Allergens. Heterogeneity of molecular sensitization profiles in grass pollen allergy--implications for immunotherapy?

BACKGROUND: Data on molecular allergy diagnostics in adults with grass pollen allergy with regard to conjunctival and nasal provocation test outcome and specific immunotherapy are lacking to date. OBJECTIVE: To assess whether molecular allergy diagnostics for grass pollen allergens could help with predicting provocation test outcomes and serve as a basis for future component-resolved specific immunotherapy. METHODS: Sera of 101 adults with grass pollen allergy was analysed for IgE against timothy grass pollen (Phleum pratense), rPhl p 1, rPhl p 2, nPhl p 4, rPhl p 5b, rPhl p 6, rPhl p 7, rPhl p 11 and rPhl p12 and correlated with the individuals' outcome in the nasal and conjunctival provocation tests and investigated in regard to a potential component-resolved specific immunotherapy. RESULTS: An increasing number of sensitizations to timothy grass allergens was correlated to a positive reaction in the conjunctival (4.9 vs. 3.6, P = 0.003) and nasal provocation tests (4.5 vs. 2.2, P = 0.0175). In molecular sensitization profiles, a substantial heterogeneity was detected, with none of the patients exactly matching the allergen composition of a previously published component-resolved specific immunotherapy containing Phl p 1, Phl p 2, Phl p 5a/b and Phl p 6. The results indicate that in 95% of the patients, a proportion of 50% of timothy-IgE would be targeted with such a specific immunotherapy, while in 50% and 10% of patients, 80% and 90% of timothy-IgE would be targeted, respectively. CONCLUSION AND CLINICAL RELEVANCE: Molecular allergy diagnostics is a prerequisite for future component-resolved specific immunotherapy due to the high heterogeneity of sensitization profiles. However, of current clinical relevance is the observed correlation between the number of sensitizations and provocation test outcome.

Can immunoglobulin E-measurement replace challenge tests in allergic rhinoconjunctivits to grass pollen?

BACKGROUND: There is minimal data available concerning the dose-response relationship between allergen exposure and clinical reactivity for outdoor aeroallergens, such as timothy grass pollen. Timothy pollen-specific IgE (sIgE) determinations might assist in predicting the clinical reactivity in patients with allergic rhinoconjunctivitis (ARC). METHODS: Allergen-sIgE antibody levels of timothy grass pollen were correlated with individual threshold doses eliciting allergic reactions in skin prick test (SPT), conjunctival (CPT) and nasal (NPT) provocation tests in patients suffering from pollen-induced rhinoconjunctivitis and healthy controls. RESULTS: One hundred and four patients with ARC (median age: 27 years; range: 18-64; females: 58%) and 36 controls (25 years (22-77); females: 70%) were included in the study. Ninety-six percent of the patients showed a positive reaction in the nasal and 57% showed a positive reaction in the conjunctival provocation. With regarding to titrated SPT, 98% of the patients showed a positive skin test reaction; correlating with the level of sIgE for timothy (P < 0.001). For both provocation protocols, there was no correlation between the provocation concentration at the reaction and the level of sIgE for timothy. The ratio of sIgE/total IgE correlated with the dilution level of SPT (P < 0.002) and CPT (P < 0.01), respectively. CONCLUSION AND CLINICAL RELEVANCE: A dose-response relationship between the levels of sIgE and clinical outcome of timothy allergen exposure could not be established. Although IgE-determination remains an important key element in allergy diagnosis, provocation tests are procedures of choice if the clinical relevance of an allergen has to be confirmed.

The utility of specific immunoglobulin E measurements in primary care.

BACKGROUND: The identification of atopic patients may not be considered a necessary step in the diagnosis process in primary care. This study investigated the impact of the addition of a specific immunoglobulin E (IgE) antibody test on the current management by primary-care physicians of patients with respiratory and skin symptoms. METHODS: The study had a prospective before-after design. It was conducted in two geographic areas of Italy and Spain and consisted of two parts, Part I and Part II. In each part patients were recruited according to inclusion and exclusion criteria. After the clinical examination, the patients were classified into one of the following categories using a physician's classification: allergic, nonallergic or uncertain. A blood sample was taken from each included patient for specific IgE antibody determination using a Pharmacia CAP System, including either Phadiatop Infant (0-5 years of age) or Phadiatop and food mix (fx5e) (>5 years of age). If a positive result was found, an additional 6-26 specific IgE tests were performed. In Part I the result of the specific IgE antibody determinations was not available before the physician's classification was made. In contrast, in Part II, the result of the IgE test was available at the time when the physician's classification was made. Between Part I and Part II an educational intervention for physicians to improve their knowledge of blood testing for IgE-mediated allergy was carried out. RESULTS: A total of 721 patients were included in the study. The agreement between classifications based on clinical data and IgE antibody results changed from a kappa coefficient of 0.13 in Part I to 0.86 in Part II. With regard to the allergic status the proportion of uncertain cases was reduced from 26.3% in Part I to 4.1% in Part II. The proportion of patients that were advised to avoid allergens increased from 18% in Part I to 62% in Part II in the group of patients classified both by the clinician and the IgE test. CONCLUSIONS: The use of specific IgE antibody determinations improves the clinical management of patients with allergy related symptoms in primary care, allowing advice to be given on specific allergen avoidance. However, the applicability of this diagnostic tool in different areas and countries should be further assessed in cost-effectiveness studies.

Increased fragility in patients with fracture of the proximal humerus: a case control study.

The aim of this study was to evaluate whether a fracture of the proximal humerus is associated with an increased prevalence of preceding fractures or a risk of subsequent fractures. All patients who were treated at the Malmö General Hospital in 1987 for a fresh fracture of the proximal humerus were identified, representing practically all fractures of the proximal humerus in Malmö city (250,000) that year. Two hundred fifty-three adult patients, 54 men with an average age of 66 (24-90) and 199 women with a mean age of 74 (22-98) years, were included in the study together with 475 age- and gender-matched control persons. In 1999, fracture prevalence of patients and controls were rated by a survey at the Dept. of Radiology. There was a significantly increased prevalence of previous fractures before 1987 in the humerus fracture group with an odds ratio (OR) of 3.5 [95% confidence interval (95% CI), 2.2-5.5] for a spinal fracture, OR 1.8 (95% CI, 1.3-2.6) for a previous fracture to the upper extremity, and OR 1.8 (95% CI, 1.2-2.6) for a preceding fracture of the lower limb. The proximal humerus fracture also predicted a significantly increased risk of a subsequent fracture. The hazard ratio (HR) was 2.5 (95% CI, 1.7-3.7) for a forthcoming spinal fracture, HR 2.8 (95% CI, 2.0-3.7) for a future fracture of the upper extremity, and HR 2.0 (95% CI, 1.2-3.5) for a lower limb fracture. In a subgroup of male patients, an almost five times increased risk of sustaining subsequent extremity fractures was observed. In summary, a fracture of the proximal humerus is associated both with increased prevalence of previous fractures of the spine and extremities and also predicting an increased risk of future fractures.

Antibodies against human tissue transglutaminase and endomysium in diagnosing and monitoring coeliac disease.

BACKGROUND: Coeliac disease (CD) patients often present a variety of uncharacteristic symptoms and therefore sensitive and specific screening tests are needed as an aid in making an accurate diagnosis. A recently developed ELISA, using human recombinant tissue transglutaminase (tTG) as antigen, was evaluated for its significance in the diagnosis of CD. The patient's compliance to a gluten-free diet and the serological reaction during gluten challenge were also monitored. The results were compared with IgA-endomysium antibody (EMA) results. METHODS: Sera previously collected from 365 patients (0.4-76 years) with jejunal biopsy on a gluten-containing diet and from 41 patients on a gluten-free diet or challenge were tested for IgA anti-human tTG antibodies (IgA tTG ab) with Celikey (Pharmacia Diagnostics). The study population comprised 208 CD patients and 157 controls. The diagnostic performance and cut-off for the assay were estimated with ROC analysis. EMA was analysed by indirect immunofluorescence microscopy on cryostat sections of monkey oesophagus. RESULTS: 200/208 patients with CD had positive IgA tTG ab (median >100 U/ml), while only 1/157 of the control patients were positive (median 1.67 U/ml). The area under the ROC curve was 98.3% and the sensitivity and specificity of the test were 96% and 99% for the study population. Only 4/365 patients (1%) presented discordant IgA tTG ab and EMA results, 2 of them had only IgA tTG ab and 2 only EMA. The IgA tTG ab levels and the EMA titres were closely correlated to the duration of gluten-free diet and gluten challenge, respectively. CONCLUSION: IgA tTG ab can be used as an accurate observer-independent alternative to EMA in diagnosing or monitoring CD.

Synoviorthesis with radioactive gold in haemophilia.

According to the experiences of the Malmö Haemophilia Centre, the best way to avoid recurrent joint bleedings and synovitis in haemophilic patients and to prevent progressive joint disease is prophylactic factor treatment. If prophylaxis is impracticable and also in patients with factor inhibitors, radioactive synoviorthesis seems to be a good treatment option if started early.

Mid-clavicle fractures in adults: end result study after conservative treatment.

OBJECTIVE: The aim of the present study was to analyze the long-term outcome of mid-clavicle fractures in adults and to evaluate the clinical importance of displacement and fracture comminution. DESIGN: Two hundred twenty-five mid-clavicular fractures that had been nonsurgically treated at Malmö University Hospital were retrospectively evaluated, both clinically and radiographically, an average of seventeen years after injury. There were seventy-one undisplaced fractures, sixty-nine displaced two-fragment fractures, and eighty-five displaced and comminuted fractures. The average patient age at the time of trauma was thirty-three years (range 15 to 70 years). Patients were interviewed, and careful clinical and radiological examination of their shoulders was performed. Two patients had experienced transient neuritis, and another two underwent operative treatment because of progressive neuropathy. SETTING: All 225 consecutive patients were treated primarily at the Malmö University Hospital, which serves the Malmö city population (250,000). PATIENTS/PARTICIPANTS: Since the beginning of this century, all radiographs taken at the Malmö University Hospital have been classified and filed for easy retrieval. In this retrospective study, all patients treated between 1970 and 1979 were identified, and those still living were called for follow-up examination. INTERVENTION: Of the 225 fractures reviewed, 197 fractures were originally treated with a figure-of-eight splint for an average period of three weeks without any attempt to reduce the displaced fractures; twenty-four patients were allowed immediate free shoulder mobilization. MAIN OUTCOME MEASUREMENTS: Clinical rating and healing were the main outcome measurements. RESULTS: At follow-up, 185 shoulders were asymptomatic. Thirty-nine shoulders had moderate pain and were rated as fair, and one patient was rated as poor. One hundred twenty-five of the fractures had healed normally, fifty-three were malunited with persistent fracture displacement, and seven were nonunions; nonunion was significantly more prevalent in cases with displaced fractures. Forty malunited fractures and three nonunions were rated as good. CONCLUSIONS: This review demonstrates that few patients with fractures of the mid-part of the clavicle require operative treatment.

Shortening of clavicle after fracture. Incidence and clinical significance, a 5-year follow-up of 85 patients.

We evaluated the incidence and clinical significance of postfracture shortening of the clavicle in 85 patients. There were 71 mid-clavicular fractures and 14 of the lateral end of the clavicle. 46 fractures were primarily undisplaced and 39 displaced. All fractures were nonoperatively treated with sling immobilization. All patients were reexamined 5 years after the fracture. 35 clavicles had healed with at least 5 mm shortening. Clavicles with originally displaced fractures were shorter and radiologically more frequently malunited. Mobility, strength and the functional Constant score were similar in the injured and normal shoulders. Our findings suggest that permanent shortening of the clavicle is common after fracture, but has no clinical significance.

Shoulder injuries common in alcoholics. An analysis of 413 injuries.

We recorded prospectively all adult patients with a fracture of the proximal end of the humerus, clavicle and scapula or a primary shoulder or acromioclavicular dislocation in the city of Malmö in 1987. Altogether there were 413 injures. The hospital records from the Department of Alcohol Diseases were searched for these patients and for 2 age- and gender-matched controls for each patient. 12% of all patients with a shoulder injury were recorded as alcohol abusers. This number was significantly greater than that of the controls. The difference was more obvious in men than in women. In men between 30 and 64 years, almost half of the proximal humerus fractures and shoulder dislocations, one third of mid-clavicular fractures and two thirds of all lateral clavicle fractures were sustained by alcohol abusers. Our findings emphasize the significance of alcohol abuse in the etiology of shoulder injuries, especially in men. Most of the men with a fracture of the lateral clavicle are registered at the Department of Alcohol Diseases, making this injury a marker of alcohol abuse.

Incidence and causes of shoulder girdle injuries in an urban population.

In a prospective population-based study of all shoulder injuries seen at Malmö General Hospital during 1987, the incidence and causes of major injuries involving fractures of the clavicle, scapula, or proximal humerus and glenohumeral or acromioclavicular dislocations were investigated in children, adults, and the elderly. Seventy-five shoulder injuries occurred in children. Sixty-five of them were fractures of the clavicle. In this age group no sex-related differences were seen in incidence, and 37 of 73 injuries were related to sports or playing. One hundred eighty-one injuries occurred in adults. Sixty fractures of the proximal humerus, 67 fractures of the clavicle, and 31 primary glenohumeral dislocations were seen. The injuries in this group were significantly more frequent in men, with most of them caused by traffic and sport injuries. Two hundred forty-eight injuries occurred in elderly people. Two hundred one were fractures of the proximal humerus. The incidence was significantly higher in women; 147 of 247 injuries were caused by an indoor fall. The variations among age groups are probably attributable to age-related differences in activity, mobility, and fragility.

Shoulder pain in middle age. A study of prevalence and relation to occupational work load and psychosocial factors.

Studies on 574 subjects demonstrated the prevalence of shoulder pain and its relationship to occupational work load and psychosocial factors. The prevalence of shoulder pain was 14% (13% men, 15% women). Women had more often myalgias with a tenderness on palpation of the shoulder muscles and rhizopathia-brachialgia type of pain, whereas men had mainly intraarticular pain. Three percent had been on sick leave because of shoulder pain in the year preceding the examination and 5% had a reduced range of shoulder joint motion. The subjects with shoulder pain were less satisfied with their jobs and had been less successful in a childhood intelligence test. No difference could be demonstrated between subjects with or without shoulder pain in estimated overall work load, but women with signs of supraspinatus tendinitis more often had jobs with physical demands.

The acromioclavicular joint in rheumatoid arthritis.

The acromioclavicular (AC) joint was clinically and roentgenographically examined in 49 rheumatic patients with painful shoulders. Clinically, the AC joint was tender and painful in about one-third of the shoulders. Roentgenographically, AC changes were encountered in 85% of the shoulders. The AC joint destruction was frequently associated with the glenohumeral joint disease. There was a time-dependent progression of subchondral bone erosion, tapering, and osteolysis of the acromial end of the clavicle corresponding to the duration and/or severity of the rheumatoid disease.

Spontaneous medial dislocation of the tendon of the long biceps brachii. An anatomic study of prevalence and pathomechanics.

Medial displacement of the tendon of the long biceps brachii muscle was analyzed in a dissection study on autopsy in 77 subjects, 42 men and 35 women. The tendon was found to be medially displaced in five shoulders in five different subjects (6.5%). Medial displacement of the tendon was always found in connection with full-thickness supraspinatus tendon ruptures. It is a common belief that the tendon is always displaced medially to the lesser tubercle riding over the subscapularis tendon. In the present series, this condition was found only in one case; in the other shoulders the tendon had slipped medially to the lesser tubercle under the subscapularis tendon, which was partially internally ruptured. In patients with rotator cuff lesions, medial displacement of the long biceps tendon might be one reason for pain over the front of the shoulder.

[The shoulder joint in chronic polyarthritis]. / Das Schultergelenk bei der chronischen Polyarthritis.

In patients with rheumatoid arthritis, shoulder problems are very common. In the present study, 96 of 105 patients, i.e., 91%, reported shoulder problems. Thirty-one percent of the patients had such severe shoulder disability that they considered it to be their main rheumatic problem. With increasing duration of the rheumatic shoulder disease, there are progressive destructive changes and a decrease in the range of motion and functional capacity even with conservative treatment, indicating that intervention with surgical procedures may be warranted. In the early effusive stages of rheumatic shoulder disease, radiological synovectomy with beta-emitting radionuclides may be indicated. In proliferative synovitis, surgical synovectomy gives good pain relief and increased shoulder mobility and function. In shoulders with more advanced painful shoulder arthropathy, shoulder replacement is gaining in popularity. However, it is mandatory that candidates must be selected very carefully for shoulder replacement and in patients with severe fibrotic capsulitis, muscular atrophy or mutilation with severe loss of bone, the results after shoulder replacement surgery are often less successful.

Shoulder surgery in rheumatoid arthritis.

Surgery was performed on 43 shoulders in 38 rheumatic patients with disabling pain. Fifteen of 22 synovectomized shoulders were available for examination an average of 2 years postoperatively. Twelve patients were satisfied with their operations and had painfree shoulders. Nine shoulders had almost normal mobility but four patients with an advanced shoulder arthropathy had gained little motion. Two patients with severe pain had been re-operated on with arthroplasty. In 15 patients with 18 shoulder replacements, the postoperative gain in motion was limited in all shoulders. Seven out of eleven shoulders had significant pain after hemi-arthroplasty, whereas five out of seven shoulders were painfree after total replacement. It seems that synovectomy can give results which are comparable with total arthroplasty if applied in early stages of rheumatoid disease.

Painful shoulders in patients with rheumatoid arthritis. Prevalence, clinical and radiological features.

The shoulder joints of 105 patients with rheumatoid arthritis were examined. The patients were on average 62 years old and their mean RA duration 17 years. Ninety-six patients (91%) reported shoulder problems. Thirty-three patients had actual severe painful shoulder disability. The acromioclavicular joint was clinically tender in 36 shoulders and subacromial hypertrophic bursitis was recorded for 22 shoulders. One hundred and sixteen shoulders in 61 of the patients with shoulder pain were examined radiologically and classified according to the Larsen system. With increasing duration of the RA there was a progress of destructive changes and a decrease in the range of motion, indicating that intervention with surgical procedures may be warranted.

Effect of electrogalvanic elements on nonfractured bone.

Bimetallic devices composed of silver and platinum were placed in the periosteum of the right femora of 20 rats. In 40 additional rats silver or platinum rods were placed in the right femora. After six weeks there was an increase in ash weight and 85Sr activity in the femora from the animals with bimetallic rods as compared with those in which pure silver or platinum rods were implanted. After three months no differences were found between the groups.

Ruptures of the supraspinatus tendon. Cadaver dissection.

Ninety-nine shoulders from 50 decreased with an average age of 73 years were dissected. There was a significant decrease in the thickness of the supraspinatus tendons with full thickness ruptures but not in partial ruptures. A highly significant increase in the length of the extramuscular supraspinatus tendon in shoulders with partial or full thickness supraspinatus ruptures was found. However, the total length of the supraspinatus aponeurosis was the same in shoulders with ruptures as in normal shoulders of the same age. This might indicate that the increase in length of the extramuscular portion of the tendon in ruptures is not caused by elongation of the tendon but is the result of muscular decay.

The subacromial space in normal shoulder radiographs.

The subacromial space in standard anteroposterior radiographs of 175 normal shoulders was between 9 and 10 mm. The space was significantly greater in men, with a slight reduction with age. In middle age, a subacromial space less than 6 mm is pathological, possibly indicating supraspinatus tendon rupture.

Resection of the lateral end of the clavicle. A 3 to 30-year follow-up.

Fifty patients, operated on with resection of the clavicle, were evaluated postoperatively after an average of 9 years. There was no significant difference between the traumatic and non-traumatic group. The initial results did not alter significantly with time. Nearly half of the patients with poor outcome had psychiatric or alcoholic problems. Radiographic examination of 30 shoulders showed newly formed bone at the resected clavicle in one third and radio-opaque deposits in the resection gap in another third. These findings were consistent with good outcome.