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Evaluation of assays of serum IgG subclasses and IgG antigen-specific antibodies in the investigation of recurrent infection.

Patients who have recurrent infections require laboratory investigation for possible underlying immunodeficiency. We retrospectively evaluated the usefulness of two relevant assays (serum IgG subclass concentration and levels of IgG antigen-specific antibodies to a panel of relevant carbohydrate and protein antigens) in the management of patients referred to a regional clinical immunology service over a 3-year period. Of 97 patients for whom both assays were performed, five (5.2%) had a low result for IgG subclasses but this did not influence the management of any patient; 51 patients (53%) had a low result for antigen-specific antibodies and this influenced management in 43 cases. We conclude that knowledge of the serum IgG subclass concentrations is of dubious relevance and this calls into question whether the assay should continue to be offered. This regional service has ceased to perform the assay routinely in such patients. Our findings require confirmation by a larger multicentre study that should assess the clinical outcome of any changes in practice.

Adolescent↗

A simple method for estimating equilibrium constants for serum testosterone binding resulting in an optimal free testosterone index for use in elderly men.

An algorithm was developed to evaluate equilibrium constants for testosterone (Te) and sex hormone-binding globulin (SHBG) or albumin from serum free testosterone (FTe) measurements performed in a panel of 30 healthy elderly men by means of a near-reference method, i.e., symmetric dialysis (affinity constants: SHBG-Te, 1.13 x 10(9) L/mol; albumin-Te, 4.4 x 10(4) L/mol). Using these estimates, a free testosterone index (FTeI) was calculated from total Te and SHBG concentrations in a further 35 elderly men. This FTeI perfectly matches with actually measured free testosterone concentrations by symmetric dialysis in this second group, with a mean ratio index/measurement of 0.998+/-0.016 (SEM). The efficacy of the algorithm, which represents a simple alternative to previous cumbersome methods for estimation of equilibrium constants, is thereby demonstrated.

Aged↗

Clinical signs, magnetic resonance imaging features, and outcome after surgical and medical treatment of otogenic intracranial infection in 11 cats and 4 dogs.

Brainstem dysfunction resulting from central extension of infection is a life-threatening complication of otitis media/interna (OMI) that has been described infrequently in dogs and cats. We review the clinical signs of disease, diagnostic findings, and results of surgical and medical treatments of brainstem disease attributable to otogenic intracranial infection in cats and dogs. Eleven cats and 4 dogs were examined because of acute, subacute, or chronic clinical signs of brain disease including central vestibular signs, altered mentation, abnormal posture/gait, cranial nerve deficits, and seizures. Results of a minimal database (CBC, serum biochemical panel, urinalysis, thoracic radiographs, and abdominal ultrasonographic images or radiographs) were within reference intervals in all animals. Magnetic resonance (MR) images of the head were acquired for all animals, and cisternal cerebrospinal fluid (CSF) from 9 of 11 cats and 3 of 4 dogs was examined. Surgical exploration and ventral bulla osteotomy were done for 12 of 15 animals, followed by 1-3 months of antibiotic therapy; the remaining animals were euthanized before treatment. In all animals, MR imaging was effective in characterizing the location and extent of the pathologic changes intracranially as well as within middle/inner ear structures. Results of CSF analysis were characteristic of bacterial infection in most of the animals with acute or subacute disease. Since long-term outcome in all treated animals was very good to excellent, it was concluded that dogs and cats with intracranial disease secondary to extension of otitis media/interna have a good-to-excellent prognosis when the condition was diagnosed and was treated by surgical exploration and appropriate antibiotic therapy.

Actinomyces↗

Immunohistochemical localization of S100 proteins in dorsal root, sympathetic and enteric ganglia of several mammalian species, including man.

The occurrence of S100 proteins in neurons of the mammalian peripheral nervous system is still controversial. This study was designed to investigate this topic in dorsal root ganglia (DRG) and the enteric nervous system (ENS) of several mammalian species (horse, buffalo, cow, sheep, pig, dog, rabbit and rat), as well as in DRG, paravertebral sympathetic ganglia (SG) and ENS of the adult man. Rat embryos of E17 and E19 were also examined. The material was fixed in Bouin's fixative, paraffin-embedded and processed for immunohistochemistry, combined with image analysis, using a panel of mono and polyclonal antibodies against S100alpha, S100beta or S100alpha + beta (referred to here as S100) proteins. In all species examined, strong S100 protein immunoreactivity (IR) was found in satellite glial cells and Schwann cells, which also showed S100alpha and S100beta IR in humans. Furthermore, faint S100 protein IR was observed in a subpopulation of DRG intermediate- and large-sized sensory neurons in humans, buffalo, sheep, and pig. The rat was the only species showing clear S100 and S100beta in neurons, labelling in about 30-35% in adults (small, intermediate and large in size), and about 88% at E17 and 42% at E19, respectively. Weak S100alpha protein IR was observed in most of human SG neurons. In ENS, S100 protein IR was restricted to enteric glial and Schwann cells, with the exception of cow and goat in which a subset of neurons in both the myenteric and submucous plexuses displayed strong S100 protein IR. Neuronal S100alpha IR and glial S100beta IR was found in the human ENS. The present results demonstrate intra- and inter-specific differences in the expression of S100 proteins by neurons of the peripheral nervous system among mammalian species. Furthermore, they also suggest that neuronal S100 protein, at least in humans, consists of both S100alpha and S100beta.

Animals↗

Results of a physician and respiratory therapist collaborative effort to improve long-term metered-dose inhaler technique in a pediatric asthma clinic.

BACKGROUND: Despite advances in therapy, asthma continues to be the chronic condition most responsible for school absenteeism and pediatric hospitalizations. This is especially true for inner-city children. We operate an inner-city Pediatric Asthma Compliance and Technique (PACT) clinic in which physicians and respiratory therapists collaborate to improve metered-dose inhaler (MDI) technique and outcomes among asthmatic children. OBJECTIVE: To determine the efficacy of our strategy for improving MDI technique and asthma outcomes. METHODS: Children referred to the PACT clinic underwent standardized assessment based on the Expert Panel Guidelines of the National Heart, Lung, and Blood Institute (NHLBI). Clinicians demonstrated and reinforced correct MDI technique at each visit. Using a standardized format we prospectively collected, at the patient's first visit (T1) and most recent visit (T2), data on demographics, MDI-technique scores (MDI steps done correctly; scale of 0-8), pulmonary function, and asthma severity (NHLBI classification scale: 1 = mild intermittent to 4 = severe persistent). Statistical analyses were performed using parametric and non-parametric tests. RESULTS: Of the 60 patients who attended the PACT clinic between 1999 and 2002, 15 were excluded from the study because of incomplete data recording. Mean duration from T1 to T2 was 11.8 +/- 9.5 months. At T1 and T2, respectively, the mean MDI-technique scores were 53% and 81%, the mean overall asthma severity scores were 2.6 and 2.3, and the mean overall pulmonary function severity scores were 2.4 and 2.1. MDI-technique scores significantly improved between TI and T2 (p < 0.001). The black patients had the largest improvement in MDI technique (p < 0.001), but their pulmonary function test results, overall asthma severity, and pulmonary function severity did not improve significantly. The white patients significantly improved both their MDI technique (p = 0.004) and their overall asthma severity scores (p = 0.005). CONCLUSION: In our PACT clinic asthmatic children showed sustained improvement in MDI technique, and some of the patients improved in pulmonary function and overall asthma severity score.

Administration, Inhalation↗

Neuro-ocular Lyme borreliosis.

Any patient who has a Bell's palsy (unilateral or bilateral), aseptic meningitis, chronic fatigue syndrome, atypical radiculoneuropathy, presenile dementia, atypical myopathy, or symptoms of atypical rheumatoid arthritis should be asked specifically about the following: visits to highly endemic areas, any known tick bites, any skin lesion suggestive of erythema migrans, any history of palpitations or of prior Bell's palsy, aching in joints (especially the knees), paresthesias, chronic fatigue and depression, forgetfulness, and eye problems. Any patient showing a chronic iritis with posterior synechiae, vitritis in one or both eyes, an atypical pars planitis-like syndrome, big blind spot syndrome, and swollen or hyperemic optic discs should be asked the same questions. The physician should send one red-top tube of blood containing 2 to 3 ml serum to Microbiology Reference Laboratory, 10703 Progress Way, Cypress, CA 90630-4714, requesting a Lyme/treponemal panel. For $90 the patient will receive an RPR test with titer, serum FTA-ABS test, serum Lyme IFA IgG and IgM, and a serum Lyme ELISA test. If these tests are within normal limits and the physician is still suspicious, a Western blot can be ordered on serum. A green top tube with fresh white blood cells sent out by overnight express on a Monday or Tuesday will produce a Lyme PCR and a lymphocyte stimulation test. Finally, R.K. Porschen, director of MRL Laboratory, will provide information on the urine antigen test on an investigational basis. A careful history with emphasis on the specific questions noted above, a complete neuro-ophthalmological and physical examination ruling out other causative problems, and the laboratory studies here discussed will usually provide sufficient data to choose therapy. Much further active research into Lyme borreliosis is an important priority in medicine.

Adult↗

The treatment of sleep disorders of older people.

The National Institutes of Health Consensus Development Conference on the Treatment of Sleep Disorders of Older People brought together clinical specialists in pulmonology, psychiatry, psychology, geriatrics, internal medicine, other health care providers, and the public to address the cause, diagnosis, assessment, and specific treatments of sleep disorders of older people. Following 1 1/2 days of presentations by experts and discussion by the audience, a consensus panel weighed the scientific evidence and prepared a consensus statement. Among their findings, the panel concluded that although sleep patterns change during the aging process most older people with sleep disturbances suffer from any of a variety of medical and psychosocial disorders. The panel recommended that the diagnostic evaluation of sleep disorders begin with a careful clinical evaluation performed by an informed primary care physician. When necessary, referrals should be made to individuals or centers with specialized skills and tools for therapy. The panel recognized two types of disorders for which treatment may be beneficial: obstructive sleep apnea and insomnia. The mainstay for treatment for sleep apnea is the use of nasal continuous positive airway pressure. A thorough medical evaluation is essential prior to initiating treatment for insomnia, as its causes may be of psychiatric, pharmacological, or medical origin. The panel recommended that hypnotic medications not be the mainstay of treatment for insomnia as they may have habit forming potential if overused. The full text of the consensus panel's statement follows.

Aged↗

Differential effect of human and mouse beta 2-microglobulin on the induction and the antigenic profile of endogenous HLA-A and -B antigens synthesized by beta 2-microglobulin gene-null FO-1 melanoma cells.

beta 2-Microglobulin (beta 2-mu) gene-null human melanoma FO-1 cells display lower reactivity with anti-HLA class I monoclonal antibodies (mAb) following transfection with a wild-type mouse beta 2-mu gene (referred to as FO-1C cells) than following transfection with a wild-type human beta 2-mu gene (referred to as FO-1H cells). Furthermore, binding assays with a panel of anti-HLA class I mAb detected higher reactivity of FO-1C cells with mAb TP25.99 than with mAb CR1-S63, CR10-215, CR11-115, TP67, and W6/32 but similar reactivity of FO-1H cells with all the mAb tested. While mAb TP25.99 recognizes a determinant expressed on beta 2-mu-free and beta 2-mu-associated HLA class I heavy chains, the remaining mAb recognize determinants expressed only on beta 2-mu-associated HLA class I heavy chains. The differential effects of mouse and human beta 2-mu on the reactivity with anti-HLA class I mAb of FO-1 cells reflect more than one mechanism. Besides abnormalities in the processing of HLA class I heavy chains associated with mouse beta 2-mu, this molecular complex appears to be unstable on the plasma membrane of FO-1 cells. To analyze the interaction of mouse beta 2-mu with HLA-A and -B antigens, the HLA phenotype of FO-1 cells was determined, using a combination of isoelectric focusing analysis of antigens immunoprecipitated from radiolabeled cells with mAb to monomorphic determinants of HLA class I antigens, binding assays with a limited number of mAb recognizing HLA class I allospecificities, and sequence-specific oligonucleotide probe typing. Although association with mouse beta 2-mu does not cause marked differences in the expression of HLA-A25 and -B8 antigens on the cell surface of FO-1 cells, it causes a selective reduction in the expression of determinants recognized by anti-HLA-A mAb F4/72 and VF19-LL67 and by anti-HLA class I mAb W6/32 on HLA-A25 allospecificities. The differential effect of the association with mouse beta 2-mu on the antigenic profile of HLA-A25 and -B8 antigens may reflect the different characteristics of the amino acids at residue 12, which interact with residue 33 of beta 2-mu. The latter residue is the only one to differ between human and mouse beta 2-mu in the stretch of amino acids interacting with the alpha 1 and alpha 2 domains of HLA class I heavy chains.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Discovering asymptomatic biochemical abnormalities on a Baltimore internal medicine service.

To assess the frequency of abnormalities that could be discovered through biochemical profile screening on patients admitted to a city hospital internal medicine ward service, we conducted a prospective cross-sectional chart and laboratory review. All unassigned patients admitted to the general medicine service during 1- to 2-month period in late 1993 and the spring of 1994 were eligible. The main outcome measures were frequency of abnormal test results and identification of significance. Admitted patients (N = 222) were evaluated with a 24-panel biochemical profile. Of 5,328 tests, 29% were outside the standard reference range. Of 3,851 tests classified as screening, 1,049 (27%) were outside the reference range. Of overall screening tests, 741 (19%) were judged potentially important by the predetermined criteria. The prevalence did not differ significantly when analyzed by age, race, gender, or history of substance abuse. Our experience indicates that asymptomatic biochemical abnormalities are common in patients admitted to a city hospital medical service and that admission biochemical screening is an effective method of identifying potential comorbidity. Further studies are needed to assess the impact of this approach.

Adolescent↗

Some views of psychic reality.

This paper is based on the Presidential Address given at the end of the San Francisco Congress in August 1995. The author concentrates on discussing the three main Panel presentations on psychic reality from the technical, clinical and theoretical perspectives and in the context of the life cycle. Referring to Grinberg's introduction to the Congress, he reiterates that psychic reality forms the central point from which psychoanalysis can be contemplated. A special mention is given to the Panel on multidisciplinary perspectives of psychic reality, which includes contributions from two well-known philosophers, in connection with the current epistemological status of psychoanalysis in the context of the Congress's main theme. The author concludes by quoting a sonnet, which he feels illustrates the complex dialectic between reality and fantasy, between truth and lies.

Deception↗

[Serologic studies on the occurrence of bovine ehrlichiosis in the cantons Zürich, Schaffhausen, Thurgau, St. Gallen and Obwalden].

The purpose of this study was to investigate the geographical distribution of bovine ehrlichiosis in the Cantons Zürich, Schaffhausen, Thurgau, St. Gallen and Obwalden. To this end, an indirect immunofluorescence assay was established. The diagnostic sensitivity and specificity was estimated to be close to 100% based on the results obtained with several reference sera from the US National Veterinary Services Laboratories and the seroconversion panels of 20 heifers and cows. Blood samples from 2557 healthy cattle were tested for antibody response against Ehrlichia phagocytophila. Ninety-three animals (3.6%) were seropositive with titers ranging from 1:20 to 1:320. Most of the positive animals were found in the area north of lake Zürich spanning to the german border, in the area between Walensee and Bad Ragaz, the Rhine valley and Klein Melchtal. All seropositive animals had grazed on pastures or alps with a favourable biotope for the tick Ixodes ricinus.

Animals↗

Use of a major medical center clinical laboratory as a reference laboratory for a developing country: ordering patterns help set laboratory priorities.

BACKGROUND: The test menus for developed and developing countries may differ, depending on many factors, including the expected volume of testing, disease frequency and therapies available, clinical impact of the test, technical skill and equipment needed, cost, the patient population served, and whether alternative testing sites are available, and some of them may not be exactly known. We assessed test priorities in a developing country by making a broad range of tests available and then assessing which tests were actually used by the physicians in the country for the care of their patients. METHODS: The Barnes-Jewish Hospital laboratory and Washington University Medical Center provided patients in the developing country of Eritrea access to the same tests as patients in St. Louis for all analytes that are stable at 4 degrees C, the lowest temperature that could be used for shipping. RESULTS: The use of the St. Louis laboratories increased steadily from 1998 to 2001. More than one-half of the physicians in Eritrea used the reference laboratories, with requests for thyroid function and female fertility representing 48-71% of the test requests over the 4 years evaluated. The high degree of utilization for these test batteries was not predicted. Testing for thyroid function, female fertility, and lipid panels are now performed, or soon will be performed, in Eritrea based on the experience of the reference laboratory system. The reference laboratory system is continuing so that the test priorities of the country can be evaluated on an ongoing basis and specialized tests can be made available at a low cost. CONCLUSION: The experiences of a reference laboratory for a developing country can help to identify unanticipated priorities for medical testing within the country.

Clinical Laboratory Techniques↗

A government sponsored clinic for the evaluation and treatment of chronic hepatitis C in an underinsured population in Puerto Rico.

BACKGROUND: Chronic hepatitis C (CHC) is a major health problem in Puerto Rico (PR). More than 50% of the population is insured by a government-sponsored managed care system that does not cover treatment for CHC. Lack of access to treatment will result in an increase in end-stage liver disease with its high socioeconomic impact in the future. In an attempt to identify strategies for the treatment of CHC in the publicly insured population, the PR Health Department and the University of Puerto Rico (UPR) Gastroenterology (GI) Division have developed a pilot clinic for the evaluation and treatment of CHC. METHODS: UPR and the PR Health Department negotiated a fee per patient to include all medical care and follow-up laboratories. Viral studies were covered by a grant to the Health Department. Medications were bought at a discount price by the government and dispensed at a government pharmacy. The Health Department allocated funds for 200 patients with government insurance. A dedicated clinic was established at the UPR, staffed by an internist under the supervision of the GI faculty. Patients with a positive HCVab were referred to this clinic. The public insurance covered the CBC, liver tests, metabolic panel, TSH, HBsAg, HIV, ultrasound and liver biopsy, which were required prior to evaluation for possible treatment. In the initial visit, patients underwent a medical evaluation, including assessment of suitability for therapy and counseling. Those deemed to be candidates who still needed a liver biopsy had it performed by the GI staff. Genotype and viral titers were ordered after the decision on treatment had been made. The clinic physician prescribed pegylated interferon and ribavirin, which were dispensed by the government pharmacy. Instruction on proper drug administration was given. Clinic visits were scheduled for 1, 3, 6 and 12 months but also allowed on demand. Laboratory tests were done at the clinic and reviewed by the physician expediently to monitor for toxicity. Any medical problems or treatment for complications of therapy were covered by the primary insurer. Viral load was repeated at 12 weeks to discontinue therapy in those unlikely to respond. The budget per patient for medical visits and laboratory tests was dollars 1,500.00, HCV RNA titers plus genotype costs dollars 200.00, and HCV qualitative RNA costs dollars 123.00 RESULTS: 405 patients have been referred between February 2002 and April 2003 (the number was increased at adjust for no-shows and those not treated). 30% are female, the major risk factor is IVDU, and 80% are unemployed. 101 have started treatment and 48 are awaiting biopsy. A support group has been established at the clinic. CONCLUSIONS: The treatment for CHC in practice is not only costly but also resource consuming. Most gastroenterologists in our community refer these patients for treatment. The establishment of a dedicated clinic with a primary physician supervised by the specialists reduces costs and facilitates caring for a larger number of patients. The volume of services allows for negotiation of medical, laboratory and drug costs. In allocating funds for this project, the PR Health Department recognized the importance in reducing the potential spread in the community by treating infected patients as well as reducing the future medical and socioeconomic burden of end-stage liver disease. Although the outcome of this project is still unseen, we believe that this model may serve to establish other clinics for the treatment of CHC at lower costs with the same effectiveness.

Adult↗

[Dose reduction of radiographs of the pediatric pelvis for diagnosing hip dysplasia using a digital flat-panel detector system].

PURPOSE: To evaluate a possible dose reduction in pediatric pelvic radiographs in congenital hip dysplasia using a digital flat-panel system instead of a phosphor-storage system. MATERIALS AND METHODS: During a six-month period, all pediatric patients referred for pelvic radiography for the evaluation of congenital hip dysplasia were randomly assigned to be examined by either a phosphor-storage system or a digital flat-panel system, whereby the latter system was operated with half the radiation dose. Thirty pairs of radiographs were assessed for the visibility of 16 anatomic details and for 5 orthopedic-radiographic measurements (5-point scale with 1 = excellent; three independent observers). The projection indices of Ball and Kommenda and of Tönnis and Brunken were calculated for all radiographs. The Student's t-test was used to compare the flat-panel and the phosphor-storage radiographs for observers' assessments, patients' age and projection indices. RESULTS: In a total of 7560 observations, the scores for the visibility of anatomic details and orthopedic-radiographic measurements were respectively 2.72 and 2.64 for the flat-panel system and 2.93 and 2.79 for the phosphor-storage system. No significant differences were found between both systems (p > 0.05) and between patient age and projection indices (p > 0.05). CONCLUSION: Pediatric pelvic radiographs can be obtained with a digital flat-panel system using half the radiation dose instead of a phosphor-storage system without sacrificing relevant information in the diagnosis of congenital hip dysplasia.

Age Factors↗

Performance of panel-based criteria to evaluate the appropriateness of colonoscopy: a prospective study.

BACKGROUND: Prospective data describing the appropriateness of use of colonoscopy based on detailed panel-based clinical criteria are not available. METHODS: In a cohort of 553 consecutive patients referred for colonoscopy to two university-based Swiss outpatient clinics, the percentage of patients who underwent colonoscopy for appropriate, equivocal, and inappropriate indications and the relationship between appropriateness of use and the presence of relevant endoscopic lesions was prospectively assessed. This assessment was based on criteria of the American Society for Gastrointestinal Endoscopy and explicit American and Swiss criteria developed in 1994 by a formal panel process using the RAND/UCLA appropriateness method. RESULTS: The procedures were rated appropriate or equivocal in 72.2% by criteria of the American Society for Gastrointestinal Endoscopy, in 68.5% by explicit American criteria, and in 74.4% by explicit Swiss criteria (not statistically significant, NS). Inappropriate use (overuse) of colonoscopy was found in 27.8%, 31.5%, and 25.6%, respectively (NS). The proportion of appropriate procedures was higher with increasing age. Almost all reasons for using colonoscopy could be assessed by the two explicit criteria sets, whereas 28.4% of reasons for using colonoscopy could not be evaluated by the criteria of the American Society for Gastrointestinal Endoscopy (p < 0.0001). The probability of finding a relevant endoscopic lesion was distinctly higher in the procedures rated appropriate or equivocal than in procedures judged inappropriate. CONCLUSIONS: The rate of inappropriate use of colonoscopy is substantial in Switzerland. Explicit criteria allow assessment of almost all indications encountered in clinical practice. In this study, all sets of appropriateness criteria significantly enhanced the probability of finding a relevant endoscopic lesion during colonoscopy.

Algorithms↗

Fine analysis of immunoreactivity of V3 peptides: antibodies specific for V3 domain of laboratory HIV type 1 strains recognize multiple V3 sequences synthesized from field HIV type 1 isolates.

Production of cross-reactive antibodies recognizing the V3 loop--that is, the principal neutralizing determinant (PND)--of various HIV-1 isolates is an important challenge in the development of passive immunotherapy or vaccinations against AIDS. We have produced two types of antibodies to the V3 domain of HIV-1: (1) antibodies against the HIV-1 MN laboratory strain generated in rabbits and (2) antibodies targeted to the HIV-1 LAI laboratory strain induced in chimpanzees. These antibodies were shown to be specific for HIV-1 subtype B. The cross-reactivity of these antibodies has been evaluated against a large panel of peptides representing different parts of the V3 loop. Seventy-five peptides, referred to as clinical peptides, were synthesized according to HIV-1 sequences recovered from PMBCs of 27 patients followed in three Parisian hospitals. Thirteen V3 peptides derived from 4 HIV-1 laboratory strains (MN, LAI, SF2, and RF) were also included in the study. The results show that both the amino-terminal and central parts of the V3 loop are immunogenic. The rabbit antibodies against the amino-terminal end of the PND proved to be highly cross-reactive against the clinical peptides. The anti-gp160 antibodies induced in one chimpanzee recognized a significant proportion of the panel of V3 clinical sequences. These antibodies cross-reacted mainly with the apex of the V3 loop. These data give some additional indications on the immunogenicity of the V3 loop and further demonstrate that extensive cross-reactivity of anti-V3 antibodies can be obtained on field HIV-1 isolates despite the high variability of the V3 loop amino acid sequence.

Animals↗

Antibody to Aspergillus fumigatus antigens in normal sera: influence on positive-negative discrimination in ELISA.

The response of precipitin-negative sera from non-selected asthmatic patients against a range of somatic and culture filtrate antigens of Aspergillus fumigatus in ELISA for anti-A. fumigatus IgG is described. Antibody to the various antigens was widely distributed but the precise distribution was dependent upon antigen type. To determine how the selection of negative reference sera from precipitin-negative sera can influence the discrimination between precipitin-positive and -negative sera in ELISA, panels of 10 sera were chosen from the extremes of the frequency distribution and by random selection. The closest agreement between precipitin testing and ELISA was seen when randomly-selected negative reference sera were incorporated in the assay, although the degree of correlation was dependent upon the detector antigen. These findings demonstrate the requirement for careful selection of sera included as negative reference sera in ELISA for anti-A. fumigatus IgG.

Antibodies, Fungal↗

The importance of adequate follow-up in defining treatment success after external beam irradiation for prostate cancer.

PURPOSE: We reviewed our institution's experience treating patients with localized prostate cancer with external beam radiation therapy (RT) to determine how differences in the length of follow-up affect the determination of treatment outcome using the American Society for Therapeutic Radiology and Oncology (ASTRO) Consensus Panel Definition of biochemical failure (BF). METHODS AND MATERIALS: From January 1987 through December 1997, 1109 patients with localized prostate cancer were treated with definitive external beam RT at William Beaumont Hospital, Royal Oak, Michigan. All patients received external beam RT to a median total prostate dose of 66.6 Gy (range: 59.4-70.4 Gy). A total of 1096 patients (99%) had sufficient prostate-specific antigen (PSA) follow-up to determine their biochemical status. To test the impact of differences in follow-up on the calculation of BF, 389 patients with at least 5 years of PSA follow-up were selected as the reference group for the initial analysis. BF was then retrospectively determined using the Consensus Panel definition at yearly intervals, ignoring the remainder of each patient's follow-up. The median follow-up for this group of patients was 6.6 years (range: 5.0-11.6 years). In a second analysis, patient cohorts were randomly selected with varying median PSA follow-up intervals in order to more accurately represent a population whose follow-up is distributed continuously over a defined range. Seven cohorts were randomly selected with 200 patients in each cohort. Cohorts were individually identified such that half of the patients (100) had 2 years or less follow-up than the stated time point for analysis and half (100) had up to 2 years more follow-up than the time point chosen for analysis. For example, in the cohort with a median follow-up of 3 years, 100 patients with a PSA follow-up from 1 to 3 years were randomly selected, and 100 patients with a follow-up from 3 to 5 years were randomly selected, thus generating a median follow-up of 3 years for this cohort (range: 1 to 5 years). This process was repeated five times for five random samples of seven cohorts each. Biochemical failure was calculated according to the Consensus Panel definition. RESULTS: In the first analysis, significantly different rates of biochemical control (varying by 6-21%) were calculated for the same actuarial year chosen for analysis depending only upon the length of follow-up used. For example, the 3-year actuarial rate of biochemical control (BC) varied from 71% when calculated with 3 years of follow-up versus 50.4% with 7 years (p < 0.01). These differences in actuarial rates of BC were observed in all subsets of patients analyzed (e.g., PSA < 10, Gleason < or = 6, n = 132,p < 0.001; PSA < 10, Gleason > or = 7, n = 33, p = 0.03; PSA > or = 10, Gleason < or = 6, n = 109, p < 0.001; and PSA > or = 10, Gleason > or = 7, n = 72, p = 0.002). The absolute magnitude of the difference in actuarial rates of BC was greatest during years 2 (range 18-30%), 3 (range 16-25%), and 4 (range 15-24%) after treatment. In the second analysis using median PSA follow-ups (as defined above), statistically significant differences in actuarial rates of BC were again observed. For example, the 3-year actuarial rate of BC varied from 74.8% with a median follow-up of 2 years versus 49.2% with a median follow-up of 6 years. These dramatic differences in BC were still observed beyond 5 years. CONCLUSION: When the ASTRO Consensus Panel definition of BF is used to calculate treatment success with external beam RT for prostate cancer, adequate follow-up is critical. Depending upon the length of time after treatment, significantly different rates of BC (varying by 15% to 30%) can be calculated for the same time interval chosen for analysis. These results suggest that data should only be reported if the length of follow-up extends at least beyond the time point at which actuarial results are examined for the majority of patients.

Aged↗