Comparison of Multi-Test device skin testing and modified RAST results

The initial purpose of this study was to determine the potential correlation between allergy test results obtained with the Multi-Test skin testing method and the radioallergosorbent test (RAST) blood test (used as a “standard”). Twenty patients with a history and physical examination findings suggestive of inhalant allergy underwent both a Multi-Test system screen (14 antigens plus histamine and glycerine controls) and RAST testing. The relationship between wheal size and Multi-Test system grade for each antigen and the corresponding RAST class was studied. The correlation between positive Multi-Test system and RAST results was poor, with an average agreement by antigen of 56.26% and overall agreement of 67.86%. However, the overall agreement between negative Multi-Test system results (≤1+) and negative RAST results (≤class I) was 95.15%, with an average agreement by antigen of 83.99%. On the basis of results of this preliminary study, it appears that a negative Multi-Test system result indicates that significant inhalant allergy is unlikely, whereas a positive Multi-Test system result necessitates follow-up with more definitive testing by additional skin testing or RAST. (Otolaryngol Head Neck Surg 1998;118:797-9.)     

Audiovestibular dysfunction associated with adoptive cell immunotherapy for melanoma

Objective To understand the audiologic and vestibular toxicities associated with adoptive cell immunotherapy (ACI) targeting pigment-pathway antigens on melanoma and to investigate the use of intratympanic steroid injections in the treatment of these toxicities. Study Design Prospective nonrandomized study. Setting Tertiary clinical research center. Methods Thirty-two patients with progressive metastatic melanoma who failed conventional therapy underwent ACI with T cells genetically modified to target MART-1 (n = 18) or gp100 (n = 14). All patients received serial audiometric testing. Vestibular testing was performed on patients with vestibular complaints. Patients with significant deficits received intratympanic steroid injections. Results Of 32 patients, 15 had no hearing change, 9 had mild hearing loss, and 8 had moderate hearing loss following treatment. Ten patients received intratympanic steroid injections for mild (n = 2) or moderate (n = 7) hearing loss or for significant imbalance (n = 1). Of those with mild hearing loss (n = 9), all but 1 recovered to pretreatment hearing levels. Four of 8 patients with moderate hearing loss recovered to baseline hearing levels, and 4 had partial recovery. All 7 patients with posttreatment vestibular complaints had demonstrable vestibular dysfunction. Three of these patients demonstrated recovery to normal vestibular function. The number of modified T cells infused for therapy correlated with the degree of audiovestibular deficit. Conclusion Adoptive cell immunotherapy targeting pigment-pathway cell proteins, a novel therapy for melanoma, can induce hearing loss and vestibular dysfunction. The presumed mechanism of autoimmune attack on normal melanocytes in the cochlear stria vascularis and in the vestibular organs demonstrates the importance of melanocytes in normal inner ear function.     

Allergen vial mixing and immunotherapy: Risks of infections and vial contamination.

OBJECTIVE: To study the risks of vial contamination and infection associated with immunotherapy vial mixing and injection. STUDY DESIGN: Retrospective review of patient immunotherapy records from January 2000-June 2006. SETTING: Tertiary care outpatient otolaryngology clinic. RESULTS: Two hundred seventy-two patients were given 26,795 injections (average of 98.5 injections per patient). Three hundred ninety-nine total local reactions were reported by the subjects (1.49%; 95% CI 1.34%-1.63%). The majority (82%) of the local reactions occurred during escalation dosing. There were 23 episodes of wheezing or shortness of breath after injections (9.6 of 10,000). No patients experienced anaphylaxis. There was no documented skin or systemic infections as a result of the allergy injections. None of the patients experienced fever, discharge from the injection site, cellulitis, or required antibiotics. CONCLUSION: This review of immunotherapy records revealed no complications of infection from the preparation and administration of immunotherapy performed in an outpatient clinic.     

Comparison of modified PhadezymRAST,* ImmunoCAP,* and serial dilution titration skin testing by receiver operating curve analysis

Improved technology in in vitro tests for allergen-specific immunoglobulin E has led to increased efficiency and faster turnaround times. ImmunoCAP (Pharmacia Diagnostics, Clayton, N.C.) is an in vitro–specific immunoglobulin E test that uses a three-dimensional cellulose solid allergen phase, which allows quick results in 6 hours. In comparison, modified PhadezymRAST (Pharmacia Diagnostics) uses a two-dimensional solid phase, and results take 3 days to obtain. This study compares the sensitivity and specificity of CAP with that of modified RAST in the detection of specific immunoglobulin E, and it assesses the correlation of the individual class scores of CAP and modified RAST with end points obtained from skin-dilutional end-point titration. The reproducibility of CAP was also assessed. Patients evaluated at the University of Chicago Allergy Clinic who had a history and physical examination consistent with immunoglobulin E–mediated allergy and in whom skin testing was clinically indicated as part of their allergy management, were asked to donate some blood for simultaneous in vitro testing by PhadezymRAST and ImmunoCAP. Testing was performed in batches. Random samples from the CAP batches were chosen for duplicate runs under conditions blinded to the technician. Receiver operating curve analysis was used for comparison of the sensitivity and specificity of RAST vs. that of CAP. We used Pearson product-moment correlation coefficients to compare the correlation of RAST and CAP classes with the end points from skin testing. Our results indicate that the sensitivity and specificity of RAST and CAP are similar, that the classes of these two tests correlate well with the end points from skin testing, and that duplicate samples of CAP also correlate well. (OTOLARYNGOL HEAD NECK SURG 1995;112:665-9.)     

Safety and efficacy of radioallergosorbent test-based allergen immunotherapy in treatment of perennial allergic rhinitis and asthma.

OBJECTIVE: This study was undertaken to demonstrate the safety and efficacy of in vitro, radioallergosorbent test (RAST)-based inhalant allergen immunotherapy. STUDY DESIGN AND SETTING: Prospective 22 year single site clinical study, with outcome evaluations of 480 perennial allergic rhinitis patients, including 96 with concomitant asthma. RESULTS: Rhinitis symptom control after 2 years of immunotherapy was excellent in 32.5% of patients, good in 45.6%, and fair in 14.2%. There was no improvement in 7.7%. For patients with asthma, 81% had good or excellent pulmonary symptom improvement, and no patient failed to improve. No severe reactions occurred, but there were 5 limited systemic reactions, or 0.008% of injections, during a 2.5-year mean immunotherapy treatment course. CONCLUSION: RAST-based immunotherapy is safe and effective for patients with perennial allergic rhinitis, with or without concomitant asthma. Significance This is the first large, multiyear study of safety and efficacy of RAST-based immunotherapy for treatment of perennial allergic rhinitis and asthma. EBM rating: C.     

Safety of home-based and office allergy immunotherapy: A multicenter prospective study.

During a 1-year period, 27 otolaryngic allergy practices recorded all systemic reactions to immunotherapy resulting from 635,600 patient visits and 1,144,000 injections. Sixty percent of injections were given at home. Major systemic reactions were observed after 0. 005% of injections. There were no hospitalizations or deaths. Eighty-seven percent of major reactions began within 20 minutes of injection. Frequently observed risk factors for major reactions were buildup phase of immunotherapy, active asthma, and first injection from a treatment vial. Home and office injections had similar rates of total systemic reactions, but home-based immunotherapy had far fewer major reactions. Home-based immunotherapy was found to be safe. The methods and precautions used to treat patients with this degree of safety are specified and discussed.     

Cost analysis of employing multi-test allergy screening to guide serial endpoint titration (SET) testing versus SET alone.

OBJECTIVE: We analyzed the cost differences between 2 different modalities of allergy testing.Study design and setting Material costs, labor costs, and overhead expenditures were compared for 2 different allergy-testing algorithms. Fifty patients were placed in each group. The first group was tested for 14 allergens and 2 control substances by using multi-test II. These patients were compared with 50 patients tested for similar allergens and control substances by using serial endpoint titration. RESULTS: The initial round of tests with serial endpoint titration was nearly 3 times as costly as the multi-test for the 14 allergens and 2 control substances.Conclusion and significance Multi-testing is a cost-effective initial testing modality that can screen out negative results and enable the identification of positive reactions. These results could then be further investigated by using serial endpoint titration or RAST to quantify the patient's sensitivity and establish a starting dose for immunotherapy.     

Mold testing by RAST and skin test methods in patients with allergic fungal sinusitis.

RAST tests have traditionally been considered less sensitive than skin tests during investigation of atopy involving molds. This has been attributed to technical problems such as difficulty in binding the mold antigen to the carrier substrate. Ten patients with proven allergic fungal sinusitis were evaluated for sensitivity to 11 important molds by both RAST and dilutional intradermal testing. A predictable correlation between RAST and skin test scores was observed in many, but not all, cases. Most often this disparity was in the form of greater sensitivity indicated by skin testing than by RAST, sometimes differing by as many as 3 classes. The lack of concordance was not confined to testing for the fungi cultured from the sinuses, nor was it more or less pronounced in the case of dematiaceous fungi. The most likely causes for the disparity noted in this series are subtle differences in antigens used in skin test material and for RAST standards. Skin tests allow for evaluation of delayed and late-phase reactions, a measurement not possible by specific IgE testing with RAST. Delayed skin test reactions were not noted in this series of patients. An additional important finding was the sensitivity of patients with allergic fungal sinusitis to virtually every fungal antigen to which they were tested.     

Early experience of performing a modified Kugel hernia repair with local anesthesia

PURPOSE: We report our results with the modified Kugel hernia repair, a relatively new and minimally invasive open technique offering the advantages of preperitoneal repair without the need for general anesthesia. METHODS: We performed 42 inguinal or femoral hernias (44 sides), including incarcerated femoral hernias, using this modified technique, giving the patient local anesthesia with very little sedation. We describe the operative techniques used and the postoperative complications encountered. RESULTS: The mean operation time was 55 +/- 26 min and the mean hospital stay was 4 days (2-8 days). There were no major postoperative complications and patients were followed up for a mean period of 1 year. Only one patient complained of mild discomfort in the inguinal area after 6 months. There was no incidence of recurrence. CONCLUSION: The modified Kugel hernia repair is easy to learn, and it seems to have a lower recurrence rate and fewer postoperative complications than conventional types of hernia repair. Moreover, it offers the advantage of allowing the patient to undergo preperitoneal inguinal hernia repair under local anesthesia, which is especially beneficial for older patients with preoperative morbidity.     

Prospective analysis of epicutaneous testing for inhalant allergy: comparison of arm and back subsites with mRAST.

OBJECTIVES: 1) To compare epicutaneous testing (ET) from four skin subsites (forearm, upper arm, upper back, lower back) and 2) to compare ET to modified RAST (mRAST) for inhalant allergens. STUDY DESIGN: Prospective clinical trial. SUBJECTS AND METHODS: Fifty one patients underwent ET at four skin subsites and mRAST to six antigens and positive and negative controls. RESULTS: The forearm and upper back showed best sensitivity to positive controls and all subsites demonstrated similar specificity to negative controls. The forearm and upper back demonstrated best sensitivity and specificity for most antigens. No statistically significant differences were noted for antigen sensitivity and specificity for the four subsites. ET and mRAST agreed best on D. farinae and timothy grass and least on short ragweed and dog epithelium. CONCLUSION: This study confirms that forearm and upper back demonstrate very good sensitivity and specificity for positive and negative controls and most tested antigens. This has important diagnostic implications for clinical practice of inhalant allergy.     

Below-knee amputation using a medial saphenous artery-based skin flap

BACKGROUND: A modified below-knee (BK) amputation with the medial saphenous artery-based skin flap coverage was designed to preserve a functional BK stump for those who were unable to receive the conventional long posterior flap or skew-type amputation. METHODS: In designing, the medial skin flap was outlined with the margins beginning 1 to 2 cm medial to the tibial crest to close to the middle of the posterior calf, with the length of the flap being equal to the transverse diameter of the leg at the anticipated level of bone section. The posterior margin of the flap was placed close to the middle of the posterior calf or adjacent to the interrupted posterior skin incision line. After elevation of the medial skin flap and performance of the rest of the procedure with the standard BK amputation methods, the posterior muscle mass was carried anteriorly to cover the bony stump and the medial skin flap was brought laterally to cover the defect. RESULTS: This modified BK amputation was successfully done in a total of nine patients during the period January 1998 to January 2004. There were four females and five males, with ages ranging from 44 to 74 years (average 59.1 years). All the skin flaps survived completely without major complications, except for one patient who developed a wound infection. CONCLUSIONS: With a skin flap that was perfused by a direct cutaneous vessel, saphenous artery, and innerved by the saphenous nerve, the medial saphenous artery-based flap used in the modified BK amputation comprises one valuable alternative when conventional techniques are unsuitable.     

Phase II clinical trial of Wilms tumor 1 peptide vaccination for patients with recurrent glioblastoma multiforme

OBJECT: The object of this study was to investigate the safety and clinical responses of immunotherapy targeting the WT1 (Wilms tumor 1) gene product in patients with recurrent glioblastoma multiforme (GBM). METHODS: Twenty-one patients with WT1/HLA-A*2402-positive recurrent GBM were included in a Phase II clinical study of WT1 vaccine therapy. In all patients, the tumors were resistant to standard therapy. Patients received intra-dermal injections of an HLA-A*2402-restricted, modified 9-mer WT1 peptide every week for 12 weeks. Tumor size, which was obtained by measuring the contrast-enhanced area on magnetic resonance images, was determined every 4 weeks. The responses were analyzed according to Response Evaluation Criteria in Solid Tumors (RECIST) 12 weeks after the initial vaccination. Patients who achieved an effective response continued to be vaccinated until tumor progression occurred. Progression-free survival and overall survival after initial WT1 treatment were estimated. RESULTS: The protocol was well tolerated; only local erythema occurred at the WT1 vaccine injection site. The clinical responses were as follows: partial response in 2 patients, stable disease in 10 patients, and progressive disease in 9 patients. No patient had a complete response. The overall response rate (cases with complete or partial response) was 9.5%, and the disease control rate (cases with complete or partial response as well as those in which disease was stable) was 57.1%. The median progression-free survival (PFS) period was 20.0 weeks, and the 6-month (26-week) PFS rate was 33.3%. CONCLUSIONS: Although a small uncontrolled nonrandomized trial, this study showed that WT1 vaccine therapy for patients with WT1/HLA-A*2402-positive recurrent GBM was safe and produced a clinical response. Based on these results, further clinical studies of WT1 vaccine therapy in patients with malignant glioma are warranted.     

Adverse skin lesions after methylene blue injections for sentinel lymph node localization

BACKGROUND: Methylene blue dye (MBD) is being used as an alternative to isosulfan blue dye in sentinel lymph node (SLN) biopsies for breast cancer patients. Complications using MBD for SLN localization have not previously been reported. METHODS: A retrospective study was conducted of 24 consecutive patients who received MBD. Patients were given 3 to 5 cc of 1% MBD as peritumoral injections within the breast parenchyma and intradermally. Patients who developed local skin lesions at the injection site were queried regarding lesion appearance and when subsequent adjuvant therapy was initiated. RESULTS: Five of the 24 patients (21%) developed skin lesions at the injection site. Intradermal injections were discontinued, and only deep parenchymal injections were performed. All 5 patients had improvement of their skin lesions with silver sulfadiazine cream and no patient required debridement. Each patient received adjuvant therapy after surgery without delay. CONCLUSIONS: Our institution has experienced patients who developed skin lesions at the MBD injection site when using combined deep parenchymal and intradermal injections. With the increased use of MBD, caution should be used to avoid intradermal injections with SLN localization.     

Early motion of the ankle after operative treatment of a rupture of the Achilles tendon. A prospective, randomized clinical and radiographic study.

BACKGROUND: Different regimens of early motion of the ankle after operative treatment of a ruptured Achilles tendon have been suggested since the late 1980s. However, as far as we know, no controlled studies comparing these regimens with conventional immobilization in a cast have been reported. METHODS: In a prospective study, seventy-one patients who had an acute rupture of the Achilles tendon were randomized to either conventional postoperative management with a cast for eight weeks or early restricted motion of the ankle in a below-the-knee brace for six weeks. The brace was modified with an elastic band on the posterior surface, in a manner similar to the principle of Kleinert traction. Metal markers were placed in the tendon, and the separation between them was measured on serial radiographs during the first twelve weeks postoperatively. The patients were assessed clinically when the cast or brace was removed, at twelve weeks postoperatively, and at a median of sixteen months postoperatively. RESULTS: The separation between the markers at twelve weeks postoperatively was nearly identical in the two groups, with a median separation of 11.5 millimeters (range, zero to thirty-three millimeters) in the patients managed with early motion of the ankle and nine millimeters (range, one to forty-one millimeters) in the patients managed with a cast. The separation was primarily correlated with the initial tautness of the repair (r[S] = 0.45). No patient had excessive lengthening of the tendon. The patients managed with early motion had a smaller initial loss in the range of motion, and they returned to work and sports activities sooner than those managed with a cast. Furthermore, there were fewer visible adhesions between the repaired tendon and the skin in the patients managed with early motion, and these patients were subjectively more satisfied with the overall result. The patients in both groups recovered a median of 89 percent of strength of plantar flexion compared with that of the noninjured limb, as measured with an isometric strain-gauge at 15 degrees of dorsiflexion. The heel-rise index was similar for both groups: 0.88 for the patients managed with early motion and 0.89 for those managed with a cast. CONCLUSIONS: Early restricted motion appears to shorten the time needed for rehabilitation. There were no complications related to early motion in these patients. However, early unloaded exercises did not prevent muscle atrophy.     

Comparison of intradermal dilutional testing, skin prick testing, and modified quantitative testing for common allergens.

OBJECTIVES: To compare and correlate wheal size using the Multi-Test II applicator with the endpoint obtained by intradermal dilutional testing (IDT) for 5 common allergens. To examine the safety of modified quantitative testing (MQT) for determining immunotherapy starting doses. STUDY DESIGN: Prospective comparative clinical study. SUBJECTS AND METHODS: A total of 134 subjects were simultaneously skin tested for immediate hypersensitivity using the Multi-Test II device and IDT. RESULTS: There was a 77% concordance between results from IDT and results from MQT. When there was a difference, MQT predicted a safer endpoint for starting immunotherapy in all but 2 cases. CONCLUSION: Wheal size by SPT is predictive of endpoint by IDT. MQT is nearly as effective as formal IDT in determining endpoint. SIGNIFICANCE: Modified quantitative testing appears to be a safe alternative to IDT for determining starting doses for immunotherapy.     

Allergy management of refractory serous otitis media

Twenty patients classified as having otitis media with effusion (OME) refractory to all previous medical and surgical therapy were entered into a prospective study to see if classic allergy techniques could diagnose and treat otherwise unresolved effusion and persistent hearing loss in lieu of the re-insertion of tympanostomy tubes. RAST testing, skin end point titration and food elimination diets identified a possible allergic etiology in all patients. Among those choosing allergy immunotherapy, 65% maintained normal hearing, normal tympanograms, and the elimination of recurrent infections for three years. The remaining 35% resolved on appropriate food elimination diets. None of the control's symptoms resolved. The history of chronic disease is defined. The pathophysiology of allergic mechanisms and studies attempting to prove or disprove an allergic effect on the middle ear and eustachian tube are reviewed.     

Less-invasive sublabial unilateral transseptal approach for transsphenoidal surgery

A less-invasive sublabial approach was developed to overcome the disadvantages associated with the conventional sublabial approach. The basic differences between this modified sublabial approach and the conventional approach are: a smaller incision (1-1.5 cm long) and almost midline vertical skin incision underneath the upper lip; minimal development of an inferior tunnel; no widening of the maxillary rim of the piriform aperture; and a strictly unilateral approach. This less-invasive approach uses a slim and small nasal speculum originally designed for the transnasal approach. This modified sublabial approach was applied to 41 of 133 patients who underwent transsphenoidal surgery between August 1998 and the end of 2000. These cases confirmed that this approach is a simple, rapid, and less-invasive technique with significantly fewer mucosal complications compared to the conventional approach. We conclude that this modified sublabial approach offers a good alternative to the conventional standard sublabial approach.     

Combination of a Hetzer operation and a Sebening stitch for Ebstein's anomaly

OBJECTIVE: In order to improve the function of the anterior leaflet as a monocusp valve in tricuspid valve repair for Ebstein's anomaly, a single-stitch technique after Sebening, creating a hinge point of the anterior leaflet on the ventricular septum on the opposite side, was newly incorporated into the Hetzer operation (either posterior annulorrhaphy or the double-orifice technique). We describe the operative technique of the modified operation and present the initial results. METHODS: Eleven patients who underwent the modified operation were involved in the study. Tricuspid valve function was assessed by echocardiography preoperatively and 3 months after the operation. Its improvement was studied, and compared with that after the conventional Hetzer operation (n=15). RESULTS: After a mean follow-up period of 18.4 months (range 8.2-32.6 months), there were no early deaths and no cases of reoperation on the tricuspid valve in patients who had undergone the modified operation. At the last follow-up, 7 patients were in New York Heart Association class I, and 4 patients were in class II. The function of the tricuspid valve was significantly improved 3 months after the modified operation (P < 0.01, Wilcoxon signed-ranks test). Among the patients with Carpentier's classification type A or B, 85.7% of patients showed a tricuspid valve regurgitation (TR) grade of less than 2 after the modified operation, and this rate was significantly higher than that of 30.0% of patients in the group who underwent the conventional operation, (P < 0.05, Fisher's exact test). CONCLUSION: The initial results of the new modification are satisfactory. However, a further follow-up and an accumulation of operative cases are necessary.     

Comparison of transarterial and multiple nerve stimulation techniques for an initial axillary block by 45 mL of mepivacaine 1% with adrenaline

Background : The single-injection axillary block is rapidly performed but gives unpredictable results. Axillary block by multiple nerve stimulation technique (MNS) gives better results, but takes longer to perform. Transarterial (TA) injections of high doses of local anaesthetics are very successful. This double-blind study compared both block effectiveness and anaesthesiologic time consumption in 100 patients, having an axillary block by either TA or MNS techniques. Methods : 45 mL of 1% mepivacaine with adrenaline 5 μg/mL was used in each patient. Five mL was injected subcutaneously. In the TA group, 20 mL was injected deep to, and 20 mL superficial to the axillary artery. In the MNS group, four terminal motor nerves were electrolocated in the axilla, and injected with 10 mL each. Analgesia was assessed every 10 min and when needed supplemented after 30 min. The block was considered successful when analgesia was present in all sensory nerve areas distal to the elbow. Results : MNS group required 10δ2 min (meanδ1 SD) for the initial block performance compared with 7δ2 min for TA group, P<0.001. Latency of the initial block was shorter and the frequency of supplemental analgesia lower in the MNS group (mean 17 min and 12%), than in the TA group (25 min and 38%, respectively), P<0.001. All incomplete blocks were successfully supplemented by electrolocating the unblocked nerves. However, the total time to obtain 100% success rate was shorter in the MNS group (30 min), than in the TA group (38 min), P<0.001. The adverse effects (accidental intravascular injections and axillary haematomas) were fewer in the MNS group. Conclusion : In the hands of anaesthetists experienced in nerve electrolocation, the MNS technique of an initial axillary block by four separate injections of 10 mL of mepivacaine produces faster and more extensive block than the TA technique by two separate injections of 20 mL. Hence, the MNS technique requires fewer supplementary blocks and results in faster patient readiness for surgery than the TA technique.