[Cerebokrast as a corrector of postischemic phenomena in acute transient cerebral ischemia]. Acute cerebral ischemia in cats (both carotid arteries occlusion during 30 min after permanent occlusion of both vertebral arteries) was accompanied by postischemic hypoperfusion and hypo-oxygenation of the cerebral tissue. Intravenous infusion of cerebrocrast (1 micrograms.kg-1.min-1 during 60 min) prevented manifestation of the postischemic phenomena. Antihypoxic effect of cerebrocrast involved the cerebral blood flow increase, brain oxygen consumption lowering and Hb-O2-affinity decrease.


[The effect of calcium antagonists on blood deoxygenation processes]. The effect of verapamil, nifedipine and sensit on the whole rat blood deoxygenation was studied by polarographic coulometry with consequent calculation of deoxygenation rate (DR) and blood deoxygenation constant (BDC). These drugs were studied in concentrations 10(-8)-10(-4) M according to their therapeutic range in vivo. Both verapamil and nifedipine significantly decreased DR, and the latter drug decreased BDC as well in concentration 2.9.10(-7) M. In contrast to verapamil and nifedipine, sensit caused mild, but statistically significant dose-related increase in DR with concomitant decrease in BDC. The data presented failed to establish relationships between chemical structure and deoxygenative effect of the drugs. Deoxygenation effect of sensit favours its administration in the treatment of ischemia-related arrhythmias.


[The effect of a high external temperature on cellular immunity]. The study was made of spleen cells proliferative response to mitogens PHA, Con A or alloantigens in relation to hyperthermia effects. Acute hyperthermia (rectal temperature 42 degrees) enhanced lymphocyte function, proliferative responses to allo-antigens, PHA and Con A increased. Thermal shock was associated with suppression of the spleen cell response. Mice suffering from hyperthermia for 20 min (43-44 degrees) daily during 10, 20 and 30 days showed suppressed T-cell immune response. Normal splenocyte proliferation recovered 40 days after hyperthermia induction.


[The prophylactic administration of interleukin-2 increases the survival of mice with an acute intra-abdominal infection caused by Staphylococcus aureus]. The effect of RIL-2 on the survival of mice with acute Staphylococcus aureus strain 5/2 intra-abdominal [correction of intraperitoneal] infection was studied. RIL-2 was ineffective when administered simultaneously with the LD100 dose of bacteria. Antibiotics (gentamycin or combination of penicillin and streptomycin) administered in the same fashion cured 100% of animals. However, RIL-2 proved to be effective when administered simultaneously with LD70 dose of bacteria. The prophylactic course of RIL-2 consisting of repeated injections on days 3, 2 and 1 before the challenge with LD100 dose of bacteria also resulted in the marked increase of the survival of mice. The hypothetical mechanisms of action and the prospects of RIL-2 application are discussed.


[The effect of recombinant interleukin-2 on the course of experimental staphylococcal peritonitis in mice]. The effect of RIL-2 on the survival of mice with S. aureus--induced peritonitis was studied. Animals received bacterial suspension and RIL-2 as following: bacteria--on days 0, +2, RIL-2--day 0 (group 1); bacteria--days 0, +4, RIL-2--days 0, +2 (group 2); bacteria--days 0, +6, RIL-2--days 0, +2, +4 (group 3). RIL-2 exerted no protective effect in group 1. However, in groups 2 and 3, where the control animals survival was, resp., 56% and 38%, the RIL-2 treatment increased survival up to, resp., 84% and 70%. Antibiotics given instead of RIL-2 in analogous regimen decreased the survival in group 3 to the level of 25%. Thus, RIL-2 proved to be a potent therapeutic agent in the 2nd of 3d studied models of S. aureus--induced peritonitis in mice. The perspectives of RIL-2 use in the treatment of bacterial peritonitis, including porous ones, and of the immunodepression--aggravated conditions are discussed.


[The immunomodulating properties of the diuretic bufenoks]. Bufenox, a diuretic with a sodium-uretic and light potassium--uretic effect, has an immediate but short-term effect, stimulates IgM antibody production, depressed delayed-type hypersensitivity. The immunomodulating effect of bufenox may be due to changes in Na+ ions concentrations since sodium load abrogates immunoactive properties of the drug.


[The effect of dalargin on stress-induced changes in the 5'-nucleotidase activity of the macrophages and in the level of endogenous blood cortisol in mice]. The action of dalargin, synthetic analogue of leuenkephaline, on stress-induced changes in 5'-nucleotidase activity and endogenous hydrocortisone levels was investigated in mice. It was found that there is a direct relation between the activity of 5'-nucleotidase and the level of hydrocortisone in CBA mice. For C57Bl/6 mice the relation was inverse. Dalargin is able to change the dependence from direct to opposite in CBA mice.


[The antimicrobial cationic proteins of the neutrophilic granulocytes in experimental Q rickettsiosis]. Blood of 56 guinea pigs with experimental Q rickettsiosis was studied cytochemically (lysosomal cationic test) to measure the level of cationic proteins in neutrophil granulocytes. Development of Q rickettsiosis resulted in a decrease in the killing ability of neutrophils, depending on infection dose introduced. However, by day 7 of the disease, the level of cationic proteins in blood neutrophil granulocytes returned to the initial range. Similar situation was noted after subcutaneous injection of Coxiella burnetti corpuscular antigen. Subcutaneous infection with the living culture stimulus induced the wave-like decrease of the cationic proteins content. Infection of pre-immunized animals led to smaller decrease in the cationic proteins levels and to their more rapid recovery. Aspects of antimicrobial activity of neutrophil granulocyte cationic proteins in experimental Q rickettsiosis is discussed.


[The effect of intra-articular emoxipin injections on the course of immune arthritis in rabbits]. Immune arthritis in sensitized rabbits was induced by intraarticular injection of bovine serum albumin. The development of the arthritis was accompanied by an increase in ESR, a rise of the level of serum CRP, caeruloplasmin and CIC. A chemiluminescent response of the whole blood phagocytes to stimulation by barium sulfate crystals, serum beta-glucuronidase and red cell superoxide dismutase activity enhanced, plasma malone dialdehyde content rose, serum SH groups diminished.


[The detoxifying and immunocorrective properties of some sorption treatment methods in suppurative-septic poisoning in experimental diffuse peritonitis]. During septic intoxication in diffuse peritonitis poisoning is accompanied by circulatory and volemic failures, considerable changes in immune status, basically of the cellular component of T-system. Several sorption methods were applied which produced different effects on the pathologic process. Extracorporeal application of spleen-xeno and ultraviolet irradiation of autoblood considerably increased the immune reactivity. Plasmapheresis and hemosorption administration had low immunocorrective effect. It is believed reasonable to employ a combination detoxication methods.


[The use of flow cytofluorometry for determining antisperm antibodies by sperm immobilization and sperm toxicity methods]. During antisperm antibody detection by conventional methods of immobilization and cytotoxicity investigators used flow cytometry to detect dead and/or immovable sperm cells. It was shown that after incubation of sperm cells with low antiserum dilution immovable spermatozoa are still living. Evidently, cytotoxicity test in this case brings about false-negative results. Therefore, flow cytometry will be a success for ASAB detection through immobilization test.


[The selective accumulation of monoclonal antibodies in the lungs after cyclophosphane administration to rats]. The study has demonstrated the possibility to use cyclophosphamide as a model of "impairment" agent for lung tissue cells to provide access of monoclonal antibodies to nuclear antigen structures. Biodistribution of monoclonal antibodies to various intracellular antigens was studied on Wistar rats pretreated with various doses of cyclophosphamide. Accumulation of 2C5 antibodies to cell nuclei was found to be dependent on the dose of cyclophosphamide administered.


[The evaluation of the possibility of using prodigiozan for isolating extracts that stimulate proliferative processes in the resected liver]. The experiments were performed on 126 white male rats. The inclusion of 3H-thymidine in nuclear DNA of the liver was studied on h 24 and 48 after 70% resection of the liver versus prodigiosan injection or combination of prodigiosan with 70% resection of the liver. Liver extracts stimulating proliferation (ESP) obtained under the above schedules were studied on the model of 30% liver resection. It is shown that prodigiosan (0.25 mg/kg) injected to intact rats and rats with 70% resected liver initiated ESP production promoting the inclusion of 3H-thymidine in nuclear DNA of the liver after 30% resection of the liver.


[The insulin-secreting and proliferative activity of established islet cells in the presence of sulfonylurea]. Exponentially growing rat islet cells (RINr) and hamster islet cells (HIT T-15) were incubated in presence of tolbutamide (10-1000 microM), gliclazide (0.1-10 microM) or glibenclamide (0.01-10 microM) for 15 hrs. Accumulation of insulin in culture medium was estimated by RIA. Effects of sulfonylureas (SU) on cell proliferation were assessed by 3H-thymidine (3H-T) incorporation into cellular DNA. All of SUs used stimulated insulin production in RIN and HIT cell cultures (with an exception of tolbutamide, which markedly suppressed insulin secretion in HIT cells at 1000 microM). 3H-T incorporation into RIN cells was elevated only in presence of gliclazide (10 microM), whereas tolbutamide at 1000 M significantly inhibited RIN cell proliferation. Gliclazide (0.1 microM) and glibenclamide (0.01-10 microM) enhanced 3H-T incorporation into HIT cells. Further detailed investigations of mechanisms of SU effects on islet cell reproduction will be of use for designing optimal strategy of hypoglycemizing therapy of diabetes mellitus.


[A morphological study of rat liver cells after the administration of phenobarbital and ziksorin]. Male Wistar rats were inducted with phenobarbital and ziksorin. The inducing effect has been shown by hepatocyte hypertrophy involving the cytoplasm and nuclei. After phenobarbital injection cytoplasmic hypertrophy was due to redistribution of the plastic material in favour of the smooth-surface endoplasmic reticulum (SER). This redistribution occurred with the decrease of the energy forming and external synthetic functions of hepatocytes. After ziksorin injection SER hyperplasia was combined with proportional hyperplasia of the whole cytoplasmic organelles of the liver cells. This points to more optimal response of hepatocytes after ziksorin induction as compared with phenobarbital. Therefore, ziksorin can be recommended for clinical practice if it is necessary to stimulate processes of reparative regeneration in the liver.


[The modelling of cerebral ischemia in dogs with pathological kinking and occlusion of the carotid arteries]. An experimental model of brain ischemia in pathological kinking and occlusion of carotid artery has been developed on 40 dogs. Each model was documented angiographically, controlled with radionuclides, evaluated morphofunctionally. Basing on the results, surgical indications for correction of brachiocephalic artery lesions are provided.


[The characteristics of the hemodynamics and oxygen regimen of the rat uterus]. For biomicroscopic study of architectonic and hemodynamic features of uterine vascular bed wide ligation was carried out. It is shown that the vascular bed serves for blood deposition with cyclic change of inflow and outflow intensity. A rhythmic hypoxia results in a decrease of PO2 in the myometrium. The revealed biorhythm is considered evolutionary, determining physiological mechanism of plastic supply of generative function and development of the fetus resistance to hypoxia.


[The morphofunctional characteristics of the cecum in experimental influenza]. On the model of experimental influenza using morphological, immunomorphological, cytochemical, electron microscopy and morphometric methods, the authors provided morphofunctional characteristics of the caecum, showed the progression of infectious process and confirmed the dissemination of the virus, availability of virus particles in different cell populations, among them in lymphoid cells.


[The characteristics of the morphofunctional status of the adenohypophysis in lethally irradiated recipients after bone marrow transplantation]. The effect of lethal irradiation and transplantation of syngenic bone marrow in a dose of 1 x 10(7) cell/ml on the morphofunctional state of hypophysis at various stages of the posttransplantation period has been studied for 3 months using 100 linear male mice of a F1 (CBA x C57 B) line. The experiments conducted have shown that bone marrow transplantation reduces the intensity of the negative effect of irradiation on hypophysis and facilitates normalization of its histological structure. There was a correlation between changes in the number of secretory cells in the anterior lobe of the hypophysis and the level of corticosterone in irradiated and bone marrow-protected animals.


[The morphofunctional characteristics of the thymus in rat fetuses and progeny in venous occlusion]. Using histological and morphometrical methods, morphofunctional state of the thymus was studied in fetuses and offspring of rats in physiological pregnancy and under conditions of phlebo-occlusion. Phlebo-occlusion resulted in hypertrophy of the fetus, thymus and offspring, changes in structural zones and cellular reactions.


[The morphogenetic patterns of the higher autonomic centers in a pathological pregnancy]. Neurosecretory, parasympathetic and sympathetic centers of 49 mature fetuses subjected to toxicity were studied using light and electron microscopy. These centers were characterized by similar regularities of neurocytes development. Higher degree of maturity was typical for neurosecretory, while minimal for sympathetic centers. A higher degree of maturity and functional performance of vegetative regulatory system predominated in large fetuses. A general rule was a relative independence of forming truncal and spinal morphosystems and their nuclei on body and brain masses. Dyschronia of vegetative centers development reduces an adaptive potential of the fetus and causes fatal outcome in intranatal period.


[The characteristics of thrombocyte morphological structure in patients with endogenous depression during antidepressant therapy]. The study of platelets surface in patients with endogenous depressions made before the beginning of therapy, 1-3 days later and during the first days of clinical recovery with scanning electron microscopy showed that the platelets of patients who had not received antidepressants were activated. More marked activation took place after long-term therapy in the form of platelets with distinct pseudopodia, which were 2-3 times longer than cells body and with inclination to form large aggregations. This cell type is also characterized by formation of a new type of rod platelets. It is suggested that antidepressants accumulation takes place on cell membrane during long-term therapy that causes selective or general increase of membranes permeability, cytotoxicity.


[The effect of chemical damage to the adrenal cortex on its ontogenetic development]. We studied adrenal gland of rats at the age of 1 month, which underwent injections of dioxin-preparations during a week. In 1, 6, 12 days; 1, 3, 5, 5, 7, 13 months adrenal gland mass, adrenal cortex size, adrenocorticocytes number, 3B-ol-steroid dehydrogenase and succinate dehydrogenase activities of the experimental animals differed greatly from that of the control. It was found that chemical damage of the gland at an early stage changes it greatly during the following ontogenic development.


[The use of cryopreserved arteries as arterial vascular prostheses]. The aim of the study is investigation of possibility to bypass small and medium-size arteries with cryopreserved artery allografts, storing 7-10 days at -196 degrees C under the protection of 15% dimethylsulfoxide. In experiments on 40 rabbits were placed a region of the left renal artery by cryopreserved bioprosthesis. Graft patency was 80% after observation up to 6 months. By angiography it was 8 cases of graft thrombosis (all during the 1st week after implantation) and 5 cases of moderate graft dilation (in 4 of them it was accompanied with stenosis of distal anastomosis). In 20 dogs we replaced a region of the femoral artery by cryostoring bioprosthesis. It was only one case of graft thrombosis which occurred on month 2 after the implantation during 1-year follow-up. After 3 months in 3 cases there developed 3 cases of diffuse narrowing of graft lumen without decreasing of blood flow through the prosthesis. Later, the graft lumen did not change. Histological investigations have revealed a viability of cryopreserved vessels, its almost complete de-endothelialization at 3 days and total re-endothelialization 2 weeks after implantation. During the first 2 weeks there were morphological events of graft rejection, which disappeared after 3 months.


[The role of dyslipoproteinemia in the genesis of chronic hepatitis]. The dynamics of structural changes in the liver in experimental dyslipoproteinemia (DLP) and its correction was studied. Vessel-tissue changes found in the liver of rabbits in a short-term and stable DLP (4, 8 weeks) can be estimated as different stages of chronic active hepatitis. The microcirculation disorders and structural changes in the liver appeared at the early stages of DLP in the absence of atheromatosis in large arteries. The pathological changes in the liver existed 36 weeks after the rejection of atherogenic diet and correlated with DLP. Thus, DLP can be the risk factor as cardiovascular diseases as chronic nonspecific changes in the target organs.


[The morphological changes in the erythrocytes and in the blood iron level of rats under the action of E. coli endotoxin]. Development of endotoxin shock in rats is accompanied by decreasing dry mass and content of dense substances in red blood cells. Endotoxin reduces circulating iron concentration as well. During endotoxin administration morphological changes of erythrocytes become stable, appearance of echinocytes promotes elevation of hemostatic potential and enhancement of blood cells aggregability.


[The morphofunctional characteristics of the cecum in experimental escherichiosis]. Using the model of experimental escherichiosis in mice by means of morphological, immunomorphological, morphometrical and electron microscopy methods, the authors give morphofunctional characteristics of caecum 15 minutes to 2 weeks after inoculation. The authors show the dynamics of infectious process, characterized by changes of microcirculation, increasing lymphoplasmocellular infiltration, dystrophic changes in cells of neuroplexes and degranulation of mast and endocrine cells. The data obtained show that pathological process in caecum during experimental escherichiosis has an immune character, that the above portion of the intestine is a part of endocrine system.


Pituitary tumors: diagnosis and treatment. This article reviews the current general approach to the biochemical diagnosis and the treatment of pituitary tumors with special reference to medical treatment with dopamine agonists and somatostatin analogs. Dopamine agonists are the treatment of choice in patients with prolactin producing tumors. Octreotide is a major advance in the adjunctive treatment of growth hormone producing tumors. Trans-sphenoidal surgical decompression remains the primary treatment modality in gonadotrofinomas, clinically non-functioning pituitary tumors and thyroid stimulating hormone (TSH) producing tumors. Adrenocorticotrophin (ACTH) producing tumors are treated primarily by selective adenomectomy. The biochemical diagnosis of Cushing's syndrome is complex. Bilateral inferior petrosal sinus sampling for ACTH measurement is highly reliable in the differential diagnosis of ACTH dependent Cushing's syndrome, but needs expertise.


Neurotoxicity of interferon-alpha.

Neurotoxicity of interferon-alpha. Interferon (IFN) related neurotoxicity includes somnolence and confusion, fatigue, lethargy, psychiatric symptoms, conceptual disorganization, neurological deficits, cortical blindness, coma and, rarely, death. The neurologic syndromes seem to be more common in elderly patients, following intramuscular or intravenous administration, at higher doses of frequent injections of IFN-alpha and in primary renal cell carcinoma. The duration of the treatment was not strongly related to neurotoxicity. Computed tomography findings were non-specific and included atrophy or periventricular lucencies. Electroencephalograph studies demonstrated a generalized increase in slow wave activity which returned to normal after cessation of treatment. Behavioral and mental changes in patients treated with IFN are warning signs, and indicate the need to withdraw treatment.


The impact of phase I clinical trials on the quality of life of patients with cancer. This prospective, non-randomized study was designed to evaluate the quality of life (QOL) of cancer patients receiving new cytotoxic therapy. QOL was measured using a linear analog self assessment scale (LASA). Cancer patients who received a phase I agent (n = 45) had no significant changes in any of the individual QOL variables, overall QOL (p = 0.77) or performance status (p = 0.08) following one course of phase I therapy. However, patients who were not eligible for entry on a phase I protocol and who received supportive care (n = 10) experienced significant decreases in overall QOL (p = 0.02) and performance status (p = 0.003) after 1 month of follow-up. This pilot study suggests that participation in phase I trials does not adversely affect one's QOL.


Evaluation of combinations of antineoplastic ether phospholipids and chemotherapeutic drugs. Combinations of drugs are used clinically for the therapeutic advantages they may provide over single agents. We have studied the cytotoxic interaction between four either phospholipids ET-18-OCH3, BM 41.440, BN 52205 and BN 52211, and several chemotherapeutic drugs (ADM, CDDP, VLB, VP-16, MMC, BLM and MTX) on two human tumor cell lines, A427 (lung) and HT29 (colon). We have used the MTT colorimetric assay to evaluate growth inhibition and performed isobologram analysis on the IC50 data. For both cell lines a synergistic effect has been found between each of the four ether phospholipids in association with CDDP and ADM. In both cell lines only BM 41.440 and BN 52211 act synergistically with VLB while, in A427 cells, only BN 52205 behaves similarly with MMC. These results show that a positive interaction exists between ether phospholipids, spindle poisons and DNA-interactive drugs.


Intratunical versus parenteral administration of methotrexate. Methotrexate (MXT) distribution in serum, testicle and epididymis after administration into the tunica vaginalis cavity or intravenously was studied in 36 dogs. The dogs were divided into two equal groups: (1) an intratunical group in which 20 mg MXT solution was injected into the tunica vaginalis sac of each dog and (2) a parenteral group in which the same MXT dose was administered intravenously. The MXT concentration in serum, testicle and epididymis was determined 2, 4 and 24 h after MXT administration. Clinical and histologic examination of the tunica vaginalis was performed weekly for four consecutive weeks. The intratunical route, in contrast to the parenteral route, achieves a high MXT level in the testicle and epididymis with a low serum level, resulting in low toxicity and high drug efficacy. This route may therefore be suitable for a more effective treatment of testicular and epididymal lesions, notably malignant tumors.


Interaction of epirubicin with other cytotoxics and anti-emetic drugs. Epirubicin is usually administered in combination with other cytotoxics. Few pharmacological studies address whether relevant clinical interactions occur in vitro between these drugs. This study investigated whether epirubicin interacted with other cytotoxics or anti-emetics. The following drugs were prepared at pharmacological concentrations, etoposide (200 micrograms/ml), 5-fluorouracil (120 micrograms/ml), cisplatin (100 micrograms/ml), vincristine (100 micrograms/ml) and cyclophosphamide (1 micrograms/ml) respectively were admixed with epirubicin (1 micrograms/ml). Epirubicin was analysed by high performance liquid chromatography using in-line UV and fluorescence detectors. Experiments were performed in quadruplicate. No significant interactions were noted. The experiments were repeated for stemetil and maxolon. Maxolon did not interact with epirubicin but stemetil produced an interfering peak in the assay. We conclude that interaction studies are an important step in the workup of chemotherapy regimens.


Immunomodulatory activity of two new aza alkyl phospholipid antineoplastic drugs. The present work reports the modulation of immunocompetent cell functions by two aza alkyl phospholipids (AAP), BN 52205 and BN 52211. Each compound was compared with 1-O-octadecyl-2-O-rac-glycero-3-phosphocholine (ET-18-OCH3) and/or three drugs used for cancer treatment, i.e. cisplatyl (CIS), 5-fluorouracil (5-FU) and cytosine arabinoside (ARA-C). Interleukin (IL)-1 release from P388D1 cells was increased 2-fold in the presence of 5 micrograms/ml BN 52205 or BN 52211. However, these stimulations were lower than those obtained with ARA-C, 5-FU and CIS. Compared with ET-18-OCH3, CIS and 5-FU, BN 52205 and BN 52211 were more efficient in increasing tumor necrosis factor production induced by lipopolysaccharide (LPS) from human monocytes. In vitro, all compounds exhibited similar activity in enhancing IL-6 production from human monocytes stimulated with LPS, with the exception of 5-FU and CIS that were inactive. At 20 mg/kg (i.v.), a peak of IL-6 production was reached 2 h after injection of ET-18-OCH3 [> 1280 U/ml (n = 4, p < 0.001) versus 3.5 +/- 0.2 U/ml (n = 7)], whereas BN 52211 induced a maximum of IL-6 production after 4 h (77 +/- 27 U/ml, n = 5, p < 0.001). BN 52205 induced peaks of IL-6 production after 3 and 6 h (90 +/- 62 and 68 +/- 35 U/ml, respectively, p < 0.001, n = 4). The proliferation of rat splenocytes was abolished in the presence of BN 52205 and BN 52211 at 10 micrograms/ml, corresponding to only a partial reduction of IL-2 production at the same concentration. The production of interferon-gamma was stimulated 6- to 10-fold in the presence of 1-5 micrograms/ml BN 52205, BN 52211 and ARA-C. BN 52211 and BN 52205 were also potent enhancers of IL-3 production, whereas 5-FU and ARA-C were inhibitory. These results indicate that in addition to a direct antitumoral effect, AAP may also exhibit immunomodulatory activity both in vitro and in vivo.


Clavine alkaloids and derivatives as mutagens detected in the Ames test. Eight cytostatic clavines were investigated for mutagenicity in Salmonella typhimurium (reversion of the his-strains TA98, TA100, TA102 and TA1537), directly and in the presence of a mammalian xenobiotic metabolizing system, S9 (NADPH-fortified postmitochondrial fraction of liver homogenate from Aroclor 1254-treated rats). Four compounds (festuclavine, 17-bromofestuclavine, 1-allylelymoclavine and 1-methyllysergol methyl ether) were direct mutagens, whose activity was enhanced in the presence of S9. The other compounds (1-cyclopentylfestuclavine, 13-bromo-1-cyclopropylmethylfestuclavine, 6-cyano-1-propyl-6-norfestuclavine and 6-allyl-1-propyl-6-norfestuclavine) showed mutagenic effects only in the presence of S9, as previously observed with other clavines (agroclavine and its 1-propyl and 1-pentyl derivatives). Thus, all investigated clavines may be metabolized to mutagenic products by mammalian enzymes. Bacteriotoxic activities did not correlate with mutagenic activities. The bacteriotoxicity of several clavines was reduced in the presence of S9. The results are discussed with regard to the potential therapeutic use of clavine alkaloids as antimicrobial and antineoplastic agents.


A possible modulatory influence of melatonin on representative phase I and II drug metabolizing enzymes in 9,10-dimethyl-1,2-benzanthracene induced rat mammary tumorigenesis. The oncosuppressive effect of melatonin on 9,10-dimethyl-1,2-benzanthracene (DMBA) induced rat mammary tumorigenesis led us to assess its possible modulatory influence on representative hepatic and mammary drug metabolizing enzymes in DMBA treated female Holtzman rats, reared in short and long photoperiods. Melatonin treated rats in either photoperiod showed a significant induction in hepatic and mammary levels of glutathione (GSH) and cytosolic activities of glutathione S-transferase (GST) when compared with the corresponding controls, along with a significant drop in hepatic microsomal contents of cytochromes b5 and P450. This induction of GSH and GST, and depletion of cytochromes b5 and P450 by melatonin may possibly be related to its anticarcinogenic potential in this tumor model.


Synergistic cytotoxicity of combinations of dimethyl sulfoxide and antineoplastic agents against P388 leukemia in CD-F1 mice. We have reported that dimethyl sulfoxide (DMSO) and antineoplastic agents exhibit synergistic cytotoxicity against human tumors in vitro. This study was undertaken to investigate this effect in vivo. Groups of mice were given intraperitoneal (i.p.) injections of P388 leukemia cells. Groups were treated with i.p. injections of either saline, DMSO alone, mitoxantrone hydrochloride (DHAD) alone, methotrexate alone, DHAD in DMSO or methotrexate in DMSO. Combinations of DMSO and DHAD produced 46-61% increases above expected survival, demonstrating synergistic cytotoxicity in vivo. Following confirmatory animal studies, trials utilizing i.p. delivery of antineoplastics in DMSO as treatment for peritoneal tumors should be undertaken.


Bone marrow stromal cells attenuate mitoxantrone cytotoxicity against HL-60 leukemic cells. We evaluated the effect of cultured human bone marrow (BM) stromal cells on the cytotoxicity of mitoxantrone (MIT) against the HL-60 leukemic cell line. BM-derived fibroblastoid cells (BMFC) suppressed colony formation of HL-60 cells in the absence of MIT. BMFC increased the survival of HL-60 colony-forming cells in the presence of 50 ng/ml MIT. A significant decrease in the drug concentration was not detected on BMFC. Our results suggest that BM stromal cells can modulate the antileukemic effect of an anticancer drug.


Murine macrophage activation after cisplatin or carboplatin treatment. Murine peritoneal macrophages when treated in vitro with cisplatin (9 micrograms/ml) or carboplatin (50 micrograms/ml) for 2 h are stimulated to form cytoplasmic extensions seeking out tumor cells and establishing cytoplasmic connections; however, no contact is observed with normal cells (fibroblasts and hepatocytes). In addition, cisplatin and carboplatin treatment leads to an increase in the number of lysosomes and their transfer to the tumor cells resulting in lysis (as studied by confocal microscopy). Although calcium seems to be involved in the signalling of macrophage activation, cytosolic calcium does not seem to influence this activation.


Activity of a chartreusin analog, elsamicin A, on breast cancer cells. The in vitro activity of elsamicin A (ELS) was investigated compared with that of doxorubicin (DX) on two sensitive breast cancer cell lines: one estrogen receptor-positive (ER+, MCF7) and one estrogen receptor-negative (ER-, MDA-MB-231) line, and on a DX-resistant subline (MCF7DX). The activity of the two drugs was also investigated on 19 clinical breast cancer specimens from untreated patients. The drugs were tested at pharamcologically relevant concentrations, as calculated from the area under the curve for a 3 h exposure to the lethal dose producing 10% mortality (LD10) in mice, and at 10- and 100-fold concentrations. In DX-sensitive lines, a greater inhibition of RNA and DNA precursor incorporation, as well as of cell proliferation, was caused by ELS than by DX. Moreover, the antiproliferative effect was 10-fold higher in the ER+ MCF7 than in the ER- MDA-MB-231 cell line (IC50: 0.25 versus 0.21 micrograms/ml). ELS was cross-resistant to DX in the MCF7DX subline. In clinical specimens, effects on DNA precursor incorporation were more often observed for ELS than for DX at the same drug concentrations. The in vitro sensitivity to ELS was more pronounced for ER+ than for ER- tumors: minimal inhibiting concentrations of the drug were 0.1 and 3.5 micrograms/ml, respectively, in the two groups. If confirmed in a larger series of human breast tumors, these in vitro results would indicate a promising role for ELS in clinical treatment, mainly of ER+ breast cancer patients.


Methylglyoxal bis(butylamidinohydrazone) exhibits antitumor effect on human malignant melanoma cells but reduces the antitumor action of cisplatin. The antitumor effect of a polyamine biosynthetic pathway inhibitor methylglyloxal bis(butylamidinohydrazone) (MGBB) on human malignant melanoma (HMG) cells and its combination effect with cisplatin were investigated. The growth of cultured HMG cells was inhibited in a dose dependent manner by either MGBB or cisplatin; complete inhibition of cell proliferation was attained with 5 micrograms/ml of MGBB or 50 micrograms/ml of cisplatin. Pretreatment of HMG cells with MGBB diminished the antitumor action of cisplatin. The cultured HMG cells were inoculated in nude mice and aliquots of the resulting solid tumors (HMG tumor) were transplanted. The growth of transplanted HMG tumors in mice was inhibited markedly by cisplatin (3.8 mg/kg) and moderately by MGBB (10 or 20 mg/kg). The in vivo antitumor effect of cisplatin was also reduced by combined treatment with MGBB.


Interferon-alpha and -gamma in combination with chemotherapeutic drugs: in vitro sensitivity studies in four human mesothelioma cell lines. Mesothelioma is a tumor of the serous surfaces in the thorax and abdomen. This tumor has proved to be exceptionally resistant to treatment, although a variety of multi-modality therapies have been tried. We have used four human mesothelioma cell lines, originating from diffuse asbestos-related malignant (pleural) mesothelioma, to assess in vitro sensitivity to five chemotherapeutic drugs, to recombinant human interferon (IFN)-alpha and -gamma and to combined immuno-chemotherapy. The cytotoxic effects were assayed by vital dye exclusion. The drugs tested were etoposide, cisplatin, mitoxantrone, 4-epirubicin and vindesine. The combinations tested were etoposide+cisplatin, and etoposide+cisplatin+mitoxantrone. All the drugs and combinations were also tested with recombinant human (rHu) IFN-alpha 2C (rHuIFN-alpha), rHuIFN-gamma, and rHuIFN-alpha+rHuIFN-gamma. The cell lines were most sensitive to mitoxantrone, 4-epirubicin and vindesine (TC50 < or = 0.001 micrograms/ml), and least sensitive to etoposide and cisplatin (TC50 > or = 0.1 micrograms/ml) used singly. There was no improvement in sensitivity when the drugs were combined. To further investigate the lack of response to cisplatin treatment, we examined the binding of cisplatin to the mesothelioma cell DNA. The tumor cell DNA bound markedly less cisplatin than human fetal fibroblast DNA. Three cell lines were tested with rHuIFN-alpha and rHuIFN-gamma on their own or rHuIFN-alpha+rHuIFN-gamma. They were consistently sensitive to rHuIFN-alpha, but the sensitivity to rHuIFN-gamma varied with the cell lines. Finally, we tested two cell lines with the drugs singly and in combination, together with 0.01 micrograms/ml each of rHuIFN-alpha and rHuIFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)


Individual performance review--meeting staff needs. One of the main components of job satisfaction is the recognition of one's achievements. It can be argued that nursing has been slow to recognise the positive effects of honest feedback on individual performance. Individual Performance Review (IPR) or staff appraisal is one way of providing that feedback.


The manager's role in developing standards. Pick up any health care journal nowadays and you are bound to find at least one article on quality standards and audit. More and more professional staff of all disciplines are examining their practice and documenting standards of care which aim to promote a desired and achievable level of performance against which actual performance can be compared.


The combined effects of cocaine and amphetamine on primary postnatal rat heart cell cultures. Recent reports demonstrated that perinatal exposure to cocaine (Coc) and amphetamines (Amph) predisposed the infant to adverse cardiovascular consequences. Dose- and time-dependent effects of Coc and Amph on postnatal rat myocardial cell cultures are described. Contractile activity, morphology, lactate dehydrogenase (LDH) release, MTT formazan production, and neutral red (NR) retention were determined. No contractile activity was observed in cultures treated with the highest drug doses. After 24 h, the percentage of areas exhibiting contractile activity was decreased in cultures exposed to the lowest doses of both drugs. When Coc and Amph were combined, beating rates were significantly altered. Morphologic alterations were observed in all treatment groups. LDH release occurred in cultures exposed to the highest doses of both drugs. No significant differences were observed for MTT or NR. These data demonstrate that Coc and Amph doses > or = 1 x 10(-5) M induce adverse effects on morphology and contractile activity of postnatal myocardial cell cultures.


Endpoints of spermatotoxicity in the rat after short duration exposures to fourteen reproductive toxicants. Multiple endpoints of spermatotoxicity in short duration tests (1-5 days exposure; 2.5-week assay interval) were investigated in a number of chemicals reported to produce minimal to severe reproductive effects when administered subchronically. Six of these chemicals (boric acid, dinoseb, 2,5-hexanedione, methoxychlor, metronidazole, ornidazole) produced substantial spermatotoxicity after 1 to 5 doses. Spermatotoxic effects of chlordimeform were equivocal while p,p'-DDT, n-hexane, and sodium chlorite were judged negative. Four chemicals with known acute effects (benomyl, busulfan, ethylene glycol monomethyl ether, nitrobenzene) elicited expected histopathologic responses after a single dose. Testicular histology, testicular sperm head counts, cauda sperm counts, sperm morphology, and sperm velocity proved to be the most toxicologically sensitive endpoints in one or more of the studies, but histopathology of the testis and epididymis was the most consistent indicator of reproductive damage. The percentage of motile sperm and sperm concentration in the epididymal fluid were the least sensitive measurements. The data suggested that most chemicals with the potential to produce moderate to severe sperm damage are detectable with a short duration test. Complementary multiple endpoints enhanced the interpretation of results, often identified cellular targets, and provided insight on possible mechanisms. Specific responses were often similar to specific effects reported for subchronic exposures. A short duration test could be of value as a screen in structure-activity studies or to set priorities for chemicals requiring further evaluation. As a supplement to breeding studies, the data generated in the short test could also be used to enhance the design and interpretation of the longer tests.


Effects of three male reproductive toxicants on rat cauda epididymal sperm motion. The sensitivity of the CellSoft computer-assisted sperm analysis (CASA) system to detect changes in rat sperm motion was evaluated. CASA motion endpoints were measured in cauda epididymal sperm from Long-Evans rats treated with each of three known male reproductive toxicants reported to affect the epididymis and epididymal sperm motility: alpha-chlorohydrin, ornidazole, and trimethylphosphate. Significant changes in endpoints describing sperm swimming vigor (curvilinear velocity and straight-line velocity) and pattern (linearity and amplitude of lateral head displacement) were observed for rats dosed with each agent when evaluations included mean values and other statistical parameters (i.e., percentiles and distributional shape). alpha-Chlorohydrin (ACH) treatment (10 mg/kg/day; 8 days) resulted in reductions in the mean percentage of motile sperm, curvilinear velocity (VCL), straight-line velocity (VSL), lateral head displacement (ALH), and linearity (LIN). Treatment with ornidazole (ONZ) (200 mg/kg/day/14 days) reduced the percentage of motile sperm. Mean VCL, VSL, and ALH were reduced by 400 mg ONZ/kg/day treatment. Trimethylphosphate (TMP) treatment led to (a) a reduction in the 75th and 90th percentiles for ALH (100 mg TMP/kg/day; 5 days) (P < or = 0.04), (b) a reduction in VCL, VSL, and ALH (250 mg TMP/kg/day), (c) a reduction in the percentage of motile cells and in the 10th and 25th percentiles for VSL (600 mg TMP/kg/day), and (d) increases in the 90th percentile for VSL, in the mean, 75th, and 90th percentiles for VCL, and in the 75th and 90th percentiles for ALH (600 mg TMP/kg/day). The general utility of these analytic approaches in reproductive toxicology studies was demonstrated in the observations of effects at or below dose levels previously reported.


Fertility and semen quality of workers exposed to high temperatures in the ceramics industry. The objective of this study was to test the hypothesis that chronic occupational exposure to high temperatures may be detrimental to male reproduction. The study was based on 92 healthy ceramics oven operators with a long exposure to high temperatures, and 87 controls, recruited from the shipment department of the same industry. Interviews with all subjects provided data on sociodemographic characteristics, health status, and fertility problems. Semen analysis was carried out on 46 of the workers exposed to high temperatures, and 14 of the controls, and included evaluation of the sperm concentration, morphology, and motility, including computer-assisted sperm motion analysis (velocity, linearity, ALH, BCF). The results of the questionnaire showed that exposed individuals had a higher incidence of childlessness and of self-reported difficulty in conceiving than controls. The semen analysis showed no significant differences except in sperm velocity. Although differences in semen parameters, taken singly, were not statistically significant, the overall evaluation of the sperm parameters indicated a higher prevalence of pathologic sperm profiles among the exposed compared to the controls.


Caffeine-mediated effects on reproductive health over two generations in rats. The present study was designed to investigate the mechanism(s) underlying previously observed birth weight differences found in the first litter of the second (F2) generation bred from caffeine-exposed F1 females. The effect of exposure to caffeine in utero on subsequent sexual receptivity, fertility, gestation length, parturition, nesting activity, maternal behaviour, and reproductive senescence in the F1 mothers, and the viability of the F2 offspring was investigated. This information was collected by breeding control or caffeine exposed females for 8 consecutive litters. It was demonstrated that exposure to caffeine did not affect the sexual receptivity, fertility, gestation length, or maternal behaviour of the F1 females, but parturition was prolonged and the viability of the F2 generation was seriously jeopardized. Many F2 pups were born significantly larger than their control counterparts and a significant proportion of litters (after the first two litters) were wholly stillborn. It was concluded that a changed genetic program, mediated via the F2 fetus, delayed the normal progression of parturition. This, in turn, compromised the F1 mothers and caused increased mortality of their offspring. The severity of the outcome was dose dependent.


Susceptibility to teratogenicity of hypervitaminosis-A in X-monosomy mice. We previously showed that the incidence of external malformations induced by biotin deficiency did not differ either between XO and XX dams or between XO and XX fetuses. To clarify whether this phenomenon is specific to biotin deficiency or more generally associated with other teratogens, we examined whether XO mice are more susceptible to teratogenic effects of hypervitaminosis-A. Pregnant XO and XX mice were given an excessive vitamin A diets (1.0 to 1.5 x 10(6) IU/kg) from days 0 to 17 of gestation. Maternal hypervitaminosis-A produced a high incidence of external malformations (65 to 80%), skeletal anomalies (33 to 47%), and variations (99 to 100%) in the fetuses. However, there is no difference in their incidences between XO and XX dams or between XO and XX fetuses. Together with previous findings, this suggests that developmental stability of the mouse embryo is not affected by missing of one whole X chromosome even with exposure to teratogens.


[Measurement errors in determination of electrolyte concentrations with ion selective electrodes in the presence of inorganic or metabolizable anions]. Ion-selective electrodes (ISE) from various manufacturers were tested with regard to their accuracy in determining the concentrations of sodium, potassium and calcium in aqueous solutions when uni- or polyvalent, inorganic or organic anions are being present in physiological concentrations. The results obtained by all measuring instruments using ISE revealed that the presence of anions such as acetate, citrate, malate, lactate, phosphate or sulfate, either in physiological or therapeutic concentrations, may lead to considerable errors when determining the concentrations of sodium and calcium. A certain caution is therefore recommended in order to minimize the risk when using ISE for the electrolyte diagnosis of infusion solutions, blood derivatives, dialysates and urine samples.


Superiority of gel centrifugation in antibody screening and identification. We report on the direct comparison of gel centrifugation technique and tube testing for antibody screening (ABS) under controlled routine conditions. 3,000 blood samples were screened for antibodies (AB) by gel centrifugation (ID-System, bromelin 37 degrees C and room temperature, indirect antiglobulin test with LISS) and a sensitive tube test (TT; bromelin two-phase test, 37 degrees C and room temperature, and indirect antiglobulin test with 22% bovine albumin) in parallel. By ID significantly more relevant and potentially hemolytic AB (51 vs. 35 AB/1.7 vs. 1.2%) could be detected: anti-E 4, -C 1, -D 4, -CW 2, -c 2, -Jk(a) 2, -Jk(b) 1. Eleven of these even remained negative in TT when retested with increased sensitivity and taking additional (homozygous) test cells. In addition, naturally occurring but rarely hemolytic AB (35 vs. 23 AB/1.2 vs. 0.8%) were more frequently detectable by ID: anti-Le(a) 6, -Le(b) 2, -P1 6. In contrast, only two AB were only positive in TT: anti-Le(a) 1, -Le(a, b) 1. The main disadvantage of the ID was its frequent positivity (7.7 vs. 4.3%) due to irrelevant cold AB (anti-I, -HI, -H) and unspecific factors. This can be partly reduced by omission of the bromelin test at room temperature (ID 3.0%, TT 1.5%) as the detection of relevant AB is not affected. The frequency of naturally occurring AB was still the same as in TT (0.7%) when bromelin at room temperature was omitted in both techniques. Further advantages of the ID are simplicity, small volumes of sera and reagents, and easy evaluation.


[Effect of various plasma preparations and i.v. immunoglobulins on the function of lymphocytes and monocytes in vitro]. Transfusion of whole blood or blood components has an immunosuppressive effect on the recipient and induces changes of several immunological parameters. Especially blood plasma or plasma components were suspected to show an immunosuppressive action. We therefore studied in vitro the effects of autologous and homologous fresh frozen plasma (FFP), fresh plasma (FP) and heparin plasma (HP) as well as the influence of different commercial i.v. immunoglobulins (IVIG) on the mixed lymphocyte reaction (MLR), the mitogen-induced lymphocyte transformation and the inhibition of phagocytosis of red blood cells, measured in the monocyte-monolayer assay (MMA). We demonstrate that autologous and homologous plasma inhibit the PHA and ConA response of lymphocytes (p < 0.025). Minimal differences between homo- and autologous plasma were only observed for FP in PHA-induced lymphocytes. IVIG reduced, in a dose-dependent manner, the MLR and PHA response to basal values. In contrast, plasma and IVIG showed only small effects on the PWM response rates. The addition of FFP, FP, HP or IVIG to cultured monocytes resulted in a significant inhibition of red blood cell phagocytosis, ranging from 76 to 87%. We conclude from our study that, besides unspecific mechanisms, an unknown plasma factor which is enriched in the immunoglobulin fraction of plasma is able to suppress the T-cell immune response.


Anticoagulation-dependent inhibition of in vitro complement activation by anti-apo-B sepharose 4B CL. During LDL apheresis, various combinations of heparin and citrate are used for anticoagulation. With an in vitro batch system we examined whether heparin/citrate combinations can be optimized in terms of complement activation inhibition without the loss of anticoagulant potency. Plasma anticoagulated by using six clinically applicable regimens was incubated with anti-apo-B antibody-coupled Sepharose 4B CL, and the anaphylatoxin content of the supernatant was investigated. A significant dose-dependent reduction of complement activation was achieved by anticoagulating whole blood with 10 U/ml heparin (p < 0.05) if compared with serum whereas citrate inhibited more effectively the generation of C5a (desarg) even at a low concentration (ACD-B 1:20) (p < 0.01). The lowest anaphylatoxin level was generated when heparin (10 U/ml) plus citrate (ACD-B 1:10) were applied, although such an approach may be of limited clinical interest. The empirically chosen heparin plus citrate ratio (2 U/ml, 1:20, respectively) provides for an optimal and almost ideal inhibition of complement activation and contributes considerably to the good tolerability of the immunoadsorbent.


Effects of leukocyte depletion on the formation of anaphylatoxins in stored whole blood. As reported earlier, factors of the complement cascade get activated in CPD-A1-stabilized whole blood. As early as after 10 days of storage under normal blood bank conditions the elevations of the concentrations of C3a-desArg and C4a-des-Arg were highly significant. By contrast, the concentration of the C3 activator complex C4b2b remained unchanged even after 3 weeks of storage. Leukocyte depletion partially inhibited the activation of C4 but had no effect on C3a concentrations. Therefore, cleavage of C4 during storage of whole blood seems to be partially leukocyte-dependent, whereas the activation of C3 is possibly due to the activation of the alternate pathway of the complement system by contact of blood to plastic surfaces. Even through the radioimmunologically measured C3a might be inactive as an anaphylatoxin, these observations are of clinical importance since the inactivated C3a-desArg still possesses biological activities such as activation of platelets which may lead to hypercoagulability and thrombosis.


Anaphylatoxin generation and distribution during in vitro LDL apheresis. The extent of anti-apo-B IgG-Sepharose-induced complement activation in serum and plasma (heparin 2 U/ml and ACD-B 1:20) was investigated using an in vitro model of LDL apheresis. The total volume of serum or plasma loaded to the chromatography column was collected in defined aliquots. The washing, desorption and regeneration fluids were processed in the same way. From the obtained values of generated complement split products C3a (desarg), C4a (desarg), C5a (desarg) and complement proteins C3, C4, C5, the conversion rates of the precursor were calculated. In the experiments with serum, 19% of C3, 8% of C4 and 2.3% of C5 were converted by the immunoadsorbent, whereas with plasma 7, 6, and 0.6%, respectively, were found. Furthermore, only 60-74% of total anaphylatoxins were found in the effluent during the loading process. The residual 26-40% was removed from the column with the subsequent washing fluids. Therefore, in the clinical routine, only a reduced part of generated anaphylatoxins will be retransfused to the patient. The fact that C5 is converted to the most limited extent to its biologically active fragment additionally contributes to the understanding of the good clinical tolerability of the LDL apheresis.


Platelet apheresis with Vivacell BT798 DEA, haemonetics V-50 and PCS-Plus: preparation efficiency and product quality using identical donors. Different platelet apheresis techniques were used for preparing platelet concentrates: the continuous flow method with Vivacell BT 798 DEA, the discontinuous flow method with V-50 of Haemonetics, and their plasmapheresis device PCS-Plus. 20 of our donors underwent all three procedures. All platelet separations led to suitable platelet concentrates of 3 x 10(11) platelets within less than 90 min. However, the contaminating leukocytes reached 2 x 10(8). Due to less intense citrate reactions and a shorter donation time the donor acceptance of the continuous flow method was higher as compared with the discontinuous flow method.


Evaluation of the Haemonetics V50--time saver protocol. 196 platelet apheresis procedures using the cell separator Haemonetics V 50 were performed applying 8 cycles under varying conditions. The anticoagulant ACD-A was used in a whole-blood to anticoagulant ratio of 8:1. The flow rate was selected for a range of 40-70 ml/min and the centrifuge speed was established at 4,800 and 4,400 rpm. The PWC factor was chosen between 0 and 4. 162 procedures could be statistically evaluated. 34 apheresis were accompanied with technical complications. The mean yield was (4.3 +/- 1.05) x 10(11) platelets, and the average of extraction efficiency (EE) was 53.9 +/- 8.2%. An analysis of variance confirmed that a higher flow rate decreased the EE (p < 0.002) and also the leukocyte counts (p < 0.0005). Increasing the PWC factor led to a higher EE; however, the leukocyte counts of the platelet concentrate were also increased (p < 0.0005). The g force has an essential effect. A high g force of the centrifuge permits to obtain a large quantity of platelets which is combined with a higher leukocyte contamination. Decreasing the centrifuge speed to 4,400 rpm by using PWC factors of 0 and 4 with different flow rates (50 and 60 ml/min) decreased the EE and the leukocyte counts in the product.


[Immunologic factors in habitual abortion]. Recent advances in immunology have discovered two immunological factors in part of the patients with habitual first-trimester abortions. Antibody formation against the major histocompatibility antigens (HLA = human leukocyte antigen) which can be demonstrated during normal pregnancy is often not detectable in these patients, sometimes presumably because of compatibility in the HLA antigens between mother and fetus. In a high percentage of these patients immunotherapy by subcutaneous leukocyte injections can lead to antibody formation and successful pregnancy. As another immunological factor, a genetic variant of the complement-inactivating leukocyte differentiation antigen CD46 (= TLX antigen, = membrane cofactor protein) could be identified, which can be seen more frequently in patients with habitual abortions as compared to healthy controls. Both factors seem just to contribute to a predisposition for early-pregnancy abortions rather than to be an absolute barrier, as they can also be seen in normal pregnancy and successful carriages can also occur without any therapy in early-pregnancy aborters with an immunological background.


[Laparoscopy-assisted vaginal hysterectomy: initial experiences with an extrafascial technique]. This is a report on 4 cases of vaginal hysterectomy assisted by laparoscopy. The indications were dysfunctional hemorrhages, uterus myomatosus as well as 1 case of cervical intraepithelial neoplasia. Postoperatively, no complications were observed. It can therefore be concluded that with laparoscopic assistance the technical spectrum of hysterectomy can be enlarged. The disadvantage, if one can refer to it as such, implies the necessity of the gynecologist being a well-trained laparoscopist.


[Effect of high performance sports on female menstrual cycle exemplified by windsurfing]. Questionnaires were sent to all female members (n = 60) of the Austrian Funboard Association (funboard = the most athletic windsurfing class). They included questions about the menstrual cycle, physical capacity, libido and performance dependent on the particular cycle phase. There was no significant libido or capacity peak, neither for the windsurfers nor for a normal collective (n = 100); on the other hand there was an evident low during menstruation. A mean length of the menstrual cycle of 26.5 +/- 2.8 days and a bleeding time of 4.4 +/- 1.2 days were found, while metrorrhaghia and dysmenorrhea were less frequent than in the normal collective. One reason for these findings could be that physical activity reduces dysmenorrhea.


Clinical assessment of fetal blood flow velocimetry. A statistical procedure is presented to analyze the relation between Doppler indices (DIs) such as pulsatility index (PI), resistance index (RI), A/B and clinical data of pregnancy and fetal outcome of three groups: (1) uncomplicated pregnancy, eutrophic fetus (NF), (2) pregnancy-induced hypertension (PIH), and (3) pregnancy and delivery of a dystrophic fetus (IUGR), and the acidity classes according to Saling, respectively. Proceeding and mathematical requirements as well as the possibilities to validate the methodology are introduced, and an application to previously published data is presented. By multivariate analysis of the data a fair prognosis of NF, PIH and IUGR was possible. The variability inherent to the data sampling requires a mathematical postprocessing in the framework of an adequate model before any clinical conclusions can be derived from DIs.


[Lung hypoplasia as a complication of prolonged, premature rupture of fetal membranes in the 24th week of pregnancy]. We examined 4 gravidae with rupture of membranes before the 24th week of gestation. In contrast to pathophysiological models we observed fetal respiratory movements and a reduced amount of amniotic fluid in all patients.


Bone physiology and metabolism in dental implantology: risk factors for osteoporosis and other metabolic bone diseases. Placing a dental implant elicits a time-dependent bone response controlled by wound-healing factors (cytokines, bioelectrical signals), biomechanics (gravitational, functional, and therapeutic loads), and mineral metabolism (hormones, diet, excretion). The osseous response to an implant involves four physiological stages: (1) endosteal and periosteal callus formation; (2) compaction and remodeling of the callus; (3) remodeling (turnover) of the nonvital interface and adjacent bone; and (4) maturation (secondary mineralization) of new bone. Long-term maintenance of a rigid implant interface is related to continual bone remodeling. Common metabolic bone disorders affecting potential implant patients are osteopenia ("osteoporosis"), renal osteodystrophy, osteomalacia, and Paget's disease. The most prevalent problem is a long-term negative calcium balance leading to a compromise in bone strength. Symptomatic osteoporosis (usually wrist, hip, and/or spine fractures) affects 4 to 50 percent of the population depending on age, race, sex, endocrine status, and life-style. Postmenopausal white and Asian females present the greatest risk. The jaws of "osteoporotic" adults are variably affected because of the moderating influence of mechanical function. Management of metabolic bone disorders is an important consideration in diagnosis, treatment planning, and long-term monitoring of dental implants. Bone metabolic counseling, a natural extension of preventative dentistry, is an unexpected benefit readily appreciated by patients and their families.


How to treat ailing and failing implants. This article describes treatment of the ailing implant (bone loss with pocketing but static at the maintenance checks) and the failing implant (bone loss with pocketing, bleeding upon probing, purulence, and evidence of continuing bone loss irrespective of therapy). Because the surface of the implant is contaminated with endotoxin, it must be detoxified before any regenerative therapy. Studies have shown that citric acid is effective in detoxifying the hydroxyapatite-coated surfaces while tetracycline is more effective in sterilizing the metallic substrate fixtures. Guided tissue regeneration is useful as a "barrier" to prevent exfoliation of the grafted material. Both nonresorbable and resorbable materials have been used with great success. Allografts (freeze-dried bone) and alloplasts (synthetic materials) may be used to achieve a sulcus of decreased depth and possibly some type of osseous regeneration. The author recommends the use of the allograft if the surface is completely detoxified and the alloplast if it is not certain that the surface is sterilized and free of endotoxin. The allograft, being resorbable, will not effect biologic healing against a contaminated surface; hence, the use of the alloplast to "fill" the defect and prevent epithelial invagination.


Retrieval analyses of a blade implant after 231 months of clinical function. A blade implant that was retrieved in 1990 after 231 months of clinical function (since 1971) was analyzed with respect to clinical, histological, and biomechanical characteristics. The implant clinical records demonstrated no abnormalities or pathological lesions over the tenure of treatment. The bone to implant interface showed a mixture of interfacial tissue components and conditions with adequate direct bone contact (46.4 to 82.3 percent) for classification as osseointegrated. The abutment fracture leading to removal was characterized as a cyclic fatigue mechanism and the distribution of tissue components along the interface could not be correlated with specific biomechanical loading directions. This report considers the clinical and biomechanical records as they relate to the detailed histological investigation.


The influence of implant design, application, and site on clinical performance and crestal bone: a multicenter, multidisciplinary clinical study. Dental Implant Clinical Research Group (Planning Committee). This investigation is designed to provide scientific data that is directly relevant to the placement of dental implants. The study is concerned with the influence of implant design, application, and location on long-term clinical performance and crestal bone response over 5 years of function. It involves approximately 700 patients at 30 Veterans Administration Medical Centers from various geographic regions. Patients are being entered into the study over an 18-month period and monitored (post-loading) over 5 years. The participating centers were randomly assigned to one of two separate, independent study groups. Complications and adverse responses associated with the placement and use of the implants will be evaluated and all failures thoroughly documented. The experimental design and sample size are based on the primary hypothesis that an implant-supported prosthesis will be successful/functional over a 5-year period in at least 90 percent of the cases treated. Secondary hypotheses to be tested are (1) the success rate among implant designs are the same over a 5-year period; (2) the success rate among implant applications are the same over a 5-year period; (3) the success rate of individual implants are the same with regard to jaw location over a 5-year period; (4) the loss of crestal bone at the individual implant sites are the same among the implant designs over a 5-year period; and (5) the complications and adverse responses experienced with the different implant designs are the same over a 5-year period. The experimental design of this multicenter, multidisciplinary, randomized investigation is a cooperative effort of the Department of Veterans Affairs and several United States dental schools.


Antibacterial activity of dental implant metals. This study was conducted to investigate the specific in vitro antibacterial effect of seven dental implant metals on oral bacteria which have often been identified in failing implants. The metals chosen for evaluation were titanium, chromium, cobalt, aluminum, iron, gold, and vanadium. These metals were selected because they are contained in many commonly used dental implants. The bacteria selected for this study included isolates of Porphyromonas endodontalis, Porphyromonas gingivalis, Prevotella intermedia, Prevotella melaniogenica, Actinobacillus actinomycetemcomitans, Actinomyces naeslundii, and Actinomyces viscosus. Sets of tubes containing either supplemented trypticase soy broth, brain-heart infusion-yeast extract, or brain-heart infusion-yeast extract with 5 percent defibrinated rabbit blood were aseptically prepared with doubling dilutions of the seven metals starting at an initial concentration of 500 micrograms/ml and terminating at 0 microgram/ml. Cultures of each organism were inoculated into each set of broth tubes containing all concentrations of metals. Tubes were incubated either anaerobically or in an atmosphere of 5 percent carbon dioxide for 48 hours at 35 degrees C and then assayed for ATP content which was proportional to the viable cellular biomass. The results showed that, although being bacteria and concentration dependent, all seven metals suppressed the growth of each organism. The rank order of antibacterial activity expressed by dental implant metals was gold > titanium > cobalt > vanadium > aluminum > chromium > iron.


Tissue-supported implant overdentures.

Tissue-supported implant overdentures. Overdenture techniques can be modified for use with implants. Generally the implants, which replace the tooth roots, can be placed in a position to permit optimum retention and stability as well as enhancing esthetics. Bony undercuts, which at times are present with the retention of tooth roots, are not a problem when using implants. Various retentive schemes are available to retain the prosthesis and can be matched to the individual needs of patients in regard to retention, stability, and the ability to insert and remove prostheses. Two implants can adequately support an overdenture. The superstructure must be designed to enable the patient to maintain a healthy oral environment. The patient must understand and be able to perform required oral hygiene procedures. The use of overdentures over implants affords the dentist another option in meeting the needs of the patients.


Estimating the validity of radiographic measurements of marginal bone height changes around osseointegrated implants. The accuracy of determining marginal bone height changes around osseointegrated implants depends on the validity of comparing serial films and the reliability of the measurements. X-ray beam orientation changes can alter the validity of serial films. A human dry mandible containing a Brånemark implant was irradiated +/- 12 degrees in the vertical plane at 1-degree intervals to the perpendicular to the long axis of the fixture. The thread width was recorded on both sides of each fixture image using a computer. Twenty-five randomized unclassified images were remeasured and the vertical angle of the x-ray beam was estimated from the previous measurements to test for validity of comparing images. The reliability of measurements with altered image magnification and penumbra were calculated. The reliability of 24 repeated thread width measurements was a SD of 0.01 mm. Of the 25 unknown beam angulations, 32 percent matched correctly, 20 percent +/- 1 degree, 16 percent +/- 2 degrees, or 68 percent < or = +/- 2 degrees. Alteration from a short to a long cone technique was estimated to produce magnification errors similar to the reliability SD of 0.01 mm. Similarly the penumbra varied from 0.057 mm to 0.032 mm with short to long cones using a 1.0-mm focal spot. With a 0.6-mm focal spot, the smallest penumbra of 0.19 mm was twice the measurement reliability. This method demonstrated x-ray beam angulation and validity for comparing serial films can be estimated for the extreme variations but not accurately for +9 to -6 degrees from a tangent to the fixture.(ABSTRACT TRUNCATED AT 250 WORDS)


Early detection of osseointegration using scanning electron microscopy and the interfacial biopsy chamber: a pilot study. This pilot project attempted to demonstrate microscopic evidence of osseointegration in a controlled environment as originally presented by Brånemark. The Interfacial Biopsy Chamber was developed to collect titanium/tissue serial biopsies of the implant-tissue interface at various stages of wound healing. It was surgically placed in two Flemish giant rabbits and titanium/tissue biopsies were collected at 35 and 70 days. The biopsies were examined using scanning electron microscopy (x2000, x3200, and x7500) and light microscopy (x230). Osseous tissue was found in intimate contact with the titanium implant surface with no evidence of an intervening fibrous layer. Cells with the morphological characteristics of osteoblasts were observed covering the titanium surface. Processes extending from the main body of these cells were in intimate contact with the titanium surface, following the machining striations. The photomicrographs were similar to those presented earlier by Brånemark. The project also suggested the use of the Interfacial Biopsy Chamber as a research instrument for the collection of implant/tissue interface serial biopsy samples.


Intraoral corrosion resulting from coupling dental implants and restorative metallic systems. Materials used for the construction of dental restorations and implants include a wide range of metals and alloys, ceramics and carbons, and polymers. When metals and alloys are placed in direct contact in the oral cavity, a galvanic cell can be formed that may compromise the longevity of one or more of the materials in the couple. In vitro electrochemical corrosion analyses have proven to be a valuable tool for providing guidance on the selection of metallic materials. These analyses can provide basic data on electrochemical potentials, current rates, and the evaluation of galvanic corrosion conditions. This article seeks to provide the clinician with information that can be valuable in the selection of metallic materials that may be placed in direct contact with one another in the oral cavity.


Microscopy of bone cells, bone tissue, and bone healing around implants. Newer methods of scanning microscopy using both light and electrons are particularly relevant to the study of bone cells, bone matrix organization, matrix mineralization, bone modeling and remodeling, and the adaptation of cells and matrix to implants. Most of such studies are conducted on retrieved implants, at least after the death of the related tissue. Because the retention of the tissue-implant relationship in such preserved tissue is crucial for critical evaluation of the implant, methods based on the study of flat surfaces of embedded tissue blocks are very important. Using electrons, the backscattered electrons in a scanning electron microscope can be employed to evaluate mean atomic number (density) and cathodoluminescence can identify polymers and fluorescent labels. Using light, confocal microscopical techniques permit the examination of layers deep to the block face. Confocal reflected and fluorescence methods allow the study of cell behavior upon both transparent and opaque substrates in the laboratory. Examples of the above are presented and interpretation problems discussed. Current experiments are aimed at enabling the study of bone wound healing and bone adaptation to implanted materials in vivo, through the implantation of optical quality windows and/or newly conceived and designed microscopical objective lenses.


A surgical guide for insertion of implant fixtures. Successful prosthodontic rehabilitation of edentulous ridges with implants is dependent upon the alignment of multiple fixtures. A simple technique for fabricating a surgical guide is presented in this article.


Utilization of 3D/Dental software for precise implant site selection: clinical reports. Preoperative planning is an essential aspect of endosteal implant placement. Three-dimensional imaging allows the surgeon and restorative dentist to accurately visualize potential implant receptor sites relative to adjacent vital structures. This information is correlated with the planned occlusion, and transferred to the patient by means of a surgical prosthetic guide, which is developed on the diagnostic cast. The steps involved in planning and placing implants in an atrophic mandible in the first case illustrates the value of three-dimensional scanning in treating patients with limited bone volume. The second case presented with a mandibular bilateral distal extension partial denture, which was ultimately replaced with two implant-supported fixed prostheses. The use of three-dimensional imaging showed the location of the inferior alveolar neurovascular bundle which allowed utilization of all of the bone above it without encroaching on the nerve. The third case illustrates an edentulous maxilla where visualization of the osseous contour allowed for implant placement at an optimal angulation to provide support for the planned prosthesis.


An evaluation of the Periotest system. Part I: Examiner reliability and repeatability of readings. Dental Implant Clinical Group (Planning Committee). The clinical success of endosseous dental implants is related to the extent of osseointegration. Many of the presently used methods of evaluating osseointegration are highly subjective. The Periotest is claimed to offer a more objective means to assess osseointegration and supporting bone stability of implants by means of microcomputer-controlled percussion. Investigators involved in a clinical study on dental implants being conducted by the Dental Implant Clinical Research Group participated in a two-part in vitro evaluation of the Periotest system. The first part, with which this article is concerned, involved each of 35 investigators taking three readings for each of 16 models designed to simulate an implant in place in the oral cavity and to cover most of the effective measuring range of the instrument. The Periotest system generally demonstrated a high degree of reliability and repeatability, with higher variability associated with specific model samples. Further evaluation of the Periotest as a research instrument will be conducted within the clinical environment of the Dental Implant Clinical Research Group study.


Detoxification of endotoxin-contaminated titanium and hydroxyapatite-coated surfaces utilizing various chemotherapeutic and mechanical modalities. The surgical repair of the ailing implant may be complicated by the surface effects of pathogenic bacteria and their products. This study evaluated the ability of various chemotherapeutic modalities to detoxify endotoxin-contaminated titanium alloy and hydroxyapatite-coated test strips. Grit-blasted titanium alloy and hydroxyapatite-coated test strips were contaminated with purified outer membranes of Escherichia coli labeled with radioactive 14C. The titanium alloy strips were treated with citric acid, stannous fluoride, tetracycline HCl, chlorhexidine gluconate, hydrogen peroxide, chloramine T, sterile water, a plastic sonic scaler tip, and an air-powder abrasive unit. Hydroxyapatite-coated strips were treated with chloramine T, citric acid, or burnished with sterile water on cotton pellets. Residual lipopolysaccharide levels were measured by liquid scintillation spectrometry. The air-powder abrasive unit removed significantly greater amounts of lipopolysaccharide than all other treatment modalities on titanium samples (P < 0.05). A 60-second burnish with sterile water was able to remove significant amounts of lipopolysaccharide when compared with untreated controls (P < 0.05). Citric acid was superior in the removal of lipopolysaccharide from hydroxyapatite-coated surfaces when compared with the controls or chloramine T (P < 0.01). Detoxification of an implant infected surface may be beneficial when surgical repair of the ailing implant is indicated.


Current status of tissue expanders in alveolar ridge augmentation: a review. The need for major surgery involving bone and skin grafting procedures in the treatment of severe alveolar atrophy has, for many patients, been obviated by the advent of reliable endosseous implant systems. However, some patients, usually for medical, psychological, or financial reasons are unsuitable for endosseous implant therapy. In such patients, ridge augmentation with particulate hydroxyapatite may result in significantly improved denture function. However, hydroxyapatite tends to disseminate throughout any surgically created subperiosteal space, resulting in an undesirable ridge form. This problem may be overcome by the use of tissue expanders in a two-stage surgical procedure. This article briefly reviews the concept of tissue expansion and describes its application to the technique of alveolar ridge augmentation.


The surgical template: a prescription for implant success. The surgical template is utilized in the planning and execution of a successful implant rehabilitation. A method of template fabrication is presented which is useful for cases requiring precise root form fixture placement. Stents are fabricated using a duplicate denture or acrylic base and orthodontic wire, which is contoured to create the acceptable perimetric limits of fixture placement. This approach provides good visual access, operator flexibility, and template stability. The technique can be utilized for the edentulous and the partially edentulous arch.


Fibroblastic growth and attachment on hydroxyapatite-coated titanium surfaces following the use of various detoxification modalities. Part I: Noncontaminated hydroxyapatite. Hydroxyapatite-coated titanium alloy test strips were treated with chlorhexidine gluconate, stannous fluoride, citric acid, tetracycline HCl, polymyxin B, hydrogen peroxide, and a plastic Cavitron tip: untreated sterile strips served as controls. The strips were incubated with cultured human gingival and periodontal ligament fibroblasts. Image analysis of three photomicrographs of each test strip (original magnification x350) indicated that the tetracycline HCl treatment resulted in significantly greater cellular surface area coverage compared with the other treatments. Citric acid and the plastic Cavitron tip also stimulated cell attachment, although the results from the Cavitron tip were not significantly different from citric acid or the other treatment groups. The remainder of the modalities and the untreated cellular controls experienced similar cellular coverage.


Fibroblastic growth and attachment on hydroxyapatite-coated titanium surfaces following the use of various detoxification modalities. Part II: Contaminated hydroxyapatite. This study evaluated the ability of various chemotherapeutic and mechanical modalities to detoxify endotoxin-contaminated hydroxyapatite-coated dental implant surfaces as determined by the early attachment and growth of human gingival fibroblasts. Hydroxyapatite-coated test strips were contaminated with purified outer membranes of Escherichia coli and treated with citric acid, hydrogen peroxide, stannous fluoride, chlorhexidine gluconate, tetracycline HCl, polymyxin B, a plastic sonic scaler tip, or left untreated (contaminated and sterile controls). Human gingival fibroblasts were then seeded onto the test strips and incubated for 48 hours. The citric acid-treated strips showed greater cell growth than the other treatments. The plastic sonic scaler tip and the polymyxin B-treated samples exhibited greater cell coverage than the sterile control specimens. The use of citric acid and/or a modified plastic sonic scaler tip may be a valuable adjunct when surgical repair of an ailing hydroxyapatite-coated dental implant is contemplated.


Lingualized integration: tooth molds and an occlusal scheme for edentulous implant patients. The interface of bone and soft tissue to dental implants has been extensively documented, while the influence of biomechanics and the occlusal interface continues to be overlooked. Yet that same occlusal interface may ultimately be the prime factor in the lifetime survival rate of dental implants. What is lacking, for the practitioner, is a clear concept of the occlusal rehabilitation which is required and appropriate for the totally edentulous implant patient. Lingualized integration represents an occlusal scheme using specific tooth molds designed to improve the likelihood of maximum intercuspation and an absence of deflective occlusal contacts, provide cusp height for selective occlusal reshaping, and achieve a natural and pleasing appearance. Factors in the articulation and arrangement of the posterior teeth to assure the attainment of the fundamental goals of comfort, function, and appearance in occlusal rehabilitation for edentulous implant patients are included.


Finite element analysis of interface geometry effects on the crestal bone surrounding a dental implant. Using a two-dimensional axisymmetric finite element analysis technique, different geometrical configurations of implants, abutments, and interfaces have been investigated to alter the stress distribution in the crestal bone region. The crestal bone region is of particular interest due to observations of progressive bone resorption (saucerization). The ability of a prosthetic restoration-implant construct to transfer an appropriate stress at this region will, by definition of Wolff's law (bone's response to strain) and principles of bone remodeling, help to maintain the integrity of the surrounding bone via force transfer. The two geometries investigated involved a traditional flat mating surface and a slanted (oblique) mating surface. In both models a vertical load of 400 N (63 N/rad across 2 pi radians) was applied to the abutment apex. In the crestal bone region the oblique mating surface increased the transfer of horizontal stress 67 percent over the traditional flat mating surface design. The magnitude of stress transferred and the area which it was transferred across was increased in this region. Results indicate potentially more favorable mechanical conditions for bone maintenance surrounding an endosseous dental implant may be achieved if force is transferred preferentially via circumferential grooves and an oblique (dished) implant-abutment mating surface. These theoretical results are consistent with basic principles of stress transfer, stress shielding, and remodeling as well as clinical observations of bone maintenance and resorption.


An evaluation of the Periotest system. Part II: Reliability and repeatability of instruments. Dental Implant Clinical Research Group (Planning Committee). Investigators involved in a clinical study on dental implants being conducted by the Dental Implant Clinical Research Group participated in a two-part in vitro evaluation of the Periotest system. The first part involved each of 35 investigators taking three readings for each of 16 models designed to simulate an implant in place in the oral cavity and to cover most of the effective measuring range of the instrument. The second part, with which this article is concerned, was conducted by three study investigators to determine the level of agreement in readings for six different Periotest instruments. Readings were taken according to the manufacturer's instructions until two coincident readings were obtained. The readings were compared to evaluate inter- and intrainstrument reliability. Instrument repeatability was evaluated by examining the number of attempts required to obtain the two coincident readings. The Periotest system generally demonstrated a high degree of repeatability and reliability, with higher variability associated with specific model samples.


[Differentiation antigens of hematopoietic cells (CD system)]. Monoclonal antibodies allowed recognition and identification of a series of hematopoietic cell membrane antigens expressed on plasma membranes of leukemia patients and on cells of healthy subjects. Monoclonal antibodies produced in different laboratories were clustered on the basis of their reactivity with normal and malignant hematopoietic cells into CD (cluster of differentiation) groups, with defined properties of recognized antigens (glycoprotein, phosphoprotein or glycolipid nature, molecular weight, isoelectric point, amino acid or carbohydrate sequence, etc.) and with functional characteristics of the corresponding antigen and its distribution on cells of the hematopoietic system. This "CD system" of human hematopoietic cell differentiation antigens was established in a series of international laboratory workshops (1982-1989). The present state of the CD classification system, as assessed after the IVth International Workshop on Hematopoietic Cell Differentiation Antigens (1988/89), in which more than 100 laboratories analyzed over 1,000 monoclonal antibodies, is described. An overview of the data concerning properties of monoclonal antibodies produced in the authors' laboratory (monoclonal antibodies series Bra-) is presented.


[Embryotoxic effects of N-nitrosodimethylamine in mice]. N-nitrosodimethylamine was administered intraperitoneally in the dose of 5.5 mg.kg-1 body eight to pregnant ICR mice on days 3, 5, 9, 12 of gestation. The administered dose caused a statistically significant increase of resorptions at each stage of pregnancy studied. The pregnancy rate of females treated at any stage of organogenesis studied was reduced, most markedly in mice treated on day 12 of gestation. No malformations or skeletal anomalies were observed.


[Properties of skeletal muscle sarcoplasmic reticulum membranes prepared in the presence of dithiothreitol]. The authors studied the effect of dithiothreitol (DTT), an agent modulating the redox state of SH-groups, on functional properties of sarcoplasmic reticulum membranes of skeletal muscle. DTT (5 mmol.l-1) exerted a protective effect not only on (Ca2 + Mg2)-ATPase activity but also on the activity of Ca2+ uptake by vesicles, while the most pronounced effect was recorded at low levels of ionized Ca2+. The presence of DTT in the isolation medium decreased also passive permeability of membranes for Ca2+. In the light of the results obtained, modulation of the redox state is recommended for each isolation of membranes designed for the study of ion transport.


[Abnormal CT brain scan during acute lymphoblastic leukemia in children]. The results of CT brain scans were evaluated in 96 children with acute lymphoblastic leukemia in different stages of the disease. Practically normal findings were recorded at establishing the diagnosis (17 children), with the exception of infiltration of the brain and meninges in one patient. Examinations performed after induction chemotherapy (31 children) revealed abnormal CT scans in 55% of the children concerning most frequently dilatation of the cerebrospinal fluid pathways and exhibiting less frequently hypodense foci in the white matter. At check-up examinations after 9 months (following prophylaxis of CNS leukemia) these deviations from the norm had disappeared in some patients, in others they persisted and in the rest of the patients they were found to be aggravated. Examinations carried out several years after treatment completion (40 patients) showed abnormal CR scans in 43% of the patients. These involved particularly derangements in the density of the white matter which were of leuko-dystrophic type and atrophic changes characterized by dilatation of the cerebrospinal fluid pathways. The recorded changes in the CT brain scans were more pronounced in patients with high-risk forms of leukemia and intensive prophylaxis of CNS leukemia.


[Super Duo latex fixation test--an alternative diagnostic method for trichomoniasis?]. The reliability of the new latex-agglutination test super duo for the detection of antigens of T.vaginalis and Candida, a prospective screening method for trichomoniasis, was verified. In a group of 27 women the microscopic and culture diagnosis of trichomoniasis was established in 22 patients and 21 of them were positive in the latex-agglutination test for T.vaginalis. The immunochemical examination was not positive in either of the five women with findings of negative cultivation for the parasite. The intensity of agglutination was in good correlation with the clinical signs of inflammation. In asymptomatic women the reaction was indistinct. Vaginal candidiasis was revealed by culture in two women, one of them was positive on the latex-agglutination test for Candida. One woman with negative cultivation finding for yeast microorganisms was positive in the immunochemical test. Examination of asymptomatic sexual partners of trichomoniasis patients would be necessary to evaluate the suitability of the set for T.vaginalis infection screening.


[Female sterility after appendicitis in childhood]. The aim of the study was to establish the rate of sterility in women who had been operated on in childhood for perforated and non-perforated appendicitis. The group with perforated appendicitis consisted of 58 women who had been operated on at the age of 3 to 15 years and at the time of the follow-up examination they were in the age range of 23 to 41 years. Of these women 51 were married and 49 of them had one to three children. Two women (3.9%) were sterile. One had been operated on in adulthood for tubo-ovarial abscess in the right and pyosalpinx in the left tube and the other one was treated for repeated adnexitis in adulthood. The group with non-perforated appendicitis consisted of 168 women who had been operated on at the age of 3 to 15 years and at the time of the follow-up examination they were in the age range of 23 to 40 years. Of these women 145 were married and 141 had one to four children. Four women (2.8%) with the history of noncomplicated appendicitis were sterile. Our retrospective study showed no statistically significant difference in the occurrence rate of sterility in women operated on in childhood for perforated and non-perforated appendicitis.


[Prostaglandin E1 in the long-term treatment of erectile dysfunction]. Intravenous injections of Prostaglandin E1 were administered to 65 men suffering from erectile dysfunction. Later on, 59 of them administered the substance to themselves. Our experience as well as literary data have confirmed the efficacy of prostaglandin E1 administered intracavernously in the therapy of different forms of impotence, including the so-called psychogenic form. Its advantage is that it metabolizes directly in the cavernous tissue. Virtually no significant systemic side reactions were recorded and neither priapism nor fibrosis of the corpora cavernosa were observed after long-term treatment. Prostaglandin E1, a product of Léciva Praha, was used within the clinical study of this preparation.


[History of the Surgery Clinic at the Slovak University Medical School in Bratislava during the war years (1941-1945)]. The aim of the present study was to contribute to a good and objective understanding of the development of the Department of Surgery of the Medical School in Bratislava over the war years of 1941-1945. After Prof. MUDr. Kostlivý had left Slovakia, his student, Prof. MUDr. Konstantín Cársky was appointed head of the Clinic of Surgery, as it was officially named. Already during the period of World War II, Prof. Cársky became a remarkable and reknown personality of the School of Medicine of the Slovak University in Bratislava. The first Slovak school of surgery developed under his guidance. On the basis of archival sources and documents, the paper presents statistical data concerning some aspects of the pedagogical activities of the Clinic of Surgery, its staffing, and the complicated process of competence growth, particularly appointments to the highest academic ranks.


[The role of polymorphonuclear leukocytes in the development of gastric lesions induced by indomethacin and ethanol and the relation of vascular permeability]. The relationship between a reduced number of polymorphonuclear leukocytes (PMN), activated PMN/NBT (+) PMN/, permeability of gastric vessels, and disposition for the development of gastric lesions was studied following administration of indomethacin or ethanol in rats. Decrease in the number of circulating neutrophils and in the number of NBT (+) PMN after 3- or 6-day administration of methotrexate was found to diminish the disposition for the development of gastric lesions. Six-day administration of pentoxifylline resulted in a decreased number of NBT (+) PMN and in a diminished disposition for gastric mucosa injury induced by indomethacin, yet failed to reduce the occurrence rate of lesions after ethanol administration. No direct relationship was established between changes in gastric vascular permeability and decreased disposition for the development of gastric lesions after administration of methotrexate or pentoxifylline. (Fig. 3, Ref. 30.)


[Changes in myocardial sensitivity after sudden with withdrawal of calcium channel blockers]. Our previous experiments have suggested that besides the receptor cont and/or sensitivity a decrease of intracellular calcium level significantly participates in the mechanism of beta-blocker withdrawal 'rebound' phenomenon. This suggestion initiated studies in which possible changes in myocardial responsibility to cardioactive drugs were investigated in the condition of withdrawal of treatment with calcium entry blockers. The results showed increased cardiotoxicity of ouabain, aconitine and CaCl2, as well as an increased response of the heart to isoprenaline 24 hours after sudden cessation of treatment with verapamil (2 mg.kg-1 x 12 hours-1), diltiazem (3 mg.kg-1 x 12 hours-1) and nifedipine (0.5 mg.kg-1 x 12 hours-1). These results support the hypothesis of a common mechanism of the withdrawal syndrome of beta-lytics and calcium antagonists involving changes in intra-cellular calcium level. (Tab. 2, Fig. 4, Ref. 33.).


[Prenatal virus infections and orofacial clefts]. A potential teratogenic activity of virus infections caused by the viruses of rubella, influenza, parotitis, hepatitis B, cytomegalovirus and the Epstein-Barr virus was investigated. Specific antibodies against these viruses were examined serologically in children with orofacial clefts and in their mothers and the results were compared with those obtained in control children and their mothers. Different micromethods were used in performing the examinations (ELISA, RIA, NIR, KFR, HIT). Evaluation of the results and their statistical processing supports the assumption that prenatal infection may have occurred in the series studied induced by the viruses of influenza, rubella, cytomegalovirus, and possibly also by the Epstein-Barr virus. No association with the viruses of parotitis and hepatitis B was established. (Tab. 5, Ref. 36.)


[Lungs and their function in heart disease]. Pulmonary manifestations of cardiac diseases are reviewed and the contribution of pulmonary function assessment in diagnosis, management and prognosis of these diseases is being emphasized. Inborn and acquired diseases of the heart exert pathological effects on pulmonary hemodynamics and later on also on lung structure, clinically manifested by pulmonary symptomatology and abnormalities in pulmonary function. The basic mechanisms of pulmonary function derangement include pulmonary congestion and hyperreactivity of the airways as a consequence of increased blood pressure or flow in the pulmovascular network (postcapillary or hyperkinetic pulmonary hypertension). The severity of the given cardiac disease determines also the condition of pulmonary function. Thus examinations of pulmonary function substantially contribute to the classification of the functional state and to optimal choices in therapeutic strategy. Appropriate surgical or medical therapeutic procedures can improve the hemodynamic conditions in the pulmonary vascular network. This, in turn, leads to partial regression of morphological changes in the pulmonary parenchyma and thus to gradual improvement of pulmonary function. (Tab. 4, Fig. 4, Ref. 62.)


[Primary culture in chemically defined medium of human fetal mammary epithelial cells within reconstituted matrix]. A serum-free primary culture system has been developed which allows for three-dimensional growth and differentiation of normal human fetal mammary epithelial cells within an extracellular matrix preparation. Human fetal mammary epithelial cells were isolated from the mammary glands of human female fetuses, 17 to 39 weeks-old. The "organoids" were embedded within a reconstituted basement membrane matrix prepared from the Engelbreth-Holm-Swarm (EHS) sarcoma according to the method of Hahm and Ip. "Organoids" were grown in either serum-free medium or in medium with fetal calf serum (FCS). The "organoid" proliferated over a 2 to 3 weeks culture period and remained viable for 1 or 2 months within the basement membrane matrix in serum free medium. Several types of colonies were observed; including alveolar-like budding clusters obtained from cultures of mammary gland from fetuses of over 20 weeks age, units with ductule-like projections and stellate-type colonies. Cell proliferation was dependent on the culture medium (with FCS no proliferation was obtained) and on the substratum (without matrix, significantly less growth and development occurred). These types of colonies are obtained when a glandular differentiation of cells budding from the malpighian epithelium is observed. Light microscopic and transmission electron microscopic studies were undertaken at the time of culture. This unique system using normal fetal mammary epithelial cells thus provides a model in which the regulation of human mammary development can be investigated.