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Biomedical subjects

J A Baker

Publications and source records attributed to J A Baker.

At least 73 records · Page 4Linked to original sources

Laboratory detection of primary and acquired drug resistance in human lymphatic neoplasms.

We tested the ability of the differential staining cytotoxicity (DiSC) assay to discriminate between sensitive and resistant cell populations in human lymphatic neoplasms. First, the in vitro activity spectra of the most important drugs paralleled the known clinical activity spectra of the same agents. Second, there were highly significant correlations between in vitro chemosensitivity and the results of clinical chemotherapy. Third, specimens from previously untreated patients were significantly more sensitive to the most important drugs than were specimens from patients who had previously received chemotherapy. Finally, metachronous assays performed on specimens from the same patients showed little change in chemosensitivity if there had been no intervening chemotherapy between the times that the first and second assays were performed. However, if the patients had received intervening chemotherapy between the times of the first and second assays, the specimens in the second assays tended to be significantly more resistant than were the specimens in the first assays. These data indicate that the DiSC assay may be of value in the design of strategies to circumvent drug resistance in human lymphatic neoplasms.

Antineoplastic Agents↗

A comparison of immunofluorescent assays to detect anti-granulocyte antibodies.

Three immunofluorescent assays were compared to detect anti-granulocyte antibodies (AGA) in patients with immune disorders: the granulocyte immunofluorescence test (GIFT), the avidin-biotin coupling test (ABCT), and the modified staphylococcal protein A test (MSPAT). The ABCT was more sensitive than both the GIFT and MSPAT for patient sera, but it also detected more positivity among random normal sera. Although less sensitive than the ABCT, the GIFT and MSPAT showed greater specificity and higher predictive values for positivity. When normal lymphocytes were run in parallel with normal granulocytes, 68% of positive AGA sera were nonreactive with lymphocytes, indicating the antibody specificity for granulocytes. Comparison of three direct and indirect immunofluorescent assays suggested a general co-existence of both cell-bound and circulating AGA. However, the direct test displayed minimal amounts of fluorescence for negative controls in contrast to the variable levels of fluorescence seen in normal sera for the indirect test.

Autoantibodies↗

A model lung with the capacity for simulated spontaneous breathing.

A model lung is described which can be ventilated artificially but which also has the capacity to breathe spontaneously at pre-determined rate and depth. It appears particularly suitable for studying the performance of ventilators which interact with the patient, including those with the facility for triggering, synchronization and mandatory minute ventilation. An additional facility is the blocking of a simulated spontaneous inspiration during an artificial inflation (" Hering -Breuer reflex").

Electronics↗

Comparison of the sodium dependency of uptake of meta-lodobenzylguanidine and norepinephrine into cultured bovine adrenomedullary cells.

Radioiodinated meta-iodobenzylguanidine (MIBG), a scintigraphic agent used for the detection of human pheochromocytomas, is thought to utilize the same uptake and retention mechanism(s) as norepinephrine (NE). Using cultured bovine adrenomedullary cells, we compared the mechanism(s) of uptake of MIBG to that of NE. Two different uptake systems were identified. NE and MIBG were taken up by a sodium-dependent system that was characterized by: 1) temperature dependency; 2) high affinity: Km of 1.22 +/- 0.12 microM for MIBG and 1.41 +/- 0.50 microM for NE; 3) low capacity: Vm (picomoles/10(6) cells/10 min) of 64.3 +/- 3.3 for MIBG and 36.6 +/- 7.2 for NE; 4) saturability; 5) ouabain sensitivity; and 6) energy dependency. However, NE and MIBG also were taken up by a temperature-dependent, sodium-independent, apparently unsaturable, and energy-independent system. The sodium-dependent uptake system fulfills many of the criteria for Uptake1 whereas the sodium-independent uptake system is most likely a passive diffusion process. NE uptake proceeded predominantly by the sodium-dependent process. Uptake of MIBG occurred by both pathways at low concentrations, but at high concentrations (greater than 10 microM) uptake was predominantly (75 to 100%) by the sodium-independent process. Inhibition studies suggest that MIBG and NE are transported by the same carrier involved in the sodium-dependent system. Scintiscans of the human adrenals and pheochromocytomas appear to reflect uptake of [131I]MIBG by the sodium-dependent system.

3-Iodobenzylguanidine↗

Statistical methods to predict morbidity and mortality: self assessment techniques for burn units.

The medical records of 806 adult and paediatric burn patients were retrospectively reviewed. Patient data was summarized, coded and entered in a computer for subsequent analysis. This report describes the use of multiple regression analysis to produce equations useful for the prediction of the morbidity parameters: length of hospital stay, number of transfusions required and number of operative procedures. The multiple regression equations developed are useful as prediction tools, in patient medical audit and in assessing improvements in burn care. The classical technique of probit analysis for predicting the probability of mortality was used to develop the LA50's of burn injury. These LA50's were used as the basis for comparison of survival statistics between burned patients in this series and those registered in the National Burn Information Exchange (Feller, 1979). There is an apparent significantly improved survival in the children, young adults through 34 yrs and the older adults (60-74 yrs) in the current series of patients. This observation would support the adoption of the protocol of burn care used in treating these patients. The newer technique of discriminant analysis is also described. Discriminant analysis is a multifactorial method for discriminating between dichotomous outcomes (survivors and non-survivors). The technique of discriminant scoring proved to be 95.8 per cent accurate in predicting burn survival. Use of a burn severity scoring technique will also assist in recognition of the high risk patient.

Adolescent↗

Capping of the dental pulp mechanically exposed to the oral microflora -- a 5 week observation of wound healing in the monkey.

The healing capacity of mechanically exposed and bacterially contaminated dental pulps was assessed in monkeys after capping with 2 commercial Ca(OH)2 containing compounds. One hundred eighty teeth in 7 monkeys were employed, 45 as untreated controls and 135 as treated exposures. Class V buccal cavity preparations resulting in pulpal exposure were prepared, left open to the oral cavity for 0, 1, 24 h or 7 days and employed as controls, or debrided, capped, restored with amalgam and left undisturbed for 5 weeks as treated exposures. Zero and 1 h untreated exposures presented damage from the mechanical trauma only, whereas 24 h and 7 day pulp wounds exhibited pronounced infiltrations of polymorphonuclear and mononuclear leukocytes. In addition, the 7 day exposures demonstrated several teeth with partial and total necrosis. Treated 0, 1 and 24 h exposures demonstrated wound healing, minimal pulp tissue inflammation, reorganization of soft tissue and formation of new hard tissue at the exposure site in 86 of 99 teeth. Treated 7 day exposures healed less frequently, showing signs of dentin bridging in 15 of 27 teeth. This study indicated that mechanically exposed and orally contaminated dental pulps in monkeys have a high capacity to resolve inflammation and initiate healing with new dentin formation at the exposure site when treated as described.

Animals↗

Lipid and salt effects on carbocyanine dye-induced photo-voltages in bilayer membranes.

Voltage transients induced by flash illumination of bilayer membranes with sorbed dye, 3,3' -dimethyl-2,2' -oxacarbocyanine chloride (diO-C1-3-CI), vary with membrane lipid composition and aqueous solution salt concentration. The voltage transients are probably induced by physical movements of sorbed dye molecules following photo-isomerization. Increased salt (NaCl and NaBr) concentrations in the aqueous solutions reduced the photo-voltage amplitudes by reducing the amount of dye sorbed to the membranes, and by decreasing the effective membrane thickness. The photo-voltage risetimes and falltimes varied systematically with salt concentration and membrane lipid composition, reflecting structural changes in the membrane's surface layer.

Carbocyanines↗

Ixodicidal resistance in Boophilus microplus (Canestrini) in the Republic of South Africa and Transkei.

A series of in vitro trials using unfed larvae and fully fed adult ticks confirmed ixodicidal resistance in the one-host Pantropical Blue Tick, Boophilus microplus (Canestrini). Fifty-seven of 64 field isolates were resistant to arsenic; 10 of 56 were resistant to toxaphene; 1 of 5 were resistant to lindane; 3 of 5 were resistant to dieldrin; 3 of 19 were resistant to DDT and 8 of 55 were resistant to the organophosphorus ixodicide, dioxathion. One of the field isolates resistant to dioxathion was also highly resistant to the carbamate, carbaryl, and to the organophosphorus ixodicides benoxophos and diazinon. A second was resistant to the organophosphorus ixodicides benoxophos, diazinon, carbophenothion, dicrotophos, ethion, fenitrothion and quintiofos. Low levels of resistance, less than 3X, were shown to chlorfenvinphos and coumaphos. No resistance was shown to chlorpyrifos, bromophos ethyl or the diamidine ixodicide, amitraz. In hand-spraying trials no variation in the susceptibility of an organophosphorus resistant strain or the susceptible laboratory strain to amitraz was observed. This is the first recorded resistance to ixodicides by B. microplus in Africa.

Animals↗

Management stretegy for the diffusion of innovation: unit dose drug distribution.

The concepts of the change agent and opinion leader are explored as means to aid the pharmacists in affecting the diffusion of an innovation such as unit dose. A four-part model which describes one possible management strategy for the diffusion of innovation into the organization is presented. The effect of changes in the environment of hospital pharmacy, which may result in the recognition of performance gaps and thus stimulate the introduction of innovation, is discussed. Aspects of diffusion of an innovation--supplying the appropriate information, the knowledge function; creating a positive attitude toward the implementation of the innovation, the persuasion function; the adoption or rejection of the innovation, the decision function--are explained. The successful diffusion of an innovation requires a conscious management strategy, such as the four-component model discussed in this paper.

Decision Making↗

The current status of resistance to organophosphorus ixodicides by the blue tick, Boophilus Decoloratus (Koch) in the Republic of South Africa and Transkei.

In a four year survey 253 isolates of Boophilus decoloratus from the Republic of South Africa and Transkei were tested in the laboratory for their susceptibility to certain organophosphorus ixodicides. Fifty-seven of these isolates were susceptible to organophosphorus compounds, 88 isolates showed a range of susceptibility between that of the susceptible laboratory strain and a strain having a resistance greater than that for the Berlin type strain. A field trial confirmed degrees of resistance shown in the laboratory to the organophosphorus ixodicides benoxophos, chlorfenvinphos, dioxathion, dicrotophos, quintiofos and chlorfenvinphos/dioxathion.

Drug Resistance↗

Resistance to certain organophosphorus ixodicides in the bont tick, Amblyomma hebraeum Koch, in the Republic of South Africa and Swaziland.

A series of in vitro trails confirmed resistance in the three-host tick, Amblyomma hebraeum Koch, to the organophosphorus ixodicides, dioxathion, chlorfenvinphos, quintiofos, bromophos-ethyl and a dioxathion/chlorfenvinphos combination. The results of a routine survey showed that a resistance factor of greater than 100x was present in the offspring of ticks in six of 115 field isolates tested. These six isolates were confined to the lowveld areas of the province of Natal, Republic of South Africa, and Swaziland. Ticks in a further 59 isolates were less susceptible than the reference strain. Resistance was present in all three tick instars. This is the first recorded resistance to the organophosphorus group of ixodicides by multi-host ticks in Africa.

Drug Resistance↗

Antigen-initiated B lymphocyte differentiation. XIV. Nonspecific effects of antigen stimulation cause proliferation in the "pre-progenitor" subset of primary B cells.

The effect of specific and nonspecific stimuli on the cycle status of subsets of primary B lymphocytes was assessed by preinjecting donor CBA mice 1 to 2 days previously with various substances, and then incubating the isolated spleen cells with high specific activity 3H-TdR before assay. AFC-progenitor activity was assessed as a response to NIP-POL antigen, either by adoptive transfer to irradiated recipients or by cell culture. Previous studies showed these assays reflected the activity of different subsets of B cells, termed "pre-progenitors" (adoptive assay) and "direct progenitors" (culture assay). Most functional primary B cells, whether assayed in culture or by adoptive transfer, were not initially in rapid cell cycle in normal adult mice. However, nonspecific stimulation for 1 day caused NIP-specific adoptive transfer IgM AFC-progenitors to enter rapid cell cycle. This effect was independent of T cells and not related to the antigenicity of the stimulus: particulate peritoneal irritants were the most effective stimulants. In contrast to adoptive transfer results. AFC-progenitors assayed in cell culture were unaffected by nonspecific stimuli, but were activated into cell cycle by specific antigen.

Animals↗