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A modified technique of pre-operative aortography to demonstrate the complete arterial tree of the lower limb.

One hundred consecutive aortograms were studied to establish the efficacy of conventional arteriography in demonstrating distal vessels and the pedal arch. The standard technique was modified by using a long injection time, a large volume of contrast material (iopamidol 370), prolonged filming and multiple exposures of the feet. On the basis of these examinations each limb was classified as having aorto-iliac disease (18 limbs), superficial femoral disease (103 limbs), combined segment disease (28 limbs) or generalised disease (51 limbs). Calf and ankle arteries were seen in 196 of the 200 limbs (98%). Patency of the pedal arch was established in 184 (92%). Fourteen percent of the group of patients with combined segment disease did not have their pedal arch visualised and this group contained most of the examination failures. This modified method of aortography can demonstrate the entire arterial tree from the aorta to the foot in 92% of limbs with symptomatic chronic atherosclerotic disease. This allows the majority of peripheral vascular reconstructions to be planned and performed without the need for intra-operative arteriography.

Angiography↗

[Diseases of the cardiovascular system and the function of the endocrine glands in veterans of Soviet Antarctic expeditions].

The authors examined 58 men who had repeatedly participated in the Antarctic expeditions. In addition to a profound study of the cardiovascular system, the insulin tolerance test (0.1 U/kg simple insulin injected by intravenous drip for 90 minutes) was made, permitting the degree of tissue insulin resistance to be quantitatively estimated with measurements of the content of cyclic nucleotides in blood leukocytes and of immunoreactive insulin, C-peptide and counterinsular hormones in the blood before and after the functional test. It was established that with the increase of the number of Antarctic winterings tissue insulin resistance naturally grows regardless of the age of the examinees, manifesting itself in an increase of basal insulinemia, the content of cyclic adenosine monophosphate in blood leukocytes, appreciable increment of insulinemia after infusion of exogenous insulin. Analogous changes were detected in polar researchers suffering from coronary disease, essential hypertension irrespective of the number of winterings. It is concluded that the rise of tissue insulin resistance occurring under the influence of multiple exposures to natural and social factors of high latitudes is a predisposing factor of the formation of cardiovascular pathology.

Adaptation, Physiological↗

Conditions influencing the expansion of the circulating hemopoietic progenitor cell compartment.

Eighteen patients (6 breast cancer, 10 non-Hodgkin's lymphoma, 2 Hodgkin's disease) were treated with high-dose cyclophosphamide (7 gr/mq), while 12 (2 breast cancer, 5 non-Hodgkin's lymphoma, 5 multiple myeloma) were additionally treated with rhGM-CSF for 14 days after cyclophosphamide. During recovery, increased peak values of circulating CFU-GM were observed in 23 out of 30 patients (13 patients after cyclophosphamide, median: 5,000 CFU-GM/ml; 10 patients after cyclophosphamide + rhGM-CSF, median: 20,150 CFU-GM/ml); five of these "high releaser patients" were in 1st relapse after MACOP-B. Seven patients showed low release of CFU-GM; they had either a history of multiple exposures to chemoradiotherapeutic treatments or bone marrow replacement by neoplastic cells or both. Four out of 23 patients with high CFU-GM release were subsequently studied after administration of high-dose etoposide (2 gr/mq): increased levels of circulating progenitors were seen again, although peak values were reduced when compared to post-cyclophosphamide period. Three patients with low release and bone marrow involvement had a clear increase of circulating CFU-GM after etoposide. The results show the influence of high-dose chemotherapy, rhGM-CSF, type of previous treatment and bone marrow involvement on the degree of circulating CFU-GM release.

Antineoplastic Agents↗

Kinins contribute to the contractile effects of rat glandular kallikrein on the isolated rat uterus.

Glandular kallikrein is known to promote contractions of the isolated, estrogenized rat uterus, perhaps independently of kinin formation. The recent availability of kinin receptor antagonists led us to study whether they might affect the oxytocic activity of kallikrein. DArg0-Hyp3-Thi5,8-DPhe7-bradykinin (8.5 x 10(-7) M) displaced the dose-response curves to both bradykinin (from 1.0 x 10(-9) to 4.0 x 10(-6) M) and kallikrein (from 4.7 x 10(-11) to 8.0 x 10(-9) M) approximately one order of magnitude to the right. This inhibition could not be due to a nonspecific effect on the uterine muscle, as the contractile response to oxytocin was not altered. In addition, carboxypeptidase B (a potent kininase) and kinin antibodies reduced the contractile response to kallikrein by 70 and 60%, respectively. Removal of the intervening agent restored the normal response. The effect of kallikrein depended on its enzymatic activity, inasmuch as kallikrein inactivated with D-Phe-Arg-Arg-CH2Cl was not oxytocic. Prolonged or multiple exposures to kallikrein completely abolished uterine response, whereas the effect of bradykinin was unaltered. Uterine horns rendered insensitive to kallikrein by prolonged exposure still contracted in response to trypsin. Kininogen was present in the uterine tissue in a concentration of 1.5 +/- 0.3 ng of bradykinin equivalents per mg wet wt. No more than 15.9 +/- 1.2% of this total was due to plasma contamination. Only 21.5 +/- 2.9% of total kininogen could be cleaved by kallikrein. We conclude that part of the oxytocic activity of kallikrein is related to generation of kinins from a kallikrein-sensitive kininogen present in the isolated rat uterus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Detection of antisperm antibodies: a cytotoxicity immobilization test.

The sera of 110 couples with unexplained infertility were examined for anti-sperm immobilizing antibodies with the aid of multiple-exposure photography. The sera of 10 females and 3 males had immobilizing activity. Eleven pregnancies occurred in 10 female patients in the group without immobilizing antibodies. None of the 13 females in the couples with immobilizing activity conceived. A negative correlation was found between the occurrence of serum immobilizing antibodies and incidence of pregnancy. No such correlation could be found between the occurrence of autoagglutination in the male's ejaculate and the female partner conceiving. In light of detection of anti-sperm antibodies in a patient with habitual abortions, a possible immune mechanism is suggested.

Adult↗

Absorption, distribution, metabolism, and excretion of 1,2-dihydro-2,2,4-trimethylquinoline in the male F344 rat.

1,2-Dihydro-2,2,4-trimethylquinoline (TMQ), an antioxidant used in the rubber industry, was readily absorbed from the gastrointestinal tract of the male Fischer 344/N rat and rapidly distributed throughout the body tissues. Absorption, distribution, metabolism, and excretion were not significantly affected by dose in the range 11.5-1150 mumol/kg. Following iv administration, the greatest amounts of TMQ-derived radioactivity were present in the high volume tissues including muscle, adipose, skin, liver, and blood. TMQ had no particular affinity for any tissue. TMQ-derived radioactivity was excreted primarily in urine (60-70%) and feces (20-30%) within 3 days after administration. Greater than 99% of the TMQ dose excreted in urine and feces was in the form of metabolites. Urine contained two major and ten minor metabolites while feces contained two major and four minor metabolites. The two major TMQ metabolites in urine were identified by NMR and mass spectroscopy as the O-sulfate conjugate of 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline and the monosulfate conjugate of 1,2-dihydro-1,6-dihydroxy-2,2,4-trimethylquinoline. In vitro studies with liver subcellular fractions suggest that most of the metabolites present in urine, feces, and bile are the products of mixed function oxidase activity and conjugates of these metabolites. Multiple exposure of rats to high TMQ doses (1150 mumol/kg) resulted in some bioaccumulation of TMQ-derived radioactivity in all tissues examined, but these residues did not persist when dosing was discontinued.

Animals↗

In vivo effects of monoclonal anti-L3T4 antibody on immune responsiveness of mice infected with Schistosoma mansoni. Reduction of irradiated cercariae-induced resistance.

Mice can be partially protected against challenge infections of Schistosoma mansoni cercariae by either single or multiple exposure to irradiated cercariae (x-cerc). The participation of L3T4+ lymphocytes on this resistance phenomenon was evaluated by selectively depleting this cell population through in vivo administration of mAb anti-L3T4 (hybridoma GK 1.5) at three different times in relationship to the challenge infections. Treatment with anti-L3T4 before challenge such that depletion was effective during the time of cercarial skin penetration and dermal/s.c. residence significantly reduced the level of resistance induced by x-cerc sensitization. When treatment was delayed until after challenge, depletion of L3T4+ cells coincided with either the lung or post-lung/liver phases of schistosomular migration, and normal levels of x-cerc-induced resistance were induced. In contrast to once-immunized mice, mice hyperimmunized by five exposures to x-cerc and then depleted of L3T4+ cells at the time of challenge (skin phase) still expressed resistance to the challenge. These data suggest that when mice are sensitized only once with x-cerc the challenge infection provides a necessary immunologic boost which requires L3T4+ cells for effective expression of resistance. The requirement for this anamnestic effect by the challenge infection can be circumvented by hyperimmunization. Evaluation of the immune response of one-time sensitized or hyperimmunized mice demonstrated that cellular Ag-specific proliferative responses and mitogen-induced lymphokine production were abrogated after any of the various in vivo regimens of anti-L3T4 antibody. In contrast, immunoblot analysis of humoral responsiveness revealed a correlation between the expression of resistance and the ability of sera from immunized and anti-L3T4 treated mice to recognize a 75-kDa parasite antigenic component.

Animals↗

Stimulated chemiluminescence of polymorphonuclear leukocytes in rheumatoid arthritis: in vivo enhancement by auranofin.

The aim of the study was to investigate the interaction of opsonized zymosan with polymorphonuclear leukocytes (PMNLs) from 26 rheumatoid arthritis patients (six males and 20 females; mean age, 51.88 +/- 11.15 years; range, 33-72 years) and 11 control subjects (two males and nine females; mean age, 56.54 +/- 12.1 years; range, 33-75 years) using a luminol-amplified chemiluminescence (CL). The data obtained suggest that the opsonized zymosan stimulated CL is decreased in untreated rheumatoid patients compared with control subjects. The decreased stimulated CL may be the result of a physico-chemical alteration of the membrane (including decreased membrane fluidity and translocation of receptor sites) induced by free radicals of oxygen and/or by multiple exposures to chemotaxins. Auranofin enhances stimulated CL although the mechanism is not clear. Auranofin could interact with membrane lipids, induce changes in membrane surface charges and increase membrane fluidity. Our results are difficult to compare with those of previous studies, since different assays, and chemoattractants were applied. In addition, the disease activity and medication were also different.

Adult↗

Significance testing for correlated binary outcome data.

Multiple logistic regression is a commonly used multivariate technique for analyzing data with a binary outcome. One assumption needed for this method of analysis is the independence of outcome for all sample points in a data set. In ophthalmologic data and other types of correlated binary data, this assumption is often grossly violated and the validity of the technique becomes an issue. A technique has been developed (Rosner, 1984) that utilizes a polychotomous logistic regression model to allow one to look at multiple exposure variables in the context of a correlated binary data structure. This model is an extension of the beta-binomial model, which has been widely used to model correlated binary data when no covariates are present. In this paper, a relationship is developed between the two techniques, whereby it is shown that use of ordinary logistic regression in the presence of correlated binary data can result in true significance levels that are considerably larger than nominal levels in frequently encountered situations. This relationship is explored in detail in the case of a single dichotomous exposure variable. In this case, the appropriate test statistic can be expressed as an adjusted chi-square statistic based on the 2 X 2 contingency table relating exposure to outcome. The test statistic is easily computed as a function of the ordinary chi-square statistic and the correlation between eyes (or more generally between cluster members) for outcome and exposure, respectively. This generalizes some previous results obtained by Koval and Donner (1987, in Festschrift for V. M. Joshi, I. B. MacNeill (ed.), Vol. V, 199-224.(ABSTRACT TRUNCATED AT 250 WORDS)

Biometry↗

Mentally retarded and nonretarded subjects' long-term recognition memory.

Mentally retarded and nonretarded teenagers' long-term recognition for faces was compared. Initially, subjects viewed 255 face pictures, with multiple exposures of some pictures provided to equate immediate memory for the groups for a portion of the data. The majority of the subjects were then tested immediately and after 1 day and 1 week using a forced-choice method. The retarded subjects performed at a lower overall level than did the nonretarded subjects, there was significant memory loss across the retention intervals, and there was no differential memory loss between the groups. A 6-month follow-up retention test revealed no further memory differences. Results suggest that long-term memory is unrelated to intelligence level.

Adolescent↗

Radiosensitization in multifraction schedules. II. Greater sensitization by 2-nitroimidazoles than by oxygen.

The objective of this study was to characterize the extent of and mechanisms involved in radiosensitization by 2-nitroimidazoles in multifraction schedules using low doses per fraction. For this purpose, contact-inhibited monolayers of C3H 10T1/2 cells were given 1.7 Gy every 12 h and plated 12 h after the last dose received to allow full repair of potentially lethal damage (PLD). Severe hypoxia was obtained by a 1-h gassing procedure at room temperature immediately before each irradiation. No toxicity occurred as a consequence of multiple exposures to 5 mM misonidazole (MISO) or SR 2508 (2508) during the deoxygenation procedure. Experimental conditions during the pregassing and irradiation (presence of drug and gas mixture) were appropriately manipulated to test for the different mechanisms of radiosensitization demonstrated by nitroimidazoles. A very low oxygen enhancement ratio (OER) results under these conditions (1.34). Exposure to 5 mM MISO or 2508 during the deoxygenation and irradiation of hypoxic cells resulted in greater radiosensitization than could be accounted for by oxygen-mimetic sensitization alone (MISO and 2508 enhancement ratios were greater than the OER). Pregassing cells with N2 in the presence of 5 mM drug sensitized cells which were subsequently irradiated under aerobic conditions (drug free), indicating the occurrence of the "preincubation effect" (which does not require hypoxia or the drug's presence during the irradiation). Thus, for the hypoxic irradiations, the preincubation effect could account for the greater sensitization by nitroimidazoles than by oxygen. The presence of 5 mM drug only during the irradiation of aerobic cells produced radiosensitization in both multifraction and single-dose experiments with delayed plating. This sensitization has been previously shown to involve reduced PLD repair. Finally, maximum radiosensitization occurred in the multifraction schedule when a transient period of hypoxia with drug preceded an aerobic irradiation with drug present, thus combining the benefits of both the preincubation effect and PLD repair inhibition. This work demonstrates the possibility that effects other than oxygen-mimetic radiosensitization could be largely responsible for the sensitization seen in multifraction schedules, particularly when the OER is already low and only transient periods of hypoxia occur.

Animals↗

Histogenesis of UV light-induced blister formation.

Histological examination of ultraviolet light (UVL)-induced blister formation in guinea pig skin is reported. Light and electron-microscopic examination was performed on skin exposed to single and multiple exposures of a large dose of UVB. In light microscopy, intracellular edema was prominent, especially in the lower part of the epidermis, where it developed into a blister. It seemed to be a subepidermal bulla. The PAS-positive basement membrane was observed at the floor of the blister. The positive Nikolsky's sign seemed to be due to a separation between the degenerated and regenerated epidermis. Electron microscopy revealed a marked intercellular as well as intracellular edema and well-preserved desmosomes. The basal lamina was always located at the floor of the blister. The difference in UVL-induced blister formation between normal and pathological conditions is discussed.

Animals↗

[Double blind study of the hypoxia protective effect of a standardized Ginkgo biloba preparation after repeated administration in healthy subjects].

A randomised, placebo-controlled, double-blind, crossover study was run in 8 healthy, male subjects (mean age 27.3 +/- 2.6 years, mean BW 75.3 +/- 9.7 kg) to demonstrate a possible hypoxia-protective effect of standardised Ginkgo flavone glycosides after subchronical administration. After a 14-days' treatment with Ginkgo bilobae extract (Tebonin) performance of subjects was studied--concerning assessments of oculomotor and complex choice reaction system as well as simple cardiorespiratory parameters under multiple exposure to hypoxic hypoxia (10.5% oxygen, 89.5% nitrogen)--using oculodynamic methodology (ODT). Hypoxia increased the corneoretinal resting-potential of the eye and stimulated respiration. Both parameters were significantly reduced by verum administration. Under cumulative exposure to hypoxic hypoxia fixation time of saccadic eye movements and complex choice reaction time were significantly improved by Ginkgo flavone glycosides vs placebo. These results could be explained as a hypoxia-protective phenomenon--supporting the therapy of cerebral insufficiency.

Adult↗

Halothane hepatitis.

This report describes five cases of hepatocellular injury following halothane anesthesia. Four patients had multiple exposures to the anesthetic. Three of the five died from submassive to massive liver cell necrosis. The two survivors developed jaundice and/or dark urine following each exposure to halothane; liver biopsy in one showed centrilobular and linear areas of necrosis. Fever, anorexia, nausea, vomiting, abdominal pain and jaundice were present in all cases. In the two survivors the prothrombin time was less than 20 seconds throughout the course of the disease, whereas in the three who died the prothrombin time was more than 20 seconds from the onset. The English literature to the end of 1971 is reviewed. Approximately 600 cases of halothane-related hepatitis have been reported

Adult↗

Effect of hyperbaric oxygenation on experimental scrapie in mice.

The effect of hyperbaric oxygenation upon experimental infection of BALB/c mice with the scrapie agent was investigated by virological methods, histology and electron microscopy. A multiple exposure of scrapie-infected mice to hyberbaric oxygenation during the incubational period led to a certain aggravation of infection as evidenced by a greater accumulation of the agent in the central nervous system (CNS) and spleen, as well as by more pronounced ultramicroscopic changes in CNS. A single exposure to hypoxia failed to alter any manifestations of infection.

Animals↗

Factors affecting sperm motility. IV. Incubation of human semen with caffeine, kallikrein, and other metabolically active compounds.

The effect of six metabolically active compounds, namely caffeine, kallikrein, cyclic adenosine 3':5'-monophosphate, prostaglandin E, triiodothyronine, and insulin on spermatozoal motility was investigated. Hypokinetic and normokinetic semen specimens from fertile and infertile patients were incubated with various concentrations of these compounds. Spermatozoal velocity and percentage of motility were determined periodically with the objective multiple exposure photography (MEP) method before and during the following 4 to 8 hours. No significant differences was found between experimental and control specimens as to these parameters under the influence of the tested compounds, with the exception of caffeine. Caffeine immediately increased the percentage of motile spermatozoa by 30% to 50% of initial values in approximately two-thirds of cases. No influence on sperm velocity was detected during this period. By using the combined MEP and supravital staining techniques it was found that nonmotile live spermatozoa were activated by caffeine without any effect on the percentage of dead sperm. Some practical implications of these findings, the difference between our results and those reported by others, and the mechanism of action of these compounds are reviewed and discussed.

Caffeine↗

Clinical experience with polyelectrolyte-fractionated porcine factor VIII concentrate in the treatment of hemophiliacs with antibodies to factor VIII.

Circulating antibodies to factor VIII (anti-VIII, "inhibitors") occurring in patients with hemophilia neutralize porcine factor VIII less readily than human factor VIII in vitro. Over an 18-mo period, 8 patients with anti-VIII were treated with 45 courses (297 infusions) of polyelectrolyte-fractionated porcine factor VIII concentrate (PE porcine VIII). Where no anti-PE porcine VIII was detectable, mean post-infusion rise in plasma factor VIII was 1.29 U/dl/units infused/kg. Above 13 Old Oxford units of anti-PE porcine VIII and 48 Bethesda units of anti-human VIII, there were no postinfusion rises in plasma factor VIII. Where postinfusion rises were detected, clinical responses were good and conventional methods could be used to guide dosage. Ten percent of infusions were followed by febrile reactions, but these were usually mild and decreased in frequency and severity with increasing exposure. Multiple and prolonged courses of therapy were given to some patients without evidence of loss of clinical or laboratory efficacy. PE porcine VIII could provoke anamnestic rises of anti-VIII in susceptible patients, but appeared to have a lower immunogenic potential than human VIII. PE porcine VIII is a rational and effective therapeutic alternative for patients with anti-VIII, particularly those with intermediate level inhibitors who cannot be managed effectively using human factor VIII.

Adolescent↗

[Isoflurane anesthesia in the Gottinger minipig. Hemodynamic and cardiac changes under controlled ventilation].

10 adult, female Göttingen minipigs were anaesthetized with isoflurane under controlled ventilation. A mixture of O2: N2O = 1:3 was used to vaporize isoflurane in an inspiratory concentration of 1.75-2.0 Vol%. Electrocardiogram, blood pressure, cardiac output and central venous pressure were continuously monitored. To determine the maximum rate of rise of intraventricular pressure (dp/dt max) as an indirect measure of myocardial contractility we placed a micro-tip manometer in the left ventricle before and during (30 min value) the experiment. Acid-base balance was controlled by collecting arterial blood samples anaerobically. We found a negative chronotropic and marked inotropic effect of isoflurane on the heart-muscle. This probably is the main cause for the depression of arterial pressure, though peripheral vasodilatation has some effect. All cardiovascular changes were fully reversible within a few minutes of completing anaesthesia. After only 15 min all animals were fully conscious and data values had returned to control levels. Because of its deficient metabolism and toxicity isoflurane seems to be well qualified for use in experimental medicine in minipigs, especially when the animals require long or multiple exposure. But we recommend the use of isoflurane in combination with a basic anaesthesia, for example NLA or Ketamine to reduce cardiovascular depression.

Acid-Base Equilibrium↗