ADRB2 Gene Polymorphisms and Salbutamol Responsiveness in Serbian Children with Asthma.

Inhaled ß2 adrenergic receptor (ß2-AR) agonists are the mainstay of asthma therapy. The ß2-AR protein is encoded by the ADRB2 gene and variants within this gene can have significant consequences for modulating the response to asthma therapy. This cross-sectional study performed at the University Children's Hospital in Belgrade, included 54 children with asthma. The subjects were genotyped for ADRB2 +46A>G (Arg16Gly, rs1042713) and +79C>G (Gln27Glu, rs 1042714) polymorphisms and the association with asthma severity and response to inhaled salbutamol was examined. In Serbian asthmatic children, allele +46A was detected with a frequency of 41.7% and allele +79G was detected with a frequency of 23.1%. Allele +46G was found to be associated with a better response to inhaled salbutamol (p <0.05) and with mild form of asthma (p <0.05). Polymorphism ADRB2 +46A>G may be a determinant of asthma severity and response to salbutamol in children with asthma. We did not find any association of +79C>G polymorphisms with the asthma severity and bronchodilator response to inhaled salbutamol. The results of this study can be potentially useful for personalization of asthma treatment.

Induced sputum in systemic sclerosis interstitial lung disease: comparison to healthy controls and bronchoalveolar lavage.

BACKGROUND: Induced sputum (IS) is a noninvasive tool, which can be used to collect cellular and soluble materials from lung airways. OBJECTIVE: To evaluate if IS may be a useful and safe tool for the detection of airway inflammation in patients with interstitial lung disease (ILD) in systemic sclerosis (SSc). METHODS: Sixty-eight patients with SSc and ILD as well as 18 healthy individuals (controls) were selected and submitted to IS examination. In 34 of 68 patients with SSc, bronchoalveolar lavage (BAL) was also performed. Safety of IS was assessed by comparison of forced expiratory volume in the first second (FEV(1)), FEV(1)/forced vital capacity ratio and peak expiratory flow before and after the IS procedure. Cell composition in samples collected by BAL and IS was correlated, and IS total and differential cell count in SSc patients and controls were compared. RESULTS: The total number of cells was significantly higher in IS samples of SSc patients compared to those of healthy controls. Mean percentage of neutrophils was also higher in SSc patients (41.79 +/- 23.89 vs. 27.37 +/- 17.90), as well as lymphocytes (17.42 +/- 19.70 vs. 3.13 +/- 2.28) and eosinophils (2.35 +/- 4.43 vs. 0.41 +/- 0.46). On the other hand, mean percentage of macrophages was higher in healthy individuals (69.10 +/- 19.15 vs. 36.96 +/- 20.68). In fluid recovered by BAL, the most frequent cells were macrophages (67.89% +/- 17.26), while neutrophils (14.77 +/- 17.18%) and lymphocytes (15.62 +/- 13.46%) were less frequent and eosinophils (1.66 +/- 2.08%) were rare. A similar pattern of cell composition was found in IS samples (41.15 +/- 21.67% of macrophages, 39.72 +/- 23.15% of neutrophils, 15.28 +/- 19.46% of lymphocytes and 2.56 +/- 5.03% of eosinophils). Strength of correlation between BAL and IS was significant for macrophages and neutrophils. After IS procedure was performed, improvement of FEV(1) (mean value before IS was 85.09 +/- 14.44 and 88.93 +/- 16.40 after IS) and FEV(1)/forced vital capacity (mean value before IS was 98.53 +/- 12.11 and 105.22 +/- 10.78 after IS) was observed. CONCLUSION: The IS method may allow a noninvasive assessment of cell composition in airway fluid and may contribute to the better understanding of upper/medium airway inflammation in SSc. Future studies are needed to verify whether IS can replace invasive procedures for the detection and monitoring of lung inflammation in SSc.

[Morphologic analysis of the coexisting anomalies of the arteries of the cerebral base and aneurysms: clinical study].

During operations of the aneurysms showing anatomical details is the means that leads to the aim, and it is not only a purpose in itself. Data on details that the surgeons come across during their work and which sometimes represent difficulties during interpretations of angiographic findings and planning operations, as well as the intraoperative orientations and identifications of the elements . Frequency of occurrence of such anatomical details and anomalies may be completely different from the one that autopsy series show. Knowledge of this makes the work of surgeons easier and gives a necessary feeling of confidence during operations. Thus, we decided to conduct a clinical, morphological study based on angiographic and surgical analyses of the explored segments of the Wilson circle. The study included 344 patients from the Institute for Neurosurgery, during the period of 2 years; the patients had complete angiographic diagnosing and operative exploration. Our findings confirm differences in localization of aneurysms according to sex. Aneurysms on the front communicant complex are to a great extent associated with anomalies of the front part of the Wilson circle.

[Screening of risk groups for discovering intracranial aneurysms before rupture].

In development of intracranial aneurysms contribute genetic factors together with smoking, hypertension, diabetes mellitus. Epidemiology studies suggest that as many as 5% of people harbour a cerebral aneurysm by age 75. Rupture of cerebral aneurysm is the most frequent cause of spontaneous subarachnoid haemorrhage (up to 80%.) Annual incidence of SAH is 10-14/100 000, but only 15-20% of aneurysms will rupture, and that will happen probably between 40-60 years. The morbidity and mortality of aneurismal subarachnoid (SAH) continues to be high. It is not possible to predict who has aneurysm and is it going to bleed or not, but it is possible to reveal high risk groups (polycystic kidney disease, Ehlers-Danlos sy, Marphan sy, family history of cerebral aneurysms, suspect de novo aneurysm formation in patients with prior history of cerebral aneurysm). Reviewing data from literature and reporting cases from each group with high risk, that have been screened and aneurysms discovered, authors wish to focus interest on this matter and propose screening program for these groups of patients. The mortality and morbidity in cases treated before rupture is significantly lower than after SAH, so screening programs could save many lives. According to our preliminara data, mostly based on control angiographies after 8-10 zears in patients previouslz operated for intracranial aneurysmas, from 15 angipgraphies 4 revealed new aneurysms (26% in 10 years period) with total number of 6 de novo formed aneurysms, which is not valid due to small number of patients but strongly suggests the importancy of screening program for risk groups.

[Subarachnoid hemorrhage caused by a rupture of a spinal arteriovenous malformation].

The authors report on a patient presenting with subarachnoid hemorrhage that was caused by a rupture of an spinal combined arteriovenous malformation at cervicothoracic junction. The patient was a 30-year-old female, who had exhibited an abrupt onset of severe low neck and occipital pain with radiation into shoulders and vomiting. Neurological examination revealed severe meningism without motor or sensory deficit. Digital subtraction angiography did not demonstrate any intracranial source of bleeding, whereas spinal angiography revealed a spinal arteriovenous malformation at cervicothoracic junction. Endovascular treatment of the malformation was considered for this patient. Occipital and neck pain with radiation into schoulders and severe meningism are clues pointing to a spinal origin of the haemorrhage.

[Cerebral vasospasm after subarachnoid hemorrhage].

Cerebral vasospasm causes permanent neurolological deficit or death occurance in 13% of clinical cases. Peak frequency is from 8-10th day after SAH. The purpose of this study is factor analysis that may have influence on vasospasm development , as well as predictor determination. The study is prospective and analysis 192 patients treated in Institute of Neurosurgery, Clinical Centre of Serbia, Belgrade. The majority of patients were admitted in hospital in first four days after SAH, and 184 had GCS over 7. Univariate methods of factor analysis were used, and for significance of predictors influence testing multivariante regression analysis was used. Vasospasm occurred in 22,40% of all cases. No relationships have been found between sex, age, previous hypertension, timing of surgery, appearance of hydrocephalus and intracerebral hematoma, hypertermia or mean arterial blood pressure, with occurrence of cerebral vasospasm. Factors with significantly associated with the occurance of vasospasm were: hearth disease, hypernatriemia, Hct, clinical grade on admission as well as preoperative clinical grade and Fisher CT scan grade. In the first four days after SAH, Fisher scan grade, preoperative clinical grade and Hct, appeared as predictors. After four days, clinical grade on admission and hypernatiemia, showed as poredictors.

[Results of the surgical treatment of patients with brain cavernoma that manifested by intracerebral hemorrhage].

Although, for a long time, they have been known as a kind of vascular lesion, cavernomas have mostly been incidental or causative autopsy finding or have subsequently been histologically confirmed after surgical interventions undertaken due to intracerebral and spinal spontaneous hematoma of various localization. The aim of this study was to establish on the basis of the outcome of the operative treatment, whether the surgical interventions were justified and to systematize indications for surgical treatment of the cerebral cavernoma that initially manifested by hemorrhage. The subject of the study was a group of 38 patients who had been operated at the Institute for Neurosurgery during a ten-year period, from 1990 until 2000. The study group consisted of 16 male and 22 female patients. All operated patients had cyst intraparenchymal lesions. In our group of surgically treated patients three had been treated urgently due to spontaneous intracerebral hematoma, and intraoperatively taken material after inspection of the cavum pointed to the fact that cavernoma had been the cause of hemorrhage. All the others, after postoperatively done MRI of the brain, in some even DSA, were completely evaluated, and histologically confirmed. Not one hemorrhaging cavernoma showed signs of subarachnoid hemorrhage, although 60% of operated patients had cortically localized lesion. Most of the operated patients, except for the three mentioned because of urgent intervention did not give massive intraparenchymal lesion that, in the clinical picture, would lead to the change of the state of consciousness. Focal neurologic deficit was a dominant clinical presentation. On the basis of the analysis of the clinically pathologic correlations and direct and longstanding operative results of the surgical treatment of cavernoma, operative treatment is indicated in all superficial lobar lesions as well as in those that are localized in the brain chambers and pineal region regardless of the type of the clinical presentation.

[Surgical treatment of brain stem cavernoma--current approaches].

Results of our series of 10 operated patients who had cavernous malformation of the brain stem, in accordance with the findings of other authors, have confirmed that surgical removal of cavernomas is an absolutely appropriate approach as regards the prevention of repeated and disabling hemorrhages, also from the point of view of the recovery of the neurological deficit. In patients with disturbed vital functions (breathing, swallowing) evacuation of hematomas and removal of the malformation eliminate life endangering compressive effect on the vital structures of the brain stem. It is not disputable that patients with superficially localized cavernomas and progressing neurological deficit should be subjected to surgical treatment. In cases of deep lying lesions that are covered by a considerable layer of nervous parenchyma, it is indispensable to have a very careful preoperative planning of a safe entry into the brain stem, without damage to the vital functional structures. In case of a complete neurological recovery after a single hemorrhagic episode, the decision to perform surgery is delicate and demands individual appraisal of each patient. As regards the procedure with incidentally found and clinically asymptomatic lesions, regardless of the MR-signs of hemorrhage in the form of the hemosiderin ring around the lesion, we support the view of those authors who think that such lesions should not be operated but should be subjected to clinical treatment and MR with periodical MR check-ups.

Tolerability of meropenem in children with IgE-mediated hypersensitivity to penicillins.

BACKGROUND: Administration of meropenem to penicillin-allergic patients who might benefit from this treatment is usually avoided because of a 47.4% rate of cross-reactivity to imipenem, the prototype of the carbapenem class of beta-lactam antibiotics, demonstrated in a single study on the basis of positive responses to skin tests with imipenem reagents. However, recent studies of ours have demonstrated a very low rate of cross-reactivity between penicillins and both meropenem and imipenem in adults. OBJECTIVE: To assess cross-reactivity and tolerability of meropenem in children with documented penicillin allergy. METHODS: One hundred and eight consecutive children who had suffered a total of 129 immediate reactions (120 urticarial and/or angioedematous manifestations and 9 anaphylactic shocks) to penicillins and had positive results to skin tests for at least one of the penicillin reagents tested underwent skin tests with meropenem and negative subjects were challenged with it. RESULTS: One subject (0.9%) displayed a positive intradermal test to meropenem. The remaining 107 subjects with negative skin tests to meropenem tolerated challenges. Challenges were not followed by full therapeutic courses. CONCLUSIONS: Our results demonstrate a low rate of cross-reactivity between penicillins and meropenem. Therefore, the practice of avoiding meropenem in children with immunoglobulin E-mediated hypersensitivity could be abandoned; in those who especially require meropenem treatment, prophylactic skin tests are advisable, because negative results indicate tolerability.

Enlargement to a saccular aneurysm and subsequent rupture of infundibular widening of posterior communicating artery.

A small dilatation known as infundibular widening (IFw) is frequently seen (7%-25%) on the posterior communicating artery (PComA) at its origin from the internal carotid artery. Development and subsequent rupture of an aneurysm on a previously radiographically demonstrated IFw has rarely been documented. We present two patients who suffered from subarachnoid hemorrhage (SAH). Initial cerebral angiography demonstrated IFw on PComA. They were readmitted to the hospital 9 and 11 years later, after a new SAH. Repeated cerebral angiography revealed an aneurysm arising from the site where the IFw had been seen previously in both cases. The aneurysms were clipped with favorable outcome. This report adds two new cases documenting enlargement of PComAIFw into an aneurysm. Patients with PComAIFw, especially those who have experienced SAH, should be considered for periodic follow-up to rule out the development of an aneurysm over time.

Congenital myopathy with uniform type 1 fibers.

Congenital myopathy with uniform type 1 fibers is a rare form of nonprogressive congenital neuromuscular disease. We report a 40 year old woman with proximal muscle weakness, waddling gait and decreased deep tendon reflexes. The serum creatine kinase level was decreased. Peripheral nerve conduction velocity as well as electrocardiogram and echocardiogram were normal. The electromyogram showed myopathic changes. A biopsy specimen from the left deltoid muscle revealed a uniformity of type 1 fibers. This is the first case of congenital myopathy with uniform type 1 fibers reported in Serbia.

[The significance of individual inhalation allergens in the sensitization of children with respiratory allergy]. / Znacaj pojedinih inhalacionih alergena u senzibilizaciji dece sa respiratornim alergijskim oboljenjima.

Four hundred children were skin tested with following allergens: Dermatophagoides pteronyssinus, moulds, animal dander (mixture of dog, cat, sheep and horse dander), tree pollens, weed pollen (Ambrosia artemisifolia), and six grass pollens, as well as three nutritive allergens in children less than three years of age. Results demonstrated that in 200 children with perenial rhinitis and/or asthma. Dermatophagoides gave positive results in over 90%. In 200 children with pollen allergy, grasses were major allergens, and among them Timothy (Phleum pratense) gave over 90% of positive results. It is to be concluded than skin testing with many inhalatory allergens is not necessary in patients with typical clinical picture. Skin test with Dermatophagoides and Timothy should be done, and further evaluation taken into consideration only if these are negative.

[Response to histamine in the skin prick test in children]. / Reaktivnost na histamin u prick koznom testu kod dece.

Allergen skin reactivity to histamine assessed by Prick testing was studied in 183 children with different allergic symptoms, aged from 4 months to 15 years. No significant difference was noted in male children versus female in different parts of the arm (antecubital fossa of the left arm, wrist of both arms) and in different allergic disorders (respiratory, pollen and skin allergy). The volume of reaction was not significantly changed in repeated applications of histamine. The peak reaction to histamine appeared 5 minutes after the application of histamine in the majority of children; it gradually declined after 10 and 15 minutes.

Peutz-Jeghers' syndrome--juvenile intestinal polyposis--review of five cases.

During the past 30 years, authors observed and followed 5 patients with Peutz-Jeghers' syndrome. Four of them had diffuse polyposis of stomach, small bowel and colon. They also had severe clinical presentation of the disease, with recurring colicky pain, haemorrhage, anaemia and intussusception, all of which necessitated frequent surgical treatment. Excised polyps presented as benign hamartomas, without malignant alteration. Mucocutaneous pigmentations were present in 4 patients. Family history was revealing in only 2 cases. One patient, a girl aged 2 years, died due to the complications of the surgical intervention (intestinal obstruction). She has had the most severe form of the disease with diffuse polyposis.