Partial recessive IFN-γR1 deficiency: genetic, immunological and clinical features of 14 patients from 11 kindreds.

We report a series of 14 patients from 11 kindreds with recessive partial (RP)-interferon (IFN)-γR1 deficiency. The I87T mutation was found in nine homozygous patients from Chile, Portugal and Poland, and the V63G mutation was found in five homozygous patients from the Canary Islands. Founder effects accounted for the recurrence of both mutations. The most recent common ancestors of the patients with the I87T and V63G mutations probably lived 1600 (875-2950) and 500 (200-1275) years ago, respectively. The two alleles confer phenotypes that are similar but differ in terms of IFN-γR1 levels and residual response to IFN-γ. The patients suffered from bacillus Calmette-Guérin-osis (n= 6), environmental mycobacteriosis (n= 6) or tuberculosis (n= 1). One patient did not suffer from mycobacterial infections but had disseminated salmonellosis, which was also present in two other patients. Age at onset of the first environmental mycobacterial disease differed widely between patients, with a mean value of 11.25 ± 9.13 years. Thirteen patients survived until the age of 14.82 ± 11.2 years, and one patient died at the age of 7 years, 9 days after the diagnosis of long-term Mycobacterium avium infection and the initiation of antimycobacterial treatment. Up to 10 patients are currently free of infection with no prophylaxis. The clinical heterogeneity of the 14 patients was not clearly related to either IFNGR1 genotype or the resulting cellular phenotype. RP-IFN-γR1 deficiency is, thus, more common than initially thought and should be considered in both children and adults with mild or severe mycobacterial diseases.

[Invasive aspergillosis (IA) in patients treated in the Institute of Tuberculosis and Chest Diseases in the years 1993-2005--diagnostic problems]. / Inwazyjna aspergiloza u chorych leczonych w Instytucie Gruzlicy i Chorób Pluc w latach 1993-2005--trudnosci diagnostyczne.

The aim of this study was to present the diagnostic problems in pts treated for invasive aspergillosis (IA) in the IIIrd Clinic of the Institute of Tuberculosis in the years 1993-2005. The material consisted of clinical documentation of 18 pts. 15 out of 18 pts (83,4%) died. In all those cases autopsy examination was done. In 13 pts IA was the main and in another 2 only the accessory cause of death. All pts were treated with corticosteroids and/or cytostatic drugs because of lung cancer (13 pts), haematologic disorders (1 pts), Wegener's granulomatosis (3 pts) and idiopathic pulmonary fibrosis (1 pts). In 13 out of 18 pts granulocytopenia was revealed (on an average from 0,008 x 10(9)/L to 0,95 x 10(9)/L) one month before death. In 13 pts IA was limited to the lungs, in 5 others there were also fungal lesions in brain, kidneys, liver, spleen, pleura, pericardium and heart. Pts with disseminated form of IA had significantly lower granulocyte count and were treated with higher doses of corticosteroids than others. Immunosupressive drugs and granulocytopenia can be regarded as predisposing factors. IA was diagnosed before death only in 5 out of 18 pts. This was mainly caused by the lack of the symptoms of infection (4 pts) and negative results of mycological (6 pts) and serological examination (8 pts). We should underline that mycological examination was only done in 11 pts and serological examination of blood for fungal antigen only in 6 pts. We conclude that mycological infection ought to be searched in all pts treated with high doses of corticosteroids and those with prolonged granulocytopenia, especially if they have the symptoms of infection which does not respond to antibiotic therapy.

[The significance of the serum tumour markers as a prognostic and predictor factors in nonsmall cell lung cancer patients]. / Znaczenie wybranych biochemicznych markerów nowotworowych dla prognozowania wczesnej odpowiedzi na leczenie i rokowanie u chorych na niedrobnokomórkowego raka pluca.

The aim of the study was to assess the role of serum tumour markers (NSE, Cyfra 21-1, CEA, LDH, ferritin) as a prognostic and predictive factors in 79 patients with advanced NSCLC treated with chemotherapy. Objective response to treatment was significantly more frequent in the patient with serum NSE > 12.5 ng/ml. Progression of disease was observed more often in patients with serum Cyfra 21-1 >10 ng/ml or LDH >480 U/L. CEA >3 ng/ml, LDH >480 U/L, for coefficient >1, NSE >20 ng/ml and Cyfra 21-1 >10 ng/ml had a negative impact on survival in univariate analysis. Independent negative prognostic significance of fer coefficient >1 was confirmed by multivariate analysis.

[Evaluation of mediastinal lymph nodes in the course of lung diseases in dynamic contrast-enhanced magnetic resonance imaging]. / Ocena wezlów chlonnych sródpiersia w przebiegu chorób pluc z zastosowaniem dynamicznych badan metoda rezonansu magnetycznego po podaniu preparatów kontrastowych.

The purpose of this study was to evaluate the ability of dynamic contrast-enhanced magnetic resonance to provide differentiation between malignant and benign mediastinal or hilar lymph nodes. The group of 109 patients were examined, with lung carcinoma (63 patients) and sarcoidosis (46 patients). Relative signal intensity increase after administration of Gd-DTPA in standard dose (0.1 mmol/kg) was measured four times (20 s-3 min after injection). There was no significant difference between all groups. In conclusion, differentiation between types of enlarged lymph nodes could not be achieved using the described protocol.

[Prognosis in limited disease (LD) small cell lung cancer (SCLC) patients according to status performance, local extension of lesions, type of treatment and the completeness of staging]. / Rokowanie chorych na ograniczona postac drobnokomórkowego raka pluca w zaleznosci od stanu sprawnosci, lokalnej rozleglosci zmian, sposobu leczenia oraz stopnia precyzji w ustaleniu zaawansowania.

The aim of this study was to assess the prognosis in LD SCLC pts according to their performance status, local extension of lesions, type of treatment and the completeness of staging. In the period 01.01.1986-31.12.1996 in the Institute of Tuberculosis and Chest Diseases 579 consecutive SCLC pts were treated. LD was diagnosed in 345 pts. In 193 out of them the staging was complete that is in addition to chest x-ray, abdomen USG/CT, brain CT/MRI and bilateral bone marrow trepanobiopsy was done. 152 pts were also regarded as limited but the staging was not complete. LD pts proved by complete staging survived significantly longer (median survival 15.7 months) than others (median survival 10.2 months). The pts in whom complete staging was done were however in better performance status and had smaller local extension of lesions and had more often radiotherapy than others. Status performance, local extension of lesions and radiotherapy but also completeness of staging were independent prognostic factors in multivariate analysis.

[Organizing pneumonia--analysis of 18 own cases]. / Organizujace sie zapalenie pluc--analiza 18 przypadków.

Organizing pneumonia (OP) is a rarely diagnosed disease, however the incidence ratio was estimated as 6-7/100000. Disease can occur in cryptogenic form or as a secondary reaction to various noxious agents, drugs, and ionising radiation, as a concomitant disease to infections, lympho- and myeloproliferative disorders, and connective tissue diseases. Symptoms of OP are non-specific therefore lung biopsy and histological examination are necessary for diagnosis. Eighteen cases of OP, 15 women and 3 men, aged 40 to 76 years, are presented with analysis of clinicopathological characteristic and therapeutic problems. In all cases diagnosis was confirmed by open lung biopsy. In one case radiotherapy and in one trastuzumab treatment was the cause of OP. In further 3 women antibodies against Chlamydia pneumoniae and in one--against Mycoplasma pneumoniae were found in serum. Probably Hashimoto disease was the cause of one case. In 12 patients the OP was idiopathic. Majority of patients were treated by prednisone (0.5 mg/kg). In one patient regression without any treatment was noticed and in other one--after cessation of trastuzumab. Five women were treated by clarithromycin. In 3 of them regression was observed but in other 2 corticotherapy was necessary. The observation period ranged from 1 month to 9 years, mean 34 months.

[Pulmonary mycobacterioses--frequency of occurrence, clinical spectrum and predisposing factors]. / Postaci plucne mykobakterioz--czestosc wystepowania, obrazy kliniczne i czynniki predysponujace.

Various types of non-tuberculous mycobacteria can be the aetiologic factors of chronic lung infections especially in patients with underlying chronic lung diseases. The aim of this study is to present the cases of pulmonary mycobacterioses observed in Institute of Tuberculosis and Lung Diseases in the years 1995-2001. There were 23 patients, 12 men and 11 women in the age between 35-77 years, mean 56 years. 16 out of 23 patients had underlying respiratory problems, mainly healed tuberculosis (7) and COPD (6). Two additional patients suffered from other diseases with potential immunosuppression (leukopenia). In 5 patients no disease other than mycobacteriosis was found, but they were chronic smokers. In 19 cases cough and expectoration of purulent sputum lasting from several months to several years was observed. In 5 patients onset of disease was acute or subacute with high fever. Eight patients had haemoptysis. In chest X-ray pathological lesions including (18 cases) lung cirrhosis (10) and cavities (15) were found. In 4 cases disseminated bronchiectases with small nodules were the main radiologic feature. Mycobacteriosis was caused by M. kansasii in 11 cases, by M. intracellularae in 6, by M. xenopi in 5 and by M. scrofulaceum in 1 case.

[A case of a patient with idiopathic pulmonary arterial hypertension treated with lung transplantation: a "bumpy road" to success]. / Przypadek idiopatycznego nadcisnienia plucnego leczony transplantacja pluc. Trudnosci okresu przed transplantacja i po transplantacji.

We describe a case of 29 year old man, a first Polish patient with idiopathic arterial hypertension (IPAH) listed from Poland and successfully treated with lung transplantation in Vienna. Time from diagnosis to lung transplant was merely 11 months. Rapid clinical deterioration required treatment with most of currently approved or emerging methods, including oral and parenteral prostacyclin analogues administration by inhalation and chronic subcutaneous infusion. Atrial balloon septostomy was used to bridge the patient to transplant. We describe multiple problems in providing pharmacotherapy and in arranging logistics for lung transplantation. Peri- and multiple post-transplantation complications including dehiscence of right main bronchial anastomosis and its successful therapy are also presented. We consider good long term outcome as assessed 26 months post transplantation as an encouragement for other attempts at lung transplantation in patients with IPAH and for development of this method of therapy in Poland.

Disseminated Mycobacterium avium infection in a 20-year-old female with partial recessive IFNgammaR1 deficiency.

We report the case of a 20-year-old female with disseminated Mycobacterium avium disease involving bones, lungs and brain. She was completely healthy up until the present illness and had been vaccinated with BCG in infancy without complications. Mycobacteriosis progressed in spite of treatment with antituberculous drugs and was controlled only after addition of interferon-gamma subcutaneously. A homozygous hypomorphic I87T mutation was found in the gene encoding the ligand-binding chain of the IFN-gamma receptor (IFNgammaR1). This mutation is the only known recessive hypomorphic lesion in IFNGR1 and had been reported before in only 1 child with curable BCG infection and his sibling with primary tuberculosis. Our report illustrates the clinical heterogeneity of patients sharing exactly the same form of partial recessive IFNgammaR1 deficiency. A diagnosis of partial recessive IFNgammaR1 deficiency should be contemplated in adults with unexplained environmental mycobacterial diseases.