A seven-year follow-up study of lung function and methacholine responsiveness in sensitized and non-sensitized workers handling laboratory animals.

Lung function, studied with spirometry, nitrogen washout technique, and methacholine responsiveness, was prospectively investigated in a seven-year follow-up study of 35 laboratory animal workers (19 women and 16 men) of whom 11 were skin prick test (SPT) positive to laboratory animal allergens; five had asthma and six had rhinitis symptoms. During the follow-up, 82% of the SPT positive subjects had stopped animal work, compared with 29% of the SPT-negative subjects. In baseline spirometry, there was no decrement in the lung volumes or differences between SPT-positive and SPT-negative subjects. At follow-up, no difference was found in vital capacity (VC), forced expiratory volume during one second (FEV1), or residual volume (RV), but the volume of trapped gas (VTG), which is assumed to measure small airways, had increased with a median of 11 mL (P = 0.03). Subjects sensitized to laboratory animals had a minor increase in methacholine responsiveness in FEV1 at follow-up (P = 0.03). The VTG responsiveness was already increased in the first examination (P = 0.035) and remained so at follow-up. Furthermore, the FEV1 responsiveness could predict a subsequent decline in baseline VC and FEV1. In conclusion, our results support the hypothesis that airway responsiveness in immunoglobulin E-mediated allergy might start in small airways and subsequently affect large airways.

Human leukocyte antigens in occupational allergy: a possible protective effect of HLA-B16 in laboratory animal allergy.

Human leukocyte antigens (HLA-A, -B, -C, and -DR loci) and possible associations with occupational allergy to laboratory animals and atopy indicators were studied in laboratory animal workers with airway symptoms (n = 92) and in those who were symptom free (n = 27), as well as in a population reference group of blood donors in good health (n = 123). The laboratory animal workers, but not the population reference group, were allergologically examined with skin prick testing to common environmental and animal allergens together with measurement of total serum IgE levels. Seven HLA antigens, i.e., HLA-A9, -B5, -B12, -B16, -DR4, -DR5, and -Drw6, suggested possible associations with symptoms and/or atopy indicators. When correcting the p-values for the number of studied antigens, only the HLA-B16 differences remained statistically significant. HLA-B16 was elevated in symptom-free subjects compared to the population reference group and in subjects with serum IgE < 10 kU/L. Subjects with serum IgE > 100 kU/L and sensitized against environmental and/or laboratory animals, including LAA asthmatics, lacked HLA-B16. It is suggested that HLA-B16 or an immunosuppressive gene linked to HLA-B16 reduce the risk of producing IgE antibodies against animal protein allergens. However, our a priori hypothesis of a possible risk associated with HLA B15-DR4 could not be confirmed.

Predicting postoperative adverse events. Clinical efficiency of four general classification systems. The project perioperative risk.

BACKGROUND: The Project Perioperative Risk in Gothenburg is a prospective clinical-epidemiological study designed to elucidate factors affecting the perioperative risk in unselected adult patients undergoing elective general or orthopaedic surgery. In this report on postoperative adverse events of varying severity, the predictive ability of four simple classification systems, ASA physical status, patient age, surgical stress and a visual analogue scale for intuitively appreciated global risk (RISK-VAS), is described. METHODS: 1361 patients undergoing 1471 surgical procedures were subjected to a detailed and standardised preoperative assessment and classified according to ASA, age, procedure magnitude and RISK-VAS. Postoperative adverse events were prospectively registered during the entire hospital stay. RESULTS: The four classifications all correlated to postoperative adverse events. ASA physical status, RISK-VAS and patient age all appear to be more efficient in predicting severe than mild events, while surgical stress predicted severe events and mild ones equally well. CONCLUSION: The most efficient predictor of severe events appeared to be RISK-VAS, where a relative risk of 28.1 of acquiring a severe postoperative adverse event could be demonstrated for those who had a score of 4 or more compared with those who had scores less than 4.

Development of allergy to laboratory animals is associated with particular Gm and HLA genes.

To find out whether IgG genes are involved in atopy we studied 26 of 101 laboratory technicians who had developed laboratory animal allergy (LAA). The genes for the constant region of the heavy chains of IgG subclasses were analyzed by serum Gm allotypes, representing products on allelic level of the IGHCG1, IGHCG2 and IGHCG3 on chromosome 14q32. There was a significantly increased frequency of the GM(f,f;n,n;b,b) genotype (57.7 instead of 22.3%, p < 0.001) representing IgG1, IgG2 and IgG3 molecules and in particular increased frequency of Gm genotypes with the homozygous expression of G2m (n,n) (69.2 instead of 27.4%, p < 0.001) and of the Gm(f,n,b) haplotype (75 instead of 44.8%, p < 0.001) compared to a normal Caucasian population. An increased HLA-DR4 content of the LAA group (61.5 instead of 33.7%, p < 0.01) was further investigated for Gm allotypes. Among 16 HLA-DR4 LAA individuals, the Gm(f,f;n,n;b,b) genotype (56.3 instead of 22.3%, p < 0.01) and the Gm genotypes with the homozygous expression G2m(n,n) (62.6 instead of 27.4%, p < 0.01) dominated. However, the HLA-DR4 frequency among Gm(f,f;n,n;b,b) of LAA patients did not deviate from the frequency of healthy individuals of the same Gm genotype. The increased frequency of HLA-DR4 antigen in LAA patients might be due to its association to the Gm(f,f;n,n;b,b) genotype. This study supports the following concept: the susceptibility of developing LAA is associated with Gm allotypes Glm(f) expressed from IGHCG1, G2m(n) from IGHCG2 and G3m(b) from IGHCG3 on both alleles situated close to IGHCE on chromosome 14q32. The association of LAA to Gm allotypes [Gm(f,f;n,n;b,b)] expressed from chromosome 14q32 and of HLA class II antigens (HLA-DR4) expressed from chromosome 6p21.3 further confirms the polygenic inheritance of the immune response in atopy.

Peroperative and immediate postoperative adverse events in patients undergoing elective general and orthopaedic surgery. The Gothenburg study of perioperative risk (PROPER). Part II.

All anaesthetic and surgical procedures impose a certain risk of complications. However, reliable estimates of this risk from prospective studies are rare. This study is a prospective clinical epidemiological study of 1361 consecutive patients subjected to elective general and orthopaedic surgery. These patients were followed from an extensive preoperative assessment to three months after the operation. In this report the peroperative and early postoperative period in the postoperative care unit or intensive care unit is described. General anaesthesia was given to 59% and regional/local anaesthesia to 41%. Adverse peroperative events occurred in 19%. The most common were circulatory events (11%), respiratory (4%), and allergic events (1%). Most events were of minor severity. However, with the official registration system, only 1 out of 8 events was detected. In the postoperative unit one or more adverse event was noted in 47% of the cases. These were dominated by circulatory (18.4%) and respiratory events (5.0%). CNS depression was noted in 6.8% of the cases. Most per- and postoperative event variables were highly correlated to the degree of surgical stress. In conclusion, a new concept for preoperative assessment and the registration of events during and after surgery was used. In this way, a large number of events of importance, not least for quality assurance, were found that would be missed with the official coding system. In a previous report we could show that even minor events affected the cost of care substantially.

The Gothenburg study of perioperative risk. I. Preoperative findings, postoperative complications.

The Gothenburg study of Perioperative Risk is a prospective clinical-epidemiological study designed to elucidate factors affecting the perioperative risk in unselected adult patients undergoing elective general or orthopaedic surgery. In this report reference data regarding preoperative characteristics and postoperative complications are presented. 1770 adult patients scheduled for elective general, urological, peripheral vascular or orthopaedic operative procedures were invited to a preoperative clinic. 81% agreed to participate and were assessed in a standardised way by means of questionnaires, interview, physical examination and laboratory screening. 82% had a previous or present condition in the medical history of some concern to the assessor. 71% had a finding of significance on physical examination. In 8% the assessment prompted further investigations or precautions. Throughout their hospital stay, all the 1361 participating patients were visited daily by an especially trained nurse with the task of registering the occurrence of complications. In 30% an untoward event occurred postoperatively--in 1% a severe one, in 21% a mild event, and in 8% an intermediate one. The complication rate was higher in vascular surgery (69%) than in orthopaedic (33%) and general/urological surgery (26%). Not only the severe and intermediate but also the mild complications affected the number of days in hospital.

A follow-up study of laboratory animal exposed workers: the influence of atopy for the development of occupational asthma.

In a 5-year follow-up study of 88 animal exposed laboratory technicians, the incidence of laboratory animal allergy (LAA), lung function, and the development of allergy test reactivity were investigated. Only two individuals developed test positive LAA rhinitis during the follow-up period. Furthermore, one subject who had previously had LAA rhinitis developed LAA asthma. In the remaining subjects the results of skin prick tests against laboratory animals and environmental allergens, total serum IgE levels, and lung function were unchanged. Atopy defined as parental and childhood allergy, raised total serum IgE levels, and positive skin prick tests against nonanimal environmental allergens and nonlaboratory animals (dog and horse) were risk indicators for development of test positive LAA asthma. The low incidence of LAA during the 5-year follow-up is interpreted as a result of an early LAA development in atopic subjects.

Perioperative risk assessment. The Project Perioperative Risk (PROPER).

Surgical operations are preceded by an assessment of the anticipated risks for the patient due to the operation. The present assessment procedure is not optimally organised and the scientific base is weak. In this project a new organisation was tested that provides more relevant data on the risk and more optimal timing if the risk has to be modified. All elective patients from a defined geographical area (n = 1361) were seen one week before the operation for risk assessment. They were then followed up during and after the operation. About 30% of the operations were followed by complications. More than half of them were mild. Severe complications were rare. Three risk assessment classifications were tested. They were all fairly good estimators of the risk but had different properties. The next step in this project is to systematically evaluate the main risk-affecting factors to improve the quality of risk assessment.

Predisposing factors in laboratory animal allergy: a study of atopy and environmental factors.

A population of 101 laboratory technicians handling laboratory animals was studied with regard to predisposing factors for allergy. Twenty-seven had symptoms indicating laboratory animal allergy (LAA); of these, nine had asthma and were skin prick test positive for animal allergens. The LAA asthmatics had an increased frequency of a family history of allergy (relative risk, RR = 3.8); the predictive value was 0.27. There was also an increase of skin prick positivity against common nonanimal allergens (RR = 15); the predictive value was 0.60. All persons with marked positive skin prick tests (greater than or equal to +2) to environmental allergens had developed animal-test-positive LAA asthma. In 56% of the LAA asthma cases the serum IgE levels were elevated (greater than 100kU/L). In preemployment screening of susceptible individuals two important selection criteria emerged, viz., family history of allergy and positive skin prick reactions against environmental allergens.

Laboratory animal allergy--possible association with HLA B15 and DR4.

In 101 laboratory technicians working with laboratory animals 30 presented laboratory animal allergy (LAA) symptoms. Twenty-seven of these LAA technicians were HLA tested. In these the HLA B15 and DR4 frequencies were raised.

Allergy to laboratory animals in laboratory technicians and animal keepers.

The prevalence of allergy to laboratory animals (LAA) was investigated in laboratory technicians and animal keepers. In a questionnaire 41 of 101 technicians reported symptoms provoked by work with laboratory animals. On clinical investigation 30 were found to have symptoms and signs related to contact with animals, and allergy was confirmed by radioallergosorbent tests (RAST) and skin tests in 19. All had rhinitis and 10 also had bronchial asthma. Forty seven other technicians who had stopped working with laboratory animals showed the same relative numbers of respiratory tract symptoms and of confirmed allergy to laboratory animals as did those currently handling animals. Seven of 23 animal keepers had work related symptoms. LAA symptoms were found in four and confirmed animal allergy in two. All four animal keepers with animal related symptoms had rhinitis, none had bronchial asthma. Positive animal RAST and skin tests were found only among people with animal related symptoms. A history of atopic disease was commoner among those with positive animal test results than among those with negative test results. No relation between smoking and the development of allergy to laboratory animals emerged. Simple prophylactic measures often sufficed to help technicians with animal related symptoms to remain at work.

Contact urticaria in laboratory technicians working with animals.

The occurrence of contact urticaria was studied in 101 laboratory technicians investigated for allergy to laboratory animals. Fourteen cases of contact urticaria caused by rat were found. Other animals causing contact urticarial reactions were mouse (7), guinea-pig (4), and cat (2). Hand eczema was not found in laboratory technicians with contact urticaria and IgE-antibodies to laboratory animals.

Hemodialysis in schizophrenia: psychiatric aspects of treatment failure in a pilot study.

In order to examine the reported curative effects of hemodialysis in patients with chronic schizophrenia a pilot study approved by the Committee of Ethics at the University of Lund was initiated in September 1977. 13 patients, 10 men and 3 women, 21--44 years old, were treated. All but one were diagnosed as chronic schizophrenia. The duration of illness was 4--20 years. All the patients functioned defectively psychosocially, and conventional therapy had failed. Our goal was to give at least one dialysis treatment a week during 13 weeks. 10 patients completed the treatment series. The patients were scored according to the Brief Psychiatric Rating Scale and the Rockland and Pollin scale before, during and after the treatment. Conventional therapy was given throughout. Analysis of hemofiltrates for endorphins did not reveal any abnormal levels. 1 patient reported a distinct and hitherto lasting improvement. Marginal and temporary improvements were noted in 3 patients. Therefore placebo effects or spontaneous remission seemed probable. The ratings showed no significant changes in any patient during the treatment period. All patients including those who showed improvement remained seriously incapacitated by their psychiatric illness. Different psychiatric aspects of our failure to reproduce the American findings including cultural discrepancies in diagnostic criteria are discussed.

Glomerular filtration rate and calcium metabolism in long-term lithium treatment.

Does long-term lithium treatment induce an irreversible renal damage, and does polyuria or changes in the calcium metabolism indicate this? To elucidate these questions GFR, diuresis, S-Ca, S-Mg, S-PTH and bone mineral content (photonabsorptiometry) were determined in 29 consecutive patients on long-term lithium therapy for 2.5--12 years and in 4 patients, who had been admitted to the Renal Clinic with lithium-induced polyuria. Only 1 of the patients had had a known lithium intoxication (S-Li > 2 mmol/l). None had a history of renal disease or significant analgesic consumption. In the consecutive series the GFR was not significantly reduced and no correlations were found between this parameter and the duration of lithium therapy, average S-Li, highest S-Li noted, diuresis or any of the calcium parameters. The morning diuresis was significantly increased in comparison with a control group with normal kidney function. 2 of the 4 polyuric patients had a decreased GFR, but in 1 case it was normalized on desmopressin supplementation. Renal biopsy in the patient with one S-Li of 2.35 and a low GFR in the consecutive series, and in 3 of the polyuric patients, revealed focal interstitial fibrosis and nephron atrophy. The mean S-Ca, S-Mg, S-PTH and bone mineral content were increased, but no significant intercorrelations between these parameters were found. Neither were any intercorrelations found between the calcium parameters and time on lithium therapy, average S-Li, highest S-Li noted or morning diuresis. In conclusion a relatively well-managed lithium therapy for up to 12.5 years does not seem to influence the GFR, even if renal biopsy in 4 of our patients revealed interstitial nephritis and data in the literature indicate a progressive interstitial nephritis. The present study did not support the proposition that polyuria is an alarming sign of pronounced renal lesion. Calcium metabolism is influenced by lithium therapy but from the clinical point of view no negative effects could be found. S-Ca should probably be checked regularly in patients on long-term lithium therapy.