High-dose exposure to cat is associated with clinical tolerance--a modified Th2 immune response?

BACKGROUND: Allergen-specific IgG4 antibodies, it is suggested, may be protecting against allergy development by blocking responses. Levels are proposed as a marker of modified Th2 response. OBJECTIVES: To assess the levels of IgE, IgG1 and IgG4 antibodies to cat in relation to cat exposure, asthma and allergic diseases. METHODS: We studied a population-based sample of 412 schoolchildren of 12-13 years of age. Parents of 402 children completed a questionnaire covering their child's medical history, the keeping of cats and other background data. Skin prick tests (SPTs) to common aeroallergens were performed in 371 of the children. Blood samples for the analyses of IgE, IgG1 and IgG4 antibodies were obtained from 309 of them. RESULTS: All children had an immune response to cat, predominantly of the IgG1 subclass. The levels of cat-specific IgG1 and IgG4, but not IgE, were high in children currently keeping a cat. Children with asthma had increased levels of cat-specific IgE and IgG1, and children with a positive SPT to cat also had increased IgG4. The presence of IgG4 was not associated with asthma or sensitization, unless there was a simultaneous production of IgE. Twenty-five percent of the children had an immune response with only IgG4, and no IgE antibodies to cat. This group of children had the highest frequency of cat-keeping, but a similar prevalence of asthma and allergy as those with neither IgE nor IgG4 antibodies to cat. CONCLUSION: Cat-keeping was associated with a modified Th2 response, producing IgG4 but not IgE antibodies. This immune response was not associated with an increased risk of asthma or allergy. However, the IgG4 antibodies did not directly mediate any protective effect.

A Swedish study of chemoradiation in squamous cell carcinoma of the esophagus.

This multicenter study describes the development of a chemoradiation protocol for the treatment of non-metastatic squamous cell carcinoma of the esophagus. Eighty patients were treated with three courses of chemotherapy (cisplatinum and 5-fluorouracil) with concomitant radiotherapy (40 Gy) during the last two courses of chemotherapy. Esophagectomy was performed, when feasible. If no operation was performed, patients were planned to receive a target dose of 64 Gy. Toxicity was mainly attributable to hematological impairment and led to two adjustments of the treatment protocol (addition of filgrastim and lowering of the 5-fluorouracil dose). These changes made it possible to administer the planned treatment in a gradually higher proportion of patients (13/23 [57%] before changes of treatment compared with 30/36 [83%] after changes). Treatment-related mortality was 3.75% (3 patients, associated with leucopenic septicemia after chemotherapy). Fifty-four patients were resected. No per- or postoperative mortality was encountered. The complete response (pathological CR) rate in operated patients was 46% (27/59 patients) after chemoradiation. In the whole series the CR rate (including clinical CR for non-resected patients) was 44%. With a minimum follow-up of 37 months, the 3-year survival for the whole group was 31% compared with 57% for the CR patients. Total 5-year survival thus far (July 1999) is 26%.

Allergic rhinoconjunctivitis, eczema, and sensitization in two areas with differing climates.

In this 5-year follow-up study we compared the prevalence of allergic rhinoconjunctivitis, eczema, and sensitization, in relation to several background factors, in two Swedish regions (Göteborg and Kiruna). In Göteborg, a city on the southwest coast, the climate is mild and humid. Kiruna is a town north of the Arctic Circle. Questionnaire replies and results of interviews were collected from all 412 7-8-year-old children of a population-based sample (203 in Göteborg and 209 in Kiruna); in addition, 192 children from Göteborg and 205 from Kiruna were skin-prick tested for sensitization to common aero-allergens. After 5 years, at 12-13 years of age, almost all of the initial study cohort were re-investigated. At follow-up the prevalence of allergic rhinoconjunctivitis was 17%, eczema 23%, and sensitization 32%. Allergic rhinoconjunctivitis and eczema were as common in Göteborg as in Kiruna, whereas sensitization was far more common in Kiruna. Children born during the pollen season had allergic rhinoconjunctivitis less often -- and were sensitized to pollen and animal protein less often -- than those born during the rest of the year. Sensitization to birch pollen, cat protein, and horse protein was less common in children living in Göteborg, the region with the highest frequency of cat ownership and horseback riding, and with the longest birch-pollen season. The girls were more commonly horseback riders but the boys were more often sensitized to horses. The results reinforce our previous findings: indoor climate may affect the development of sensitization and allergic diseases, to some extent independently; and if exposure to antigen is unavoidable, high doses might be better than low doses.

[Policy document. Catheter-based diagnosis and treatment of coronary diseases]. / Policydokument. Kateterburen diagnostik och behandling av kranskärlssjukdom.

Diagnostic coronary angiography and percutaneous coronary interventions (PCI) are rapidly developing fields. In-house thoracic surgery backup is no longer a prerequisite for PCI. The demand for physicians trained in interventional cardiology has created a need to formalise such education. The Swedish societies of cardiology and thoracic radiology have agreed on a policy document establishing the details of this education. It is the responsibility of the tutor to decide when the pupil has achieved adequate skills.

Asthma in children: prevalence, treatment, and sensitization.

This study compares the prevalence of asthma and sensitization in children from two Swedish regions with different climates: Göteborg on the southwest coast and Kiruna in the northern inland, north of the Arctic Circle. The 412 children of a population-based sample, 203 in Göteborg and 209 in Kiruna, were investigated at age 7-8 and 12-13 years. Questionnaire reports and interviews were obtained from all children at 7-8 years of age, and 192 children were skin-prick tested for common aeroallergens in Göteborg and 205 in Kiruna. At the follow-up, 5 years later, almost all the children were re-investigated. The prevalence of asthma, wheeze, and sensitization had increased with increasing age during the follow-up period. The questionnaire reports revealed that the prevalence of asthma was 8.5% at 12-13 years of age. All children who in the questionnaire reported current asthma, were using asthma medication. The interviews indicated that the prevalence of a clinically significant asthma might be even higher, reaching approximately 12%. Asthma and wheeze were as common in Göteborg as in Kiruna despite large differences in prevalence of sensitization. Sensitization, and especially sensitization to animals, was far more common in Kiruna than in Göteborg. This study shows that asthma and wheeze are increasingly prevalent even in school age children and that sensitization does not necessarily reflect the prevalence of asthma in a population.

Computed tomography of the sternum and mediastinum after median sternotomy.

BACKGROUND: Computed tomography is used in our hospital to diagnose complications after median sternotomy, but its efficiency is unknown. Nor is the computed tomographic appearance of normal healing of a median sternotomy known. Computed tomography was evaluated for its ability to diagnose mediastinitis and sternal dehiscence, and a reference material of normally healing median sternotomies was created. METHODS: In a prospective study, 20 patients with a normally healing median sternotomy were examined 1 week, 1 month, 3 months, and 6 months after operation. In a retrospective study, 87 scans from 65 patients that were made because a postoperative complication was suspected were reviewed. RESULTS: In the prospective study, all patients had clinically uneventful healing. None of the computed tomographic scans showed radiologic signs of healing at 3 months. At 6 months, half of the patients had healed completely. In the retrospective study, 49 scans were performed on suspicion of infection; 7 of them indicated mediastinitis, 2 were false-positive, while mediastinitis was present in a total of 16 of the scans. Thirty-eight scans were made because of sternal pain or suspected dehiscence; after 21 of the scans, recovery was uneventful, and in 11, the definite diagnosis was dehiscence or pseudarthrosis. CONCLUSIONS: Clinical healing of the sternotomy does not correlate with the computed tomographic image. Computed tomography is not a sensitive tool for diagnosing mediastinitis, and in patients with sternal pain, it adds little information.

Does early exposure to cat or dog protect against later allergy development?

BACKGROUND: It is unknown which factors in modern western society that have caused the current increase in prevalence of allergic diseases. Improved hygiene, smaller families, altered exposure to allergens have been suggested. OBJECTIVES: To assess the relationship between exposure to pets in early life, family size, allergic manifestations and allergic sensitization at 7-9 and 12-13 years of age. METHODS: The prevalence of allergic diseases and various background factors were assessed in 1991 and 1996 by questionnaire studies. In 1991, the study comprised representative samples of children from the Göteborg area on the Swedish west coast (7 years old, n = 1649) and the inland town Kiruna in northern Sweden (7-9 years old, n = 832). In 1992, a validation interview and skin prick test (SPT) were performed in a stratified sub-sample of 412 children. In 1996, this subgroup was followed up with identical questions about clinical symptoms as in 1991, detailed questions about early pet exposure were added and SPT performed. RESULTS: Children exposed to pets during the first year of life had a lower frequency of allergic rhinitis at 7-9 years of age and of asthma at 12-13 years. Children exposed to cat during the first year of life were less often SPT positive to cat at 12-13 years. The results were similar when those children were excluded, whose parents had actively decided against pet keeping during infancy because of allergy in the family. There was a negative correlation between the number of siblings and development of asthma and allergic rhinitis. CONCLUSION: Pet exposure during the first year of life and increasing number of siblings were both associated with a lower prevalence of allergic rhinitis and asthma in school children.

The effect of thymectomy on autoreactive T- and B-lymphocytes in myasthenia gravis.

Eleven patients with myasthenia gravis were followed for three years after thymectomy. Acetylcholine receptor-specific T-cell stimulation was found in 8/11 patients before operation as compared to 2/11 three years after thymectomy. Changes of T-cell antireceptor-reactivity were commonly paralleled by changes in disease severity. The numbers of cells secreting IL-2 upon stimulation with human acetylcholine receptor correlated with those secreting IFN-gamma. T-cell reactivity against a monoclonal acetylcholine receptor antibody did not decrease after thymectomy. Such reactivity could reflect a beneficial immune response counteracting anti-receptor reactivity. The frequency of autoantibody-secreting cells remained unchanged, while the serum concentration of acetylcholine receptor antibodies started to decrease one year after thymectomy. All examined thymus-cell suspensions contained autoreactive T- and B-lymphocytes. There was a preferential enrichment of autoreactive lymphocytes in the thymus in a few patients with recent onset of disease.

Diagnosing sternal wound infections with 99mTc-labeled monoclonal granulocyte antibody scintigraphy.

BACKGROUND: Postoperative mediastinitis is a serious complication of thoracic operations. The diagnosis can sometimes be difficult, especially in cases with subacute clinical presentation. The aim of this study was to assess the clinical use of granulocyte scintigraphy and tomography in the diagnosis of postoperative wound infection and mediastinitis. METHODS: Twenty-nine patients after cardiothoracic operations were included, of whom 5 patients with a normal postoperative course formed the control group. We injected technetium 99m-monoclonal antigranulocyte antibodies and performed single-photon emission computed tomography after 4 and 20 hours. RESULTS: Twenty-three patients had both the early and the later scan; the remaining 6 had only the early scan. Seven scans indicated infection: 3 cases of mediastinitis, 2 cases of superficial wound infection, 1 case of infection in a synthetic aortic graft, and 1 case of osteitis. All were verified by bacterial culture. There was one false-negative scan; this patient had only the early registration and then was explored. CONCLUSIONS: This method when combined with the tomographic scan option is able to distinguish between deep and superficial infections. Two registrations must be made for optimal results.

The effect of inhaled and intranasal sodium cromoglycate on symptoms of upper respiratory tract infections.

BACKGROUND: A well established drug for the treatment of asthma and allergy, sodium cromoglycate, was found in open trials to be useful as a symptomatic treatment for upper respiratory tract infections. OBJECTIVE: To compare the efficacy of inhaled and intranasal sodium cromoglycate and matching placebos on the symptoms of upper respiratory tract infections. METHODS: Adult subjects with symptoms of runny nose, throat pain, or cough for less than 24 h were recruited. They were treated for 7 days using a randomized, double-blind, placebo-controlled, group comparative design. The medication given was: sodium cromoglycate dry powder 20 mg per inhalation in spincaps; sodium cromoglycate aqueous nasal spray delivering 5.2 mg per dose; or matching placebo as dry powder and nasal spray. One spincap and one spray per nostril were taken every 2 h during waking hours on days 1 and 2 and then four times daily on days 3-7. Severity of nine symptoms (general malaise, body aches and pains, chills and shivering, sneezing, nasal running, nasal blocking, sore throat, cough and voice disturbance) was recorded twice daily by subjects on diary cards, using a scale of 0 (absent) to 3 (severe). RESULTS: The study was conducted between February and April 1993. One hundred and eighteen patients aged 21-63 years (mean 41 years) were included. Symptoms resolved faster (P < 0.001) and the severity in the last three days of treatment was significantly less in patients treated with sodium cromoglycate than with placebo (P < 0.05-day 5; P < 0.01-day 6; P < 0.001-day 7). Side effects were local and mild and did not differ between the treatment groups. CONCLUSION: Sodium cromoglycate administered both by inhalation and intranasally is an effective treatment for the symptoms of upper respiratory tract infection. Its combined safety and efficacy would make it an acceptable form of treatment for these conditions.

Prevalence of allergic diseases in schoolchildren in relation to family history, upper respiratory infections, and residential characteristics.

The prevalences of asthma, allergic rhinitis (AR), and eczema were analyzed in relation to retrospective risk factors from birth in a questionnaire study of schoolchildren in two areas covering the whole climatic span of Sweden: the Göteborg area on the southwestern coast (7-year-olds, n = 1649) and Kiruna, a mining town in the northernmost inland mountains (7-9-year-olds, n = 832). The strongest background factor, a family history of the diseases, was more common in children with another strong risk factor, particularly for asthma: high frequency of upper respiratory tract infection (URTI). Other significant risk factors related to high indoor humidity caused an increased prevalence of both allergic diseases and URTI. Active mechanical ventilation of the homes caused a slight reduction of the prevalence of allergic diseases, and repainting or new wallpaper in the bedroom of the child after birth caused a moderately increased risk of allergic disease. This study illustrates the interaction between genetic and environmental risk factors with special emphasis on factors related to an unventilated indoor climate, which may have substantially contributed to the current increase of the diseases in the country.

Elevated serum levels of S-100 after deep hypothermic arrest correlate with duration of circulatory arrest.

OBJECTIVE: Cerebral damage is a major problem after reconstructive surgery of the aortic arch and the descending aorta. Current protective strategies, including deep hypothermia and retrograde cerebral perfusion, are used to prolong the tolerated duration of circulatory arrest, and the latter may also decrease the possibility of air/particle embolization. The aim of the current study was to investigate whether the neurochemical marker S-100 is related to the duration of circulatory arrest, when the influence of embolic injury has been minimized by the use of retrograde cerebral perfusion during the last part of circulatory arrest. METHODS: Arterial serum levels of S-100 were followed before, during and after reconstructive surgery of the thoracic aorta during deep hypothermic arrest in ten adults. Retrograde cerebral blood perfusion was used during the latter part of the arrest period in eight of the ten patients. Neurologic status was followed daily. RESULTS: All patients survived the operation. The median (range) duration of cardiopulmonary bypass (CPB) was 184.5 (121-386) min. The median duration of circulatory arrest and retrograde cerebral perfusion was 50 (3-118) min and 16 (0-84) min, respectively. S-100 increased from 0.10 (0.02-0.18) microg/l preoperatively to 2.37 (0.64-10.80) microg/l after CPB (P<0.01), followed by a decrease to 0.79 (0.21-2.64) microg/l on the first postoperative day (P<0.01). The duration of circulatory arrest correlated with S-100 levels after CPB (r(S) = 0.71, P<0.05) and even better with the S-100 levels on the first postoperative day (r(S) = 0.83, P<0.01). However, there was no significant correlation between duration of arrest and duration of CPB. The duration of circulatory arrest without retrograde cerebral perfusion correlated well with S-100 levels on the first postoperative day (r(S) = 0.88, P<0.01), but not significantly with S-100 levels after CPB. CONCLUSIONS: S-100 levels after aortic surgery with deep hypothermic arrest correlate with the duration of circulatory arrest, indicating that the duration of circulatory arrest is damaging to the brain despite the use of deep hypothermia and partial retrograde cerebral perfusion. The highest correlation between S-100 and duration of arrest was seen on the first postoperative day. S-100 appears to perform well under clinical circumstances as a sensitive and discriminative marker for neuronal injury.

Increase of asthma, allergic rhinitis and eczema in Swedish schoolchildren between 1979 and 1991.

BACKGROUND: A previous study has shown a twofold increase in prevalence of asthma and allergic rhinitis (AR) in Swedish recruits during the 1970s. The increase was higher in more northerly colder regions. OBJECTIVES: To follow up the previously found trend to increasing prevalences with time as well as the climatic variations within the country. METHODS: The prevalences of asthma, allergic rhinitis and eczema were assessed using two questionnaire studies, 12 years apart (1979 and 1991) with identical questions about the diseases. The study comprised representative samples of children from the Göteborg area on the south-western coast (in 1979: 7-year-olds, n = 4255, in 1991: 7-year-olds, n = 1649) and in Kiruna, a mining town in the northernmost inland mountains (in 1979: 7-year-olds, n = 427, in 1991: 7-9-year-olds, n = 832). In 1991 there was also a personal interview and a skin-prick test (SPT) on subsamples. RESULTS: The prevalence of all these diseases present over the last year had roughly doubled over the 12-year period. On both occasions, most symptoms were more prevalent in the northern area. In 1991, the prevalence of one or more symptoms in Göteborg was 23.8% and 32.5% and in Kiruna 29.9% and 44.8% in the questionnaire and the interview, respectively. CONCLUSION: Asthma, AR and eczema increase continuously in prevalence in Sweden and the climatic distribution of the prevalences suggests possible major risk factors to be found in a closed indoor climate.

Comparison of vascular effects of ropivacaine and lidocaine on isolated rings of human arteries.

Ropivacaine is a new local anaesthetic agent. Previous animal studies have indicated that vasoconstrictor effects are elicited by ropivacaine in vitro and subcutaneously and that it produces blanching of the skin if injected subcutaneously in humans. Lidocaine is a widely used local anaesthetic reported to exert a biphasic effect on the microvasculature with contraction at low concentrations and relaxation at high concentrations. There is a need for pharmacologic tools able to counteract local arterial vasoconstriction. In this study, the contractile effect of ropivacaine and lidocaine were investigated in vitro on isolated human arteries. Experiments were performed on 43 internal mammary artery (IMA) rings obtained from 22 patients and on 14 radial artery (RA) rings from 7 patients. The rings were mounted in organ baths and isometric contractile activity was measured. Experiments were conducted by cumulative adding ropivacaine or lidocaine (1.5 x 10(-5) M; 4.5 x 10(-5) M; 1.5 x 10(-4) M; 4.5 x 10(-4) M; 1.5 x 10(-3) M; 4.5 x 10(-3) M; 1.5 x 10(-2) M) to the organ baths. The endothelium was mechanically removed in 19 IMA rings and in 9 RA rings. Ropivacaine and lidocaine produced a biphasic response with contraction at low concentrations (1.5 x 10(-5)-1.5 x 10(-3) M) and release of the maximal contraction at higher concentrations. No statistically significant differences in contractile or relaxing effects were seen between the two drugs. Removal of the endothelium did not significantly affect contractile activity. In this study of human mammary artery preparations, ropivacaine is not a stronger vasoconstrictor than lidocaine.

Pathologic fibrin formation and cold-induced clotting of membrane oxygenators during cardiopulmonary bypass.

In 1,800 patients undergoing cardiac surgery over a 2-year period, 11 incidents of abnormal inlet pressure elevations occurred before the membrane oxygenators. In 3 patients, the oxygenators had to be changed during cardiopulmonary bypass. This complication was found to be caused by fibrin formation possibly secondary to precipitation of fibrinogen with other coagulation factors in the heat exchangers of the oxygenators during the cooling phase. Large amounts of fibrin were demonstrated in the heat exchanger of the oxygenators. After careful washing of the apparatus, plasmin was added and fibrin was detected by measuring D-dimer levels. In heat exchangers from uneventful operations, only trace amounts of fibrin were found. Because there were no cold agglutinins demonstrated in the patients before surgery, cryoprecipitation studies were performed soon after surgery. When the patients' plasma samples were studied at different temperatures, from 37 degrees C down to 3 degrees C, cryoprecipitates or a gel (in 1 patient only) were formed. This indicated that there might be something abnormal with regard to fibrinogen-fibrin formation. The study patients were therefore investigated after the acute phase of the operation had ended for various coagulation factors, as well as for fibrin gel network characteristics. The results were compared with those of a control group (n = 10) with uneventful operations. There were no differences between the groups with regard to levels of coagulation factors VII and VIII and von Willebrand factor, although they were increased in both groups. The mean levels of coagulation inhibitors, antithrombin and Protein S, were slightly lower in the study patients. All of these patients had a highly pathologic, ie, tight fibrin gel network, except for the patient in whose sample a gel formed, despite being treated with aspirin or oral anticoagulants. The network was also tighter in some of the controls (v middle-aged reference individuals), although it was significantly tighter in the patients. It is concluded that some individuals who have an increased tendency to form tighter fibrin gel networks might be at increased risk for a severe complication during cardiac surgery performed under hypothermia.

Involvement of aberrant p53 expression and human papillomavirus in carcinoma of the head, neck and esophagus.

Biopsies from 34 patients with cancer of the head, neck or esophagus, 2 laryngeal papillomas, and 2 normal tonsils were analysed for human papillomavirus (HPV), Epstein Barr virus (EBV) genomes and mutated or elevated levels of p53. In 4 biopsies p53 was also analysed by DNA sequencing. HPV type 31 was found in one laryngeal cancer with normal p53 and HPV type 16 in two tonsil cancers with aberrant p53 expression. EBV was detected by PCR in 11 biopsies, but in situ hybridisation and immunohistochemistry, did not confirm this finding. Aberrant p53 expression was observed in approximately half of the tumours. These results support the involvement of both aberrant p53 expression and HPV in the aetiology of squamous cell carcinoma of the head and neck.