Treatment with cyclosporin A in a patient with Omenn's syndrome

Unless treated with haematopoetic stem cell transplantation, Omenn's syndrome, a rare variant of severe combined immunodeficiency, is associated with a fatal outcome. We describe a male infant showing all the typical features of Omenn's syndrome, who was successfully treated with cyclosporin A to improve clinical condition prior to haematopoetic stem cell transplantation.     

A long-term follow-up study of women with asymptomatic endometriosis diagnosed incidentally at sterilization

OBJECTIVE: To evaluate whether asymptomatic endometriosis diagnosed in connection with tubal sterilization is likely to cause symptoms later in the woman's life. DESIGN: Controlled, clinical follow-up study of women who were examined for endometriosis in connection with tubal sterilization performed between 1986 and 1989. SETTING: University hospital. PATIENT(S): Thirty-nine women with mostly minimal endometriosis discovered at sterilization and 157 control women with no endometriosis discovered at sterilization. INTERVENTION(S): Interview in 2001 by a posted questionnaire. MAIN OUTCOME MEASURE(S): Report on pain, pelvic operations, menopausal status, and use of hormone replacement therapy. RESULT(S): Pelvic pain was more frequently reported by controls than by women with endometriosis (28% vs. 6%). There was no significant difference between the groups concerning dysmenorrhea, premenstrual pain, or dyspareunia, nor was there any significant difference in the hysterectomy rate. CONCLUSION(S): There is little risk that asymptomatic, minimal endometriosis found incidentally will become symptomatic.     

Component-resolved diagnosis with recombinant allergens in patients with cherry allergy

BACKGROUND: In pollen-related food allergy, extracts for skin prick tests (SPTs) are often not standardized, and the test reliability is affected by false-negative reactions. OBJECTIVE: We sought to evaluate a panel of recombinant allergens (RAs) derived from one allergenic food for use in component-resolved in vivo diagnosis, taking cherry as a model food. METHODS: Seventy-nine subjects were included in the study: 24 Swiss patients (group 1) with a positive double-blind placebo-controlled food challenge result to cherries, 23 patients with birch pollen allergy but without cherry allergy (group 2), 23 nonatopic subjects (group 3), and 9 Spanish patients with a history of a cherry allergy (group 4). SPTs were performed in duplicate by using recombinant cherry allergens (Bet v 1-related allergen: recombinant (r) Pru av 1; profilin: rPru av 4; and lipid transfer protein: rPru av 3) in concentrations of 10, 50, and 100 microg/mL. Furthermore, IgE reactivity to rPru av 1, rPru av 4, and rPru av 3 was assessed by means of immunoblot analysis. RESULTS: SPT responses with rPru av 1, rPru av 4, and rPru av 3 were positive in 92%, 17%, and 4% of the patients in group 1; in 74%, 30%, and 0% of the patients in group 2; in 0%, 22%, and 89% of the patients in group 4; and negative for all nonatopic subjects (group 3). Thus the sensitivity of a positive SPT response to at least one of the 3 RAs was 96%. The specificities, negative predictive values, and positive predictive values with the 3 RAs were 100%, 96%, and 100% if calculated in relation to the nonatopic control group but 17%, 79%, and 60% when calculated in relation to the control group with birch pollen allergy. The correlation between SPT and immunoblotting results was excellent. Sensitization to rPru av 3 was associated with more severe symptoms than sensitization to rPru av 1. CONCLUSIONS: SPTs with RAs proved to be highly sensitive for diagnosis of cherry allergy. Component-resolved in vivo diagnosis with standardized amounts of stable RAs allows us to determine sensitization patterns directly, to correlate them with severity of clinical symptoms, and to analyze geographic differences.     

The fine specificity of the myelin oligodendrocyte glycoprotein autoantibody response in patients with multiple sclerosis and normal healthy controls

Antibodies directed against the extracellular immunoglobulin (Ig)-like domain of the myelin oligodendrocyte glycoprotein (MOG(Igd)) mediate demyelination in experimental autoimmune encephalomyelitis (EAE) and are implicated in the immunopathogenesis of multiple sclerosis (MS). In this study we investigated the epitope specificity of MOG(Igd)-specific autoantibodies immunopurified from MS patients (n=17) and normal healthy controls (HD; n=9). ELISA, using a panel of synthetic MOG(Igd) peptides, revealed that the epitope specificity of this response was heterogeneous in both groups. The most frequently recognised epitopes were located in amino acid sequences (a.a.) 1-26 (13/17) and 63-87 (15/17) in MS patients, and 14-39 (6/9) and 63-87 (6/9) in HDs, but there was no association between MS and any particular peptide specificity. We therefore investigated the ability of the immunopurified antibodies to recognise native MOG(Igd) expressed on at the membrane surface by FACS. Unexpectedly, antibodies fulfilling this essential criterion for a demyelinating antibody response were detected only in one of the MS samples. These results indicate that the epitope specificity of the human B cell response to MOG is not only heterogeneous, but may only mediate demyelination in a limited subset of MS patients.     

Supraspinal vs spinal sites of the antinociceptive action of the subtype-selective NMDA antagonist ifenprodil

The N-methyl-D-aspartate (NMDA) antagonist ifenprodil and several structurally related compounds are highly selective for the NR2B-containing receptor subtype. This selectivity could provide an explanation for the reported difference of the analgesic and side-effect profile of ifenprodil-like compounds from other NMDA antagonists. In this work, we have queried if the ifenprodil-induced antinociception can be attributed to the block of NMDA receptors in the spinal cord. Ifenprodil and some other NMDA antagonists (MK-801, memantine) were tested in a model of inflammatory pain (Randall-Selitto) in rats. The in vivo NMDA antagonism was assessed in anaesthetised rats on responses of spinal dorsal horn (DH) neurones to iontophoretic NMDA and in the model of single motor unit (SMU) wind-up. Ifenprodil, MK-801 and memantine dose-dependently increased nociceptive thresholds in the Randall-Selitto model. Antinociceptive doses of the channel blockers selectively antagonised NMDA responses of DH neurones and inhibited wind-up. In contrast, antinociceptive doses of ifenprodil did not show any NMDA antagonism in electrophysiological tests. Although ifenprodil did not inhibit the SMU responses to noxious stimuli in spinalised rats, it markedly and dose-dependently inhibited nociceptive SMU responses in sham-spinalised rats. These results argue against the spinal cord being the principal site of antinociceptive action of ifenprodil; supraspinal structures seem to be involved in this effect.     

Sarcoidosis: case report and review

Sarcoidosis is a granulomatous disorder of uncertain aetiology that can affect almost any organ. Anterior uveitis is a feature of the condition in about 30 per cent of those affected. We describe a patient with sarcoidosis presenting with anterior uveitis and describe a diagnostic approach. Sarcoidosis is a condition that must be considered in patients presenting with symptomatic uveitis, as the underlying disease is serious and usually treatable. The diagnosis of sarcoidosis is aided by an understanding of the pattern of organ involvement and may ultimately require tissue confirmation through biopsy of granulomata, including those found in the ocular adnexa.     

Perfusion imaging using spin-labeling methods: contrast-to-noise comparison in functional MRI applications.

In this study the performance of FLASH imaging with selective inversion preparation for functional perfusion studies was investigated. In addition to the absolute quantification of perfusion by measurement of the longitudinal relaxation times with global (T(1glob)) and selective (T(1sel)) inversion, the measurement of absolute (BASE) and relative (FAIR) perfusion increases by subtraction of appropriately weighted images was also considered. The subject averages of absolute perfusion obtained by the quantitative method were 70.7 +/- 4.0 ml/100g/min in gray matter, 10.2 +/- 3.4 ml/100g/min in white matter, and 89.0 +/- 3.1 ml/100g/min in visual cortex. These values, as well as the average increase of perfusion due to visual stimulation (44.4 +/- 3.7 ml/100g/min), agree well with respective data reported by PET and other MRI studies. However, for individual subjects the standard deviations over single ROIs inside the visual cortex lay around 100% which prevented the detection of significant activation. BASE and FAIR, on the other hand, were able to detect significant activation in single subjects. The measured average perfusion increases were 51.7 +/- 6.6 ml/100g/min and 56.5 +/- 13.8%, respectively. Magn Reson Med 46:172-182, 2001.