Revisiting human IL-12Rβ1 deficiency: a survey of 141 patients from 30 countries

Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guérin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years ± 9.8 years (range, 0.5-46.4 yr). IL-12Rβ1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought.     

Assessment of alveolar epithelial permeability with Tc-99m DTPA aerosol scintigraphy in patients with Sjogren syndrome

Sjögren’s syndrome (SjS) is a systemic autoimmune disease that mainly affects the exocrine glands and usually presents as persistent dryness of the mouth and eyes. Lung disease in SjS has been reported to occur early following clinical presentation of the disease. In this study, technetium-99m diethylene triamine penta-acetic acid (Tc-99m DTPA) aerosol inhalation scintigraphy was used to assess the pulmonary membrane permeability in patients with primary SjS. A total of 18 patients with primary SjS and 13 healthy controls were investigated. Clinical evaluation, chest X-ray examination, pulmonary function tests, Tc-99m DTPA aerosol scintigraphy were performed in all the cases. The presence of respiratory symptoms (dyspnea and cough), duration of sicca symptoms were recorded. The clearance half time of Tc-99m DTPA radioaerosols in patients with SjS (20.49 ± 2.56 min) was faster when compared to normal controls (42.32 ± 13.28 min) (P = 0.000) which means that there is a significant increase in lung permeability in patients with SjS compared to the controls. There is also a significant difference between PI of patients with SjS (0.34 ± 0.09) and that of controls (0.42 ± 0.07) (P = 0.012). According to the results of our preliminary study, one can detect pulmonary involvement by Tc-99m DTPA aerosol inhalation scintigraphy in patients with primary SjS.     

Evaluation of hearing loss in patients with Graves' disease

Hearing loss has commonly been reported in association with thyroid disorders and during treatment with propylthiouracil. The relationship between hyperthyroidism and the auditory system has not been previously investigated. The aim of this cross-sectional, case-control study was to investigate hearing loss in patients with Graves' disease (GD). The study population consisted of patients with newly diagnosed GD and healthy controls. Pure tone audiometry at frequencies of 250, 500, 1000, 2000, 4000 and 8000 Hz, along with immittance measures including tympanometry and acoustic reflex tests, were performed in all participants. Twenty-two GD patients and 22 healthy controls consented to inclusion in the study. The differences between groups with regards to age and gender distribution were statistically insignificant (P = 0.567 and P = 0.757, respectively). The hearing thresholds of right and left ears were also similar in both groups (P > 0.05). When single-ear evaluations were taken into account (total of 44 ears for both groups), hearing thresholds in the GD group were significantly higher than healthy controls at all frequencies (P < 0.05). Following testing at the designated frequencies, the only significant effect of thyrotoxicosis was observed with frequencies of 4000 and 8000 Hz. The odds ratio for having hearing loss at a frequency of 8000 HZ associated with GD was 14.97 (95% confidence interval 4.03-55.64). In patients with GD, right and left pure tone audiometric findings at a frequency of 8000 Hz correlated positively with FT3, FT4 and negatively with TSH. Our results are highly suggestive of a decrease in hearing ability in patients with GD, particularly at high frequencies. Further studies are needed to help elucidate the mechanisms behind hearing loss which develops in association with GD.     

Levamisole: Might It Be used in Treatment and Prevention of Atopic Diseases?

As an antihelmintic and Th₁-biased immunostimulant, levamisole has been used to restore impaired cell mediated immunity. We sought to explore whether the Th₁ driving effect of levamisole may also have an influence on the course of allergic diseases, by shifting the Th₂ dominant immunity more toward Th₁-mediated response. BALB/c mice were sensitized intraperitoneally on days 0, 7, and 15 with ovalbumin (OVA). After the sensitization, they were challenged intranasally with OVA once a day for 6 consecutive days. Levamisole (2.5 mg/kg) was administered orally three times a week during sensitization and challenge. After the last challenge, differential cell counts were performed, and IL-4 and IFNγ levels were measured in the bronchoalveolar lavage fluids (BALF). Serum total IgE level was determined, and lungs were examined histologically. The present study establishes that mice administered with oral levamisole gave significantly lower IL-4 levels on sensitization with OVA; however, IFNγ production, eosinophil infiltration, and serum IgE levels remained unaffected. In conclusion, use of levamisole may have important implications in the management of the allergic inflammation.     

Analysis of different surgical approaches for the treatment of cerebrospinal fluid rhinorrhea.

The current treatment method for cerebrospinal fluid (CSF) rhinorrhea is surgical repair of the fistula. The aim of this study was to analyse different surgical approaches used for the treatment of CSF rhinorrhea regarding several preoperative and postoperative variables to determine the optimal method in these patients. Patients' charts were retrospectively reviewed to get the required data. Twenty-six patients who underwent different types of surgical approach for the treatment of CSF rhinorrhea were included in the study. Patients who had extensive comminuted fractures of the anterior cranial base and additional brain injury besides CSF rhinorrhea, mostly as a result of gunshot injuries, underwent craniotomy (n = 14). Osteoplastic frontal sinusotomy was used in two patients with a dural defect located at the posterior wall of the frontal sinus. Uncomplicated CSF fistulas in ten patients, located at the anterior and posterior ethmoid roof and in the sphenoid sinus, were closed with an endonasal endoscopic approach. Postoperative success rate was higher (97 % for intracranial approach, 100 % for extracranial external and endonasal endoscopic approach) for all techniques. Anosmia was the most frequent permanent complication (n = 5), seen after craniotomy. In conclusion, endonasal endoscopic approach can be preferred for the closure of uncomplicated CSF fistula, located at the anterior or posterior ethmoid roof and in the sphenoid sinus, due to its minimal postoperative morbidity. Uncomplicated CSF fistula, located at the posterior wall of frontal sinuses can be repaired extradurally with osteoplastic frontal sinusotomy. Intracranial approaches should be reserved for more complicated CSF rhinorrhea which results from extensive comminuted fractures of the anterior cranial base and is accompanied with intracranial complications.     

Does Specific Immunotherapy Injection Cause an Increase in Bronchial Reactivity?

Background. Several well-controlled studies have proven the clinical benefit of specific immunotherapy (SIT) for seasonal allergic rhinitis (AR). However, whether subcutaneous SIT injection could cause a transient increase in bronchial reactivity (BR) remains unknown. Objective. To investigate whether subcutaneous SIT injection, either during or outside the pollen season, could cause an increase in BR in children with pollen allergy. Methods. Twenty-two children (mean age 13.6 ± 0.7 years) with AR who were receiving maintenance SIT for 15 months were included in the study. Pre-injection BR of the patients was evaluated with methacholine provocation test immediately before maintenance dose of SIT during the peak pollen season and outside the season. The post-injection test was administered 24 hours after SIT injection. Results. There was no difference in FEV₁ measures recorded during [98(93-109)%] and outside [102(96-111)%] the pollen season. There was no significant difference between pre- [64(7-64)mg/mL] and post-allergen injection [32(7.5-64) mg/mL] BR outside the pollen season (p = 0.9). A trend towards improvement following allergen injection [64(5.4-64)] as compared to pre-allergen injection [14.6(3.5-64)] was shown during the pollen season (p = 0.053). Although PC20 measures in the pollen season were lower than outside the season, the difference was not significant. The percentage of the patients with bronchial hyperreactivity was 62% during and 43% outside the season. Conclusion. SIT injections both during and outside the pollen season cause no increase in BR in children with AR. This calls into question the necessity of empirical dose reduction during the pollen season.     

Changing cerebral blood flow velocity detected by transcranial Doppler ultrasound during head up tilt in patients with multiple sclerosis

Background and purpose:  Multiple sclerosis (MS) is a chronic inflammatory disease of central nervous system. We aimed to investigate the cerebral blood flow velocity (CBFV) changes in MS by transcranial Doppler.
Methods:  Twenty patients with MS, 20 age-matched healthy controls were included in the study. In both groups, blood flow velocities (BFVs) of middle cerebral arteries (MCAs) were evaluated. The changes of blood pressure, heart rate along with the changes in BFV of MCA were recorded after the patients were raised to upright position.
Results:  In both groups, upon raising the tilt table to the upright position, the mean CBFV values were found to be lower in comparison with the recorded baseline values ( P values <0.05). The decline in the mean CBFV values was more significant in patients with MS ( P  = 0.01).
Conclusion:  Our study showed upon raise of the tilt table, the mean BFVs decreased more in MS patients than control group with a more prominent change in the subgroup of MS patients with expanded disability scale scores ≥2. By use of transcranial Doppler ultrasound, it may be possible to evaluate BFV changes in patients with MS.     

A Clinical Study of Colchicine in Childhood Asthma

A double-blind, randomized, crossover study was done to determine the efficacy of colchicine in 30 atopic children with moderately severe asthma. A constant dose of sustained-release theophylline and salbutamol by inhalation, as needed, was administered to all patients. Compared to placebo, colchicine, 0.5 mg twice daily, significantly reduced morning tightness and nocturnal asthma score. There was, however, no significant difference between colchicine and placebo for cough, daytime asthma, or daily combined symptom scores for each patient. Colchicine did not significantly decrease beta-2 agonist inhaler use when compared with placebo. Similarly, there was no statistically significant difference between placebo and colchicine therapy as far as pulmonary function tests and peak flow reversibility were concerned.

Thus, colchicine administered for 4 weeks demonstrated insufficient antiasthma activity. Colchicine-induced clinical improvement that was reported in a previous study may be due to selection of patients with mild asthma symptoms. However, our group, comprised of moderately severe asthmatic patients, did not show a satisfactory clinical response.