Continuous cultivation of the yeast Saccharomyces cerevisiae at different dilution rates and glucose concentrations in nutrient media.

The influence of glucose concentration in nutrient media on the specific growth rate and biomass yield in the course of continuous fermentation of Saccharomyces cerevisiae was investigated. An increase of glucose content in media decreased the specific growth rate and the biomass yield. Glucose concentration had significant effects on protein and phosphate contents of cells. However, an increased glucose concentration increased the fermentative power of S. cerevisiae (SJA-method). An increase of the dilution rate decreased the cell concentration in the fermentor. Specific growth rate approach the values of the dilution rate. The best agreement has been obtained at a dilution rate of 0.20/h. This dilution rate proved to be most convenient for the investigated microorganism and cultivation conditions (media composition, pH, aeration intensity and temperature). Biomass yield proved to be decreased by an increase of the dilution rate.

Immobilization of Saccharomyces diastaticus on wood chips for ethanol production.

Saccharomyces diastaticus cells were immobilized onto beech wood chips of different particle size and three pH values. pH values in the range 5.0-6.0, and 1.84-1.92 mm particle size had a positive effect on the immobilization process. The chosen carrier--1.84 mm-sized wood chips adsorbed 150 mg dry cell mass per g dry carrier mass. The Gibbs free energy and the activation energy for the first (monolayer) and second (multilayer) immobilization stages was 4581, 19,090 and 8590 J g mol-1, respectively. The kinetics of immobilized cell systems in ethanol production have been studied in a packed bed-reactor. Ethanol production and the respiration quotient (RQ) were at a maximum at a dilution rate of 0.16/h. The reactor was operated under steady-state conditions for 30 d at the dilution rate 0.16/h.

Effects of hydrophilic hydrocolloids on dough and bread performance of samples made from frozen doughs.

The objective of this study was to determine the effects of hydrocolloids in dough (xanthan 0.02%, 0.06%, and 0.1%; kappa-carrageenan and carboxymethylcellulose 0.2%, 0.6%, and 1.0%) and duration of frozen storage on the quality of finished bakery product. Doughs were prepared with different concentrations of gums, stored at -18 degrees C and analyzed after 0, 7, 14, and 30 d for fermentation activity of yeast and rising time of dough. At the end of each frozen storage interval, bread was prepared and characterized for specific volume, crumb firmness, and crumb structure. The addition of the gums had significant effects on dough performance and quality of the final product. Gums at all tested concentrations reduced fermentation activity of yeast and prolonged the rising time of dough, which was similar to the effects of frozen storage. However, specific volume of bread for the control sample significantly decreased on the 30th d of frozen storage. Addition of hydrocolloids resulted in higher specific volume of loaves compared to the specific volume of control sample loaves. With the increase of the duration of frozen storage the specific volume of bread decreases in all analyzed samples. This decrease is less in the samples with hydrocolloids compared to the decrease in the control sample. The addition of 0.1% xanthan accomplished the same or higher values for specific fermentation activity, specific volume, and penetrometric's number compared to the values accomplished by the addition of 1% carboxymethylcellulose and kappa-carrageenan, respectively.

[Present possibilities of treatment of chronic B-cell lymphocytic leukemia]. / Savremene mogucnosti lecenja B-hronicne limfocitne leukemije.

Chronic lymphocytic leukemia (CLL) belongs to the group of diseases with a malignant course and bad outcome. Clinically, the course of CLL exceptionally varies, survival ranges from one to twenty years. The choice of treatment for those affected with CLL is not simple because of the different course of the disease in individual patients and because of the different attitudes in the application of available means of therapy. By introducing antitumor drugs (Interferon alpha-2, Interleukin 2b), new chemotherapeutics (Fludarabin, Pentostatin), monoclonal antibodies and especially by introducing allogenic bone marrow transplantation into therapy, new possibilities are attained for the more efficient treatment of these patients.

Continuous cultivation of Saccharomyces cerevisiae at different biotin concentrations in nutrient media.

An increase of biotin concentration in nutrient media increased the content of protein, phosphorus, total ribonucleic acids, activity of pyruvate carboxylase and isocitrate lyase in cells and decreased the content of trehalose, glycogen and respiratory quotient of yeast cells in the course of continuous cultivation of Saccharomyces cerevisiae.

Effect of benomyl on Saccharomyces cerevisiae during continuous cultivation.

The effect of Benomyl on Saccharomyces cerevisiae during continuous cultivation was investigated. The RNA, total protein and phosphorous contents decreased while the trehalose content increased with increasing Benomyl concentrations when an RD mutant and the parent strain were cultivated at different Benomyl concentrations under continuous conditions. The specific oxygen uptake rate of the respiratory deficient mutant (RD mutant) was approximately 5 times lower in comparison to the parent strain. The RQ value for the RD mutant was higher than 1 which clearly indicated the anaerobic metabolism of glucose degradation. The RD mutant lacked cytochrome aa3, while the cytochromes a and b contents were lower than those of the parent strain.

[A simple model of the optimal time for allogenic bone marrow transplantation in chronic granulocytic leukemia]. / Jednostavni model optimalnog vremena za transplantaciju alogene kostane srzi u hronicnoj granulocitnoj leukemiji.

Allogenic bone marrow transplantation is the treatment of choice in chronic granulocyte leukemia patients, while the best results are achieved when it is performed in the chronic phase of the illness. That is why time optimization for bone marrow transplantation in chronic granulocyte leukemia means making priority lists for transplantation according to medical indications. This study comprises a very simple model of optimal time for bone marrow transplantation in chronic granulocyte leukemia. It is based on data of the International Bone Marrow Transplant Registry (IBMTR) on bone marrow transplantation results in different phases of chronic granulocyte leukemia and prognostic model for survival of younger leukemic patients according to which there are three groups of patients. The mathematical method estimated cumulative risks of the final therapeutic results. This model has shown that the time limit for transplantation is the fourth year of the disease in the low risk group; the third year of the disease in the medium risk group and the second year in the high risk group of patients.

[Postpolycythemic myeloid metaplasia in patients with polycythemia vera]. / Postpolicitemijska mijeloidna metaplazija u bolesnika s pravom policitemijom.

This study group comprised 58 patients with polycythemia vera. A retrospective study included 23/58 (39.60%) patients treated from 1968 to 1987, while a prospective study included 35/58 (60.34%) patients. Over the period 1986.-1996., 19/58 (32.76%) patients died: 10/23 (43.48%) from the retrospective group where mean disease duration was 12.7 years (6-24), and 9/35 (25.71%) from the prospective group where mean disease duration was 2.22 years (1-4). Erythrocytic phase of the disease was established in 50/58 (86.21%) patients; in 2/58 (3.45%) patients phase of spent hematopoiesis and postpolycythemic myeloid metaplasia in 6/58 (10.34%) patients. Postpolycythemic myeloid metaplasia has occurred after a mean time of 10.33 years (6-15) from establishing the first polycythemia. Two patients (10.53%) with postpolycythemic myeloid metaplasia died, one immediately after the diagnosis was established, the other patient two years after establishing the diagnosis. 16/19 (84.21%) patients died during the erythrocytic phase of the polycythemia vera, while 1/19 (5.26%) patient died in the phase of spent hematopoiesis. In regard to alive patients postpolycythemia myeloid metaplasia has been established in 4/39 (10.26%) patients, the phase of spent hematopoiesis in 1/39 (2.56%), while 34/39 (87.18%) patients are in the erythrocytic phase.

Acute myeloid leukaemia and exposure to organic solvents--a case-control study.

The objective was to study the relation between exposure to organic solvents and the risk of developing acute myeloid leukaemia (AML) in Caucasians aged 18 years and more. Ninety-eight cases of AML were diagnosed from September 1986 to March 1990 in Novi Sad, Yugoslavia, and in two London hospitals from September 1988 and May 1994 and from July 1992 and July 1994, respectively. Two controls were matched to each case by hospital, year of admission, gender and 5-year age group. Information on solvent exposure was collected by interview. Odds ratios (ORs) were derived with conditional logistic regression. The degree of solvent exposure was determined by three experts blind to the status of the subject with good agreement between them (the kappa coefficient ranged between 0.52 and 0.86). The response rate for cases was 80%. Exposure to solvents was associated with the increased risk of AML (OR: 2.52; 95% CI: 1.45-4.39; p = 0.001) and those with probable exposure to solvents were found to have an odds ratio of AML over three times greater than non-exposed. We also found an elevated OR for exposure to oils (OR: 1.56) but this was not statistically significant. There is no clear pattern of increasing risks with increasing duration of employment but a significant risk was found for exposures of 10 years or less. An induction period of less than 10 years or more than 30 years was associated with a significantly raised OR. There was a significant excess of machinery mechanics and fitters among the cases.

[Liver injury during combined chemotherapy of acute leukemias]. / Ostecenje jetre u toku polihemioterapije akutnih leukemija.

The authors observed 70 patients with acute leukemia treated by polychemotherapy. In 2 patients the signs of severe liver damage were found. The occurrence, course and results of laboratory tests suggested Purinethol predominantly as the cause of development of these alterations. The complication did not occur frequently in our patients. The changes regressed in a satisfactory way after the withdrawal of the hepatotoxic cytostatic from the therapy.

The frequency, characteristics and outcome of infections in patients with acute nonlymphoblastic leukemias.

A retrospective study was conducted in 91 patients treated at the Clinic of Hematology in Novi Sad in the period January 1, 1994,-November 15, 1997. The frequency, types, characteristics and outcome of infections were examined. The causative microorganism was determined in 65% of 133 febrile episodes, in 55% Gram-negative bacteria, 39% Gram-positive bacteria and in 6% fungi. Gram-negative bacteria were causative microorganisms in 80% of pneumonia. 77% of skin infections and 93% of urinary infections. Gram-positive bacteria were causative microorganisms in 53% of sepsis, Gram-negative in 41% of sepsis and Candida in 6%. The significant resistance to antibiotics was present in 47% of Gram-negative sepsis (causative microorganisms were Pseudomonas aeruginosa and Acinetobacter species) and in 18% of Gram-positive sepsis (susceptibility to imipenem only in Gram-negative sepsis and susceptibility to vankomycin in Gram-positive sepsis). Infections were the cause of death in 62.8% of patients.

Red blood cell deformability in diabetes mellitus: effect of phytomenadione.

Decreased deformability of red blood cells (RBC) in diabetes mellitus (DM) is considered to be linked to microcirculatory complications in this condition. As we found that phytomenadione increased RBC deformability in experimental animals, the question was raised, whether phytomenadione had the same effect on the RBC of diabetic patients. The study was performed in 10 patients with insulin-dependent diabetes mellitus, where the erythrocyte deformability was impaired. Patients received 10 mg/day phytomenadione i.m. for five days. Deformability was measured with policarbonate membranes (Nucleopore) with pore diameter 5 microns, under gravity. The results were expressed as the ratio (r) between the flow of 1.5 ml (r1) and 2 ml (r2) of RBC suspension and 1.5 ml of buffer. Phytomenadione increased the erythrocyte deformability in patients with diabetes mellitus, lowering the value r1 from 3.54 +/- 0.84 to 2.32 +/- 0.61 (p 0.02) and r2 from 7.80 +/- 2.41 to 4.65 +/- 1.07 (p 0.01). The values after treatment reached the range of healthy controls (r1 3.11 +/- 0.98, r2 6.52 +/- 3.04). The whole blood viscosity was significantly lowered after phytomenadione (5.28 +/- 0.58 mPas before, 4.64 +/- 0.74 mPas after, p < 0.02) with unchanged plasma viscosity, but significantly lowered internal viscosity of erythrocytes.

[Clinical evolution of chronic lymphocytic leukemia in Richter's syndrome]. / Klinicka evolucija hronicne limfocitne leukemije u Richterov sindrom.

Over a few year period chronic lymphocytic leukemia (CLL) is mainly characterized by stable course and only in the small per cent of patients it evolves into the aggressive form. Richter's syndrome has been diagnosed at our clinic in a patient who was for 6 years controlled and treated for CLL. In that period the patient was doing well and the out-patient treatment of CLL was being performed together with regular check-ups according to hematologic findings and clinical status of the patient. The patient was capable of work. Clinical investigation was undertaken because of the sudden aggravation of the general state and x-ray of the chest which pointed to the existence of tumorous shadow in the right lower pole of hilus. Although a complete CLL remission was established cytologic diagnosis of the newly formed tumour pointed to non-Hodgkin lymphoma of high malignity (centroblast lymphoma). Course of disease was terminated lethally very soon, because lymphoma of high malignity did not respond to polychemotherapy.

[Successful treatment of acquired F:VIII C inhibitor after delivery using plasmapheresis and high doses of immunoglobulins]. / Uspesno lecenje stecenog inhibitora F:VIII C nakon porodaja primenom plazmafereze i visokih doza imunoglobulina.

Three months after delivery a patient 34 years of age was admitted to the Clinic of haematology in Novi Sad because of sudden massive bleeding from the left ankle, left lower leg as well as for having small haematomas visible at forearms. Examining the mechanism of haemostasis, a diagnosis was made: acquired inhibitor VIII:C coagulation factor. Concentrate of VIII coagulation factor was used in treatment, as well as plasmaphaeresis, high doses of immunoglobulins and immunosuppressive drugs: prednisone and azathioprime. The result was a very quick recovery of the clinical state with loss of inhibitor to VIII: C coagulation factor. Three years after the treatment the patient has no difficulties and no antibodies to VIII:C coagulation factor.

[Our experiences in the treatment of myelodysplastic syndromes]. / Nase iskustvo u lecenju obolelih od mijelodisplasticnih sindroma.

From 1987 an abrupt increase of the number of patients presented with MDS has been registered. We present our experiences in the treatment of 42 patients. The number of the male patients was two times larger than of the females. They were most frequently diagnosed as having RAB (43%) and RAEBt (28.5%). RA was found in 14%, RARS in 9.5% and CMML. in only 5% of the cases. The treatment was accomplished with ultralow (3 mg/m2/12h s.c.) and low doses (10 mg/m2/12h s.c.) of ARA-C in 75% of the patients with RAEBt and 44.4% with RAEB, while the CMML group received hydroxyurea. The treatment improved hematologic results but the complete remission lacked. In 23.8% of the cases the disease developed into acute nonlymphoblastic leukemia. Patients excepted from cytostatic therapy were observed by the use of androgens, anabolics, vitamin A+D3 and transfusion of separated erythrocytes. In 38% of the patients with MDS a lethal outcome followed. Life of those in whom the disease developed into acute leukemia in statistically significatly shorter (p < 0.05). There was no statistically significant difference in the survival rate between the treated and nontreated patients (p > 0.05). Further treatment of these patients includes, apart from ultralow doses of ARA-C, the use of retinoic acid, a growth factor (GM-CSF) and bone marrow transplantation.

[Allogenic transplantation of bone marrow in hematologic diseases. Preparation and completion of transplantation at the Hematology Clinic in Novi Sad]. / Alogena transplantacija kostne srzi u hematoloskim oboljenjima. Pripreme i izvodenje transplantacije na Klinici za hematologiju u Novom Sadu.

The paper deals with the results of clinical preparations for the application of allogenic bone marrow transplantation at the Clinic of Hematology in Novi Sad. The obligation of the definite treatment of patients below 45 years by allogenic and autologous bone marrow transplantation results from the acceptance of the Yugoslav protocols for acute leukaemia treatment. Thus immunogenotypical analyses, so far performed in patients with severe aplastic anaemia have been extended to patients with acute leukaemia as well and then to patients with chronic myelogenous leukaemia, high risk lymphocYtic lymphoma and myeloma multiplex with resistance to standard chemotherapy and their potential sibling donors. The bone marrow transplantation Unit has been set up, the team of specialists has been formed and educated and the protocol for allogenic transplantation with Busulfan and cyclophosphamide combination for pretransplant conditioning has been adopted. In research work concerning the field of bone marrow transplantation a particular emphasis has been put on the working out of a mathematical model for optimal timing of bone marrow transplantation in patients with acute myelogenous leukaemia.

[Hematologic characteristics of leishmaniasis]. / Hematoloske karakteristike lajsmanijaze.

INTRODUCTION: Leishmaniasis is a chronic infectious disease from the group of anthropozoonoses. It is caused by protozoa in the genus leishmania flagellate. There are five major foci of this disease in the world: India, Mediterranean countries, East Africa, South China and South America. Endemic regions in the Balkans are as follows: Montenegro, Macedonia, Herzegovina and the Morava's valley (1,2). Reservoirs of infection are infected humans and animals (dogs and rodents). Infection is transmitted by insects the most significant representative of which is a sandfly. The course of the disease may be acute, subacute and chronic and several forms are differentiated such as visceral, cutaneous and mucocutaneous. Signs of disease are elevated temperature, gastrointestinal disorders, splenomegaly and hepatomegaly and rarely generalized lymphadenomegaly. Laboratory findings point to pancytopenia. The diagnosis is established on the basis of parasitological findings in macrophages of the bone marrow and is confirmed by serologic tests (4,5). However, mortality is decreased to 5% after the application of 5-valent antimony and amphotericin B (6,7). CASE REPORT: A female patient aged 19 year from Novi Sad was admitted at the Clinic of Hematology due to unclear febrile state lasting 3 months accompanied by pancytopenia and enlarged spleen. The first discomforts were experienced in the second half of August in 1997 upon the patient's return from Sutomore. The disease started gradually with uncharacteristic manifestations. Firstly, discomforts developed in the region of the gastrointestinal tract and were characterized by loss of appetite, nausea, and vomiting in addition to drastic weight loss. Secondly, fatigue occurred during effort, later on at rest as well, accompanied by increased body temperature. Temperature increased twice a day and was followed by shuddering, fever, shivering and very often by nocturnal sweating. Antibiotics and antipyretics were used, but without fall of temperature. Subjective discomforts were increasingly pronounced, so that due to unclear febrile state and in addition to the present pancytopenia the patient was referred to hospital treatment and was therefore admitted at the Clinic of Hematology. Febrile state, tachycardia, a striking paleness of the skin and visible mucosa as well as splenomegaly were confirmed. Basic laboratory findings (Table 1) pointed to pancytopenia. Apart from anemia and mild thrombocytopenia, leukopenia with neutropenia, lymphocytosis and monocytosis were pronounced. Sternal puncture was the most significant diagnostic procedure on the basis of which the diagnosis was established. In hypocellular bone marrow in macrophages, both intra- and extracellular, protozoa were found in smaller and greater groups which resembled leishmaniasis (Figure 1). The diagnosis was confirmed by serologic tests to leishmaniasis, antibody titre was > 1:32. In order to exclude other infections and hematologic diseases, other diagnostic tests were performed (Table 1) and the findings were normal. After the establishment of diagnosis the patient was transferred to the Clinic of Infectious Diseases where the causal therapy with 5-valent antimony was introduced, parenterally. As early as the first week of therapy, the patient was afebrile, subjective discomforts disappeared, she regained appetite and put on weight. Also, the decrease of the spleen was observed as well as improvement in hematological findings. DISCUSSION AND CONCLUSION: This paper predominantly deals with hematological findings which are characteristic for leishmaniasis on the basis of which the diagnosis of this disease has been quickly established (1,2). Hematological findings were the key of diagnosis being confirmed by serologic and other tests. The disease is very rare in this region, so that there is a difficulty in recognizing it. In our case, the diagnosis was made on the basis of sternal puncture survey, because protozoa were found in hy

[Successful treatment of patients with thrombotic thrombocytopenic purpura]. / Uspesno lecenje bolesnika sa tromboznom trombocitopenijskom purpurom.

The paper presents the case of a 23 years old patient diagnosed with thrombotic thrombocytopenic purpura on the basis of increased body temperature, thrombocytopenia, microangoipathic hemolytic anemia, renal function disorders and a rapid development of coma after the epileptic seizure of Jacsonian type. The treatment included the therapy with antithrombocytic drugs such as lysin acetysalicylate, dipridamol, methylprednisolon, and other symptomatic and substitutional therapies. Fifteen therapeutic plasmaphereses were made with the replacement of 33.150 ml of plasma substituted with albumin and freshly frozen plasma (20.080 ml totally). The applied therapy gradually improved patient's neurologic finding. The patient was discharged from the hospital with normal neurological finding and magnetic resonance of the brain. In the conclusion we emphasize the importance of therapeutic replacement of plasma with the infusion of freshly frozen plasma, antithrombocytic therapy and the application of corticosteroids in the treatment of thrombotic thrombocytopenic purpura.