis were determined by reversed-phase high-pressure liquid chromatography (rHPLC). Furthermore, isolated rabbit PC and PR segments were perfused with [3H]NT, reabsorption of [3H]NT was quantified, and the collected perfusate was analyzed by HPLC. Metabolites were characterized. Finally, rabbit proximal tubules were microinfused in vivo with [3H]NT to follow the tubular uptake by electron microscope autoradiography. Degradation increased with time in both vesicle fractions. The main difference was an extensive cleavage of NT in PR, as revealed by a higher proportion of end metabolites. This was also visualized as a higher proportion of the large degradation product in rHPLC fraction 39 [NT-(1-11)] in PC as compared with PR after 30 min of incubation. The isolated perfused proximal tubular segments processed NT with large efficiency. PC segments processed 90% of the perfused amount, and PR processed 88%. Only 13% in PC and 10% in PR of the processed NT were found in the bath and the tubule. The main part of processed NT was in the collected perfusate, and rHLPC profiles revealed that NT-(1-11) was the only metabolite in both PC and PR. Electron microscope autoradiography demonstrated autoradiographic grains over invaginations and over the apical part of the proximal tubule cell in endocytic vesicles and vacuoles 10 min after microinfusion of [3H]NT.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of histamine release in cord blood and adult blood.

Histamine release (HR) after stimulation with anti-IgE, concanavalin A (ConA) and Formyl-Met-Leu-Phe (FMLP) from 97 cord blood samples was compared to results obtained in identically treated blood samples from adults. The maximal HR obtained with anti-IgE did not differ significantly from the values obtained in adult blood, although a ten times higher concentration of anti-IgE was required for maximum release. Passive sensitization with IgE-rich plasma caused a significant increase in maximal anti-IgE-induced HR in the majority of cord blood samples, and the dose-response curve was similar to that obtained in adult blood. Challenge with ConA and FMLP caused a HR similar to that seen in adult blood, but the close correlation between anti-IgE- and concanavalin A-induced HR seen in adult blood was absent in cord blood.