Petar Ivanovski

Association between pet‐keeping and asthma in school children

The role of pet exposure in childhood asthma and allergy is still controversial. The aim of this study was to investigate the association between pet‐keeping during different periods of childhood and asthma and sensitization in school children.

Childhood-onset myasthenia gravis with thymoma.

Juvenile myasthenia gravis is an acquired, autoimmune disease occurring before age 16 years. Thymoma is exceedingly rare in children, especially in association with juvenile myasthenia gravis. We describe a 14-year-old boy with juvenile myasthenia gravis and thymoma. He presented with difficulties chewing and swallowing, nasal speech, and fluctuating weakness of the leg muscles. Neurologic examination revealed masticatory and bulbar muscle weakness with nasal speech, proximal muscle weakness, fatigability of the arms and legs, and distal muscle weakness of the legs. A diagnosis of juvenile myasthenia gravis was confirmed by a positive neostigmine test, a decremental response on repetitive nerve stimulation, and increased titers of serum anti-acetylcholine receptor antibodies. The patient received anticholinesterases, corticosteroids, azathioprine, and thymectomy. A pathohistologic analysis of the thymus gland indicated thymoma, Masaoka grade II. After 2 years of an unstable disease course, remission was achieved. Because only 10 cases of thymoma-associated myasthenia gravis are described in the pediatric population, this report offers an important contribution to a better understanding of this rare association.

A case of selective IgE‐mediated hypersensitivity to ceftibuten

Besides penicillins, cephalosporins represent the most commonly prescribed betalactam antibiotics, and is able to induce severe and sometimes life-threatening IgE-mediated reactions.Ceftibuten is a third-generation cephalosporin used for treating serious infections. Side-effects from ceftibuten consumption are not common and they can occur as a mild or severe skin rash, itching, hive, difficulty in breathing or swallowing (swelling of the lips, tongue or face) and wheezing. Until now, there are no documented reports of IgE-mediated hypersensitivity reactions to ceftibuten. We report a 3-year-old girl who had an anaphylactic reaction within 20 min after oral administration of the second dose of Cedax (ceftibuten) (135 mg) given for ear infection, which she had tolerated 6 months before. Symptoms included facial flush with intensive itching in the throat and eyes, swelling of the lip, and urticarial rash on her trunk, which progressed to generalized urticaria, dyspnea, shortness of breath and wheezing. After treatment with anti-shock therapy, her symptoms were considerably reduced within 1 h and completely resolved after 6 h. The patient had no other medical history, in particular no other drug allergy, and no family history of allergic desease. Ten months later the child was referred to our department in order to study the drug reactions and to determine safe alternative drugs for the future. The child underwent prick and intradermal skin tests with standard concentration of penicilloyl polylysine, minor determinant mixture, penicillin G, penicillin V, ampicillin, amoxicillin, cephalexin, cefaclor, cefotaxime, ceftriaxone and ceftibuten diluted in 0.9% sodium chloride and administered at increasing concentrations every 15–20 min, as previously described (1–3). Commercially available assays for specific IgE (UniCAP System; Pharmacia, Uppsala, Sweden) were performed for penicilloyl G and penicilloyl V, amoxicilloyl, ampicilloyl, and cefaclor. Levels of specific IgE >0.35 kU/l were considered positive. When in vivo tests were negative, independently of the results of in vitro tests, single-blind, placebo-controlled challenges with progressively increasing amounts (0.01, 0.1 and 1.0) of the respective therapeutic doses of drugs were performed at 1 h intervals (each on a different day), as previously described (1–3). The patient responded positively to prick testing with ceftibuten (wheal 15 · 25 mm) at a concentration of 2 mg/ml, 10 min after application. Urticarial rash appeared on her arm, face and neck, which required antihistamine administration immediately. Prick and intradermal histamine test produced wheals with maximum diameters 5 and 10 mm respectively. Intradermal test with the above cephalosporins and semysintetic penicillins were negative in 10 healthy control subjects, who had previously tolerated those drugs. All assays for specific IgE and challenges were negative. Therefore, it should be emphasized that assays for specific IgE for third-generation cephalosporins are not yet commercially available. Clinical findings and positive skin tests with ceftibuten imply that the child developed type-I hypersensitivity. The lack of cross-reactivity with other betalactams, emphasizes the role of the IgE epitop present on R1 side chain of ceftibuten molecule in inducing immediate hypersensitivity. To the best of our knowledge, this is the first documented case of selective immediate hypersensitivity to ceftibuten with good tolerance to other betalactams.

Mitotic crossover - an evolutionary rudiment which promotes carcinogenesis of colorectal carcinoma

Mitotic crossover is a natural mechanism that is a main source of the genetic variability of primitive organisms. In complex organisms such as mammals, it represents an evolutionary rudiment which persisted as one of the numerous DNA repair mechanisms, and results in the production of homozygous allele combinations in all heterozygous genes located on the chromosome arm distal to the crossover. This event is familiar as loss of heterozygosity, which is one of the key mechanisms responsible for the development and progression of almost all cancers. We propose the hypothesis in which mitotic crossover is a principal source of the increased loss of heterozygosity that leads to the initiation and progression of colorectal carcinoma. The hypothesis could be tested by in vitro inhibition of Rad51 protein, orthotopic grafting of human colon cancer tissue into the gut of mice, and treatment with potential inhibitors. After these procedures, the frequency of mitotic crossover would be estimated. The development of selective inhibitors of mitotic crossover could stop further carcinogenesis of colorectal carcinoma, as well as many other neoplastic events. Loss of heterozygosity is an event responsible for carcinogenesis, its reduction by selective inhibitors of mitotic crossover could have a positive effect on cancer chemoprevention, as well as on growth reduction and a cessation in the progression of earlier developed tumors.

Wiskott-Aldrich syndrome with macrothrombocytopenia

BackgroundWiskott-Aldrich syndrome is a rare X-linked immunodeficiency disorder with a variable phenotype.Case Characteristics3.5-year-old boy diagnosed with Wiskott-Aldrich syndrome.ObservationUnusual and persistent thrombocytopenia with increased platelet volume (>10fL). He did not exhibit characteristic clinical and laboratory finding for the syndrome.OutcomeMaternally inherited causative mutation in the exon 2 of the WAS gene was disclosed.MessageThis is a need for multidisciplinary assessment of patients with congenital or early infantile thrombocytopenia, including testing for mutations of the WAS gene in all unexplained cases even in the absence of characteristic microthrombocytopenia.

Metabolically based liver damage pathophysiology in patients with urea cycle disorders - A new hypothesis

The underlying pathophysiology of liver dysfunction in urea cycle disorders (UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle (UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs. Owing to our routine clinical practice to screen for iron overload in severely ill neonates, with the focus on the newborns suffering from acute liver failure, we report a case of citrullinemia with neonatal liver failure and high blood parameters of iron overload. We hypothesize that the key is in the decreased-deficient fumaric acid production in the course of UC in UCDs that causes several sequentially intertwined metabolic disturbances with final result of liver iron overload. The presented hypothesis could be easily tested by examining the patients suffering from UCDs, for liver iron overload. This could be easily performed in countries with a high population and comprehensive national register for inborn errors of metabolism. Conclusion: Providing the hypothesis is correct, neonatal liver damage in patients having UCD can be prevented by the supplementation of pregnant women with fumaric or succinic acid, prepared in the form of iron supplementation pills. After birth, liver damage in patients having UCDs can be prevented by supplementation of these patients with zinc fumarate or zinc succinylate, as well.

Peutz-Jegher’s Syndrome – A Case Report / Peutz-Jegher’s sindrom - prikaz slučaja

Abstract Peutz-Jegher’s syndrome is a hereditary disorder characterized by melanocytic macules on the lips and buccal mucosa and multiple gastrointestinal hamartomatous polyps. It is caused by a mutation localized on chromosome 19p13.3. Skin and mucosal pigmentation may be present at birth and usually occur in early childhood, but occasionally may develop later. It is associated with an increased risk of malignancy for gastrointestinal carcinoma and also for breast, ovarian, testiscular, pancreatic and gallbladder cancer. We report a 12-year-old girl who presented with disseminated petty yellowish macules on the bridge of her nose, numerous brown to bluish black macules on her lips and buccal mucosa. Mucocutaneous pigmentation has been present from the age of five, with a negative family history. In our patient, esophageal endoscopy was normal, while the endoscopy of stomach and duodenum revealed multiple diminutive polyps. After clinical evaluation, there were no indications for therapy. Further follow up was suggested. Continuous surveillance is very important for patients with Peutz-Jegher’s syndrome in order to reduce risks of cancer and prevent other morbidity and mortality. Sažetak Uvod: Peutz-Jegher sindrom je nasledno oboljenje sa karakterističnim hiperpigmentovanim makulama na usnama i bukalnoj mukozi kao i mnogobrojnim gastrointestinalnim polipima. Mutacija na hromozomu 19 p 13.3 smatra se odgovornom za ovaj sindrom. Prevalencija ovog sindroma se kreće od 1 na 8.300 do 1 na 280.000 pripadnika opšte populacije. Promene na koži i sluznicama mogu postojati od rođenja, ali češće se javljaju tokom ranog detinjstva, a u nekim slučajevima mogu se razviti i u kasnijem životnom dobu. Postoji povećan rizik od maligniteta gastrointestinalnog trakta kao i karcinoma dojke, jajnika, testisa, pankreasa i žučne kese. Prikaz slučaja: Prikazujemo devojčicu uzrasta 12 godina sa diseminovanim žućkastim makulama na korenu nosa i brojnim mrkim i tamnoplavim makulama na usnama i na bukalnoj sluzokoži levo. Promene na koži i sluznicama su bile prisutne od pete godine života. Porodična anamneza je bila negativna. Kod naše pacijentkinje endoskopija jednjaka je bila uredna, dok su u želucu i duodenumu otkriveno više diminutivnih polipa. Nakon kliničke evaluacije nije bilo indikacija za terapiju. Savetovano je dalje praćenje. Diskusija: Dijagnoza se postavlja na osnovu postojanja kriterijuma koji podrazumevaju postojanje: najmanje dva polipa, jednog polipa i prisustva mukokutanih pigmentacija, ili jednog polipa i pozitivne porodične anamneze o postojanju obolelih srodnika. Perioralna pigmentacija je od patognomoničnog značaja za postavljanje dijagnoze. U Cowden sindromu, Bannayan-Riley-Ruvalcaba sindromu i u sindromu juvenilne polipoze prisutni su hamartomski polipi ali ne i pigmentacija perioralne regije. Nasuprot tome, u Laugier-Hunziker syndromu karakteristične su benigne melaninske pigmentacije na usnama i orafaringealnoj sluznici ali nisu pristni sistemski znaci niti gastrointestinalna polipoza. Zaključak:Kontinuirano praćenje je veoma važno kod pacijenata sa Peutz-Jegher sindromom radi smanjenja rizika od karcinoma i drugih morbiditeta i mortaliteta. Kod dece sa Peutz-Jegher sindromom, kolonoskopiju treba izvoditi svake dve godine počevši od pojave simptoma, u asimptomatskim slučajevima početi u ranoj adolescenciji. Endoskopski pregled gornjeg dela gastrointestinalnog trakta treba započeti od desete godine života. Kod svakog pacijenta sa hiperpigmentovanim makulama na usnama uvek u diferencijalnoj dijagnozi treba isključiti postojanje Peutz-Jegher sindroma.

Hypohidrotic ectodermal dysplasia - a case report / Hipohidrotska ektodermalna displazija – prikaz slučaja

Abstract Ectodermal dysplasias are a large group of disorders characterized by developmental dystrophies of one or more ectodermal structures. Hypohidrotic ectodermal dysplasia is a rare genodermatosis associated with abnormal development of sweat glands, teeth, and hair. Its incidence is 1:100.000 newborns. The full expression of X-recessive forms are only seen in males, while female heterozygotes are moderately or very slightly affected. The disease is characterized by sparse hair, oligodontia, and reduced or absent sweeting, light hair, distinctive facial features, palmoplantar keratoderma. We report an 11-year-old boy with hypohidrotic ectodermal dysplasia. Despite extensive skin, teeth and hair manifestations, his physical and psychomotor growth and development were normal. Sažetak Uvod: Ektodermalne displazije predstavljaju veliku heterogenu grupu naslednih oboljenja kod kojih postoje lezije dva ili više tkiva poreklom iz embrionalnog ektoderma. Nesleđuju se X-vezano recesivno, autozomno dominantno ili autozomno recesivno. Najčešće su zahvaćeni zubi, kosa, ekrine žlezde i nokti. Hipohidrotska ektodermalna displazija - Krist −Simens−Tuarenov sindrom (Christ-Siemens- Touraine) najčešća je forma i čini 80% svih slučajeva ektodermalne displazije. Prikaz slučaja: Prikazujemo pacijenta, uzrasta 11 godina, koji od rođenja ima suvu kožu i proređenu depigmentovanu dlaku na kapilicijumu. Pri prijemu, koža kapilicijuma, lica, trupa i ekstremiteta bila je u celini suva, sa nejasno ograničenim eritemom i hiperpigmentacijama periokularno, minimalno infiltrovanim bledoeritematoznim lihenihikovanim plakovima na bočnim stranama vrata i fleksurama. Obostrano palmarno i plantarno izražena je hiperkeratoza, hiperlinearnost dlanova, distrofične nokatne ploče. Supercilije u potpunosti nedostaju, cilije proređene, izražena je hipodoncija sa dva klinasto oblikovana zuba na maksili. Lečenje: Započeta je terapija kortikosteroidnim preparatima za lokalnu primenu i emolijentnim sredstvima. Rutinske laboratorijske analize i pedijatrijski nalaz bili su uredni. Po otpustu, savetovana je upotreba emolijentnih kremova sa preporukom za negu i izbegavanje ekstremnih fizičkih napora. Pacijentu i roditeljima je objašnjen rizik od hiperpireksije. Zaključak: Hipohidrotsku ektodermalnu displaziju prvi put je opisao Ternam (Thurnam) 1848. godine. Incidencija je 1:100.000 neonatusa. Puna ekspresija X-recesivne forme viđa se samo u muškaraca, dok su ženski heterozigoti umereno ili sasvim slabo aficirani. I pored ekstenzivnih promena na koži, zubima i kožnim adneksima, fizički i psihomotorni rast i razvoj su u fiziološkim granicama za uzrast.

Pulmonary inflammatory myofibroblastic tumor associated with nephrotic syndrome

Inflammatory myofibroblastic tumor (IMT) of the lung is a benign, non-metastasizing tumor with the possibility of local infiltration, recurrence or persistent local growth. This kind of tumor arises due to an unregulated growth of inflammatory cells. To our knowledge, IMT associated with nephrotic syndrome has not yet been recognized. Therefore, we present the case of a 14-year-old girl with lung IMT associated with secondary nephrotic syndrome (NS), which was cured after tumor removal.