Photoinduced antitumour effect of hypericin can be enhanced by fractionated dosing.

The in vivo antitumour activity of the natural photosensitizer hypericin was evaluated. C3H/DiSn mice were inoculated with fibrosarcoma G5:1:13 cells. When the tumour reached a volume of 40-80mm3 the mice were intraperitoneally injected with hypericin, either in a single dose (5mg/kg; 1 or 6h before laser irradiation) or two fractionated doses (2.5 mg/kg; 6 and 1 h before irradiation with laser light; 532 nm, 70mW/cm2, 168 J/cm2). All tumours in control groups treated with hypericin alone as well as those irradiated with laser light alone had similar growth rates and none of these tumours regressed spontaneously. Complete remission of tumour in photodynamic therapy (PDT)-treated groups was similar (14-17% single dose vs. 33% fractionated dose), but the fractionated schedule of hypericin dosing was found to be more efficient than the single dose, measured by survival assay (p < 0.05). Our experimental model showed that fractionated administration of hypericin can produce a better therapeutic response than single administration.

A pilot study testing the genetic polymorphism of N-acetyltransferase 2 as a risk factor in lung cancer.

NAT2 as phase II enzyme is involved in the detoxification/activation of various drugs, environmental substances and carcinogenic compounds. A genotyping approach has been used to investigate NAT2 genotype with putative relevance in lung cancer in population of 110 Slovak-Caucasians patients and 167 non-malignant individuals from the same region. Slow acetylation was not observed to be a significant risk factor of lung cancer development (OR=1.19; 95% CI: 0.71-1.99). However, one genotype responsible for slow acetylation (NAT2*5B/*6) was observed significantly more frequently in lung cancer patients with squamous cell carcinoma compared with control subjects (OR=2.24; 95% CI: 1.14-4.34). Stratified analysis showed an increasing impact of the specific allelic combination NAT2*5B/*6 in non-smokers (OR=6.5; 95% CI: 1.25-15.08). In the case of squamous lung carcinoma an analysis revealed a tendency to adversely affect cancer risk in the individuals with the mentioned genotype in younger than 60 years (OR=3.14; 95% CI: 0.98-9.72) non-smokers (OR=10.40; 95% CI: 1.35-118.89) and in females (OR=4.25; 1.08-16.25). Additional studies are needed to confirm the results we observed and to assess the impact of other effects (specific allelic combinations, sex differences and histological subtype of lung cancer) on NAT2 susceptibility in lung carcinogenesis.

[Continuous ambulatory peritoneal dialysis and respiratory pulmonary functions]. / Kontinuálna ambulantná peritoneálna dialýza a respiracné funkcie pl'úc.

Acidobasic balance and respiratory pulmonary functions were examined in 15 patients with chronic renal insufficiency during continuous ambulatory peritoneal dialysis (CAPD) using a dialysis solution containing 1.5% or 2.5% of glucose. Patients did not suffer from any pulmonary disease nor ischemic heart disease. Biochemical indicators of acidobasic balance were in reference range or on its lower margin. Respiratory pulmonary functions were in tolerance except maximum expiratory flow volume at 50% and 25% of vital capacity (MEF50 and MEF25) and except diffusion lung capacity (DLCO) which were decreased. Decrease of maximum expiratory flow could be caused by a loss of elasticity of pulmonary parenchyma and by a beginning increased resistance in peripheral pulmonary ways. Decreased DLCO was identified in majority of patients and was caused by anaemia and a minimal interstitial pulmonary edema. Use of a single peritoneal dialysis with dialysis solutions of various glucose concentrations did not have any significant effect on acidobasic balance markers nor pulmonary respiratory functions.

Combined analysis of polymorphisms in glutathione S-transferase M1 and microsomal epoxide hydrolase in lung cancer patients.

Many genes involved in the metabolism of carcinogens have been found to be polymorphic in the human population, and specific alleles are associated with increased risk of cancer at various sites. The etiology of most commonly occurring cancers cannot be explained by allelic variability at a single locus. A combined analysis of two polymorphic enzymes, glutathione S-transferase M1 (GSTM1), microsomal epoxide hydrolase (EPHX1)) and their implication as lung cancer risk factors was performed in a case- control study of non small cell lung cancer. Polymerase chain reaction (PCR) or PCR-RFLP-based methods were used to detect variant genotypes of GSTM1 and EPHX1 (113Tyr-113His in exon 3 and 139His-139Arg in exon 4) in 150 controls and group of lung cancer patients (n=121). The slow 113His EPHX1 allele tended to be more frequent among the patients (frequency 0.587) than among the controls (0.320) (Fisher s exact test, p=0.33). The combined EPHX1 homozygote genotype His113/His139 (predicted very slow activity) versus all other genotype combination was associated with an increased risk of lung cancer (OR=2.29; 95% C.I.=0.94- 5.82), particularly in non-smokers (OR=11.23; 95% C.I.=1.48- 88.41). Polymorphism in GSTM1 had no statistically significant impact on lung cancer risk alone (OR=1.09; 95% C.I.: 0.65-1.82). However, obtained the results revealed that combinations GSTM1 null with homozygote His113/His139 genotype (predicted very slow activity EPHX1) significantly increased lung cancer risk (OR=3.65; 95% C.I.: 1.04-16.07). No overall relationship between genotype combinations predicted high EPHX1 activity and lung cancer risk was confirmed in all followed respects. However, the number of investigated individuals in our study was relatively small, therefore these findings should be judged with circumspectness.

Cardiovascular implications of sleep apnea in patients with congestive heart failure.

Recent epidemiologic studies indicate that approximately 40 to 50% of stable patients with congestive heart failure (CHF) suffer from either obstructive sleep apnea (SA) or Cheyne-Stokes respiration with central SA. In either type of sleep apnea, several mechanisms contribute to significant mechanical and adrenergic stresses upon the failing myocardium. These include hypoxemia, reductions in intrathoracic pressure, rises in systemic arterial pressure, increases in left ventricular afterload, and arousals from sleep worsening the sleep architecture. Consequently, sympathetic activation and parasympathetic withdrawal are the hallmark of sleep-related sleeping disorders that contribute to the progression of heart failure and may adversely affect its prognosis. On the other hand, recent studies indicate that successful treatment of either type of SA with continuous positive airway pressure in patients with CHF results in objective and subjective improvement in the severity of heart failure increases in left ventricular ejection fraction, and reductions in sympathetic nervous system activity. Therefore, the early diagnosis and specific treatment of either obstructive or central SA in patients with CHF is highly warranted.

Germ line polymorphisms of the tumor suppressor gene p53 and lung cancer.

Two p53 variable sites (BstUI and MspI SNPs in exon 4 and intron 6, respectively) and their haplotype combinations were studied in 109 patients (84 males and 25 females) with lung cancer and 113 healthy controls from the region of Eastern Slovakia. There were no differences found between lung cancer patients and controls carrying the distribution of p53 BstUI and MspI alleles. However, the genotype distribution showed a significantly higher proportion of MspI heterozygotes in lung cancer patients (P=0.048, OR 1.83, 95% CI 1.00-3.34) than in controls. The analysis based on haplotype frequencies showed the presence of BstUI-MspI 2-1 haplotype in cancer patients (5.4%) in contrast to the absence of this haplotype in healthy controls. The results of this study suggest that the p53 MspI polymorphism may modify the susceptibility to lung cancer as a single factor rather than in combination with BstUI polymorphism.

Polymorphism of the p53 gene within the codon 72 in lung cancer patients.

We tested the codon 72 single nucleotide polymorphism (SNP) of the tumor suppressor gene p53 for association with lung cancer. In our hospital-based case-control study, 168 lung cancer patients (134 males and 34 females) and 148 controls without malignant diseases were recruited. The genotype characteristics were determined by PCR-based RFLP method using DNA extracted from peripheral blood. Only in lung cancer patients but not in the controls we found both significant decrease of A1 allele of the p53 codon 72 (p=0.024, OR 0.56, 95% CI 0.43-0.72) and A1/A1 homozygous genotype (p=0.006, OR 0.27,95% CI 0.15-0.51). The results of this study suggest a protective effect of A1 allele against lung cancer.

Benign glomus tumor of the superior posterior mediastinum.

An unusual location of a benign glomus tumour, outside of the constantly located regions, e.g. in the subungual location or deeply sited in extremities, was diagnosed in a 56-year-old white female in her posterior upper mediastinum. The single similar case report was published before the era of electron microscopy and immunohistochemistry and single cases of atypical and malignant forms in this unusual location were published only recently. The tumour measuring 5 x 4 x 2 centimeters has caused cough and was associated with occasional righ-sided chest pain. Its rich vascular supply has caused intensive intraoperative bleeding. The postoperative course was uneventful and the patient is free of neoplastic disease or symptoms six years after surgery. Numerous mast cells present within the tumour's interstices must be considered in relation to the possible pathogenesis of the up to now unexplained pain in glomus tumours.

Genetic polymorphism of glutathione S-transferases M1 and T1 as a risk factor in lung and bladder cancers.

A combined analysis of two polymorphic enzymes, glutathione S-transferase mu (GST M1) and q (GST T1) and their implication as cancer risk factors was performed in a case-control study of lung and bladder cancers. Using a multiplex polymerase chain reaction (PCR) based method, the frequency of the homozygous deleted GSTM1 and GSTT1 genotypes was examined in 117 lung cancer patients, 67 urinary bladder cancer patients, and in a community-based sample of 248 healthy, unrelated individuals. In both cancer groups the frequency of the GSTM1 null genotype was higher in comparison with that of the control group (59% and 59.7% vs. 49.6%), but this increase did not reach statistical significance (p > 0.05). After grouping by the smoking status, among smokers in both cancer groups (62.1% in lung cancer and 71.4% in the bladder cancer group, respectively) there were statistically significantly (p < 0.05) increased frequencies of the GSTM1 deletion genotype as compared to the control group (49.6%). Smokers with absence of the GSTM1 gene were at an approximately 1.7-fold higher risk for lung cancer (odds ratio--OR = 1.67, 95% confidence interval--CI 95% = 1.0-2.7, p = 0.04) and an approximately 2.5-fold higher risk for bladder cancer (OR = 2.54, CI 95% = 1.2-5.5, p = 0.02). As related to GSTT1, our study demonstrated an overall GSTT1 effect on bladder cancer risk. Individuals with absence of the GSTT1 gene were at an approximately 2.5-fold higher risk of developing bladder cancer. In the lung cancer cases, the frequency of the putatively high risk GSTT1 null genotype was not increased as compared with controls. No effect of smoking was found on risk of lung and bladder cancer associated with the GSTT1 0/0 genotype. In combined analysis, the obtained results suggested that individuals who were both GSTM1 null and GSTT1 null may be at increased risk because they lack both enzymes. The findings suggest that the GSTM1 null genotype may be associated with susceptibility to lung and urinary bladder cancer in dependence on the exposure to carcinogens in cigarette smoke and that the GSTT1 null genotype is not a critical factor in mediating the risk of lung cancer, but may be associated with an increased susceptibility to bladder cancer.

[Surgery in patients with organ transplants]. / Operácie chorých s transplantovanými orgánmi.

Patients after successful transplantation with immunosuppressive therapy form a "new circle of surgical patients" who can develop various surgical diseases, or injuries which bring about an inevitable urgent or planned surgical treatment. The authors present the results in three patients with transplanted organs (1993-1995) who were subdued to various surgical treatments. The first patient underwent a classical cholecystectomy, choledochotomy, and extraction of concrement from the choledochus after orthotopic transplantation of the heart. The second patient underwent transplantation of the kidneys precedingly to bilateral subtotal resection of both lobes of the thyroid gland due to marked bilateral nodal goitre intervening deeply retrosternally with a severe pressure syndrome on trachea and oesophagus. The immediate and long-term results were excellent. Orthotopic transplantation of the heart in the third patient preceded to intercostal drainage of the thorax and evacuation of pus due to an extensive empyema of the thorax and septic state, and later thoracotomy and decortication with extirpation of the substantial part of the empyema sack was performed with an excellent immediate and long-term effect. The authors present the principles which must be inevitably fulfilled in coincidence with successive surgical treatment in patients with transplanted organs in a permanent immunocomplex regime. (Fig 2, Ref. 11.)