Prevalence of gold contact hypersensitivity in the west of Scotland

373 patients attending for routine patch testing were tested with 0.5% and 0.05% gold sodium thiosulfate (GST). 8 (2.1%) patients had a positive patch test, and a further 4 (1.0%) patient reactions which were interpreted as irritant 2 out of 8 patients with a positive patch test to GST suspected gold allergy prior to testing, and both of these patients reported that their eczema resolved if they avoided gold jewellery. This is the lowest prevalence of hypersensitivity to GST reported and suggests that gold contact allergy may not be as widespread as has been recently proposed.     

The management of stage I testis cancer

For clinical stage I seminoma, conventional management consists of adjuvant RT after orchiectomy. Only 5% of patients relapse. The majority can be salvaged by chemotherapy. The overall survival of 98% is excellent. Seminoma is radiosensitive. A lower dose of RT is required than for NSGCT. Standard therapy presently is 30 Gy in 3 weeks, as suggested by the MRC study. RT is generally well tolerated. There have been recent concerns about second malignancies after 10 to 15 years. Surveillance studies have shown that 18% of patients relapse, the majority in para-aortic lymph nodes. About 15% require salvage RT and 5% salvage chemotherapy. Second relapses are seen in patients treated with RT at first relapse, and occur outside of the radiation field. The main advantage of surveillance is that 80% of patients can be spared slightly toxic overtreatment. The main disadvantage is the need for long-term follow-up, which is expensive and stressful to the patient. Good patient compliance, mandatory to an observation policy, is often difficult on a long-term basis. Seminoma is clearly responsive to chemotherapy. Adjuvant carboplatin in clinical stage I has only been evaluated in two studies. Because reliable prognostic factors have not been established, a high-risk group cannot be identified, and chemotherapy must be given to all patients. Whether or not one cycle of chemotherapy is sufficient requires further confirmation, particularly in view of the results with carboplatin as compared with cisplatin in patients with advanced NSGCT. Results of the randomized MRC trial comparing RT with carboplatin are of interest.     

Severe hypersensitivity syndrome due to sulfasalazine associated with reactivation of human herpesvirus 6

BACKGROUND: A severe adverse reaction to sulfasalazine therapy has been associated with hypersensitivity syndrome, the clinical features of which are similar to infectious mononucleosis. No serologic evidence of viral infections has been reported with this syndrome; however, human herpesvirus 6 infection has not been specifically investigated, which could cause an infectious mononucleosislike syndrome. OBSERVATIONS: We report 2 cases of hypersensitivity syndrome induced by the use of sulfasalazine. The clinical features of the syndrome appeared 18 and 32 days after administration of sulfasalazine. Clinical signs included a maculopapular rash progressing to exfoliate erythroderma, fever, and lymphadenopathy. Leukocytosis, atypical lymphocytes, liver dysfunction, and renal disturbance were also observed. In 1 patient, human herpesvirus 6 variant B was isolated from peripheral blood mononuclear cells, and in both patients anti-human herpesvirus 6 IgG titers increased considerably. CONCLUSIONS: Two cases of hypersensitivity syndrome due to sulfasalazine use were associated with the reactivation of human herpesvirus 6, which may be a required cause of hypersensitivity syndrome.     

DHEA-S selectively impairs contextual-fear conditioning: Support for the antiglucocorticoid hypothesis.

The authors had reported that glucocorticoids play a selective role in fear conditioning. The adrenal steroid dehydroepiandrosterone (DHEA) has been reported to act as a functional antiglucocorticoid. If DHEA has antiglucocorticoid properties, then its effects on fear conditioning might resemble those produced by adrenalectomy. The authors now report that chronic exposure to high levels of dehydroepiandrosterone sulfate (DHEA-S; converted in vivo to DHEA) produced the same pattern of results as adrenalectomy. Specifically, treatment with DHEA-S impaired contextual fear conditioning 24 hr after conditioning but not immediately after conditioning, and like adrenalectomy, DHEA-S had no effect on auditory-cue fear conditioning. Preexposure to the context before drug treatment eliminated the amnestic effects of DHEA-S, suggesting that, like adrenalectomy, DHEA-S exerted its effect by interfering with the construction of a contextual memory representation. Thus, DHEA appears to act as a functional antiglucocorticoid in the processes that mediate learning and memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adenosine-induced transient cardiac asystole enhances precise deployment of stent-grafts in the thoracic or abdominal aorta

BACKGROUND: Anaphylaxis to the bite of Diptera and specifically the bite of the Tabanidae family (horsefly) have been sparsely documented. The coexistent hypersensitivity to both the order Diptera and Hymenoptera has not been documented. METHODS: We present a patient who experienced anaphylaxis to both insect species. Venom skin testing and RAST revealed sensitivity to several members of the Hymenoptera order. Prick, intradermal and RAST with whole body extracts of Tabanidae species is also documented in this patient. Twenty patients who are sensitive to Hymenoptera and have been bitten by horseflies but have had no reaction to the horsefly bite were used as controls. RESULTS: An anaphylactic reaction to horsefly bite has been documented in a 56-year-old white male. This patient also demonstrated evidence of anaphylactic reaction to Hymenoptera envenomation. In controls consisting of 20 patients with Hymenoptera sensitivity, there was no clinical history of reaction to horsefly bite despite the presence of positive prick and/or positive intradermal tests and/or positive RAST to mixed Tabanidae species extract. CONCLUSIONS: Skin testing to horsefly by prick and/or intradermal testing using whole body insect extract is not useful in making a diagnosis of Tabanidae hypersensitivity. RAST using Tabanidae species as antigen is similarly useless in making a diagnosis of Tabanidae hypersensitivity. In vivo and in vitro diagnosis of horsefly hypersensitivity may be achieved when the salivary gland antigen of the horsefly becomes available.     

Foreign-body granuloma and IgE-pseudolymphoma after multiple bee stings

We report a patient with an unusual combination of an eosinophilic foreign-body granuloma and a pseudolymphoma, with recurrent severe oedema on the forehead, after multiple bee stings. On immunohistology the foreign-body granuloma and lymphoid follicles reacted with monoclonal antibodies against the high- and low-affinity IgE receptors, and against IgE. Prick and intradermal tests with whole-body bee extracts showed positive immediate-type reactions. The eosinophilic granuloma formation and lymphoid follicles may have been induced by a combination of immune complex and cell-mediated hypersensitivity following antigen persistence. Although bee stings are common, as far as we are aware, this complex reaction pattern has not been reported previously.     

Depression and anxiety among women in an urban setting in Zimbabwe

There has been little investigation of the side-effects experienced by women receiving adjuvant carboplatin in the treatment of ovarian cancer. This study aimed to describe the range of problems experienced by patients and to estimate incidence and severity of side-effects over the treatment period. Eleven patients participated and completed a 75-item self-report questionnaire at each course of treatment. Severity of each side-effect was graded from 0 to 4. Patients also stated which had been the worst side effect at each course. The response rate was 94%. Seventy-two side-effects were reported. Fatigue emerged as both the most common and the most 'troublesome' side-effect. Nausea, difficulty sleeping, taste change, and constipation were also ranked highly. Although limited by a small sample size, this study suggests patients undergoing carboplatin experience a wide range of problems, many of which merit further investigation.     

Disease genes are not patentable: a rebuttal of McGee

OBJECTIVE: To describe a case of azathioprine hypersensitivity in a patient with ulcerative colitis. CASE SUMMARY: A 40-year-old white man with ulcerative colitis, treated with chronic mesalamine and occasional steroids, was admitted to the hospital with a 3-day history of fever, nausea, vomiting, and a rash. Fourteen days prior to admission, the patient had been started on azathioprine for ulcerative colitis. Upon admission, azathioprine therapy was temporarily withheld, resulting in resolution of his signs and symptoms. Symptoms returned when azathioprine was restarted. It was decided that these signs and symptoms were most likely caused by azathioprine hypersensitivity, and the agent was discontinued. DISCUSSION: To our knowledge, this is the first reported case of azathioprine hypersensitivity in a patient with ulcerative colitis. The time course and presenting signs and symptoms support the diagnosis of azathioprine hypersensitivity, as does the patient's response to rechallenge. The mechanism of this hypersensitivity reaction is unclear, but may involve the nitroimidazole portion of the azathioprine molecule. CONCLUSIONS: Azathioprine hypersensitivity often presents with signs and symptoms resembling a systemic infection such as fever, leukocytosis, and evidence of end organ dysfunction. The diagnosis of azathioprine hypersensitivity should be considered in patients who have recently either initiated or increased their dosage of azathioprine.     

Delayed hypersensitivity reaction of the knee after injection of arthroscopy portals with bupivacaine (marcaine)

The number of arthroscopic procedures performed annually for the management of intraarticular injuries has grown at an exponential rate. Whether done with the patient under general anesthesia or local anesthesia supplemented with intravenous sedation, it is common practice to postoperatively inject each portal as well as the joint with a local anesthetic to provide pain relief in the transition to the recovery room and discharge after outpatient surgery. To our knowledge, no previous reports of localized urticaria and delayed hypersensitivity reaction have been reported in the postarthroscopy setting. We are reporting a case of delayed hypersensitivity reaction and urticaria of the knee that presented after bupivacaine (Marcaine) injection of arthroscopic portals after routine meniscectomy.     

Intermittent meningitic reaction with severe basophilia and eosinophilia in CNS leukaemia

Light- and electron-microscope studies were performed on CSF cells from a patient with CNS leukaemia presenting with an intermittent meningitic reaction. Numerous fully matured basophilic and eosinophilic granulocytes with excess glycogen content accompained undifferentiated leukaemic blast cells in the CSF. Such a CSF cell reaction has not been previously reported. It is suggested that this isolated CSF reaction represents a special type of immediate hypersensitivity reaction triggered by an abnormal leukaemic giant cell clone, and mitigated by the accompanying eosinophilic granulocytes.     

Antitumor effects of the combination immunotherapy with interleukin-12 and tumor necrosis factor alpha in mice

Nickel hypersensitivity is an increasing problem in adolescents, especially in girls, with a prevalence of up to 30%. The presence of nickel in orthodontic appliances and the possibility of causing nickel hypersensitivity has been discussed in case reports. A review of the literature concerning nickel hypersensitivity in relation to orthodontic appliances has shown that the risk is very low for patients who are not nickel hypersensitive at the start of the treatment. A patient who is already nickel hypersensitive at the start of orthodontic treatment may in rare cases show adverse reactions induced by the appliance. The slow long-term release of nickel from orthodontic appliances may induce tolerance to nickel in individuals who are not hypersensitive at the start of orthodontic treatment.     

Adverse reactions to fluconazole: illustrative case with focus on desensitization

Fluconazole is an azole antifungal agent. Because it can be taken orally, it is preferred over amphotericin B for long-term treatment. Indications for fluconazole are increasing. Reports of hypersensitivity have been described. If adequate alternative therapy is not available, desensitization may be necessary. Desensitization with fluconazole has not been described. The patient described in this report required fluconazole and was successfully desensitized after manifesting a type 1 hypersensitivity reaction. The patient underwent desensitization during a 15-day period. The starting dose was less than 0.001 dose, with doubling each day. During desensitization, the patient experienced a slight transient rash that resolved with continued therapy. After desensitization, he has continued using fluconazole daily without adverse effects. This report indicates that desensitization to fluconazole can be accomplished safely in selected patients. A suggested desensitization protocol is provided.     

HIV-2 infection with a long asymptomatic period

We give details of a patient infected with HIV-2 which had what we believe to be the longest asymptomatic period so far reported. The infection was probably acquired though a blood transfusion in Africa 27 years ago. At present the patient remains asymptomatic and her cellular defence mechanisms, evaluated by CD+4 lymphocyte counts and hypersensitivity skin tests, are not severely compromised. HIV-2 has come distinct epidemiological, clinical and biological features which are different from the related HIV-1 and deserve investigation in order for its natural history to be better understood.     

Evaluation of carboplatin pharmacokinetics in the absence and presence of paclitaxel

In a clinical trial of paclitaxel (Taxol) and carboplatin in combination, the severity of thrombocytopenia was less than would be expected with an equivalent dose of carboplatin alone. To determine whether a pharmacokinetic interaction was responsible for this observation, the effect of pretreatment with Taxol on the pharmacokinetics of carboplatin was examined in 11 patients. Each patient was randomized to one of two treatment groups that determined the order of drug treatments. The treatments were carboplatin as a 30-min infusion alone or immediately following 175 mg/m2 Taxol administered as a 3-h i.v. infusion. The treatments were separated by 1 week. The carboplatin dose was chosen to produce a target area under the concentration-time curve (AUC) of 3.75 mg-min/ml according to a previously published formula (A. H. Calvert et al., J. Clin Oncol., 7: 1748-1756, 1989). The mean administered dose of carboplatin was 338 mg. Serial blood samples were collected over 24 h and analyzed for total and free platinum, and, in some patients, Taxol. The pharmacokinetics of carboplatin (i.e., total clearance and volume of distribution at steady state), was not significantly affected by pretreatment with Taxol. Total clearances of carboplatin were 67.2 +/- 28.8 ml/min and 64.6 +/- 27.9 ml/min in the absence and presence of Taxol, respectively (P = 0.56). The AUC of free carboplatin (3.45 mg-min/ml) obtained in the absence of Taxol was not significantly different from that measured in the presence of Taxol (3.27 mg-min/ml). The AUC of carboplatin in both the absence and presence of Taxol agreed with the projected target AUC of 3.75 mg-min/ml. In conclusion, the application of an individualized dosing strategy is valid for the calculation of the carboplatin dose in this combination. The pharmacokinetics of carboplatin is not altered by pretreatment with Taxol at a standard dose, and a pharmacokinetic interaction is not responsible for the altered toxicity of the combination.     

Paclitaxel, carboplatin, and extended-schedule etoposide in the treatment of small-cell lung cancer: comparison of sequential phase II trials using different dose-intensities

PURPOSE: In two sequential phase II studies, we evaluate the feasibility and efficacy of adding paclitaxel to a standard platinum/etoposide regimen in the first-line treatment of small-cell lung cancer. PATIENTS AND METHODS: One hundred seventeen patients with small-cell lung cancer were treated between June 1993 and July 1996. The first 38 patients received a lower-dose regimen: paclitaxel 135 mg/m2 by 1-hour infusion, carboplatin at an area under the concentration-time curve (AUC) of 5.0, and etoposide 50 mg alternating with 100 mg orally on days 1 to 10. When only mild myelosuppression was observed, doses of paclitaxel and carboplatin were increased in the subsequent 79 patients (paclitaxel 200 mg/m2 by 1-hour infusion and carboplatin at an AUC of 6.0). All patients received four courses of treatment, administered at 21-day intervals. Patients with limited-stage small-cell lung cancer also received thoracic radiation therapy (1.8 Gy/d; total dose, 45 Gy) administered concurrently with courses 3 and 4 of chemotherapy. RESULTS: Seventy-two of 79 patients (91%) who receive the higher-dose regimen had major responses. Thirty-two of 38 (84%) with extensive-stage disease responded (21% complete response rate); median survival was 10 months for this group. With limited-stage disease, the overall response rate was 98%, with 71% complete responses; the median survival time has not been reached at 16 months. Median survival in extensive-stage patients was longer in patients who received the higher-dose regimen (10 months) than in the previous group treated with lower doses (7 months; P = .008). The higher-dose regimen was well tolerated, with myelosuppression being the major toxicity. Compared with the lower-dose regimen, grade 3/4 neutropenia increased from 8% to 38% of courses, but the incidence of hospitalization for neutropenia and fever did not increase. Other nonhematologic toxicities were uncommon, and did not increase substantially with the higher-dose regimen. CONCLUSION: Paclitaxel can be added at full dose (200 mg/m2) to a carboplatin/etoposide combination while maintaining a tolerable toxicity profile. Median survival times in both extensive- and limited-stage patients compare favorably with other reported regimens. This regimen merits further investigation, and a randomized trial to compare this regimen with a standard carboplatin/etoposide combination is underway.     

A blood stem cell transplant in a person with concomitant Hodgkin disease and testicular carcinoma

We report a patient with concomitant Hodgkin disease and testicular carcinoma who received MOPP chemotherapy and radiation therapy followed by etoposide and cisplatin. The testicular cancer recurred and he received ifosfamide, vinblastine and cisplatin followed by a high-dose carboplatin and etoposide blood stem cell transplant. He has been in complete remission for 6 months.     

Eyeblink conditioning in the rabbit (Oryctolagus cuniculus) with stimulation of the mystacial vibrissae as a conditioned stimulus.

Eyeblink conditioning is a well-understood paradigm for the study of learning and memory and has been successfully employed with the use of auditory and visual conditioned stimuli (CSs). In this study, vibrotactile stimulation of the mystacial vibrissae was examined as an alternative CS in the rabbit ( Oryctolagus cuniculus). The technique is described and acquisition of eyeblink conditioning (EBC) with stimulation of a single row of vibrissae in a delay paradigm is reported. Extinction of EBC with presentation of the CS alone is demonstrated, as well as reacquisition with stimulation of a single whisker. Finally, control experiments ensure that the CS has no auditory components. Ipsilateral presentation of the CS and airpuff is a more effective combination for training than contralateral presentations. Vibrotactile stimulation of the vibrissae as a CS will enable further examination of the neural correlates of learning in a well-characterized sensory system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pegaspargase: an alternative?

OBJECTIVE: To review the chemistry, pharmacology, pharmacokinetics, clinical activity, adverse effects, dosage, and administration guidelines for pegaspargase. DATA SOURCES: A MEDLINE search (1980-1996), a CANCERLIT search (1983-1996), and a CURRENT CONTENTS search (1980-1996) using the terms pegaspargase, PEG-asparaginase, PEG-L-asparaginase, polyethylene glycol L-asparaginase, polyethylene glycol conjugated L-asparaginase, and Oncaspar were conducted. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in this review. Abstracts were included only when they were judged to add critical information not otherwise available in the medical literature. DATA SYNTHESIS: L-Asparaginase has been a main component of treatment regimens for acute lymphocytic leukemia. A key limiting factor of L-asparaginase use has been the development of hypersensitivity to the drug. Recently, a polyethylene glycol (PEG) conjugated form of L-asparaginase, pegaspargase, has been made available. PEG modification of L-asparaginase has been shown to alter the tendency of the enzyme to induce an immune response and to extend the half-life of the drug. The majority of patients with hypersensitivity to the native enzyme preparations tolerate pegaspargase without further clinical hypersensitivity. The adverse effect profile of pegaspargase is similar to that of the native forms of L-asparaginase. The recommended dosage of pegaspargase is 2500 IU/m2 administered by intramuscular or intravenous injection every 2 weeks in combination with other chemotherapeutic agents. CONCLUSIONS: Pegaspargase is a safe, effective alternative to L-asparaginase in patients who have had clinical hypersensitivity reactions to both Escherichia coli- and Erwinia carotovora-derived L-asparaginase. However, pegaspargase should not be routinely substituted for L-asparaginase.     

A study of the changes during heating of paracetamol

Fanconi anaemia (FA) is an accepted indication for treatment with allogeneic HLA-identical BMT. Most patients, however, lack a suitable HLA-identical donor. In our centre, six FA patients were transplanted with a matched unrelated donor. Due to hypersensitivity to DNA cross-linking agents, a low-dose cyclophosphamide (CY) and thoraco-abdominal irradiation (TAI) regimen is recommended for conditioning in FA. We added Ara-C upfront and anti-T cell antibodies to enhance engraftment and to prevent GVHD, in combination with T cell depletion in four out of six of the first transplants. One patient did not engraft. In three patients rejection was observed. In three of these four patients a second BMT, using full bone marrow grafts, resulted in successful engraftment. The other patient died before a second BMT could be performed. The incidence and severity of acute GVHD was low: only one patient with grade III acute GVHD was seen. Two out of four surviving patients suffered from chronic GVHD. Four patients survived (median survival time 43 months after BMT), three with good and one with acceptable quality of life. Two patients died, one patient due to adenoviral reactivation with multi-organ failure, and one due to sepsis complicated by ARDS. In conclusion, MUD BMT is feasible in FA patients with bone marrow failure in whom no HLA-identical sibling donor is available. In our study group, the major problem was graft rejection, despite the administration of a combination of graft enhancing anti-T cell antibodies. Multicentre studies are needed to determine a more intensive, but still tolerable, conditioning regimen.     

Biochemical evaluation of a patient with a familial form of leucine-sensitive hypoglycemia and concomitant hyperammonemia

A case of a child with recurrent episodes of severe hypoglycemia since the age of 6 months is reported. Biochemical evaluation extended to the first-degree relatives is consistent with a familial form of hypoglycemia due to a leucine-sensitive hyperinsulinism. In addition, this patient has a persistent elevation of serum ammonia levels of uncertain etiology that is more pronounced after meals. Urea cycle defects, organic acidurias, and beta-oxidation defects have been ruled out, as well as a possible excessive deamination of glucogenetic amino acids. This unexpected hyperammonemia, which was also detected in the mother, might be related to leucine hypersensitivity.