Human telomerase catalytic subunit gene re-expression is an early event in oral carcinogenesis

AIMS: Detection of telomerase catalytic subunit (hTERT) mRNA has been used as a surrogate marker for estimation of telomerase activity. The exact role and timing of telomerase re-activation, a key enzyme implicated in cellular immortalization and transformation, in the multistep process of oral carcinogenesis is still unknown. The aim was to test the hypothesis that (i) quantitative rather than qualitative differences exist in the level of hTERT mRNA expression between normal oral mucosa, different grades of oral epithelial abnormalities and squamous cell carcinomas of the oral cavity, and that (ii) hTERT gene re-expression is an important, probably early event in oral carcinogenesis. METHODS AND RESULTS: The relative quantity of hTERT mRNA was analysed in 45 frozen oral epithelia representing different morphological stages of oral carcinogenesis classified according to the Ljubljana classification and in 37 oral squamous cell carcinomas, using a commercially available LightCycler Telo TAGGG hTERT Quantification kit. hTERT mRNA was not detected in normal or reactive hyperplastic oral epithelia, but was present in 43% of atypical hyperplasias (premalignant lesions), 60% of intraepithelial carcinomas and 68% of oral squamous cell carcinomas. Statistical analysis revealed two groups of oral epithelial changes, with significant differences in the levels of hTERT mRNA expression: 1, normal and reactive hyperplastic oral epithelium, and 2, atypical hyperplasia, intraepithelial carcinomas and squamous cell carcinomas. CONCLUSION: These data suggest that hTERT gene re-expression represents an early event in the multistep process of oral carcinogenesis, already detectable at the stage of precancerous oral epithelial changes. Nevertheless, other genetic aberrations appear to be necessary for progression of oral epithelial abnormalities towards invasive squamous cell carcinoma.     

Beneficial hemorheologic therapy of chronic peripheral arterial disorders with pentoxifylline: Results of double-blind study versus vasodilator-nylidrin

Pentoxifylline (Trental 400 mg coated tablets) and nylidrin HCl 3 mg were compared for clinical efficacy and safety in an 8-week randomized double-blind trial. The study was conducted in patients with peripheral arterial disease (Fontaine stage II or III), with 30 patients receiving pentoxifylline (23 returned for follow-up), and 30 patients receiving nylidrin HCl (24 returned for follow-up). Efficacy was assessed objectively in terms of walking performance (absolute walking time and walking distance on a treadmill ergometer) and by acral plethysmography. The clear improvement shown for both variables was greater and statistically significant (p ≤ 0.05) after treatment with pentoxifylline. Laboratory data provided no evidence to suggest any adverse effect of either treatment. Subjective side effects were reported by six patients in the pentoxifylline group and by three patients in the nylidrin HCl group.     

Distribution of scalp somatosensory potentials evoked by stimulation of the tibial nerve in man

The scalp distribution of the response to stimulation of the tibial nerve at the medial malleolus was systematically analysed. The somatosensory evoked potential (SEP) was recorded with electrodes placed in a transversal line over the ipsilateral and contralateral postcentral gyri and in a sagittal line over the longitudinal brain fissure. The SEPs recorded over the ipsilateral hemisphere and along the sagittal line were similar to the F response (the response over the foot primary somatosensory region). Over the contralateral hemisphere the waveform of the responses changed obviously from point F to the point C (contralateral hand primary somatosensory region). The C response started with N37, P40 had a longer latency, N50 was not present and the subsequent waves were also considerably different. Mathematical simulation of the responses recorded from the electrodes between points F and C has shown that they represent an electrical algebraic summation of the activity over points F and C. Although the F and C responses may be 2 potentials arising from the opposite sides of a single dipole generator which is located in the medial fissure, it is more probable that the somatosensory evoked potential on tibial nerve stimulation reflects the activity of 2 separate generators.     

The early negative potential evoked by stimulation of the tibial nerve in man

The scalp response to stimulation of the tibial nerve at the level of the medial malleolus was systematically analysed. It was recorded 2 cm posterior to the vertex and at the sites corresponding to cortical representation of the hand. The existence of an early negative wave with a peak latency of 37.2 ± 2.29 ms and amplitude of ?0.69 ± 0.40 μV was established (being half the amplitude of the first positive wave (P40) over the vertex). This wave was named N37 in respect of the peak latency and polarity. N37 was the first event recorded after stimulation of the tibial nerve at this level as the onset latency was 32.2 ± 1.75 ms and that of P40 over the vertex 33.8 ± 2.28 ms. It was recorded with the highest amplitude over the hand primary somatosensory area after stimulation of the opposite foot.N37 evoked by stimulation of the tibial nerve at the ankle and N20 evoked by stimulation of the arm nerve are both the primary negativities of the evoked potential. However, N37 is not recorded with maximum amplitude over the leg primary somatosensory area and it is rounded and longer lasting than N20. In spite of these differences the two initial negative electrical phenomena are not necessarily generated by different functional structures. The possible generators of N37 are discussed.     

The environmental monitoring in hospital pharmacy cleanroom and microbiota catalogue preparation

Knowing the normal cleanroom microbiota is the basis for ensuring microbiological quality; assess changes and the introduction of new sampling methods. During our study, we prepared a catalogue of cleanroom microorganisms located in four different cleanrooms in University Clinical Centre Ljubljana Pharmacy. Catalogue is prepared as a basis for assessing the suitability of the new rapid microbiological method and subsequent correlation of the results of both methods. The results of our study showed that 78% of isolated bacteria are Gram-positive. However, in more than 70% isolated bacteria were the part of the normal human microbiota, 10–15% of the microorganisms originated from the air, mainly spore-forming bacteria of the genus Bacillus and fungi, and 5–10% of the Gram-negative microorganisms that originated from the water and represent the potential endotoxins (pyrogens).     

Management of neurosurgical patients during coronavirus disease 2019 pandemics: The Ljubljana,Slovenia experience

The novel coronavirus disease 2019 (COVID-19) is an emerging disease, caused by severe acute respiratory syndrome coronavirus-2. It bears unique biological characteristics, clinical symptoms and imaging manifestations, therefore presenting an important and urgent threat to global health. As a result, a new public health crisis arose, threatening the world with the spread of the 2019 novel coronavirus. Despite the maximal worldwide public health responses aimed at containing the disease and delaying its spread, many countries have been confronted with a critical care crisis, and even more, countries will almost certainly follow. In Slovenia, the COVID-19 has struck the health system immensely and among all the specialities, neurosurgery has also been experiencing difficulties in the service, not only in regular, elective surgeries but especially during emergencies. The management of these neurosurgical patients has become more difficult than ever. We describe our protocol in the management of neurosurgical patients in the University Medical Centre Ljubljana, Slovenia and how neurosurgical pathology was tackled during the pandemics.     

The development of nuclear medicine in Slovenia and Ljubljana; half a century of nuclear medicine in Slovenia

Background

Nuclear medicine began to be developed in the USA after 1938 when radionuclides were introduced into medicine and in Europe after radionuclides began to be produced at the Harwell reactor (England, 1947). Slovenia began its first investigations in the 1950s. This article describes the development of nuclear medicine in Slovenia and Ljubljana. The first nuclear medicine interventions were performed in Slovenia at the Internal Clinic in Ljubljana in the period 1954–1959. In 1954, Dr Jože Satler started using radioactive iodine for thyroid investigations. In the same year, Dr Bojan Varl, who is considered the pioneer of nuclear medicine in Slovenia, began systematically introducing nuclear medicine. The first radioisotope laboratories were established in January 1960 at the Institute of Oncology and at the Internal Clinic. Under the direction of Dr. Varl, the laboratory at the Internal Clinic developed gradually and in 1973 became the Clinic for Nuclear Medicine with departments for in vivo and in vitro diagnostics and for the treatment of inpatients and outpatients at the thyroid department. The Clinic for Nuclear Medicine became a teaching unit of the Medical Faculty and developed its own post-graduate programme – the first student enrolled in 1972. In the 1960s, radioisotope laboratories opened in the general hospitals of Slovenj Gradec and Celje, and in the 1970s also in Maribor, Izola and Šempeter pri Novi Gorici.

Conclusions

Nowadays, nuclear medicine units are modernly equipped and the staff is trained in morphological, functional and laboratory diagnostics in clinical medicine. They also work on the treatment of cancer, increased thyroid function and other diseases.     

The role of testosterone in laryngeal carcinogenesis

Testosterone levels in the plasma of 25 women and 25 men with carcinoma of the larynx and of 15 women and 15 men with hyperplastic aberrations in the laryngeal mucosa were determined to evaluate the etiologic relation between hyperplastic aberrations in the laryngeal mucosa (including cancer) and the male sex hormones. Patients with laryngeal cancer showed statistically significant increases in plasma testosterone levels compared with the control group. No statistically significant differences were found in plasma testosterone levels or in the testosterone/estradiol index between patients with hyperplastic aberrations of the laryngeal mucosa (including precancerous conditions) and the control subjects. The authors believe that greater attention should be paid to endogenous factors, particularly the male sex hormones, in further studies of the etiology of laryngeal carcinoma.