The influence of blood phenylalanine levels on neurocognitive function in adult PKU patients.

It is well known that hyperphenylalaninemia caused by phenylketonuria (PKU) negatively influences cognitive performance. Several tests have been used to study these functions. Until now, no universal, optimal tool has been developed for detecting PKU-caused brain dysfunctions. Using computerized neuropsychological tests during daily routine would be helpful for screening subclinical brain deficits in adult PKU patients. In a monocentric, cross-sectional study, adult patients with PKU (n = 46; median age = 29.5 years; female/male ratio = 21/25) were tested with the computerized Cambridge Cognition (CANTAB) test measuring neurocognitive functions. Patients were divided into two groups: The "on diet" group included patients whose blood Phe-level was under 600 µmol/l (n = 20), and the "loose diet" group included patients whose blood Phe-level was above 600 µmol/l (n = 26) at the examination time. The results of the PKU-affected individuals were compared with a healthy control group (n = 31; median age = 25 years; female/male ratio = 11/20). Compared with the control group, PKU patients had significantly worse test results in memory, problem-solving skills, and strategy. However, there were no significant differences in response speed or initial thinking time. There was no correlation between the blood Phe-level, tyrosine (Tyr)-level or Phe/Tyr ratio and the different cognitive test results. There were no significant differences in test results between the two PKU subgroups. Several cognitive functions measured by CANTAB are negatively influenced by hyperphenylalaninemia in adult PKU patients. However, response speed and initial thinking time were not impaired as seriously as other functions. Patients with lower Phe-levels failed to achieve better test results than patients whose Phe-levels were notably elevated.

A randomized, double-blind, phase II study of erlotinib with or without sunitinib for the second-line treatment of metastatic non-small-cell lung cancer (NSCLC).

BACKGROUND: Combined inhibition of vascular, platelet-derived, and epidermal growth factor receptor (EGFR) pathways may overcome refractoriness to single agents in platinum-pretreated non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: This randomized, double-blind, multicenter, phase II trial evaluated sunitinib 37.5 mg/day plus erlotinib 150 mg/day versus placebo plus erlotinib continuously in 4-week cycles. Eligible patients had histologically confirmed stage IIIB or IV NSCLC previously treated with one or two chemotherapy regimens, including one platinum-based regimen. The primary end point was progression-free survival (PFS) by an independent central review. RESULTS: One hundred and thirty-two patients were randomly assigned, and the median duration of follow-up was 17.7 months. The median PFS was 2.8 versus 2.0 months for the combination versus erlotinib alone (HR 0.898, P = 0.321). The median overall survival (OS) was 8.2 versus 7.6 months (HR 1.066, P = 0.617). Objective response rates (ORRs) were 4.6% and 3.0%, respectively. Sunitinib plus erlotinib was fairly well tolerated although most treatment-related adverse events (AEs) were more frequent than with erlotinib alone: diarrhea (55% versus 33%), rash (41% versus 30%), fatigue (31% versus 25%), decreased appetite (30% versus 13%), nausea (28% versus 14%), and thrombocytopenia (13% versus 0%). CONCLUSIONS: The addition of sunitinib to erlotinib did not significantly improve PFS in patients with advanced, platinum-pretreated NSCLC.

Alterations of carbohydrate and lipoprotein metabolism in childhood obesity--impact of insulin resistance and acanthosis nigricans.

AIM: To study the prevalence of alterations of glucose and lipoprotein metabolism and the impact of acanthosis nigricans (AN) in childhood obesity. PATIENTS AND METHODS: 113 obese children, 57 with simple obesity (SO) and 58 with obesity and AN (OAN). Oral glucose tolerance test was performed, serum glucose, insulin and lipoprotein parameters were determined, and insulin resistance/sensitivity indices were calculated. RESULTS: Insulin resistance, basal and reactive hyperinsulinemia, impaired glucose tolerance (IGT) and dyslipidemia were found to be frequent conditions in children with OS as well as OAN. Reactive insulinemia was more pronounced in OAN than in SO, and insulin resistance was more frequent when AN was more prominent. Triglycerides were higher and HDL-C was lower, and atherogenic dyslipidemia was more frequent in OAN compared to SO. CONCLUSION: Children with obesity form a risk population. AN is a factor which can be used in metabolic risk factor clustering estimation in childhood obesity.

Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative, for the treatment of patients with non-small cell lung cancer.

PURPOSE: The purpose of this phase I study was to evaluate the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), the recommended dose for phase II study, pharmacokinetics, and antitumor activity of TZT-1,027 (soblidotin) in patients with non-small cell lung cancer (NSCLC) when administered every 3-4 weeks. METHODS: Eligible patients had the following characteristics: stage III/b or IV NSCLC that was refractory to conventional therapy or for which no standard therapy was available; Eastern Cooperative Oncology Group (ECOG) performance status (PS) or=20 and <75 years. The patients were administered TZT-1,027 in escalating doses from 0.5 to 5.6 mg/m(2). Pharmacokinetic samples were collected during each treatment course. RESULTS: Forty-nine patients were enrolled. Three patients had DLTs, including neutropenia, neutropenia complicated by fever, myalgia, and neuropathic pain. The common toxicities included constipation, anorexia, alopecia, nausea, leukopenia, and neutropenia. One complete response and three partial responses were observed. The pharmacokinetic parameters (AUC and C (max)) of TZT-1,027 tended to increase linearly with dose. CONCLUSIONS: DLTs included neutropenia, neutropenia complicated by fever, myalgia, and neuropathic pain. The MTD was 4.8 mg/m(2). The recommended phase II study dose of TZT-1027 is 4.8 mg/m(2) administered every 3-4 weeks.

Alterations of glucoregulation in childhood obesity--association with insulin resistance and hyperinsulinemia.

AIM: To study the prevalence of alterations of glucoregulation in childhood obesity. PARTICIPANTS: 250 obese children. Oral glucose tolerance test was performed, serum glucose and insulin were determined, and HOMA-IR was calculated. RESULTS: Impaired fasting glucose (IFG) was found in 1.2% according to World Health Organisation criteria and 4.4% according to the criteria of the International Diabetes Federation. Impaired glucose tolerance (IGT) was found in 13.6%, type 2 diabetes mellitus (DM2) in 2.4%. Frequency of fasting glucose (FG) above 7.0 mmol/l was 1.2%. Basal hyperinsulinemia was increased in 70%, reactive hyperinsulinemia in 88%, frequency of elevated HOMA-IR was 78%. 120' insulin was increased in all cases with abnormal FG, IGT and DM2, HOMA-IR was elevated in 79% of patients with IGT and all patients with abnormal FG and DM2. Significant positive correlations were demonstrated between body mass index and insulin levels. CONCLUSION: Our data show that hyperinsulinemia can successfully compensate for insulin resistance in the majority of the obese children. Since IFG is less frequent than IGT there is a need for performing OGTT to demonstrate abnormality of glucoregulation in obese children.

Toxicity of a pendimethalin containing herbicide formulation and three heavy metals in chicken embryos.

The toxic effects of a widely used herbicide (Stomp 330 containing 33% pendimethalin as active ingredient) applied alone or in combination with three heavy elements (copper sulphate, cadmium sulphate and lead acetate) modelling the heavy metal load of the environment were studied on chicken embryos with injection treatment. The treatment was done on day 0 of incubation. Solutions and emulsions of different concentrations were made from the test materials and injected in 0.1 ml volume into the air space of eggs. The macroscopical evaluations were done on day 19 of the incubation. Summarizing the findings, it can be established that the individual administration of the 33% pendimethalin containing herbicide formulation was less toxic compared to the control group than the simultaneous administration of the pesticide and heavy elements. As compared with each other the results from the combined administrations of the 33% pendimethalin containing herbicide formulation and heavy elements the simultaneous administration of cadmium and the herbicide caused the highest embryomortality while the incidence of developmental anomalies were the highest in the interaction study of the copper and the pesticide.

Teratogenicity testing of a 2,4-D containing herbicide formulation and three heavy metals in chicken embryos.

The toxic effects of a widely used herbicide (Dikamin D containing 72% 2,4-D-amine Na as active ingredient) applied alone or in combination with three heavy elements (copper sulphate, cadmium sulphate and lead acetate) modelling the heavy metal load of the environment were studied on chicken embryos with injection treatment. The treatment was done on day 0 of incubation. Solutions and emulsions of different concentrations were made from the test materials and injected in 0.1 ml volume into the air space of eggs. The macroscopical evaluations were done on day 19 of the incubation. Summarizing the findings, it can be established that the individual administration of the 72% 2,4-D containing herbicide formulation was less toxic compared to the control group than the simultaneous administration of the pesticide and heavy elements. As compared with each other the results from the combined administrations of the 72% 2,4-D containing herbicide formulation and heavy elements the simultaneous administration of cadmium and the herbicide caused the highest embryomortality while the incidence of developmental anomalies were the highest in the interaction study of the copper and the pesticide.

Early embryogenesis study on a dimethoate containing formulation and Cd-sulphate in chicken embryos.

The toxic effects of a widely used organophosphate insecticide (BI 58 EC containing 38% dimethoate as active ingredient) applied alone or in combination with cadmium sulphate modelling the heavy metal load of the environment were studied on chicken embryos in the early phase of development. Solutions and emulsions of different concentrations were made from the test materials and injected in 0.1 ml volume into the air space of eggs on the first day (day 0) of incubation. Subsequently, on days 2 and 3 of incubation permanent preparations were made from the embryos in order to study the early developmental stage. Embryos fixed on slides and stained with osmium tetroxide solution were studied under light microscope. Summarising the findings, it can be established that the embryotoxicity increased after the simultaneous administration of Cd-sulphate and 38% dimethoate containing insecticide formulation compared to the control or the individually treated groups.

A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer.

BACKGROUND: Treatment options after first-line chemotherapy are limited in non-small cell lung cancer (NSCLC). Belagenpumatucel-L is a therapeutic vaccine comprised of 4 transforming growth factor (TGF)-ß2-antisense gene-modified, irradiated, allogeneic NSCLC cell lines that may be useful for maintenance after initial treatment. METHODS: Stage III/IV NSCLC patients who did not progress after platinum-based chemotherapy were randomised 1:1 to receive maintenance belagenpumatucel-L or placebo. Patients were eligible for randomisation between one and four months from the end of induction chemotherapy. The primary endpoint was overall survival. RESULTS: This phase III trial enrolled 270 patients in the belagenpumatucel-L arm and 262 in the control arm. Belagenpumatucel-L was well tolerated with no serious safety concerns. There was no difference in survival between the arms (median survival 20.3 versus 17.8months with belagenpumatucel-L versus placebo, respectively; hazard ratio (HR) 0.94, p=0.594). There were also no differences in progression-free survival (4.3months versus 4.0 for belagenpumatucel-L vs placebo, respectively; HR 0.99, p=0.947). A prespecified Cox regression analysis demonstrated that the time elapsed between randomisation and the end of induction chemotherapy had a significant impact on survival (p=0.002) and that prior radiation was a positive prognostic factor (median survival 28.4months with belagenpumatucel-L versus 16.0months with placebo; HR 0.61, p=0.032). CONCLUSIONS: Although the overall trial did not meet its survival endpoint, improved survival for belagenpumatucel-L is suggested in patients who were randomised within 12weeks of completion of chemotherapy and in those who had received prior radiation. Further studies of belagenpumatucel-L in NSCLC are warranted.

The effect of oxidative stress on inbred mice of different ages.

The effect of oxidative stress applied for 2 months was compared in adult (14-month-old) and aged (27-month-old) female BALB/c mice. The stress was administered in two ways. One group of animals received a high dose of H2O2 (0.5% H2O2 in drinking water) the other one was given a low dose of H2O2 (0.4 ml of 0.5% H2O2 by esophageal cannula every alternate day). After a 2-month treatment the activity of superoxide dismutase (SOD), catalase and lipid peroxidation capacity were measured in liver homogenates of mice. The activity of catalase and capacity of lipid peroxidation gradually decreased as a function of age while the SOD activity did not reduce even in older mice. The aged-mice could tolerate a high dose of H2O2 mainly by increasing SOD activity. As a result of intake of low dose of H2O2 in old animals SOD activity was decreased and lipid peroxidation capacity was getting higher suggesting that in this life period the liver tissue is very sensitive to chronic, oxidative stress effects of low dose.

Calcifying liver metastases in a case of primary lung cancer.

A 50-year-old man presented with primary lung cancer with bone lesions and calcifying liver nodi. Two months after stopping chemotherapy, he died. Autopsy revealed multiple organ metastases. Histologically, the calcified nodi in the liver proved to be affected by tumor metastasis.

Hematospermia.

The appearance of blood in the seminal fluid is an alarming sign, with a rather inconstant origin. The causes of hematospermia are discussed based on a review of the literature and the authors' own experience with 84 patients. The importance of differential diagnosis is emphasized and a diagnostic scheme is presented. Therapeutic opportunities depending on etiology are discussed. It is concluded that although hematospermia is an often self-limiting sign, resolving in a few weeks, all patients should undergo a careful investigation to rule out the presence of malignancy or other significant disease.

Subclinical pulmonary involvement assessed by bronchoalveolar lavage in patients with early undifferentiated connective tissue disease.

OBJECTIVE: To assess the presence of neutrophil and lymphocyte fibrosing alveolitis by bronchoalveolar lavage in patients with early undifferentiated connective tissue disease (EUCTD) and systemic sclerosis (SSc). METHOD: Bronchoalveolar lavage (BAL) was performed in 13 patients with EUCTD who exhibited signs of lung involvement by non-invasive methods including lung function tests and high resolution computed tomography. The mean age of cases was 48.1 +/- 6.6, and the mean disease duration was 1.8 +/- 0.8 years. Differential cell counts of BAL were evaluated. Eleven patients with systemic sclerosis and 5 healthy control subjects were also investigated. RESULTS: Eleven of the 13 EUCTD and 10 of the 11 SSc patients showed an elevated total cell number (above the median cell/ml of control + 2 SD) in the BAL fluid. In patients with EUCTD, the lymphocyte count was elevated in 6, and the polymorphonuclear neutrophil count in 2 patients. One of the patients with EUCTD had simultaneously elevated lymphocyte and neutrophil granulocyte counts. In the SSc group, 6 patients had an elevated lymphocyte and 6 an increased neutrophil count. Three of these cases had both increased neutrophil and elevated lymphocyte counts, simultaneously. CONCLUSION: Subclinical, predominantly lymphocyte alveolitis can be present in patients with EUCTD. Patients with SSc tend to exhibit neutrophil alveolitis.

Invasive naevus of Ota.

A slowly invasive naevus of Ota was followed for 50 yrs. During this time multiple biopsies were considered to be benign cellular blue naevus. The left globe, orbit, frontal bone and meninges were excised to achieve clearance.

Use of asymmetrically-polarised dropping-mercury electrodes in controlled-potential polarography.

It is shown that uncompensated cell resistance in controlled-potential polarography can be decreased by the use of asymmetrical polarisation of the dropping-mercury electrode.

A dc Method for the Absolute Determination of Conductivities of the Primary Standard KCl Solutions from 0 °C to 50 °C.

A new method for the absolute determination of electrolytic conductivity based on direct current and Potentiometric measurements is described. The unique design of the cell uses a removable center section whose length and cross-sectional area are accurately known. Two pairs of matched Ag, AgCl electrodes are used in a four terminal mode of resistance measurement. Measurements of the electrolytic conductivity of primary standard potassium chloride solution using [his novel dc conductance cell are compared with the currently adopted IUPAC and OIML recommendations. In addition, measurements have heen made of the electrolytic conductivity of a solution of potassium chloride having a molality of 1 mol/kg (mole KCl per kilogram H2O). The values so obtained over the temperature range of 0 °C to 50 °C are recommended as the new primary standards for electrolytic conductivity.

Actinomycosis of the ear.

A case of primary actinomycosis of the ear in a 15 year old Ethiopian girl is described and discussed.

[Herpes zoster infection with acute urinary retention]. / Herpes zoster infectio akut vizelet retentióval.

The history of a young female patient is presented. She developed urine retention of sudden onset as a complication of herpes zoster infection manifested in the sacral dermatomes. Symptomatic and antiviral treatments were introduced with full recovery of bladder function. The correct diagnosis of this rare and benign complication of herpes zoster infection can help to avoid unnecessary and invasive examinations.

[The role of computerized tomography in the staging of lung cancer]. / A komputertomográfia helye a tüdódaganatok stádiumba sorolásánál.

Staging of lung cancer place significant role in the prognosis and treatment of the disease. Beside bronchoscopy, CT one of the important method for the tumor staging. 135 CT examinations with diagnosis of suspected lung cancer were evaluated and radiologic diagnosis was compared with the cyto-histological and surgical results. In 112 cases both CT and histological diagnosis were performed: both method revealed malignant tumors in 108 cases. Five lesions were regarded as tumour by CT but histological result proved aspergilloma, or specific processes. Abnormal lymph nodes were recognised at 98 tumours patients. There was a good correlation-regarding the number, size measurement-between CT and surgery. Histological diagnosis proved that all of the lymph nodes larger, then 2 cm of diameter contained metastic cells. In the 1-2 cm size almost all of the lymph nodes were metastatic. In addition tumour cells were found in some lymph nodes smaller, than 1 cm, too. This gives warning sign: smaller lymph nodes need more attention than we assumed. CT prove to be confident method for the evaluation, measurement and localisation of the tumours and lymph nodes in the chest.

[Thoracic actinomycosis]. / Thoracalis actinomycosis.

The authors describe in their case study the history of a 51 year old man, at whom they verified without thoracotomy thoracal actinomycosis. They achieved recovery giving permanently high doses of Penicillin. In connection with this rare case the authors review pathogenesis, the symptomatology, the diagnosis and the therapy of actinomycosis. The authors have found only one case in the Hungarian literature, which was recognized without thoracotomy and was cured by antibiotic therapy within a short period of time.