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Biomedical subjects

M Bishop

Publications and source records attributed to M Bishop.

At least 73 records · Page 4Linked to original sources

Estrogens and antiestrogens: actions and interactions with fluphenazine on food intake and body weight in rats.

Treatment of ovariectomized rats for 3 days with 2 micrograms estradiol benzoate (E2B), 6 micrograms ethinyl estradiol, or 1-2 mg of either of the antiestrogens nafoxidine or tamoxifen led to similar decreases in food intake, body weight gain, adipose tissue lipoprotein lipase activity, and hepatic fatty acid synthetase activity, despite their different effects on uterine growth and induction of progestin receptors in pituitary and adipose tissue. Longer-term (2 wk) treatment with tamoxifen resulted in similar transient changes in food intake and body weight gain, as did treatment with E2B. Daily administration of 50 micrograms fluphenazine (FLU) led to significant decreases in body weight, although there was no change in food intake. Concurrent administration of FLU with either E2B or tamoxifen led to additive effects on body weight and food intake change. None of the treatments had any effect on in vitro binding of [3H]tamoxifen to antiestrogen binding sites in pooled hypothalamic-preoptic area samples.

Animals↗

Hemodynamic and oxygen transport monitoring to titrate therapy in septic shock.

Traditionally, shock has been recognized or diagnosed by subjective signs and symptoms, particularly in septic shock, where transition from localized to systemic infection and then to septic shock may be gradual and subtle. Management has been directed toward normalizing these subjective symptoms as well as BP, heart rate, urine output, hematocrit, central venous pressure, and blood gases. The major problem is that restoration to normal values of these secondary aspects of shock do not correct the underlying tissue perfusion defect. The aim of this review is to describe a physiologic mechanistic model based on the concept that uneven vasoconstriction and maldistribution of flow are directly related to tissue hypoxia, oxygen debt, shock, shock-related organ failure, and death; second, to show that titration of therapy to optimal physiologic end-points using hemodynamic and oxygen transport monitoring is a potentially cost-effective therapeutic approach. This physiologic approach is based on the hypotheses that: a) the physiologic patterns of high-risk postoperative and septic survivors are significantly different from septic nonsurvivors; b) tissue perfusion can be evaluated by the sequential patterns of cardiac index, oxygen delivery (DO2), and oxygen consumption (VO2) measurements; c) the observed increased cardiac index and DO2 in the survivors are compensations that improve tissue oxygenation, which is reflected by the VO2 pattern; and d) the supranormal values that were documented in survivors provide objective physiologic criteria for therapeutic goals. The data suggest that a mechanistic analysis of the pathogenesis of shock may be elucidated by temporal patterns of the nonsurvivors' physiologic variables. That is, the predictive indices calculated for each variable quantitatively reflect the relationship of the early changes leading to death or survival. In essence, early changes in those variables statistically related to death may reflect pathogenic mechanisms, while early changes related to survival may be used as a first approximation to therapeutic goals. The application of this approach in prospective, randomized trials has demonstrated that prompt attainment of optimal goals (empirically defined from survivors' patterns) improved outcome in postoperative shock with and without sepsis, as well as in medical sepsis and accidental trauma. Specifically, when the optimal values of cardiac index, DO2, and VO2 used as therapeutic goals were attained in 8 to 12 hrs, there was marked and significant reduction in mortality and morbidity rates. This finding was also confirmed in 12 prospective, controlled trials, four of which were randomized. We conclude that driving septic shock patients into the survivors' patterns improves outcome, as has been shown in other shock syndromes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Laparoscopic hysterectomy: how should it be done?

A laparoscopic hysterectomy technique is described using standard acceptable surgical technique, and with the primary tool being the Multifire Endo-GIA 30 stapler (U.S. Surgical Corp., Norwalk, CT, U.S.A.). Unlike the use of electrosurgical desiccation, use of this stapler provides a safe and effective method that can be used by all laparoscopic surgeons.

Adolescent↗

Prospective trial of supranormal values as goals of resuscitation in severe trauma.

We prospectively tested the effect of the early postinjury attainment of supranormal values of cardiac index (> or = 4.52 L/min per square meter), oxygen delivery (> or = 670 mL/min per square meter), and oxygen consumption (> or = 166 mL/min per square meter) on outcome in traumatized patients with an estimated blood loss of 2000 mL or more. The goals in control patients were to attain normal values for all hemodynamic measurements. During the 6-month period, 33 protocol patients and 34 control patients with similar vital signs, estimated blood losses, and severity of injuries were enrolled in the study. Eight (24%) protocol patients died, while 15 (44%) control patients died. The protocol patients had fewer mean (+/- SEM) organ failures per patient (0.76 +/- 1.21 vs 1.59 +/- 1.60), shorter stays in the intensive care unit (5 +/- 3 vs 12 +/- 12), and fewer mean days requiring ventilation (4 +/- 3 vs 11 +/- 10) than did the control patients (P < .05 for each). We conclude that attaining supranormal circulatory values improves survival and decreases morbidity in the severely traumatized patient.

Adolescent↗

Acute venous thrombosis. Therapeutic choices for superficial and deep veins.

Superficial thrombophlebitis is common in varicose veins or veins that have undergone trauma from catheters or intravenous medications. Pain and tenderness, warmth, and erythema are diagnostic features. A compression bandage and nonsteroidal antiinflammatory agent are often all that is required for treatment. Deep vein thrombosis occurs in veins beneath the deep fascia of the leg or in the pelvis or abdomen. It is often asymptomatic but must be treated to prevent pulmonary embolization and postthrombotic syndrome. Standard therapy is administration of heparin sodium for 5 days, followed by tapering and discontinuation. Warfarin sodium (Coumadin, Panwarfin, Sofarin) is sometimes given simultaneously. Longer courses of anti-coagulation therapy are necessary in patients with an ongoing risk of recurrence.

Acute Disease↗

Anti-CD33 monoclonal antibody and etoposide/cytosine arabinoside combinations for the ex vivo purification of bone marrow in acute nonlymphocytic leukemia.

Pharmacologic and immunologic methods of ex-vivo bone marrow (BM) purging for acute nonlymphocytic leukemia (ANLL) were combined to augment the effect of either method alone. Etoposide (VP16; 20 to 30 micrograms/mL) with or without cytosine arabinoside (Ara C; 10 mg/mL) was used in tandem with the anti-CD33 monoclonal antibody (MoAb), MY9, chosen because CD33 is found on the stem cell pool in the majority of patients with ANLL. The agents were tested singly or sequentially, with a 1-hour incubation of the drugs preceding complement-mediated lysis using MY9. VP16 combined with Ara C killed up to 3.9 +/- 0.3 and 5.11 +/- 0.4 logs of the human ANLL cell lines HL60 and K562 at drug concentrations that killed only 1.2 +/- 0.1 logs of normal committed granulocyte/macrophage stem cells (CFU-GM). Adding a single exposure of the MY9 and complement (C') to the drug-treated cells, greater than 5.4 logs of HL60 were killed. Similar to other pharmacologic agents, no differential kill for clonagenic leukemic cells (colony-forming unit-leukemia; CFU-L) from patients with ANLL was seen for drug only treated blasts versus normal CFU-granulocyte-macrophage (CFU-GM), with less than 1 log CFU-L kill at drug concentrations that spared 1 log of CFU-GM. Similarly, only 1.1 +/- 0.3 logs of ANLL CFU-L were eliminated using MY9 and C'. However, with the sequential VP16/Ara C----MY9 + C' treatment, synergy was demonstrated and 2.6 +/- 0.3 logs of CFU-L were eliminated. Because CD33 is also found on the normal CFU-GM pool, two-stage long-term BM cultures were performed to determine pluripotent stem cell elimination by the drug/MoAb purging combination. No difference of CFU-GM or BFU-E production at 4 to 6 weeks of culture for VP16/Ara C, MY9 + C', or VP16/AraC----My9 + C' treated cells was seen compared with untreated controls indicating sparing of early progenitor cells. Sequential ex vivo treatment of human ANLL CFU-L with VP16/Ara C followed by complement-mediated lysis using MY9 synergistically kills CFU-L while sparing early normal hematopoietic progenitor cells, and thus may be a more effective way to purge BM than either alone.

Antibodies, Monoclonal↗

Natural history of thyroid abnormalities: prevalence, incidence, and regression of thyroid diseases in adolescents and young adults.

PURPOSE: This study reports the prevalence, incidence, and regression of thyroid abnormalities in a population observed from adolescence to adulthood. PATIENTS AND METHODS: Examinations for thyroid abnormalities were performed in 4,819 school-age children, ages 11 to 18, in 1965 to 1968; two thirds of this original cohort (3,121) were re-examined 20 years later (1985 to 1986). Each subject with a thyroid abnormality detected by physical examination was studied by means of a series of re-examinations, and tests of thyroid function, imaging, and biopsy to determine the exact nature of the thyroid abnormality. RESULTS: In the initial examinations (1965 to 1968), 185 thyroid abnormalities were found (3.7%). Diffuse hypertrophy with normal function (adolescent goiter) was the most common abnormality (19.3/1,000); 12.7/1,000 had chronic lymphocytic thyroiditis, and 4.6/1,000 had thyroid nodules, including two papillary carcinomas. Hyperthyroidism or hypothyroidism was found in 1.9/1,000. In the follow-up examinations in 1985 to 1986, 298 subjects had thyroid abnormalities (10.5%), of whom 81 (28.7/1,000) had simple goiters, 145 (51.3/1,000) had chronic thyroiditis, 45 (15.9/1,000) had hypothyroidism, 11 (3.9/1,000) had hyperthyroidism, and 66 (23.2/1,000) had nodules, which included 10 carcinomas. Of the 92 subjects with simple or adolescent goiter in 1965 to 1968, 60% were normal by 1985 to 1986, 20% were unchanged, and a few had developed thyroiditis (10%) or colloid goiters (3.0%). Of 61 subjects with thyroiditis, 27% had become normal, 33% remained unchanged, and 33% had become hypothyroid. Of the 22 subjects with thyroid nodules, two had complete disappearance of the nodules, and three had nodules considered to be variants of normal. The others exhibited a variety of nodular pathologic conditions. CONCLUSIONS: The natural history of thyroid disorders, including simple goiter, chronic thyroiditis, hyperthyroidism, hypothyroidism, and nodular diseases of the thyroid, indicates they are dynamic and changeable in form, function, appearance, and disappearance.

Adolescent↗

Evaluation of a comprehensive algorithm for blunt and penetrating thoracic and abdominal trauma.

The objective was to develop a single branched-chain decision tree for both blunt and penetrating thoracic and abdominal trauma and to test its feasibility to track clinical decisions. The algorithm consisted of 14 specific patient management loops and 31 decision nodes. During a 4-month period, the management decisions and clinical course of 434 trauma patients were prospectively observed. Thirty-four patients had no signs of life on arrival to the emergency department (ED) and were excluded from the statistical evaluation; the remaining 400 patients constituted the study group. The mean Injury Severity Score (ISS), Penetrating Abdominal Trauma Index (PATI), and Trauma Score (TS) scores in the series were 21 +/- 10, 34 +/- 12, and 13 +/- 3. The overall patient mortality of the study group was 17 per cent; it was 61 per cent in those patients with major deviations from the algorithm and 6 per cent in patients who complied with the algorithm. The ISS, PATI, and TS scores were 29 +/- 9, 32 +/- 12, and 13 +/- 2 in patients with deviations and 20 +/- 10, 37 +/- 12, and 14 +/- 2 in patients who complied with the algorithm. Of the 37 patients who died with major deviations from the algorithm, the deviation was directly contributory to death in 21 cases (57%) and probably contributory in another 14 cases (38%). There were 108 patients with ISS scores between 20 and 50. In this group, mortality was 55 per cent when a major deviation occurred and 5 per cent without major deviations from the algorithm. The authors conclude that the survival of trauma patients may be improved by following the specific management criteria outlined by the algorithm.

Abdominal Injuries↗

Evaluation of a blunt and penetrating trauma algorithm for truncal injury.

The authors objective was to develop and test a single branch-chain decision tree for blunt and penetrating truncal injury. Over the 4-month study period there were 979 patients evaluated in the emergency department; 674 of these patients were admitted to the hospital. Thirty-four (5%) of the 674 admitted patients died of truncal injury. The study group consisted of 239 of the most severely injured patients; 41 of these (17%) died. Of the 44 patients managed with major deviations from the algorithm, 27 (61%) died. Only 14 of the 195 patients (7%) whose management complied with the algorithm died. The authors conclude that following the specific management criteria outlined by the algorithm may improve the survival of severely traumatized patients.

Abdominal Injuries↗

Cohort study of thyroid disease near the Nevada Test Site: a preliminary report.

The atmospheric testing of nuclear weapons in Nevada beginning in 1951 resulted in exposure of regions surrounding the Nevada Test Site (NTS) to fallout. A cohort of children born between 1947 and 1954 in two counties near the NTS, one in Utah and one in Nevada (UT/NV), were examined in 1965-1968 for thyroid abnormalities that might have been a result of exposure to radioiodine in fallout. The prevalence of thyroid abnormalities in these children (11-18 y) was compared to that in a control group selected from a county in Arizona (AZ) that was presumed to have received little or no fallout from the NTS. Thyroid nodules were found in 76 of the 4,819 children examined (15.8/1000). Of the 76 thyroid nodules, 22 were diagnosed as neoplasms. The rate of thyroid neoplasms among the UT/NV subjects was higher (5.6/1000) than among the AZ subjects (3.3/1000) (RR = 1.7), but because the number of neoplasms was small, the difference was statistically insignificant. In 1985-1986, 3,122 of the original study subjects were reexamined. In this reexamination, thyroid nodules were found in 125 individuals (44.2/1000). Of the 125 thyroid nodules detected during this later study period, 65 were considered to be thyroid neoplasms. Rates of thyroid neoplasms in UT/NV (24.6/1000) are again slightly higher than in AZ (20.2/1000) (RR = 1.2), but the difference is not significant (p = 0.65). Based on the rates of thyroid neoplasms in the two geographic locations, we conclude that living near the NTS in the 1950s has not resulted in a statistically significant increase of thyroid neoplasms in subjects from UT/NV when compared with subjects of the same age and gender living in AZ.

Adolescent↗

Bronchial circulation in pulmonary artery occlusion and reperfusion.

Obstruction of pulmonary arterial blood flow results in minimal biochemical and/or morphological changes in the involved lung. If the lung is reperfused, a syndrome of leukopenia and lung edema occurs. We used the radiolabeled microsphere technique to measure the response of the bronchial circulation in rabbits to acute pulmonary artery occlusion (PAO) and to pulmonary artery reperfusion. We found that the bronchial blood flow (Qbr) decreased from a base line of 0.37 +/- 0.10 to 0.09 +/- 0.04 (SE) ml.min-1.g dry lung-1 (P less than or equal to 0.05) after 4 h of PAO. In a separate group of animals, Qbr 24 h after PAO remained low (0.20 +/- 0.07 ml.min-1.g dry lung-1, P = 0.06). Qbr during PAO was inversely correlated with the wet-to-dry ratio after reperfusion (r = -0.68, P = 0.06). Qbr did not change during 4 h of reperfusion. We speculate that a critical level of Qbr may be necessary during PAO to prevent ischemia/reperfusion injury from occurring.

Animals↗

Dual lineage of astrocytomas.

Experimental observations suggest that type 1 and type 2 astrocytes have distinct lineages distinguished, respectively, by the absence or presence of the A2B5 antigen. To investigate the hypothesis that the strikingly different biological behaviors of low-grade and high-grade astrocytomas might be related to cell lineage, 38 astrocytomas (grades I through IV), were examined for the presence of the A2B5 antigen, glial fibrillary acidic protein (GFAP), and galactocerebroside (GC), a marker for oligodendrocytes. Twenty-nine of the tumors (76%) were composed of moderate or high densities of GFAP+ and unlabeled cells, and were devoid of A2B5+ and GC+ neoplastic cells. Only four tumors had high densities (75% to 100%) of A2B5+ cells, three of which were grade I tumors; two tumors, also Grade I, contained moderate densities (20% to 25%) of GC+ cells that had cytologic features of astrocytoma or oligodendroglioma. The findings suggest that most cerebral astrocytomas lack the A2B5 antigen and thus may represent neoplasia along the type 1 astrocyte lineage. In contrast, A2B5+ lineage among astrocytomas, ie, neoplasia with differentiation toward type 2 astrocytes and GC+ oligodendrocytes, is less common and may be correlated with prognostically favorable histopathologic features.

Adult↗

Human granulocyte activity against moxalactam-induced filamentous forms of Pseudomonas aeruginosa.

The purpose of this investigation was to study the kinetics of human granulocyte (polymorphonuclear leukocyte) phagocytosis and bactericidal activity against beta-lactam antibiotic (moxalactam)-induced filamentous bacterial forms of Pseudomonas aeruginosa. Ultrastructural observations of rod and filamentous forms of P. aeruginosa and their interaction with polymorphonuclear leukocytes are presented. Growth of P. aeruginosa 1348A in the presence of 4 micrograms of moxalactam per ml (one-fourth the MIC) resulted in filamentous forms. Phagocytosis of 75Se-radiolabeled filaments was more efficient than that of rods during the first 20 min of the assay; subsequently, phagocytosis of both forms was equal. The polymorphonuclear leukocyte bactericidal activities against both forms, which were standardized to equal bacterial particle and viable-cell counts, were equivalent. Considering the greater size and mass of filaments compared with those of rods, we concluded that filaments are more susceptible to both phagocytosis and killing than are bacillary forms.

Blood Bactericidal Activity↗

Respiratory load compensation in neuromuscular disorders.

First-breath ventilatory responses to graded elastic (delta E) and resistive (delta R) loads from 10 people with spinal muscular atrophy (SMA), 15 people with Duchenne muscular dystrophy (DMD), and 80 able-bodied people were compared. The SMA and DMD groups produced equal tidal volume, respiratory frequency, inspiratory duration (TI), expiratory duration, mean inspiratory airflow, and duty cycle responses to both delta E and delta R. Thus SMA (primarily a motoneuron disorder) and DMD (primarily a muscle disorder) have the same net effect on loaded breathing responses. The SMA and DMD groups failed to duplicate the normal group's short expirations during delta E, long inspirations during delta R, and thus, extended duty cycles during both delta E and delta R. The deficit in load compensation therefore was due to impaired regulation of respiratory timing (reflecting neural mechanisms) but not airflow defense (reflecting mechanical and neural mechanisms). One-fifth of the normal but none of the SMA or DMD subjects actively generated an "optimal" TI response (defined theoretically as TI greater than 160% control during large delta R and TI less than 75% control during large delta E). This lack of optimal responses, which is the same abnormality exhibited by quadriplegic people, suggests that SMA and DMD also impair human ability to discriminate between large delta R and delta E. These findings support the hypothesis that neuromuscular disorders can lead to disturbances in respiratory perception.

Adult↗

Respiratory load-compensating mechanisms in muscular dystrophy.

First-breath ventilatory responses to graded elastic and resistive loads were obtained from 15 people with Duchenne muscular dystrophy (DMD), 5 people with facioscapulohumeral MD (FSH), 3 people with Becker MD, and 3 people with limb-girdle MD. For each load tidal volumes from different individuals ranged from relatively small to comparatively large values, indicating a correspondingly wide range of end-inspiratory efforts; strong tidal volume defenders generally employed longer inspirations and higher mean inspiratory airflows than did weak tidal volume defenders; and individual frequency responses were mediated by changes in inspiratory and/or expiratory timing. Thus the loaded breathing responses of people with MD are qualitatively the same as those of quadriplegic and able-bodied people. Quantitatively, however, the DMD group generated considerably larger tidal volumes than did the FSH group during both elastic and resistive loading. These larger tidal volumes were achieved by both longer inspirations (a neurally mediated phenomenon) and higher mean inspiratory airflows (a mechanically and/or neurally mediated phenomenon). These findings, which could not be attributed to differences in respiratory motor function, suggest that there are differences between the respiratory sensory and/or central functions in the Duchenne and facioscapulohumeral types of MD.

Biomechanical Phenomena↗