Follow-up after anaesthetic anaphylaxis.

UNLABELLED: background: the anaesthetic allergy clinic has been established at our institution for 30 years. Our practice has been to give patients a letter detailing the results of their investigations to pass on to subsequent anaesthetists. Our aims were to assess the adequacy of this letter in ensuring this vital communication, and to quantify the effectiveness of our recommendations on the safety of future anaesthesia. METHODS: a project was undertaken to contact 606 previous clinic patients living in New South Wales by using last known addresses on our database, public telephone listing and local doctors. The review also involved collecting information, where available, about subsequent anaesthesia and the adequacy of information transfer about medications given safely or otherwise at this time. RESULTS: of 606 patients, 246 were contactable. Of these, 183 had been anaesthetised subsequently, all safely. It was found that in only 11 cases had the patient's clinic letter been updated with the information from subsequent anaesthesia. We updated the letters of 82 patients with new information to improve the safety of drug selection for future anaesthesia. CONCLUSIONS: although clinic testing allowed a high degree of safety in subsequent anaesthesia, it is evident that there is a need for systems to be implemented to improve the flow of patient anaesthetic allergy information after subsequent anaesthesia.

On the origin and specificity of antibodies to neuromuscular blocking (muscle relaxant) drugs: an immunochemical perspective.

Following the demonstration 25 years ago that substituted ammonium groups on neuromuscular blocking drugs (NMBDs) are the main allergenic structures recognized by IgE antibodies in the sera of some patients who experience anaphylaxis during anaesthesia, immunoassays for these drugs were quickly applied to supplement skin tests in the diagnostic assessment of suspected adverse reactions to anaesthetic agents. Many subjects who react to an NMBD do so on first exposure and this led to the speculation that the origin of allergic sensitization is an environmental agent(s) or another drug containing an ammonium ion. Direct antibody binding and hapten inhibition studies revealed that morphine, which contains a tertiary amino group, was strongly recognized by IgE in sera from anaphylactic patients and a morphine-solid phase immunoassay was found to be superior to NMBD-based assays for the detection of NMBD-reactive IgE antibodies. Extensive inhibition experiments indicate the likelihood of antibody combining site heterogeneity with recognition at the fine structural level of features additional, and adjacent to, ammonium ions. Further quantitative investigations are needed to identify these neighbouring groups on different NMBDs. Recent work has implicated the morphine analogue pholcodine as the sensitizing agent in Norway where, unlike Sweden, anaphylactic reactions to NMBDs are not uncommon and the medicament is available over-the-counter. This has led to the suggestion that allergenic sensitization to the ammonium group of pholcodine may account for the different incidences of anaphylaxis during anaesthesia in the two countries. This work is subjected to critical review and some alternative speculations on the nature and origin of the sensitizing agent(s) are presented.

Receptor-mediated biliary transport of immunoglobulin A and asialoglycoprotein: sorting and missorting of ligands revealed by two radiolabeling methods.

In the rat, all receptor-bindable immunoglobulin A (IgA), and 1-4% of injected asialoglycoprotein (ASG), are transported from blood to bile intact. The major fraction of the ASG is degraded in hepatic lysosomes. The study described here was designed to elucidate the sorting that occurs in hepatocytes subsequent to receptor binding of ligands not sharing the same fate. We show that conjugation of protein with the Bolton and Hunter reagent can be used as a probe for the lysosomal pathway, since 50% of the reagent is released into bile after lysosomal degradation of internalized protein. Radiolabeling by iodine monochloride was alternatively used to follow the direct pathways that deliver intact IgA and ASG to bile. After intravenous injection of labeled proteins, first intact ASG and IgA, and then radioactive catabolites from degraded protein, were released into bile. No proteolytic intermediates were detected, and the transport of IgA or ASG directly to bile was not affected by the lysosomal protease inhibitor leupeptin. These observations indicate that divergence of the direct biliary transport pathways from the degradation pathway occurs at a stage preceding delivery to lysosomes, possibly at the cell surface. Competition studies showed that all three pathways (including the biliary transport of intact ASG) are receptor mediated, but even at supersaturating doses the uptake and processing of IgA and ASG occur independently. We propose that IgA and ASG receptors are not frequently in juxtaposition on the plasma membrane, but that ASG, after binding to its receptor, is occasionally missorted into the biliary transport pool.

Human IgA as a heterovalent ligand: switching from the asialoglycoprotein receptor to secretory component during transport across the rat hepatocyte.

Asialoglycoproteins are taken up by the rat liver for degradation; rat polymeric IgA is taken up via a separate receptor, secretory component (SC), for quantitative delivery to bile. There is negligible uptake of these ligands by the converse receptor, and only a low level of missorting of ligands to opposite destinations. The two pathways are not cross-inhibitable and operate independently (Schiff, J.M., M. M. Fisher, and B. J. Underdown, 1984, J. Cell Biol., 98:79-89). We report here that when human IgA is presented as a ligand in the rat, it is processed using elements of both pathways. To study this in detail, different IgA fractions were prepared using two radiolabeling methods that provide separate probes for degradation or re-secretion. Behavior of intravenously injected human polymeric IgA in the rat depended on its binding properties. If deprived of SC binding activity by affinity adsorption or by reduction and alkylation, greater than 80% of human IgA was degraded in hepatic lysosomes; radioactive catabolites were released into bile by a leupeptin-inhibitable process. If prevented from binding to the asialoglycoprotein receptor by competition or by treatment with galactose oxidase, human IgA was cleared and transported to bile directly via SC, but its uptake was about fivefold slower than rat IgA. Untreated human IgA was taken up rapidly by the asialoglycoprotein receptor, but depended on SC binding to get to bile: the proportion secreted correlated 1:1 with SC binding activity determined in vitro, and the IgA was released into bile with SC still attached. These results demonstrate that human IgA is normally heterovalent: it is first captured from blood by the asialoglycoprotein receptor, but escapes the usual fate of asialoglycoproteins by switching to SC during transport. Since the biliary transit times of native human and rat IgA are the same, it is probable that the receptor switching event occurs en route. This implies that the two receptors briefly share a common intracellular compartment.

The investigation of bronchospasm during induction of anaesthesia.

BACKGROUND: The aim of this study was to ascertain whether anaesthetic induction-related anaphylactic bronchospasm could be distinguished from other types of bronchospasm by clinical features and response to treatment. Such features could then be used to identify a group of patients in whom skin testing is indicated. METHODS: We retrospectively studied data from 183 patients referred to an anaesthetic allergy clinic because of bronchospasm during induction. For the analysis, the patients were divided into two groups depending on whether there was evidence suggesting immunological anaphylaxis. RESULTS: When the patients in whom intradermal tests were positive were compared with those in whom intradermal tests were negative, the skin test-positive patients had significantly more severe reactions, and they were more commonly associated with other clinical signs. Mast cell tryptase (MCT) was an excellent discriminator between reactions likely to be allergic and those unlikely to be allergic. CONCLUSIONS: Anaphylactic bronchospasm related to induction of anaesthesia is more likely to be severe than bronchospasm due to non-immune causes. An allergic cause is more likely if there are associated features of anaphylaxis (skin changes, hypotension, angioedema) or elevated MCT. Patients with any of these features should undergo immuno-allergolical investigation.

Radiography for the diagnosis of spirocercosis in apparently healthy dogs, St. Kitts, West Indies.

Fifty apparently healthy island dogs presenting to the Ross University School of Veterinary Medicine (RUSVM), St. Kitts, West Indies for neutering were used in this prospective study. Twelve of the dogs (24%) were diagnosed with spirocercosis based on a positive fecal analysis and characteristic lesions seen during esophagoscopy. Routine thoracic survey radiographs revealed changes previously reported with spirocercosis in 10/12 (sensitivity=83%) infected dogs, but in none of the uninfected dogs (38/38; specificity=100%). The most common radiographic changes were an increased fluid density within the caudal dorsal thorax on the lateral view and a widening and/or bulging of the caudal mediastinum on the dorsoventral view. After oral administration of barium sulfate, barium retention or a tortuous esophagus was visible in all infected dogs (12/12; sensitivity 100%) and in one uninfected dog (1/38; specificity 97%). The results show spirocercosis is common on St. Kitts and that radiographs are as dependable as fecal analysis and/or endoscopy in diagnosing the condition.

The Canadian Liver Foundation celebrates 50 years of commitment to hepatology.

Founded in 1969, the Canadian Liver Foundation (CLF) was the first foundation worldwide to support research and education relating specifically to the liver and liver diseases. This year marks its 50th anniversary. It has been highly effective in promoting hepatology in Canada.

Magnesium-rich minerals in sediment and suspended particulates of South Florida water bodies: implications for turbidity.

Fine sediments in shallow water bodies such as Lake Okeechobee are prone to resuspension. Predominantly inorganic "mud" sediment that covers approximately 670 km2 of the lake has been recognized as a persistent source of turbidity. The objective of this study was to determine if mineral components of sediments in Lake Okeechobee and water conveyances of the northern Everglades also occur as suspended sediment and hence constitute a potential abiotic contributor to turbidity. Sediment samples were collected from nine stations within the lake and eight locations north of Water Conservation Area 2A in the Everglades. Water samples were also collected at selected locations. The silt and clay mineralogy of sediment and suspended particles was determined using X-ray diffraction, thermogravimetry, scanning-electron microscopy, energy-dispersive X-ray elemental microanalysis, and high-resolution transmission-electron microscopy. Clay fractions of the lake sediment contained the Mg silicate minerals sepiolite and palygorskite, along with smectite, dolomite, calcite, and kaolinite. Sediment silt fractions were dominated by carbonates and/or quartz, with smaller amounts of Ca phosphates and sepiolite. Mineralogy of the mud sediment was similar to that reported for geologic phosphate deposits. This suggests that the mud sediment might have accumulated by stream transport of minerals from these deposits. Suspended solids and mud-sediment mineralogy were similar, except that smectite was more abundant in suspended solids. Everglade samples also contained Mg-rich minerals. The small size, low density, and fibrous or platy nature of the prevalent mud sediment minerals make them an abiotic, hydrodynamically sensitive source of persistent turbidity in a shallow lake. Mitigation efforts focused exclusively on P-induced biogeochemical processes do not address the origin or effects of these minerals. Ecological management issues such as turbidity control, P retention, geologic P input, and suitability of dredging are related to mud-sediment properties and provenance.

The validity of DSM-III-R hypochondriasis.

BACKGROUND: Because of the uncertainty about the status of hypochondriasis, the disorder is rarely diagnosed. To address this problem we examined the validity of DSM-III-R hypochondriasis as identified by structured interview. METHODS: Patients in a general medicine clinic were screened for hypochondriacal attitudes and symptoms. Those patients who scored above an established cutoff had a structured diagnostic interview, and 50 patients who met DSM-III-R criteria for hypochondriasis and 50 age- and sex-matched controls were thus identified. Information was obtained from both groups on health perceptions, health care utilization, and level of functioning using self-report and physician-rated measures. Additional information on diagnoses and treatment recommendations was obtained from record audits. RESULTS: Clinic physicians rated hypochondriacal subjects as having more unrealistic fear of illness (hypochondriasis) and diagnosed psychiatric and functional somatic syndromes more frequently in hypochondriacal than in control subjects. Hypochondriacal subjects viewed their health as worse, had more health worries, and had more severe psychiatric symptoms than control subjects. They also reported poorer physical functioning and work performance, greater health care utilization, poorer response to medical treatment, and less satisfaction with the care received than controls. CONCLUSIONS: Results show that, although the diagnosis of hypochondriasis is rarely made, physician recognition is high. They also show that several indicators of internal and external validity of this diagnostic category exist. Findings suggest that if physicians are to reduce the functional impairment and nonproductive health care utilization of these patients, they will need to make the diagnosis of hypochondriasis and intervene appropriately. However, for this to occur, research demonstrating predictive validity and treatment responsiveness of the disorder will be required.

The effects of proprioceptive neuromuscular facilitation stretching on shoulder range of motion in overhand athletes.

AIM: The purpose of this study was to compare the effects of the contract-relax-contract (CRC) and hold-relax-contract (HRC) proprioceptive neuromuscular facilitation (PNF) stretching programs against a control, on external range of motion (ROM) of the shoulder in apparently healthy athletes. METHODS: The subjects were male and female adults between the ages of 25 to 50 years old. Subjects also had been involved in at least one overhand throwing sport (tennis, baseball, quarterback in football, etc.) in the past year. There were 30 participants whom were randomly assigned to 1 of 3 groups (CRC PNF, HRC PNF, control) with 10 subjects per group. Measurement of ROM for external rotation of the shoulder was performed prior to and after 6 weeks of training using a goniometer. The CRC and HRC PNF stretches were performed on subjects twice a week for 6 weeks. The statistical analysis conducted involved a 3x2 analysis of variance with the criteria for statistical significance set at p<0.05. Post hoc testing included paired t-tests and Tukey tests to pinpoint significant differences relative to the interaction between group and time. RESULTS: There was an increase in ROM from pretest to post-test for the HRC group (+13.50 degrees) and CRC group (+14.60 degrees), but not in the control group (+0.30 degrees). The improvement in ROM however, was similar between the HRC and CRC groups. CONCLUSIONS: The CRC and HRC PNF stretching techniques are effective at increasing external shoulder ROM when consistently performed 2 times a week for 6 weeks.

Anaphylaxis to muscle relaxant drugs: cross-reactivity and molecular basis of binding of IgE antibodies detected by radioimmunoassay.

IgE antibodies that bind the muscle relaxant alcuronium were found in sera from six patients who experienced anaphylactic-like reactions following administration of the drug during induction of anaesthesia. Drug-specific antibodies were detected by radioimmunoassay employing a covalently coupled alcuronium-Sepharose complex and 125I-labelled anti-human IgE. Quantitative inhibition studies undertaken with the sera revealed specificity differences between IgE antibodies from different patients. One serum reacted with alcuronium but not with five other muscle relaxants, decamethonium, gallamine, pancuronium, succinylcholine and tubocurarine. IgE antibodies in the other sera cross-reacted with the muscle relaxants, other quaternary ammonium compounds and some pharmacologically unrelated drugs including promethazine, morphine, neostigmine and pentolineum. The inhibition experiments revealed that the alcuronium-IgE reaction could be prevented or diminished by structures containing a substituted ammonium ion. As these ions occur widely in man's environment in drugs, cosmetics, disinfectants, foods and industrial materials, it seems possible that sensitization of patients may occur without previous exposure to muscle relaxants.

Immunoassays employing substituted ammonium compounds other than neuromuscular blocking drugs to increase the detection of IgE antibodies to these drugs.

Subjects who experience life-threatening anaphylactic reactions to neuromuscular blocking drugs frequently have serum IgE antibodies that react with substituted ammonium groups on the drugs. Failure to detect drug-reactive antibodies may be due to the nature of the drug-solid support used for testing sera. With this in mind, solid phases of some selected compounds containing substituted ammonium groups, in particular triethylamine and morphine, were prepared and used to screen sera in an attempt to increase the frequency of detection of IgE antibodies complementary to tertiary and/or quaternary ammonium groups. For subjects who experienced an anaphylactic reaction to succinylcholine or gallamine, use of the supplementary assays increased the frequency of detection from 83 to 100%. For d-tubocurarine and alcuronium, detections increased from 92 to 100% and from 67 to 88%, respectively. Molecular models revealed a clear structural similarity between the conformations of the trialkylammonium groups on one face of the molecules of morphine and d-tubocurarine.

The molecular basis of IgE antibody binding to thiopentone. Binding of IgE from thiopentone-allergic and non-allergic subjects.

Thiopentone-specific IgE antibodies from the sera of subjects who experienced a life-threatening anaphylactic reaction to the drug and IgE antibodies that cross-react with thiopentone via substituted ammonium groups in either cyclic or acyclic form, were studied by direct binding immunoassays and quantitative hapten inhibition methods. Findings provided an explanation for the apparent 'non-specific' nature of some IgE antibody reactions with thiopentone and reinforce the conclusion that the thiopentone IgE immunoassay is a valuable aid in the diagnosis of immediate allergic reactions to the drug.

Secretory component as the mucosal transport receptor: separation of physicochemically analogous human IgA fractions with different receptor-binding capacities.

This paper describes the separation and characterization of several IgA fractions from the same human monoclonal source, based on their ability to bind secretory component (SC). The study was undertaken to elucidate features of the immunoglobulin-binding site for SC, and to examine the dependence of mucosal transport on IgA-SC interaction. Enrichment or depletion of SC-binding activity was accomplished on an affinity adsorbant made with SC from human colostral whey. The affinity-purified human IgA fractions contained IgA polymers and were 77% active in rebinding to the adsorbant; this activity was diminished significantly by direct radioiodination. The non-adherent IgA fractions contained both polymer and monomer, and were only 8% active in rebinding to the adsorbant. When the polymer and monomer components were separated from each other, the non-adherent polymer was found to resemble the affinity-purified fraction by all criteria examined including J-chain content, except that the SC-binding capacity was greater than five-fold lower. These findings have two implications for the SC-binding site on human IgA: first, the presence of J-chain is insufficient to bestow IgA with SC-binding activity; second, a critical tyrosine participates in maintaining the SC-binding region, possibly on the IgA heavy chain. The relationship between SC binding and mucosal transport was tested in the rat hepatobiliary model. All radiolabeled human IgA fractions were captured rapidly from blood by the rat liver, but only the SC-binding fractions underwent substantial intact transport to bile (greater than 70% of the injected dose). Even though a nominal proportion of the SC-non-adherent IgA appeared in bile (4-15% of the dose), most IgA in these fractions was rapidly degraded within the liver. Thus, only a small amount of monomeric and polymeric IgA can use alternative receptors to get to bile by diversion from the degradative pathway. Polymeric IgA can undergo efficient transport across the cell, strictly conditional on a high binding capacity for SC. This demonstrates that membrane SC is the receptor conferring specificity on the mucosal-transport pathway.

Assays for, and cross-reactivities of, IgE antibodies to the muscle relaxants gallamine, decamethonium and succinylcholine (suxamethonium).

Two radioimmunoassays have been developed to detect IgE antibodies to succinylcholine, decamethonium and gallamine in the sera of patients who have experienced life-threatening anaphylactoid reactions following administration of a muscle relaxant drug. They involve the coupling of choline and its ethyl analogue, triethylcholine to activated Sepharose. A high degree of cross-reactivity was shown to occur between drug-reactive IgE antibodies and 6 muscle relaxants as well as choline and triethylcholine. Results suggest that the specificities of the IgE antibodies are directed towards quaternary or tertiary ammonium ions on the drugs that bind the antibodies. Molecular models of these compounds support the structure-activity relationships determined in the inhibition studies.

Postesophagectomy mediastinal chylothorax causing upper airway obstruction misdiagnosed as asthma: a report of two cases.

Injury to the thoracic duct resulting in chylothorax is an uncommon but well-documented complication of esophagectomy. In two cases, which were associated with signs of life-threatening upper airway obstruction, an initial diagnosis of asthma was made. It appears that this complication of esophagectomy has not been reported previously.

Microencapsulation of viable hepatocytes in HEMA-MMA microcapsules: a preliminary study.

Viable rat hepatocytes were encapsulated in a HEMA-MMA copolymer (80% HEMA). Encapsulated hepatocytes continued to produce urea (a measure of viability) for approximately 2 wk although urea production rates fell steadily over the course of in vitro culture in a pattern similar to those of control hepatocytes in conventional culture. Urea production was slightly higher in 0.01 M Tris buffered glycerol precipitated capsules, relative to phosphate buffered saline precipitated capsules. Hepatocytes were not viable in 0.001 M Tris buffered glycerol precipitated capsules which had a dense wall without the macroporosity seen in the walls of the other capsules. More work is needed to show that HEMA-MMA encapsulated hepatocytes retain some of the differentiated functions of hepatocytes.

Heparin-induced thrombocytopaenia complicated by bilateral adrenal haemorrhage.

Acute adrenal insufficiency due to bilateral adrenal haemorrhage is an important clinical diagnosis and its association with heparin-induced thrombocytopaenia is infrequent. We report on a patient in whom life threatening acute adrenal insufficiency occurred consequent to such an association. The clinical manifestations simulated septic shock, highlighting the need to consider specifically acute adrenal insufficiency in such settings, and institute therapy promptly prior to obtaining results of confirmatory tests.

School-based health center utilization: a survey of users and nonusers.

BACKGROUND: As school-based health centers (SBHCs) continue to grow, it remains important to study use of the centers. The extent to which mental health problems exist in the students with access to the centers, whether those students are using the available services, if they are satisfied with the services, and the reasons for nonuse by those students who do not enroll are all meaningful questions. METHODS: The above issues were studied in an urban high school with a 2-year-old SBHC by administering questions during physical education classes on health center use and mental health concerns. The 630 respondents were 45% male, 55% female, 61% black, 29% Hispanic, 54% in grades 9 or 10, 46% in grades 11 or 12. RESULTS: Sixty percent of the students were registered in the SBHC; 40% were not registered. Seventy-five percent of registered students reported average use (< or =3 visits); females were more likely than males (P=.017) to be frequent (>3 visits) users of SBHC services. Mental health problems among all participants included depression in 31%, use of alcohol 1 time or more per month in 21%, use of alcohol daily in 5%, suicidal ideation in 16%, history of a suicide attempt in 10%, knowing someone who had been murdered in 50%, and being in at least 1 fight at school in 26%. Frequent users, average users, and nonusers did not differ by age, grade, race, or any of the measured mental health problems. Among the 472 students who completed the survey section on SBHC perceptions, 305 described health center use: 92% were satisfied with health center services, 79% were comfortable being seen in the SBHC, 74% believed visits were kept confidential, 61% told their parents about each visit, and 51% considered the SBHC their regular health care source. The health center was used for mental health services by 34% and sexuality-related care by 15%. The 167 students who described reasons for not using the SBHC most frequently reported that they already had a physician (60%), did not need it (50%), prefer continuing previous health care (45%), did not get around to it (30%), parents were opposed (20%), were not comfortable (19%), did not know about the service (19%), and did not want problems known (19%). CONCLUSIONS: We conclude that, in this urban high school, (1) average users, frequent users, and nonusers did not differ in the mental health problems measured in this study; (2) those who used the SBHC indicated strong satisfaction with the care received; and (3) those who did not use the SBHC chose to stay away for a variety of reasons, most commonly the availability of other care or the perception of lack of need.

Adverse reactions to plasma volume expanders.

Plasma volume expanders are effective in the restoration of blood volume. All the available plasma volume expanders may rarely induce anaphylactoid reactions, although such reactions are extremely uncommon in shocked patients. The reactions are caused by different mechanisms depending on the solution, and there is little evidence that IgE antibodies are involved. In addition to these reactions, effects on haemostasis and renal function may occur, and the persistence of hydroxyethyl starch in the body has led to concern about its potential role as a carcinogen, although there is no evidence to suggest that this has occurred.