British Society for Immunology and United Kingdom Primary Immunodeficiency Network (UKPIN) consensus guideline for the management of immunoglobulin replacement therapy.

Currently, there is no guideline to support the use of immunoglobulin replacement therapy (IgRT) in primary and secondary immunodeficiency disorders in UK. The UK Primary Immunodeficiency Network (UK-PIN) and the British Society of Immunology (BSI) joined forces to address this need. Given the paucity of evidence, a modified Delphi approach was used covering statements for the initiation, monitoring, discontinuation of IgRT as well as home therapy programme. A group of six consultant immunologists and three nurse specialists created the statements, reviewed responses and feedback and agreed on final recommendations. This guideline includes 22 statements for initiation, 22 statements for monitoring, 11 statement for home therapy, and 19 statements for discontinuation of IgRT. Further areas of research are proposed to improve future delivery of care.

How many life years are lost in patients with rheumatoid arthritis? Secular cause-specific and all-cause mortality in rheumatoid arthritis, and their predictors in a long-term Australian cohort study.

BACKGROUND: There is an excess of mortality in patients with rheumatoid arthritis (RA) but no long-term Australian cohort data. AIMS: To determine median life years lost, all-cause standardised mortality ratio (SMR) and cause-specific SMR, their predictors and secular change in Australian patients with RA. METHODS: Study population was all patients seen by a rheumatologist between 1990 and 1994. Record linkage with Australian National Death Index was performed to determine fact and cause of death up to 2004. All-cause and cause-specific SMR, and median life years lost were determined. RESULTS: There were 35 (31%) deaths in the early 1990s cohort (n = 113), SMR 1.31 (95% 0.93, 1.80). There were 216 (44%) deaths in the pre-1990s established cohort (n = 495), SMR 1.73 (1.49, 1.95). Median life years lost in the early cohort was 6 years for males and 7 years for females compared with 8 and 10 years, respectively, in the established cohort. Patients with low disease activity score at baseline (DAS < 3.2), SMR was 0.8 (0.3, 2.2) and 1.5 (1.1, 2.2) for the early and established cohorts, and if DAS ≥3.2, SMR was 1.4 (1.02, 1.98) and 1.8 (1.5, 2.1) respectively. Primary cause of death was cardiovascular disease (SMR 1.43 (1.17, 1.74). Patients at most risk were those age 45-54 years. RA was listed as a comorbid condition on the death certificate in only 16% of patients. CONCLUSIONS: Within a period of 14 years, median life expectancy of patients with RA with disease onset in the early 1990s is reduced by 6-7 years. However, our results also suggest a secular reduction in excess mortality.

Characterization of a factor(s) present in Klebsiella culture filtrates that specifically modifies an HLA-B27-associated cell-surface component.

It has been shown that HLA-B27 lymphocytes from healthy individuals (B27+ ankylosing spondylitis [AS]-), which are not lysed by an antiserum against Klebsiella K43, can be rendered susceptible to lysis after incubation in the culture filtrate of Klebsiella K43. This finding is compatible with a specific modification by a Klebsiella K43-derived soluble factor of a B27-associated lymphoid cell component. Preliminary characterization of the factor has indicated that it is nondialyzable, but it is heat labile at 56 degrees C for 30 min and has a 35,000-50,000 mol wt. The modifying factor activity of the filtrate is destroyed by neuraminidase but not by trypsin and alpha-chymotrypsin. Furthermore, the ability of the factor to convert B27+AS- lymphocytes can be specifically absorbed by B27+AS- lymphocytes, but not by B27+AS+, B27-AS+, or by B27-AS- lymphocytes, which suggests that B27+AS- cells carry a hypothetical receptor which can specifically bind a Klebsiella K43 antigenic determinant. These results imply that the modification by environmental agents of specific major histocompatibility complex-associated gene products may be an important element in the pathogenesis of the HLA-B27-linked seronegative arthropathies.

Cytotoxic T lymphocytes against disease-associated determinant(s) in ankylosing spondylitis.

Cytotoxic T lymphocytes, induced by stimulating the PBMC of an HLA-B27+ normal individual (B27+, AS-) with the PBMC of an HLA-identical sibling suffering from ankylosing spondylitis (AS) (B27+, AS+), specifically lyse B27+, AS+ PBMC but not PBMC from HLA-27+ or B27-, AS- normal controls, or from HLA-B27- AS patients (B27-,AS+). CTL of similar specificity can also be raised by immunizing in vitro B27+,AS- cells with autologous cells modified by cross-reactive bacterial antigens. These results suggest that CTL can recognize certain bacterial antigens in association with HLA-B27 and that this interaction may lead to an inflammatory episode during the initial stages of the disease.

CLIMATE: A New Route Toward Limiting Climate Change?

Climate change mitigation strategies have focused on reductions in carbon dioxide and other long-lived greenhouse gases. Smith et al., investigate the viability of a different strategy, recently proposed by Hansen et al., which focuses on controlling short-lived pollutants such as soot and tropospheric ozone. They conclude that carbon dioxide must remain the primary focus of climate change mitigation strategies.

Concurrent treatment with a macrocyclic lactone and benzimidazole provides season long performance advantages in grazing cattle harboring macrocyclic lactone resistant nematodes.

In 2013, a 118-day study was initiated to investigate the efficacy of concurrent treatment at pasture turnout with an injectable macrocyclic lactone with activity up to 28 days and an oral benzimidazole, referred to as "conventional" anthelmintics, when compared to treatment with conventional macrocyclic lactone alone or an injectable macrocyclic lactone with extended activity of 100 days or longer. A group of 210 steers were obtained from a ranch in California and transported to Idaho, USA. A total of 176 steers with the highest fecal egg counts were blocked by pre-treatment body weights and pasture location. A total of 44 pasture paddocks were assigned with 4 steers per paddock with 12 paddocks per therapeutic treatment group and 8 paddocks per controls. The four treatments were injectable doramectin (Dectomax®, Zoetis Inc., 0.2 mg kg-1BW, SC), injectable doramectin concurrently with oral albendazole (Valbazen®, Zoetis Inc., 10 mg kg-1BW, PO), extended release injectable eprinomectin (LongRange™, Merial Limited, 1 mg kg-1BW, SC) or saline. Cattle were individually weighed and sampled for fecal egg count on Days 0, 31/32, 61, 88, and 117/118 with an additional fecal sample on Day 14. At conclusion, one steer per paddock was euthanized for nematode recovery. The results from the first 32 days found evidence of macrocyclic lactone resistance against injectable doramectin and extended release eprinomectin. During this period the concurrent therapy provided nearly 100% efficacy based on fecal egg count reduction and a 19.98% improvement in total weight gain compared to controls (P = 0.039). At the conclusion of the 118-day study and past the approved efficacy for the conventional anthelmintics, the concurrent therapy with conventional anthelmintics provided a 22.98% improvement in total weight gain compared to controls (P = 0.004). The 118-day improvement in weight gain for the extended release eprinomectin group (29.06% compared to control) was not statistically different from the concurrent therapy with conventional anthelmintics. The results indicate that concurrent treatment with a conventional macrocyclic lactone and benzimidazole may provide production benefits early in the grazing period that continue throughout the entire period for cattle harboring macrocyclic lactone resistant nematodes. By using two different anthelmintic classes together, macrocyclic lactone resistant parasites were effectively controlled early in the period. Furthermore, the use of an effective conventional anthelmintic treatment regimen without an extended period of drug release may help to promote refugia and decrease the further selection for anthelmintic resistant parasites.

A multicenter evaluation of the effectiveness of Quest Gel (2% moxidectin) against parasites infecting equids.

Controlled trials with a common protocol were conducted in Idaho, Illinois and Tennessee to evaluate anthelmintic effectiveness of Quest Gel (QG; 2% moxidectin) against lumenal parasites in horses. Candidate horses were required to have naturally acquired nematode infections, as confirmed by presence of strongylid eggs in feces. At each site, 24 equids were blocked on the basis of pretreatment strongyle fecal egg counts (EPG) and randomly assigned to treatments within blocks. Within each block of two animals, one received QG on Day 0 at a dosage of 0.4 mg moxidectin/kg b.w. and one was an untreated control. Body weights measured the day before treatment served as the basis for calculating treatment doses. Horses assigned to treatment with QG received the prescribed dose administered orally with the commercially packaged Sure Dial syringe. Horses were necropsied 12-14 days after treatment, and lumenal parasites and digesta were harvested separately from each of five organs, including the stomach, small intestine, cecum, ventral colon and dorsal colon. Parasites from stomachs and small intestines were identified to genus, species and stage. Micro- (i.e., < 1.5 cm) and macroparasites (i.e., > 1.5 cm) in aliquots from the cecum, ventral colon and dorsal colon were examined in aliquots of approximately 200 parasites until at least 600 parasites had been identified to genus, species and stage or until all parasites in the 5% aliquot were examined, whichever occurred first. Data were combined across sites and analyzed by mixed model analysis of variance to assess the fixed effect of treatment and random effects of site and block within site. Because QG does not contain a cestocide, efficacy of QG against tapeworms was not significant (P > 0.05). Based on geometric means, however, efficacy of QG was greater than 90% (P < 0.05) against 38 species and developmental stages of cyathostomes, strongyles, bots, larval pinworms and ascarids encountered in at least 6 of 36 control horses in the combined data set. None of the horses treated with moxidectin exhibited evidence of adverse effects. Study results demonstrate QG, administered to horses with naturally acquired endoparasite infections at a dosage of 0.4 mg moxidectin/kg b.w., was highly effective against a broad range of equine parasitic infections.

Growth promoting hormonal implant pellets coated with a polymeric, porous film promote weight gain by grazing beef heifers and steers for up to 200 days.

Two studies evaluated growth promoting effects of implant pellets (IP), each containing 3.5 mg estradiol benzoate (EB) and 25 mg trenbolone acetate (TBA), to which a polymeric, porous coating was applied. Trial 1 evaluated performance of heifers (n = 70/treatment, initial BW = 188 ± 2.2 kg) and steers (n = 70/treatment, initial BW = 194 ± 2.2 kg) implanted subcutaneously in the ear with 0 (SC), 2 (2IP), 4 (4IP), or 6 (6IP) pellets that delivered EB/TBA (mg/mg) doses of 0/0, 7/50, 14/100, and 21/150, respectively, over grazing periods of 202 d (heifers) or 203 d (steers). Animals received experimental treatments on d 0 and over the grazing period were managed as single groups by sex in a rotational grazing system. When pasture forage availability became limited, cattle were supplemented with preserved forage but not concentrate supplements. Weight gains by heifers treated with 2IP, 4IP, and 6IP were greater (P < 0.05) than SC heifers but not different from each other. Weight gains by steers treated with 2IP, 4IP, and 6IP were greater than SC steers (P < 0.05), and ADG by steers treated with 6IP was greater (P < 0.05) than steers given 2IP or 4IP. Trial 2 was a multisite grazing study performed with heifers and steers to compare ADG after treatment with one 6-pellet, coated implant delivering 21 mg EB and 150 mg TBA (6IP) to sham treated negative controls (SC) over a grazing period of at least 200 d. A completely random design was used at each site, with the goal to treat 70 cattle per site, treatment, and sex; data were pooled across sites. Heifers (n = 558, initial BW = 229 ± 16 kg) and steers (n = 555, initial BW = 235 ± 20 kg) grazed in rotational programs consistent with regional practices for an average of 202 d. When necessary, cattle were supplemented with preserved forage, but no concentrate supplements were fed. Over 202 d, ADG by heifers treated with 6IP was 11.3% greater (P = 0.0035) than SC heifers (0.64 ± 0.06 kg/d), and ADG by steers treated with 6IP was 17.2% greater (P = 0.0054) than SC steers (0.66 ± 0.08 kg/d). In neither study was there evidence that concurrent therapeutic treatments or abnormal health observations were influenced by experimental treatments. These studies demonstrated that a 6-pellet implant with a polymeric, porous coating that delivers 21 mg EB and 150 mg TBA improved ADG by grazing heifers and steers for at least 200 d compared to sham-implanted negative controls.

Fracture site-specific deficits in bone size and volumetric density in men with spine or hip fractures.

To study the structural basis of bone fragility in men, we compared bone size and volumetric bone mineral density (vBMD) of the third lumbar vertebra and femoral neck in 95 men with spine fractures, 127 men with hip fractures, and 395 healthy controls using dual-energy X-ray absorptiometry (DXA). The results were expressed in absolute terms and age-specific SD scores (mean +/- SEM). In controls, vertebral body and femoral neck width increased across age, being 0.46 +/- 0.11 SD and 0.91 +/- 0.08 SD higher in elderly men than in young men, respectively (both,p < 0.001). Men with spine fractures had reduced vertebral body width (-0.45 +/- 0.10 SD;p < 0.01) but not femoral neck width (-0.15 +/- 0.10 SD, NS). Men with hip fractures had reduced femoral neck width (-0.45 +/- 0.11 SD; p < 0.01) and vertebral body width (-0.25 +/- 0.10 SD; p < 0.05). The deficits in bone volume (BV) exaggerated the deficits in bone mineral content (BMC) by 40% at the vertebrae in men with spine fractures and by 9% at the femoral neck in men with hip fractures. vBMD deficits were greater at the vertebrae in men with spine fractures than in men with hip fractures (-1.37 +/- 0.08 SD vs.-0.70 +/- 0.10 SD, respectively; p < 0.01) but were similar at the femoral neck (-0.93 +/- 0.10 SD and -0.76 +/- 0.11 SD, respectively, NS), despite the men with spine fracture being 10 years younger. Bone fragility leading to spine or hip fractures in men may be the result of fracture site-specific deficits in bone size and vBMD that have their origins in growth, aging, or both.

The contribution of reduced peak accrual of bone and age-related bone loss to osteoporosis at the spine and hip: insights from the daughters of women with vertebral or hip fractures.

The genetic hypothesis states that a daughter will resemble her mother by about 50% in a given trait because she shares, on average, half her genes. We used this trait resemblance in mothers and daughters to determine whether abnormalities in volumetric bone mineral density (vBMD) or bone size in women with fractures originate in growth or aging. vBMD and volume of the third lumbar vertebra and femoral neck were estimated using posteroanterior (PA) scanning by dual-energy X-ray absorptiometry (DXA). Vertebral volume was estimated as (scan area)(3/2) and femoral neck volume was pi* (width/2)(2)* height. vBMD was bone mineral content (BMC)/volume. The data were expressed as age-specific SD or Z scores (mean +/- SEM). Vertebral vBMD was reduced by -0.98 +/- 0.14 SD (p < 0.001) in 34 women with vertebral fractures, and by -0.36 +/- 0.13 SD (p < 0.05) in their 44 premenopausal daughters. The vBMD deficit in the daughters (relative to age-matched controls) was no different from one-half their mothers' deficit (relative to their age-matched controls). Vertebral volume was reduced in the women with vertebral fractures relative to age-matched controls (-0.77 +/- 0.15 SD; p < 0.001), but not in their daughters (-0.17 +/- 0.13 SD, NS). The 31 women with hip fractures and their 41 premenopausal daughters had no deficits in vertebral volume or vBMD. Femoral neck vBMD was reduced in the women with hip fractures (-1.24 +/- 0.12 SD; p < 0.001) but not in their daughters (-0.17 +/- 0.13 SD, NS). Femoral neck volume was increased by 0.98 +/- 0.30 SD (p < 0.05) in women with hip fractures (relative to age-matched controls) and by 0.54 +/- 0.14 SD (p < 0.001) in their daughters (relative to age-matched controls); that is, about one-half that of their mothers. We propose that women with vertebral fractures have reduced vertebral vBMD because of, in large part, reduced accrual of bone during growth (because the deficit in their daughters was almost one-half their mothers' deficit); reduced vertebral volume in women with vertebral fractures is caused by reduced periosteal apposition during aging (because their daughters have no deficit in vertebral volume). Women with hip fractures have reduced vBMD because of age-related bone loss (because their daughters have no deficit in vBMD) but the increased femoral neck volume is growth related (because their daughters' femoral neck size is increased by one-half as much). The pathogenesis of bone fragility at the axial and appendicular skeleton is heterogeneous and has its origins in growth and aging.

Copper, iron, zinc, and manganese in dietary supplements, infant formulas, and ready-to-eat breakfast cereals.

High intakes of iron, zinc, or manganese can interfere with copper absorption. Thus, the purpose of this study was to determine whether the amounts and chemical forms of iron, zinc, manganese, and copper added to food products and nutritional supplements might pose a threat to copper status. More than 25% of the vitamin and mineral supplements examined contained no copper, 40% contained the poorly absorbed cupric oxide, and < 30% contained a highly bioavailable form of copper such as cupric sulfate or cupric chloride. Nearly 40% of the prenatal supplements examined contained both iron and zinc without a nutritionally significant amount of copper. More than 80% of the infant formulas examined had ratios of iron to copper exceeding 20:1, which is higher than the recommended ratios of 10-17:1. None of the 40 ready-to-eat breakfast cereals examined were fortified with copper or manganese although 50% of these cereals contained > or = 25% of the reference daily intake for both iron and zinc. Copper availability could be improved by reformulation of several food products and supplements.

Age-related hearing loss, vitamin B-12, and folate in elderly women.

BACKGROUND: Hearing impairment is 1 of the 4 most prevalent chronic conditions in the elderly. However, the biological basis of age-related hearing loss is unknown. OBJECTIVE: The objective was to test the hypothesis that age-related hearing loss may be associated with poor vitamin B-12 and folate status. DESIGN: A thorough audiometric assessment was conducted in 55 healthy women aged 60-71 y. Hearing function was determined by the average of pure-tone air conduction thresholds at 0.5, 1, 2, and 4 kHz and was categorized into 2 groups for logistic regression analyses: normal hearing (<20 dB hearing level; n = 44) and impaired hearing (> or = 20 dB hearing level; n = 11). RESULTS: Mean age was the same (65 y) for the normal hearing and impaired hearing groups. Pure-tone averages were inversely correlated with serum vitamin B-12 (r = -0.58, P = 0.0001) and red cell folate (r = -0.37, P = 0.01). Women with impaired hearing had 38% lower serum vitamin B-12 (236 compared with 380 pmol/L, respectively, P = 0.008) and 31% lower red cell folate (425 compared with 619 nmol/L, respectively, P = 0.02) than women with normal hearing. Among participants who did not take supplements containing vitamin B-12 or folate, women with impaired hearing had 48% lower serum vitamin B-12 (156 compared with 302 pmol/L, respectively, P = 0.0007) and 43% lower red cell folate (288 compared with 502 nmol/L, respectively, P = 0.001) than women with normal hearing. CONCLUSION: Poor vitamin B-12 and folate status may be associated with age-related auditory dysfunction.

Dyslexia and corpus callosum morphology.

OBJECTIVE: There is evolving evidence that developmental dyslexia is associated with anomalous cerebral morphology in the bilateral frontal and left temporoparietal regions. This study examined the morphology of the corpus callosum, as possible deviations in other important structures are poorly understood in this behaviorally diagnosed syndrome. DESIGN: Magnetic resonance imaging scans were obtained from children with developmental dyslexia and from matched control children. Morphometric measurements were examined to determine if regional differences existed in the corpus callosum between these two groups of children. SETTING: Magnetic resonance imaging studies were completed at Athens (Ga) Magnetic Imaging. PATIENTS AND OTHER PARTICIPANTS: Sixteen developmental dyslexic children (mean age, 9.7 years) and a matched sample of children who were diagnosed as being normal were examined by using a reliable comprehensive diagnostic process. MAIN OUTCOME MEASURES: Using a midsagittal magnetic resonance imaging scan, corpus callosum morphology was evaluated by segmenting the corpus callosum into five regions of interest. RESULTS: Analysis of the corpus callosum revealed that the anterior region of interest (the genu) was significantly smaller in the dyslexic children. Significant correlations existed between reading achievement and the region-of-interest measurements for the genu and splenium. Measured intelligence, chronologic age, and gender were not related to region-of-interest measurements of the corpus callosum. Consistent with previous studies, the dyslexic individuals were characterized by significant psychiatric comorbidity, particularly attention-deficit disorder with and without hyperactivity. Reported familial left-handedness also distinguished the dyslexic children. CONCLUSIONS: Subtle neurodevelopmental variation in the morphology of the corpus callosum may be associated with the difficulty that dyslexic children experience in reading and on tasks involving interhemispheric transfer.

Diaphragm function and lung involvement in systemic lupus erythematosus.

Lung involvement was assessed in 30 consecutive patients with systemic lupus erythematosus (SLE), not selected by respiratory symptoms. Pulmonary function tests revealed a higher rate of abnormality than either clinical history or radiography. The single breath carbon monoxide diffusing capacity was below 80 per cent of the predicted value in 24 patients (80 per cent), and a reduced total lung capacity was present in 13 (43 per cent). There was a weak correlation between the severity of the functional defect and disease activity, assessed antinuclear factor and DNA binding. No correlation was found with serum complement of Clq precipitation. Since pulmonary fibrosis in SLE is uncommon it cannot account for the high frequency of abnormal findings, and the pathogenesis of the functional changes is probably multifactorial. In seven of the patients with the smallest lung volumes, measurements of static pressure volume curves and of maximum respiratory pressures indicated extrapulmonary volume restriction. In five of these patients, diaphragm function was specifically assessed and found to be grossly abnormal in four. The inability of the diaphragm to generate normal pressure may be due to either severe weakness or immobility following extensive pleural adhesions. The well recognized syndrome of "shrinking lungs" and high "sluggish" diaphragms with clear lung fields on radiography is probably due to dysfunction of the diaphragm rather than to primary intrapulmonary pathology.

Cross-reacting bacterial determinants in ankylosing spondylitis.

The importance of the association between the human histocompatibility antigen human leukocyte antigen-B27 and ankylosing spondylitis is undisputed, but its biologic significance remains unresolved. We have demonstrated specific cross reactivity between a range of enteric bacteria and a specific determinant found only on the surfaces of cells from human leukocyte antigen-B27-positive persons with ankylosing spondylitis. We have proposed that the genetic element coding for this cross-reactive determinant is mobile and that its acquisition by B27-positive cells in vivo represents an important step in the eventual development of ankylosing spondylitis.

Development and validation of an automated method of the Selvester QRS scoring system for myocardial infarct size.

The Selvester QRS score for estimation of myocardial infarct (MI) size from the standard 12-lead electrocardiogram (ECG) has not yet achieved wide recognition as a valuable tool in the routine assessment of the MI patient, primarily because of the practical limitations inherent to manual application. This study examined the ECGs of 438 patients (105 normal subjects, 161 with "possible" MI and 172 with "definite" MI based on data from cardiac catheterization) to develop software for an automated method of the Selvester system in attempts to overcome the manual constraints. After a comprehensive validation process involving extensive interactions between the manual scorer and the software developer, an automated method of the Selvester system was generated that had a high correlation with manual application (r = 0.94) and was superior regarding time, training, reader bias, reproducibility and precision of measurement. These results indicate that an automated version of the Selvester QRS scoring system would resolve many of the limitations of manual application and would provide a reliable, technically accurate estimate of MI size that could be incorporated into ECG diagnostic programs and used in standard digital ECG machines.

Search for Klebsiella cell wall components cross-reactive with lymphocytes of B27+ AS+ individuals.

It has been suggested that some Klebsiella sp may cross-react with a cell surface determinant on the lymphocytes of B27+AS+ individuals. Studies were undertaken to identify culture filtrates capable of rendering the lymphocytes of B27-positive healthy controls susceptible to lysis by the anti-Klebsiella antiserum. Polyacrylamide gel electrophoresis of cell wall material of Klebsiella K43 prepared by sonication, high-speed centrifugation, and nonidet solubilization, demonstrated the presence of four major protein bands. When antisera raised in rabbits to each of these were tested for their cytotoxic effect on the lymphocytes of B27+AS+ individuals, an antiserum to one component only, of 40-52 K daltons molecular weight, reproduced the activity of the whole serum. Studies on the K43 filtrate indicated that the 'modifying' factor appeared to reside in a 25-50 K dalton component. Immunoelectrophoresis against anti-K43 serum demonstrated overlapping bands in the culture filtrate and the 40-52 K dalton cell wall fraction and these appeared to be identical on immunodiffusion. Antibody to the cell wall component removed both the 'modifying' activity and the appropriate protein band from the filtrate. The results suggest that a 40-52 K dalton component of the Klebsiella K43 cell wall is cross-reactive with a determinant on the lymphocytes of B27+AS+ individuals and is similar to or identical with a modifying factor in K43 culture filtrate which renders the lymphocytes of B27-positive healthy controls susceptible to lysis by anti-Klebsiella antiserum.

Immunochemical characterization of Klebsiella antigens which specifically modify an HLA-B27-associated cell-surface component.

Culture filtrates of some Klebsiella isolates contain a factor(s) capable of specifically modifying the HLA-B27-positive lymphocytes of normal individuals, resulting in a phenotypic change similar to that seen on lymphocytes from patients with ankylosing spondylitis (AS). To further delineate the nature of the interaction between HLA-B27 and some Klebsiella products we have undertaken a chemical characterization of B27+AS+-cross-reactive Klebsiella antigens from the culture filtrate and the bacterial cell-membrane. Biogel P-100 chromatography of the Klebsiella K43-derived modifying factor from the culture filtrate and from an NP-40-solubilized membrane extract gave a molecular weight of 26,000-30,000. Isoelectric focusing revealed that the modifying factor had an isoelectric point of approximately 5.4. Membrane-associated modifying factor activity was found only in outer-membrane preparations indicating that the cross-reactivity between Klebsiella K43 and B27+AS+ cells is defined, at least in part, by outer-membrane antigens. These studies demonstrate that membrane components of Klebsiella K43 share antigenic determinants with a modifying factor, which is released into the culture medium, and that these components are capable of specifically altering the HLA-B27 antigen or an associated cell-surface structure. Such a modification occurring in vivo following exposure to Klebsiella, or to antigenically related organisms, could explain the triggering of the B27-associated arthropathies such as AS.

Phrenic nerve paralysis after pediatric cardiac surgery. Retrospective study of 125 cases.

Phrenic nerve paralysis was diagnosed in 125 children (1.6%) from a series of 7,670 cardiac surgical procedures in infants and children during a 12 year period. The incidence was 1.9% for open heart and 1.3% for closed heart operations. In order of decreasing incidence, the open heart procedures included Mustard procedure (6.7%), right ventricular outflow tract reconstruction (5.6%), and repair of tetralogy of Fallot (2.7%). The closed heart procedures included Glenn anastomosis (6.2%), Blalock-Hanlon atrial septectomy (5.9%), and right Blalock-Taussig shunt (5.1%). Procedures following previous operations or thoracotomies had almost twice the incidence of phrenic nerve paralysis: Mustard procedure 9.9%, right ventricular outflow tract reconstruction 10.8%, and tetralogy repair 5.5%. Seven patients (5.6%) with phrenic nerve paralysis died. Patients less than 2 years old with phrenic nerve paralysis were intubated for 0 to 57 (average 15.7) days after their cardiac operations and those over 2 years old for 13 to 35 (average 7.2) days (p less than 0.001). Twelve patients had diaphragmatic plication without mortality and were extubated 0 to 6 (average 2.3) days after plication. We have made the following conclusions: (1) Phrenic nerve paralysis may occur after both open and closed cardiac procedures and is more common in children requiring reoperation; (2) it is associated with considerable morbidity; (3) eventual recovery of phrenic nerve function occurs in 84% of children; and (4) diaphragmatic plication is safe, reliable, and of most value in patients who are under 2 years of age and require mechanical ventilation for more than 2 weeks.