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Biomedical subjects

D H Johnson

Publications and source records attributed to D H Johnson.

355 records · Page 20Linked to original sources

Visual responses of crayfish ocular motoneurons: an information theoretical analysis.

Motoneuron responses were elicited by global visual motion and stepwise displacements of an illuminated stripe. Stimulus protocols were identical to those used in previous behavioral studies of compensatory eyestalk reflexes. The firing rates and directional selectivity of the motoneuron responses were measured with respect to four stimulus dimensions (spatial frequency, contrast, angular displacement and velocity). The directional selectivity of the motoneuron response was correlated to the previously measured gain of the reflex for each stimulus dimension. The information theoretical analysis is based upon Kullback-Leibler (K-L) distances which measure the dissimilarity of responses to different stimuli. K-L distances for single neurons are strongly influenced by the mean rate difference of the responses to any pair of stimuli. Because of redundancy, the joint K-L distances of pairs of neurons were less than the sum of the K-L distances of the individual neurons. Furthermore, the joint K-L distances were only weakly influenced by correlations among coactivated neurons. For most of the stimulus dimensions, the K-L distances of single motoneurons were not sufficient to account for the stimulus discriminations exhibited by the eyestalk reflex which typically required the summed output of 2 to 5 motoneurons. Thus the behaviorally relevant information is encoded in the motoneuron ensemble. The minimum time required to discriminate the direction of motion (the encoding window) for a single motoneuron is about 380 to 480 ms (including a 175 ms response latency) for stepwise displacements and up to 1.0 s for global motion. During this period a motoneuron fires 2 to 3 impulses.

Action Potentials↗

Effect of preemptive multimodal analgesia for arthroscopic knee ligament repair.

BACKGROUND AND OBJECTIVES: Administration of analgesic medication before surgery, rather than at the completion of the procedure, may reduce postoperative pain. Similarly, administration of multiple analgesics, with different mechanisms of action, may provide improved postoperative pain control and functional recovery. The purpose of our study was to compare pain scores and intravenous opioid consumption after outpatient anterior cruciate ligament (ACL) reconstruction in patients who received a multimodal drug combination (intravenous [IV] ketorolac, intra-articular morphine/ropivacaine/epinephrine, and femoral nerve block with ropivacaine) either before surgery or immediately at the completion of the surgical procedure. METHODS: Forty patients presenting for same-day arthroscopic ACL repair using a semitendinosis tendon graft were included in this study. The patients were randomized to receive the following drugs either 15 minutes before skin incision or immediately after skin closure: (1) Ketorolac 30 mg IV. (2) Intra-articular injection of 20 mL ropivacaine 0.25% + morphine 2 mg and epinephrine 1:200,000. (3) Femoral nerve block with 20 mL ropivacaine 0.25%. Verbal pain scores were obtained in the postanesthesia care unit (PACU) and on postoperative days 1, 3, and 7. IV patient controlled analgesia (PCA) morphine consumption in the PACU was also recorded. RESULTS: Verbal pain rating scores were lower in group I (preemptive) for 2.0 hours after arrival in the PACU. There was no difference between groups in pain scores on postoperative days 1, 3, and 7. Mean IV PCA morphine consumption in the PACU was lower in group I (6.4 mg) versus group II (12.3 mg), P <.05. CONCLUSION: Preemptive, multimodal administration of our 3-component analgesic drug combination resulted in lower pain scores during the initial stay in the PACU unit and lower consumption of IV PCA morphine in the PACU. However, pain scores were similar in both groups on postoperative days 1, 3, and 7; thus, there was no measurable long-term advantage associated with preemptive multimodal drug administration.

Adult↗

Lazaroids--not nitric oxide synthetase inhibitors--improve hemodynamics after thermal injury in anesthetized guinea pigs.

Our objective was to study the effects of a lipid peroxidation inhibitor (U74389G) and nitric oxide synthetase inhibitor (NG-methyl-L-arginine) on hemodynamic stability in burn shock. The design was a prospective, placebo control, randomized, and masked multigroup study in a research laboratory of a university hospital. We used 24 guinea pigs (N = 24), and induced burn shock by a scalding thermal injury (75 degrees C) to 35% of their body surface area. Hemodynamics and gas exchange were observed for 90 minutes after the burn injury in the four groups: no burn, burn-control, burn-U74 (10 mg/kg U74389G), and burn-LNMA (20 mg/Kg NG-methyl-L-arginine). The percentage of mean arterial pressure, normalized for the initial value at 30 minutes after the burn injury, decreased in all groups over time but was not significantly different in any group. The normalized percentage of flow also decreased over time in all groups with the slope of the linear regression significantly less in the burn-U74 group (-0.32 95% CI, -0.05, -0.15) and the no burn group (-0.37 95% CI, -0.48, -0.26), compared with the burn-control group (-0.66 95% CI, -0.77, -0.56) and the burn-LNMA group (-0.66 95% CI, -0.77, -0.56). The slope of the linear regression for the normalized percentage of systemic vascular resistance was significantly more marked in the burn-control group (2.45 95% CI, 1.35, 3.54) and the burn-LNMA group (1.22 95% CI, 0.89, 1.55) compared with the no burn group (0.16 95% CI, 0.11, 0.44) or the burn-U74 group (0.34 95% CI, 0.06, 0.74). The burn shock resulted in hemodynamic instability as measured with increased systemic vascular resistance, decreased cardiac output, and mean arterial pressure. Use of a lazaroid (U74389G), not a nitric oxide synthetase inhibitor (NG-methyl-L-arginine), altered the clinical course after thermal injury. These data suggest the importance of lipid peroxidation and free radicals as secondary mediators in the evolution of burn shock.

Analysis of Variance↗

The effects of U-74389G, a 21-aminosteroid, on pulmonary vascular resistance after a scald.

We tested U-74389G (C37H50N6O2-CH4O4), a 21-aminosteroid, to determine whether it ameliorates the pulmonary vascular effects of a surface scald. We studied 24-anesthetized rabbits mechanically ventilated with 100% and then 13% O2. Twelve rabbits received a scald (75 degrees C water applied to the shaved ventral surface for 90 seconds), and 12 served as control (20 degrees C water). Six control and six scalded animals additionally received U-74389G (5 mg/ kg intravenously). We measured hemodynamics and blood gases prescald, 30 minutes postscald, and 30 minutes after U-74389G or placebo administration. The strength of hypoxic pulmonary vasoconstriction (HPV) was assessed as the difference between pulmonary vascular resistance measured during 13% O2 ventilation and during 100% O2 ventilation. Hemodynamics and gas exchange were similar between groups. The strength of HPV was significantly diminished postscald, but U-74389G treatment restored HPV to baseline values. We conclude that a scald reduces the strength of HPV, and the response to U-74389G suggests this may be mediated by free radicals.

Animals↗

Parents' resources and home management of the care of chronically ill infants.

PURPOSE: To identify resources of parents or primary caretakers who managed chronically ill infants at home and to determine psychometric properties of Home Care Resources Inventory (HCRI). DESIGN: Cross-sectional, descriptive SETTING: Outpatient clinics. PARTICIPANTS: Parents or primary caretakers (N = 100) of chronically ill infants who were discharged from hospital at least one week; 93% of sample were mothers; infants' ages ranged from 1-22 months. MAIN OUTCOME MEASURES: HCRI, the Spielberger State Anxiety Inventory, and a demographic questionnaire. RESULTS: Parents reported strong resources in the area of support and inconsistent resources in areas of coping, time, and respite. The HCRI has acceptable psychometric properties. CONCLUSIONS: Identifying resources, especially personal time and respite, is essential for successful home management of chronically ill infants. The HCRI can be used to pinpoint areas that are strong or weak in the two resource areas measured.

Adaptation, Psychological↗

Ultrastructural localization of collagen IV, fibronectin, and laminin in the trabecular meshwork of normal and glaucomatous eyes.

PURPOSE: To determine whether differences in the ultrastructural characteristics or composition of the basement membranes of the trabecular lamellae and Schlemm's canal exist in normal eyes and eyes with primary open-angle glaucoma (POAG). Basement membranes play key roles in the attachment of the overlying trabecular cells and Schlemm's canal cells. METHODS: Electron microscopy used in conjunction with immunogold labeling was used to examine the ultrastructure of the basement membranes in the trabecular meshwork and to determine the presence of collagen IV, laminin, and fibronectin in 6 normal eyes and 6 eyes with POAG. To determine which cells in the meshwork synthesized these molecules in situ hybridization was studied in an additional 8 normal eyes. RESULTS: No distinctive ultrastructural changes were found in the basement membranes of glaucomatous eyes, whether early or advanced disease, when compared with normal eyes. Label for all three proteins was present in the basement membranes of the trabecular lamellae, Schlemm's canal, and in scattered patches within the juxtacanalicular tissue. Laminin and fibronectin were most abundant in the periphery of the sheath material surrounding the elastic tendons in the juxtacanalicular tissue. In contrast to previously published light microscopic studies, no increase in fibronectin was found in glaucoma. Regions of the basement membrane of the canal underlying giant vacuoles were similar to regions without giant vacuoles in both appearance and labeling. In situ hybridization revealed that mRNA for all three proteins was present in most trabecular cells throughout the meshwork; no regional differences in cellular labeling within were observed. CONCLUSION: The ultrastructural characteristics and immunogold labeling of basement membranes were similar in normal and glaucomatous eyes; no additional structures were labeled in POAG eyes that were not also labeled in normal eyes. Label of the patches of amorphous fibrogranular material within the juxtacanalicular tissue suggests it is basement membrane in origin, while the sheath material which is known to accumulate in POAG was not heavily labeled and does not appear to be basement membrane in origin.

Aged↗

5-Fluorouracil simultaneously maintains methotrexate antineoplastic activity in human breast cancer and protects against methotrexate cytotoxicity in human bone marrow.

High-dose methotrexate (MTX) cytotoxicity is maintained in MCF-7 breast cancer cells but reduced in Hs824.T human bone marrow by a priming and nontoxic 5-fluorouracil (5-FU) dose. When MCF-7 breast or Hs824.T bone marrow cells are incubated with 10 microM 5-FU and 10 microM MTX for 48 h, the growth rates of breast cancer cells were 97.59 +/- 0.97% and 21.81 +/- 3.33% of the control rate, respectively, and the growth rates of bone marrow cells were 90.61 +/- 3.71% and 29.58 +/- 2.99% of the control rate. The combinations of 5-FU 2 h prior to MTX or MTX 2 h prior to 5-FU followed by a 48 h incubation, respectively, gave growth rates of 20.96 +/- 2.44% and 19.86 +/- 2.56% of the control rate for MCF-7 cells. In bone marrow cells, the combinations of 5-FU 2 h prior to MTX or MTX 2 h prior to 5-FU followed by a 48 h incubation, respectively, gave growth rates of 79.66 +/- 7.41% (protection) and 31.39 +/- 1.77% of the control rate. Similar patterns to bone marrow emerges in platelets. These studies suggest that: a) MTX and 5-FU combination on the growth of human MCF-7 breast cancer cells is independent of sequence; and b) a priming-dose of 5-FU will protect bone marrow from MTX cytotoxicity but not breast cancer cells. Therefore, a priming and non-toxic dose of 5-FU and MTX may have maximum antineoplastic activity while at the same time provide protection to the hematopoietic system.

Animals↗

Selectivity in human breast cancer and human bone marrow using trimetrexate in combination with 5-fluorouracil.

The growth inhibitory effect of trimetrexate (TMQ) is maintained in MCF-7 breast cancer but is decreased in Hs 824.T human bone marrow cells by a priming- and non-toxic 5-fluorouracil (5-FU) dose. Incubation of MCF-7 breast cells with 10 microM TMQ alone or in combination with 10 M 5-FU (TMQ 2 h prior to 5-FU [TMQ/5-FU] or 5-FU 2 h prior to TMQ[5-FU/TMQ]) resulted in similar inhibitory effects but dissimilar effects occurred in Hs 824.T bone marrow. In breast cancer, the percentage differences among TMQ and TMQ/5-FU, TMQ and 5-FU/TMQ, and TMQ/5-FU and 5-FU/TMQ on growth rates, respectively, were 3.56%, 2.35%, and 1.68%. The percentage differences on growth rates of TMQ and TMQ/5-FU, TMQ and 5-FU/TMQ, and TMQ/5-FU and 5-FU/TMQ in bone marrow, respectively, were 5.76%, 30.03% (significant protection by 5-FU, i.e. the inhibitory effect of 5-FU/TMQ < or = TMQ), and 35.78% (sequence dependent). The growth rates of breast cancer and bone marrow cells in the presence of 5-FU were 96.03 +/- 1.17% and 94.59 +/- 1.15%, respectively, of control rates. These studies suggest that (a) TMQ and 5-FU combinations on the growth of MCF-7 breast cancer cells are independent of sequence of administration and best related to TMQ and (b) a priming- and non-toxic 5-FU dose protects against TMQ toxicity in human bone marrow while not affecting the maximum inhibitory effect of TMQ in breast cancer.

Antimetabolites, Antineoplastic↗

Sequence-dependent antagonism between tamoxifen and methotrexate in human breast cancer cells.

High-dose methotrexate (MTX) cytotoxicity is decreased in MCF-7 breast cancer cells when the chemoendocrine agent tamoxifen (TAM) is given to cells 24 hours prior to MTX (early TAM). However, when breast cancer cells are exposed to TAM 24 hours after MTX (delayed TAM), MTX cytotoxicity is enhanced by TAM. The growth of cells exposed to 10 microM TAM and 10 microM MTX alone or in combination with early TAM plus MTX had the following order: TAM > TAM (early) + MTX > MTX. The percentages of control rates for TAM, MTX, and TAM (early) + MTX are 74.71 +/- 1.36%, 22.13 +/- 2.76%, and 38.17 +/- 2.75%, respectively. The inhibitory sequence from cells exposed to MTX + TAM (delayed TAM), MTX and TAM alone is MTX + TAM (delayed TAM) > MTX > TAM; and the percentages of control rates were 16.87 87% (MTX + TAM [delayed TAM]), 25.92 +/- 2.14% (MTX), and 54.08 +/- 14.79% (TAM). These studies suggest that: (a) the interactions between TAM and MTX are sequence-dependent; (b) TAM antagonizes the effect of MTX when TAM administration precedes MTX; and (c) TAM enhances the effect of MTX when TAM administration follows MTX.

Antineoplastic Combined Chemotherapy Protocols↗

Cisplatin, vinblastine, and bleomycin in the treatment of metastatic melanoma: a phase II study of the Southeastern Cancer Study Group.

Fifty-one patients with metastatic melanoma were treated with cisplatin, vinblastine, and bleomycin. Of the 50 evaluable patients, 11 (22%) achieved an objective response, including three complete (6%) and eight partial (16%) responses. Four of the 11 responding patients had previously received dacarbazine; the remaining patients had received no prior chemotherapy. Responses were noted in cutaneous and lymph node sites as well as visceral metastases. However, with one exception, all responding patients with visceral involvement had lung metastases. Response durations were brief and toxicity was substantial. Nadir leukocyte counts less than 0.5 X 10(9)/L occurred in 28% of the patients. Debilitating neurotoxicity, primarily paralytic ileus, and severe nausea and emesis were experienced by 24% of the patients. The combination of cisplatin, vinblastine, and bleomycin is not sufficiently beneficial to warrant its use in metastatic melanoma.

Adult↗

Effect of thoracic radiotherapy on mortality in limited small cell lung cancer. A meta-analysis of 13 randomized trials among 2,140 patients.

This meta-analysis was designed to evaluate the hypothesis that thoracic radiotherapy contributes to a moderate increase in overall survival in limited small-cell lung cancer. We collected individual data on all patients enrolled before December 1988 in randomized trials comparing chemotherapy alone with chemotherapy combined with thoracic radiotherapy. The study included 13 trials and 2140 patients with limited disease. A total of 433 patient with extensive disease were excluded. Overall, 1862 of 2103 patients who could be evaluated died; the median follow-up period for the surviving patients was 43 months. The relative risk of death in the combined therapy group as compared with the chemotherapy group was 0.86 (95 percent confidence interval, 0.78 to 0.94; P = 0.001), corresponding to a 14 percent reduction in the mortality rate. The benefit in terms of overall survival at three years (+/- SD) was 5.4 +/- 1.4 percent. Indirect comparison of early with late radiotherapy and of sequential with non-sequential radiotherapy did not reveal any optimal time for treatment. There was a trend toward a larger reduction in mortality among younger patients. In conclusion, thoracic radiotherapy moderately improves overall survival in patients with limited small-cell lung cancer who are treated with combination chemotherapy.

Age Factors↗