Impact of COVID-19 on the performance of a radiation oncology department at a major comprehensive cancer centre in Poland during the first ten weeks of the epidemic.

The outbreak of SARS-CoV-2 coronavirus rapidly altered radiotherapy service delivery around the world. AIM: The main objective of this study was to assess the impact of precautionary measures implemented in response to the COVID-19 pandemic on the performance of a radiation oncology departments and on mitigation the risk of COVID-19 contagion between and among patients and staff. METHODS: The study period was from March 15 until May 22, 2020. We evaluated total number of patients irradiated and those who initiated treatments, taking into account tumours localisations. We assessed the relationship of potential risk of contagion with patients' domiciles locations in regions with high number of COVID19 case. RESULTS AND CONCLUSIONS: The number of patients treated with radiotherapy during the study period decreased due to precautionary measures. After five weeks, the number of radiotherapy treatments began to increase. Just over half of the radiotherapy patients (53.5%) treated at the GPCC reside in the city of Poznan or in one of the ten surrounding counties where COVID19 incidence was low and reached at the end of the study period cumulative number of cases n = 204. The precautionary measures were effective qRT-PCR tests were performed in 1545 individuals (patients and hospital staff) revealing four staff members and none patient with a positive PCR result. Immunoglobulin testing was performed in 1132 individuals (patients and hospital staff). A total of 63 individuals were positive for antibodies.

Debrisoquine metabolism and CYP2D expression in marmoset liver microsomes.

The objective of this study was to define CYP2D enzymes in marmoset (Callithrix jacchus) liver microsomes, both at the activity level using debrisoquine as the model substrate and at the protein level using antibodies raised to human CYP2D6. Marmoset liver microsomes were incubated with [(14)C]debrisoquine, and the structure of the generated metabolites was determined using liquid chromatography-tandem mass spectrometry and NMR. Marmoset liver microsomes were very effective in hydroxylating debrisoquine at various positions. Although 4-hydroxydebrisoquine was formed, in contrast to rat and human it was only a minor metabolite. Debrisoquine was more extensively hydroxylated in the 7, 5, 6, and 8 positions. In addition to the monohydroxylated metabolites, a dihydroxy metabolite, namely 6,7-dihydroxydebrisoquine, was identified. Finally, metabolites that had undergone ring opening were also detected but were not investigated further. Antibodies to CYP2D6 immunoreacted with protein in marmoset and human but not rat hepatic microsomes. In conclusion, we demonstrate that marmoset liver microsomes are effective in hydroxylating debrisoquine at various positions and that they contain a protein that is immunorelated to human CYP2D6.

Antimicrobial susceptibility and biochemical patterns of Neisseria gonorrhoeae strains in Vejle area, Denmark.

BACKGROUND: Strains of Neisseria gonorrhoeae resistant to penicillin and ciprofloxacin have been isolated worldwide. Increasing number of N. gonorrhoeae that lack the enzyme proline aminopeptidase (proA-negative N. gonorrhoeae) have been detected in many countries all over the world. OBJECTIVES: This study aims to assess the resistance profiles of N. gonorrhoeae isolates sent to the Department of Clinical Microbiology in Vejle, Denmark, between 2003 and 2007, and to analyse their biochemical patterns. METHODS: Sixty-two strains of N. gonorrhoeae were retrospectively analysed for their susceptibility to penicillin, ciprofloxacin and ceftriaxone. The identification of isolated strains was confirmed using both biochemical and immunological tests. RESULTS: Twenty-one (33.9%) N. gonorrhoeae isolates were resistant to penicillin and 30 (48.4%) were resistant to ciprofloxacin. All strains were susceptible to ceftriaxone. Fifty-six (90.3%) N. gonorrhoeae strains showed API NH biochemical code 10,010 (produced acid from glucose and proline aminopeptidase). Six strains showed code 10,000 that lack the enzyme proline aminopeptidase (proA-negative N. gonorrhoeae). CONCLUSIONS: Ceftriaxone should be used as the first-line treatment of gonorrhoea in Vejle community area, Denmark, both for infections with proA-producing and proA-negative N. gonorrhoeae isolates, which circulate in the region.

Interaction of dexloxiglumide, a cholecystokinin type-1 receptor antagonist, with human cytochromes P450.

Dexloxiglumide (DEX) is a cholecystokinin type-1 receptor antagonist under development for the treatment of constipation-predominant irritable bowel syndrome. Studies of the potential interaction of DEX with human cytochromes P450 (CYPs) were conducted in vitro. DEX (300 micro M), both with and without a 15-min pre-incubation, was incubated with pooled human liver microsomes and substrates selective for each of eight CYPs. This resulted in >30% inhibition of tolbutamide 4-methyl-hydroxylase (CYP2C9/10) and lauric acid 11-hydroxylase (CYP2E1) activities. Mean K(i) (SD) for CYP2C9/10 and CYP2E1 were 69.0 (24.3) and 426 (60) microM, respectively. Incubations of [(14)C]DEX with pooled human liver microsomes produced one major phase I metabolic fraction, with V(max)=131 pmol/min/mg protein and K(m)=23.7 microM. Further incubations with (i) liver microsomes from 16 individual donors (correlation analysis), (ii) Supersomes trade mark and (iii) selective chemical inhibitors, implicated CYP3A4/5, CYP2B6 and CYP2C9 in the formation of this component. Thus, DEX interacts with CYP2C9 both as inhibitor (K(i)=69.0 microM) and as substrate in vitro. However, based on the maximum concentration (27 microM) after repeated oral doses of 200 mg t.i.d. and the unbound fraction (0.03) of DEX in human plasma, no clinically relevant metabolic interactions with other CYP substrates are predicted.

Pharmacokinetics and metabolism of the cholecystokinin antagonist dexloxiglumide in male human subjects.

1. Mean concentrations of total (14)C and of dexloxiglumide at the end of single 20-min infusion doses of (14)C-dexloxiglumide (200 mg) to four healthy male subjects were 18.5 microg eq x ml(-1) and 19.5 microg ml(-1) respectively. The mean plasma clearance (0.22 l h(-1) x kg(-1)) and mean volume of distribution (V(ss) = 0.18 l kg(-1)) were low. 2. Single oral doses of a solid formulation of (14)C-dexloxiglumide (200 mg) to the same subjects appeared to be rapidly and well absorbed. Mean peak plasma concentrations (C(max)) of total (14)C (2.8 microg eq x ml(-1)) and of dexloxiglumide (2.2 microg x ml(-1)) occurred at about 1.5 h. Systemic availabilities of the oral dose based on total (14)C and dexloxiglumide were 70 and 48%, respectively. Thus, a proportion of an oral dose was subjected to presystemic elimination and the absorbed dose mainly eliminated by metabolism. Binding of dexloxiglumide to plasma proteins was extensive (96.6-99.2%). 3. Total (14)C was excreted mainly in the faeces. Mass balance of (14)C excretion was almost complete within 7 days when a mean of > 93% of the dose had been recovered. After the intravenous (i.v.) dose, mean totals of 23.7 and 69.8% of the dose were excreted in urine and faeces, respectively, during 7 days, and 19.5 and 73.7% of the dose, respectively, after the oral dose. The data were consistent with biliary excretion and perhaps some enterohepatic circulation of conjugates of dexloxiglumide and at least one of its metabolites. 4. LC-MS/MS of urine extracts showed that dexloxiglumide was metabolized by oxidation and conjugation. The former included at least two metabolites formed by monohydroxylation in the N-(3-methoxypropyl) pentyl side chain, and O-demethylation of this side chain followed by subsequent oxidation of the resultant alcohol to the dicarboxylic acid. At least one glucuronide was also present in urine. The main components in faeces appeared to be dexloxiglumide and a dicarboxylic metabolite formed by O-demethylation followed by oxidation of the N-(3-methoxypropyl) side chain. Both compounds were identified as their corresponding methyl esters formed because acid and methanol were used in the extraction procedure. Dexloxiglumide and the dicarboxylic acid were presumably excreted in bile as the glucuronic acid conjugates.

The value of quantitative bacteriological investigations in the monitoring of treatment of ischaemic ulcerations of lower legs.

The quantitative and qualitative bacteriological investigations of 63 patients were done on ischaemic ulcerations before reconstructive vascular surgery and at 7 day intervals after the operation. Among the isolated bacteria the most common were Gram positive (62.9%), especially Staphylococcus aureus. Amputations due to non-healing ulcers were performed on 8 patients, who had ankle brachial index (ABI) lower than 0.47. In 55 patients with ABI higher than 0.47 (with the exception of one case) free skin grafts were applied to reduce the time of the ulcers healing. Primary healing of ulcers covered with free-skin grafts was achieved in 44 out of 55 patients (80%). In 11 patients, were free-skin grafts had failed, ulcerations were healed following the repetition of the free-skin grafts. The healing results of skin grafts statistically were significantly better in the group where the number of bacteria in 1 cm2 of ulceration was lower than 50.000. The severity of infections in ulcers makes the healing process of skin grafts impossible. Quantitative bacteriology additionally helps in objective evaluation of granulating tissue and facilitates choice of proper skin grafting time. This study has shown the usefulness of quantitative bacteriology for the determination of the severity of infections in ulcers.

[Haemophilus isolates in children suffering from chronic upper respiratory tract infections]. / Paleckzki z rodzaju Haemophilus u dzieci z nawracajacymi zapaleniami górnych dróg oddechowych.

For a three year period, between 1992 and 1994, 271 isolates of H. influenzae and H. parainfluenzae were examined using biochemical tests, beta-lactamase production and antibiotic susceptibility patterns. H. influenzae was examined by serological typing using polyvalent and monovalent sera a-f (Difco), as well. The strains were derived from children who were treated because of chronic pharyngitis. Sensitivity tests to Erythromycin, Gentamycin, Cefradine, Ampicillin, Doxycycline, Cefuroxime, Amoxicillin/Clavulanic Acid, Co-Trimoxazole, were performed with a standard disk-diffusion method. Biotyping was performed using API NH set (bioMerieux) and the ability to produce beta-lactamase was measured using iodometric method. Of 157 H. influenzae, 58 (36.9%) were typeable with H. influenzae antisera. The most common biotypes of these strains were I and II although biotypes III-VII were presented, as well. Of 114 H. parainfluenzae most of the strains showed the biotypes I and II. Its worth noting that 14% of H. influenzae and 15.8% of H. parainfluenzae strains were capable of beta-lactamase production. The strains of H. influenzae and H. parainfluenzae were most resistant to Cefradine and Co-Trimoxazole, respectively.

[Characterization of bacteriophage nontypable patterns of S. aureus strains]. / Charakterystyka szczepów S. aureus nie typujacych sie bakteriofagami.

Out of 195 strains of S. aureus isolated from in and outpatients. 43 were proven not to be lysed by the chosen set of bacteriophages. Of these nontypeable strains 14 were isolated from blood cultures and septic wounds of patients from Poznan University Hospital. 29 strains were derived from the anterior nares or throat swabs of outpatients, who were treated for chronic pharyngitis in the children's clinic in Poznan. S. aureus was identified using standard bacteriological method. Sensitivity tests to antibiotics were performed using the ATB computer system (bioMérieux). Beta lactamase production was examined using the iodometric method. The intracellular esterases of S. aureus were separated by polyacrylamid gel electrophoresis and stained with Fast Blue using alpha-naphtyhl acetate, beta-naphthyl propionate and indoxyl acetate as substrates. A much higher percentage of S. aureus strains isolated from specimens obtained from the hospital patients showed the ability to produce beta-lactamase than the strains cultured from outpatients. The esterase patterns of S. aureus are helpful in differentiating bacteriophage nontypeable strains.

[Characterization of Candida sp strains isolated from different clinical specimens in the years 1989-1993]. / Charakterystyka szczepów Candida sp. izolowanych z róznych materialów klinicznych w latach 1989-1993.

420 Candida sp. strains, which were isolated from the following specimens: vaginal secretions, throat swabs, urine, surgical specimen, nail specimen, sputum, semen, bile, skin, swab, pus were examined. On the basis of morphological and biochemical examinations it was established that in the above mentioned specimens are presented different species of Candida genus. Most often were isolated C. albicans, C. krusei, C. tropicalis. Among 317 C. albicans strains, 306 belonged to serotype A, 11 strains belonged to serotype B. The determination of enzymatic properties made possible the differentiation of strains C. albicans species from other species, and made it possible to define the biotypes. Sensitivity tests for examined strains made the characterization more particular.

[Infection as a risk factor in biliary system surgery]. / Zakazenie jako czynnik ryzyka w chirurgii dróg zólciowych.

Infection of the biliary system in which one of the signs is the presence of bacteria in bile is connected with an increase of incidence of postoperative complications especially in elderly people. Therefore, early diagnosis of infections and their prophylaxis and treatment are an important aspect of surgical management which is particularly significant in view of large number of patients with acute and chronic cholangitis. Proper selection of the operation time and the use of antibiotic therapy with adequate utilization of even broader spectrum of antibiotics may be of decisive importance for effective treatment.

[Anaerobic bacteria in infections of lower limb ulcerations in patients with chronic atherosclerotic arterial occlusion]. / Bakterie beztlenowe w zakazeniach owrzodzen konczyn dolnych u chorych z przewlekla miazdzycowa niedroznoscia tetnic.

In 76 patients with lower limb ulcerations in the course of atherosclerotic arterial occlusion, quantitative and quantitative bacteriological examinations, angiographic examinations and ultrasonographic measurements of pressures with simultaneous calculation of ankle/arm index were performed. At the same time the progression of ulceration healing was assessed after the operation. From the samples from four patients anaerobic bacteria were cultured: three times P. prevotii and twice P. acnes. It was found that these bacteria showed resistance to antibiotics used routinely in the treatment of diseases in which they may be the aetiological factor. The usefulness was demonstrated of quantitative examination of the bacterial flora in the ulcerations for the evaluation of their healing progression. Performing of antibiograms for anaerobic bacteria was found useful.

[Bacterial flora of lower extremity ulcerations in patients with chronic sclerotic arterial obstruction]. / Flora bakteryjna owrzodzen konczyn dolnych u chorych z przewlekla miazdzzycowa niedroznoscia tetnic.

Investigations were carried in 70 patients with ulceration of lower extremities during chronic aortal obstruction. The patients were subjected to angiography, ultrasonographic determinations of pressure and quantitative and qualitative bacteriological studies. Quantitative studies were carried on by taking a smear from one square centimeter of ulceration surface. The isolated microorganisms were cultured on standard media for bacteria growing in aerobic conditions. Cultures for detection of anaerobic bacteria were performed on thioglycolate media (qualitative study). It was found that clinical symptoms of infection occur when for 1 cm2 of ulceration surface more than 5 x 10(4) of bacterial cell are present. In all patients reconstructive procedures improving blood flow were performed. Comparison of consecutive bacteriological studies performed before and after surgery permitted for evaluation of dynamics of infections and enabled choice of proper treatment and evaluation of its effectiveness.

[Characteristics of Salmonella strains isolated from different environments in the years 1982-1993]. / Charakterystyka szczepów paleczek Salmonella izolowanych z róznych srodowisk w latach 1982-1993.

The examination of Salmonella strains isolated from hospital patients and out-patients was performed. The results of sensitivity tests of strains isolated in Poland, and from patients of "Third World countries" were compared. In both groups were the strains caused nosocomial infections, which were resistant to Ampicillin and Chloramphenicol. Eight of the Polish strains of S. Typhimurium were cultured from autopsy specimens which were obtained from the newborn ward. S. Typhimurium isolated from specimens of the patients of the children's, ward of Derna Hospital was the cause of 162 cases on nosocomial infections over the period of four months. The ill children were between the ages of the two days old (newborn child in incubator) and eleven years old. It is important to note that in one case S. Enteritidis was isolated from the blood of a hospital patient in critical condition. A much higher percentage (85%) of the strains isolated from out-patients in Poland showed resistance to Tetracycline in comparison with the strains cultured from out-patients in countries of the Third World (7%). The resistance to Tetracycline may be connected with the addition of this antibiotic to food for farm animals in Poland, and can indicate the circulation of animal strains in the human population. In this research we used the latest classification of Salmonella genus.

[Effect of treatment with autologous staphylococcal vaccine on the course of the immunologic process]. / Wplyw leczenia autoszczepionka gronkowcowa na przebieg procesów odpornosciowych.

In 18 patients with furunculosis and in 9 with chronic inflammation of upper respiratory tract, some cellular immunity parameters were tested. These were: phagocytosis index and bactericidal activity against leukocytes. Humoral immunity was also investigated by measurement of serum gammaglobulins. All test were performed before treatment and 30 days after application of the last dose of autologous vaccine. In 12 patients with furunculosis, improvement of the clinical status (disappearance of furunculosis) was appearing together with an increase of phagocytosis index and bactericidal activity of leukocytes without changes in gamma-globulin levels. No such changes were found in remaining patients in whom no clinical improvement was found. The authors suggest that cellular immunity factors studied in this investigation permit for evaluation of the immunity status in patients receiving autologous staphylococcal vaccine.

Epidemiological estimation of Pseudomonas aeruginosa strains isolated from different environments.

117 P. aeruginosa strains have been isolated from hospital material (vascular ward), from ambulatory patients, from lake water samples and from animal environment. The serological characters of the above strains, their phage--typing patterns, their capability of producing ONPG hydrolase were compared in order to find out the strain with identical features responsible for nosocomial infections and also to find endemic infections. There were eleven polyagglutinable strains (isolated from sinks in the vascular ward) which agglutinated with two sera and one strain isolated from lake water. Apart from one exception there were no confirmations of the occurrence of the strains of identical features in different environments. Possible variability within the scope of somatic antigen and the phage typing of microorganism confirm the necessity to use several techniques to carry out studies of epidemiological significance.

Determination of benzalkonium chloride by gas chromatography.

A new, simple, and useful approach for the analysis of benzalkonium chloride is presented. A gas chromatography (GC) has been used to pyrolyze benzalkonium chloride in a specific and reproducible manner to yield two tertiary amines for each homologue of benzalkonium chloride present. These are separated by GC and are used to determine the homologue composition of the benzalkonium chloride. These determinations can be made with an analysis time of 25 min/sample.