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Biomedical subjects

B Becker

Publications and source records attributed to B Becker.

At least 127 records · Page 7Linked to original sources

The significance of thermotolerance after 41 degrees C hyperthermia: in vivo and in vitro tumor and normal tissue investigations.

We have investigated the development of thermotolerance in both tumors and normal tissues after 41 degrees C for durations as brief as 15 minutes. The murine RIF tumor, treated by both local radiofrequency and systemic methods, was assayed for thermotolerance by both tumor growth and cell survival analyses. The murine leg and ear, treated by conductive methods, were assayed using pre-defined tissue damage scoring systems. All of these treatments quickly induced substantial levels of thermotolerance. In the tumor studies using local heating, RIF mean diameter doubling time decreased from 17.8 days to a minimum of 13.0 days with a 9 hr interval between 41.0 degrees C for 15 minutes and 44.0 degrees C for 30 minutes (9 hr D1-D2); cell survival increased from 1.2 X 10(-2) to 3.4 X 10(-1) (same interval). Both assays showed some degree of tolerance present immediately after 41.0 degrees C for 15, 30 or 60 minutes (0 hr D1-D2). In the tumor studies using systemic heating, the kinetic pattern of the induced tolerance was similar to that observed after local heating. In the leg studies, 41.0 degrees for 30 minutes increased the time at 45 degrees C necessary to induce a specified level of tissue damage (mean score of 7) by a maximum of 1.8 times (24 hr D1-D2). The kinetic pattern was similar to that for the tumors. In the ear studies, 41.0 degrees C for 30 minutes increased the time at 45 degrees C necessary to induce ear necrosis in 50% of animals by a maximum of 3.5 times (48 hr D1-D2). The peak tolerance level occurred later for the ears, which have a lower normal temperature of 28-30 degrees C, than for the tumors or legs. These results indicate that: thermotolerance can begin to appear in tumors during treatment if hyperthermia sessions involve initial low thermal exposures (near 41 degrees C) for 15 minutes or longer; thermotolerance can develop in tumors after systemic heating and occurs with a kinetic pattern similar to that following local heating; and normal tissues also can develop high levels of thermotolerance after similar thermal exposures.

Animals↗

Neurologic, neuropsychologic, and computed cranial tomography scan abnormalities in 2- to 10-year survivors of small-cell lung cancer.

In order to evaluate the relationship between neurologic function and cranial irradiation, 20 patients treated on National Cancer Institute (NCI) small-cell lung cancer (SCLC) trials who were alive and free of cancer 2.4 to 10.6 years (median, 6.2) from the start of therapy were studied. All were tested with a neurologic history and examination, mental status examination, neuropsychologic testing, and review of serial computed cranial tomography (CCT) scans. Fifteen patients had been treated with prophylactic cranial irradiation (PCI), two patients with therapeutic cranial irradiation, and three received no cranial irradiation. All patients but one were ambulatory and none were institutionalized. Fifteen patients (75%) had neurologic complaints, 13 (65%) had abnormal neurologic examinations, 12 (60%) had abnormal mental status examinations, 13 (65%) had abnormal neuropsychologic testing, and 15 (75%) had abnormal CCT scans. Compared with those given low-dose maintenance chemotherapy during PCI using 200 to 300 rad per fraction, patients who were given high-dose induction chemotherapy during the time of cranial irradiation or large radiotherapy fractions (400 rad) were more likely to have abnormal mental status examinations (6/6 v 4/9) and abnormal neuropsychologic tests (6/6 v 4/9), but no major difference in CCT findings was present. CCT scans in the majority of cases (11/18) showed progressive ventricular dilatation or cerebral atrophy up to 8 years after stopping therapy. We conclude neurologic abnormalities are common in long-term survivors of SCLC, and may be more prominent in patients given high-dose chemotherapy during cranial irradiation or treated with large radiotherapy fractions. The CCT scan abnormalities are common and progressive years after prophylactic cranial irradiation and chemotherapy are stopped.

Adult↗

Patients with small-cell lung cancer treated with combination chemotherapy with or without irradiation. Data on potential cures, chronic toxicities, and late relapses after a five- to eleven-year follow-up.

We assessed the outcome in 252 patients with small-cell lung cancer 5 to 11 years after treatment with combination chemotherapy, with or without chest and cranial irradiation, in National Cancer Institute therapeutic trials from 1973 through 1978. Twenty-eight patients (11%) survived free of cancer for 30 months or more. Fourteen patients remain alive without evidence of cancer beyond 5 years (range, 6.4 to 11.3 years), and 7 patients have returned to a lifestyle similar to that before diagnosis. The other 14 patients who were cancer-free at 30 months have developed cancer or died; 6 patients had a relapse, 4 developed or died from non-small-cell lung cancer, and 4 died of unrelated causes. A few patients with small-cell lung cancer (5.6%) may be cured. Thirty-month, cancer-free survival is insufficient to show a cure. Although late toxicities are troublesome, they do not outweigh the benefits of prolonged survival and potential for cure with modern aggressive therapy in small-cell lung cancer.

Adult↗

Cellular sensitivity to glucocorticoids in patients with POAG. Steroid receptors and responses in cultured skin fibroblasts.

The question of a generalized hypersensitivity to corticosteroids in primary open-angle glaucoma (POAG) was investigated using cultured skin fibroblasts from patients with POAG and age-matched controls. Nuclear binding of (3H)-dexamethasone was performed to evaluate possible changes in the glucocorticoid receptors. Cortisol effects on (3H)-thymidine uptake into the cells were investigated as a measure of the cellular sensitivity to corticosteroids. When POAG and control groups were compared, no significant differences (P less than 0.05) were found for either the number or affinity of glucocorticoid receptors (POAG: Kd = 6.1 +/- 1.0 nM, Rt = 94 +/- 13 sites/cell X 10(3); control: Kd = 5.5 +/- 1.6 nM, Rt = 124 +/- 20 X 10(3) sites/cell) or for cortisol effects on thymidine uptake (POAG: C50 = 83 +/- 38 nM; control: C50 = 80 +/- 34 nM). Use of epidermal growth factor (EGF) resulted in an increased steroid sensitivity in some cell lines, but again no differences between POAG and control groups were detected. These results suggest that a generalized cellular hypersensitivity to glucocorticoids is not intrinsic to POAG. It is possible that environmental alterations and/or endogenous factors may influence the steroid responses observed in these patients.

Adult↗

Maturation of Rb+ and PAH accumulation by rabbit anterior uvea and choroid plexus.

In vitro accumulation of radioactive para-aminohippuric acid (3H-PAH) and rubidium (86Rb+) by the anterior uvea, ciliary processes, and the choroid plexus was evaluated in tissues from newborn and various aged rabbits. Accumulation of PAH was present in the anterior uvea at 1 day of age (tissue to media ratio, T/M, of 2.1 +/- 0.2) and remained at this level for the first 14 days of life. Accumulation did not rise to adult levels until 21 days of age (T/M 5.5 +/- 0.6). Rubidium accumulation in the anterior uvea, a measure of Na+, K+-pump activity, was higher than adult values 6 hr after birth (T/M25.2 +/- 0.9). Activity remained elevated through day 28 and did not fall to adult levels until day 60 (T/M 13.4 +/- 0.6). Accumulation studies on isolated ciliary processes were similar to those obtained from anterior uveal tissue. Daily subcutaneous injections of penicillin (300,000 units/kg/day) for 1 week had no effect on anterior uvea PAH accumulation (penicillin T/M was 1.7 +/- 0.1 and saline control T/M was 2.0 +/- 0.2). Accumulation of either 3H-PAH or 86Rb+ by the choroid plexus was present 1 day after birth in amounts that were similar to adult values and did not change during the 90 days of testing.

Aminohippuric Acids↗

Limbus- v fornix-based conjunctival flap in trabeculectomy. A long-term randomized study.

The safety and success rates of trabeculectomy using fornix-based or limbus-based conjunctival flaps were investigated in a randomized, prospective study. Patients with phakic eyes and uncontrolled primary open-angle glaucoma had a trabeculectomy with either a standard limbus-based conjunctival flap (18 eyes) or a fornix-based conjunctival flap (19 eyes). Filtration surgery was equally successful (intraocular pressure, less than or equal to 21 mm Hg) in both groups independent of the type of conjunctival flap: 17 (94%) of 18 eyes with a limbus-based flap (three eyes with additional medical therapy) and 17 (89%) of 19 eyes with a fornix-based flap (three eyes with additional medical therapy). Four eyes in the fornix-based group showed positive Seidel tests in the early postoperative period. Aqueous leakage was from the suture sites at the lateral margins of the flap and resolved spontaneously without surgical intervention. The fornix-based conjunctival flap was easier to perform, provided better surgical exposure, and was easier to close than the limbus-based flap.

Adult↗

Elevation of intraocular pressure by calcium channel blockers.

Topical administration of three different calcium channel blockers (verapamil hydrochloride, diltiazem hydrochloride, or nifedipine) increased intraocular pressure transiently in rabbits. Outflow facility and episcleral venous pressure were unchanged. Aqueous humor flow seemed to be increased 30 minutes after topical application of verapamil when estimated by the Goldmann equation or by changes in anterior chamber fluorescein-labeled dextran concentration. However, aqueous humor ascorbate concentrations and turnover of radioactive iodide did not differ from that in the untreated eye. Ocular blood volume was found to be increased after topical application of verapamil, which suggested vascular changes as a possible mechanism for the induced increase in IOP. Topical verapamil raised IOP in healthy human volunteers, but the elevation was less than observed in rabbits. Single oral doses of verapamil in rabbits or human beings had no effect on IOP.

Administration, Oral↗

Age-dependency of alpha- and beta-adrenoceptors on thrombocytes and lymphocytes of asthmatic and nonasthmatic children.

Among the possible mechanisms which may cause wheezing or asthmatic episodes a genetically determined beta-adrenoceptor blockade and a hyperresponsiveness of alpha-adrenoceptors has been postulated. Evidence to support this hypothesis stems from an increased bronchial sensitivity to beta-blockers, a reduced formation of cyclic AMP in response to beta-adrenergic stimulation and enhanced alpha-adrenergic responses in asthmatic subjects. The recent development of techniques for measuring the specific, high-affinity binding of radiolabeled alpha- and beta-adrenergic antagonists made it possible to study alpha- and beta-adrenoceptors in vitro. Based upon the assumption that a change in the number and/or affinity of adrenergic receptors might be a general phenomenon, we have performed alpha- and beta-receptor binding studies on lymphocytes and platelets from wheezing infants and asthmatic children as well as of infants, children, and adults not suffering from these diseases. Using 125[I]-cyanopindolol (ICYP) and 3[H]-yohimbine (HYOH) as highly specific ligands for alpha- and beta-adrenoceptors, the following results were obtained: Lymphocytes and platelets from control subjects and asthmatics bound similar amounts of ICYP and HYOH and thus showed no differences either in the number or the affinity of alpha- and beta-adrenoceptors. Lymphocytes and platelets of wheezing and nonwheezing infants also bound the same amounts of the radioligands. In asthmatic children receiving 4 X 2 puffs salbutamol beta-adrenoceptors were down-regulated and this may mimic beta-adrenoceptor blockade. When subjects were divided into four categories according to age (0-5, 5-10, 10-20 years, adults) the number of beta-adrenoceptor binding sites showed an age-dependent increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The effects of body immersion on aqueous humor dynamics in rabbits.

Rabbits subjected to free-floating body immersion demonstrated decreases in intraocular pressure followed by later increases. These intraocular pressure alterations were associated with parallel changes in aqueous humor production. Episcleral venous pressure was elevated during immersion but outflow facility was unaltered. The decrease in intraocular pressure could be partially blocked by pretreatment with vasopressin or desoxycorticosterone acetate. In cross-circulation studies between an immersed and non-immersed rabbit, a decrease in intraocular pressure was observed in both animals. This observation further supported the involvement of humoral factors in the body-immersion induced intraocular pressure response.

Animals↗

In vitro studies on steroid metabolism by gonadal tissues from ambisexual teleosts. I. Conversion of [14C]testosterone by males and females of the protogynous wrasse Coris julis L.

Gonadal tissue of females, and primary and secondary males of the protogynous wrasse Coris julis were incubated with labeled [14C]testosterone. The large majority of metabolic products consisted of free, neutral steroids. Marked 11 beta-hydroxylation was restricted to testes from secondary males. 5 beta-Reduction of ring A was predominant in both types of males, whereas ovarian tissue from normal females produced a larger share of 5 alpha-androstanes. The metabolic products of ovaries from females that were injected with testosterone 7 days before incubation were similar to those of untreated females, although the ratio of 5 alpha/5 beta reduced steroids was changed toward the "male type".

Acetylation↗

Intraocular pressure the day of argon laser trabeculoplasty in primary open-angle glaucoma.

Argon laser trabeculoplasty was performed in one eye of 57 phakic patients with primary open-angle glaucoma. The eyes received a mean of 78 +/- 7 treatments over 360 degrees to the anterior trabecular meshwork. The power was titrated to produce blanching without bubble formation. Increased intraocular pressure (range +1 to +22 mmHg) occurred in 30 of the 57 (53%) eyes 1 hour after treatment. Eight (14%) of these eyes had a clinically significant elevation defined by all of three criteria: (1) an intraocular pressure greater than 30 mmHg, (2) greater than a 30% increase over the mean prelaser intraocular pressure, and (3) greater than a 10 mmHg increase over the peak prelaser diurnal intraocular pressure curve. These eight patients received either oral glycerine or acetazolamide. A rebound increase in intraocular pressure requiring repeat medical treatment occurred in four of the eight eyes. Two additional eyes without a pressure elevation 1 hour after treatment showed a later elevation. This was first detected 4 hours postoperatively in one eye and 7 hours after treatment in another eye. The 1-hour postoperative measurement detected most patients with clinically significant increased intraocular pressure (8 of 10 eyes) but these required continued observation for rebound increases. Patients with advanced glaucomatous visual field loss should also be followed closely to detect late increases in intraocular pressure (2 of 10 eyes).

Adult↗

The dyskinetic cilia syndrome in childhood. Modifications of ultrastructural patterns.

The syndrome of cilia dyskinesia is known as a heterogenous ciliary dysfunction caused by morphological defects of the dynein arms, the nexin links, the radial spokes and by the transposition of microtubules. Supernumerary tubules have been regarded as acquired morphological defects on the background of other bronchopathies. The report of a 9-year-old girl with the clinical signs of ciliary dyskinesis is considered to be an attribution to the clinical and pathological features of this syndrome. The girl's history of chronic bronchopulmonary infections and nasal polyposis resistant to therapy made her suspected to be ill of Kartagener's syndrome. The results of ultrastructural investigations of the mucosa from ciliated epithelium revealed a ciliary structural defect in the bronchi as well as in the nose and the sinuses with supernumerary microtubular doublets and singles, a decentration of the central tubules and shortened dynein arms. The regularity of the electron optical abnormalities implicates a systemic disorder of ciliated epithelium, which is to be summarized to the syndrome of cilia dyskinesis.

Bronchi↗

Central effects of thyrotropin-releasing hormone and arginine vasopressin on intraocular pressure in rabbits.

Administration of either thyrotropin-releasing hormone (TRH) or arginine vasopressin (a-VP) into the rabbit third ventricle elevated intraocular pressure (IOP). IOP was increased 3.6 mmHg 45 min after TRH (10 ng/0.1 ml) administration and increased 6.4 mmHg 45 min following delivery of a-VP (5 micrograms/0.1 ml). Outflow facility and episcleral venous pressure were not altered by either agent. Estimated aqueous humor flow 45 min after third ventricle administration was increased 66% after TRH and 91% after a-VP delivery. Posterior chamber aqueous humor ascorbate was reduced 60 min after TRH administration. Pretreatment with either systemic or topical atropine prevented the TRH or a-VP induced increase in IOP. Body temperature (BT), which was unaltered after TRH administration, was elevated by third ventricle delivery of a-VP. The a-VP induced increase in BT was blocked by systemic pretreatment with either indomethacin or atropine.

Animals↗

[Pulmonary dysplasia in infancy. Pathogenesis, pneumologic course studies and therapy possibilities].

Some premature and mature newborns who require intermittent positive airway pressure (IPPV) and high oxygen concentrations for respiratory distress syndrome develop characteristic damage of bronchi and bronchioles termed broncho-pulmonary dysplasia (BPD). According to the radiographic findings the changes are categorized into four progressive stages. Stage 1 describes a radiographic feature with a pattern of fine, faint granularity as it is characteristic for the hyaline-membrane-syndrome. Stages 2 to 4 represent diffuse interstitial emphysema, a bubbly appearance of the lung, atelectasis and a progressive fibrosis. Electronmicroscopic investigations of bronchial imprints could demonstrate a rarefication of the cilia and a ciliary damage which took the form of compound cilia. In addition, a marked increase of goblet cells in the bronchial mucosa as well as a metaplasia of the epithelial cells was present. These findings may be a prerequisite for chronic infections, and perpetuate a cycle which may result in chronic obstructive airway disease. The significance of bronchial and bronchiolar injury in children with BPD is said to be due to IPPV, high inspiratory oxygen concentrations, high fluid intake, vitamin E deficiency or an increased intrapulmonary pressure secondary to a patent ductus arteriosus. When pulmonary mechanics were measured in a baby-body-plethysmograph a high pulmonary resistance and a low dynamic compliance occurred at the first investigation after IPPV or oxygen administration. On re-examination there was a strong tendency to normalisation of x-ray findings and pulmonary mechanics, depending upon the time which elapsed between ventilation and re-examination. Current therapy has to be symptomatic and may include secretolytics, glucocorticoids and bronchodilators. The preventive interventions have to take into consideration ventilation techniques, restrictions in O2 and fluid intake.

Bronchi↗

Serum cortisol concentrations in gilts and sows housed in tether stalls, gestation stalls and individual pens.

Three experiments were conducted to determine whether housing in tether stalls, gestation stalls or individual pens imposes a stress upon gilts and sows. Changes in serum cortisol concentrations were used as the indicator for stress. In the first experiment, gilts were placed in tether stalls and individual pens to determine cortisol concentrations after tethering and to see if this response was different from gilts that were previously tethered for two weeks. In the second experiment, gilts were tethered in order to determine if penning in tether stalls altered the circadian rhythm of cortisol. In the third experiment, breeding sows were placed in tether stalls, gestation stalls or individual pens to determine if a ten-hour profile of cortisol concentrations were altered and if such housing affected a sow's response to transfer to farrowing crates. The results indicate that the initial response to tethering varied among gilts and sows and this variation appeared to be due to previous penning and human handling experiences. When tethering was stressful, acclimation required up to four days. However, once acclimated, tethering resulted in higher morning concentrations which may be associated with the greater activity that occurs at this time. Housing in tether stalls, gestation stalls or individual pens was not a stress for breeding sows and did not alter sows' responses to transfer into the farrowing crate.

Animals↗

The relationship between pharmacodynamics and pharmacokinetics in asthmatic children receiving a sustained-release formulation of theophylline.

Pharmacodynamic response as well as serum and saliva concentrations of theophylline were monitored in 15 children under a long term theophylline treatment. Respiratory parameters, such as vital capacity and total bronchial resistance all related to bronchodilatation, were measured by use of a bodyplethysmograph. Measurements were performed before treatment and during the steady state with respect to serum levels. Due to small differences between peak and trough concentrations, no correlations between serum concentrations and respiratory parameters were found during the steady state. However, some important respiratory parameters exhibit considerable differences with respect to pretreatment values. In conclusion, one can state that during the steady state, theophylline exerts a constant influence on bronchodilatation which depends only slightly on the concentration range achieved.

Adolescent↗

Subclavian vein thrombosis in patients treated with infusion chemotherapy for advanced malignancy.

Twenty-two of 53 (42%) patients developed subclavian vein thrombosis (SVT) while receiving chemotherapy for advanced malignancy by an ambulatory pump constant infusion delivery system. The median time to thrombosis was 30 days (range, 5-270 days). Seven patients (36%) were asymptomatic and received no specific anticoagulation. Twelve patients (50%) received heparin followed by coumadin for 2 to 3 months. None of the 19 patients developed complications of the SVT. In three patients (14%), acute SVT progressed to complete or partial superior vena cava syndrome. The use of fibrinolytic therapy was successful in all three patients, and was adequate to lead to complete clinical resolution. Predisposing factors in the patient population included: (1) decreased antithrombin III levels prior to catheter insertion; (2) intrathoracic tumor, possibly creating low flow rates; and (3) improper or suboptimal home management of the catheter. The development of SVT was not related to the chemotherapeutic agent infused or the duration of therapy. The frequency of SVT in this patient population necessitates consideration of prophylactic methods in high-risk patients.

Antineoplastic Agents↗