Biomedical subjects
Publications and source records attributed to R Bartlett.
The caloric and nitrogen balances of 10 patients with head injury were studied. On the basis of caloric deficits, two groups of five patients each were identified. Both groups were similar except for the average daily caloric supply. Lower caloric deficits were associated with better neurologic outcomes. Large caloric deficits developed by the fourth or fifth day after injury when supplementation was inadequate.
Forty-three strains of coagulase-negative staphylococci were obtained from dialysis effluent during 41 episodes of CAPD peritonitis. Eighty per cent of these were found to be Staphylococcus epidermidis but several other species also occurred. A recurrent infection lasting 15 weeks was caused by Staph. haemolyticus. Multiple antibiotic resistance was found to be common. Of 13 antibiotics tested, only vancomycin was active against all strains although most strains were also sensitive to rifampicin, netilmicin and cefamandole. Vancomycin was chosen for the initial treatment of CAPD peritonitis caused by coagulase-negative staphylococci and eradicated the organism in 29 of 30 episodes.
NZB mice serve as a model for human systemic lupus erythematodes. T-cell abnormalities in this strain have previously been described. In this paper the cytotoxic T lymphocyte precursor (CTL-p) frequencies of NZB mice against H-2 allogeneic and H-2 syngeneic cells are investigated and compared with those of the normal strain BALB/c. The CTL-p frequency in NZB lymphocytes against H-2 allogeneic cells equals that in normal mouse strains (i.e. 1/7500). The NZB anti BALB/c response is in the same order of magnitude. No corresponding BALB/c anti NZB response was elicited. The results suggest abnormally high sensitivity of NZB CTL-p to helper signals.
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To study whether the thymic major histocompatibility complex (MHC) imposes a constraint on the receptor repertoire of maturating cytotoxic T lymphocyte (CTL) precursors, the restriction phenotypes of virus-specific CTL of MHC-compatible and of MHC-incompatible thymus- and bone marrow-grafted (A X B)F1 chimeric mice were compared. Dependent on the mode of in vitro sensitization, thymocytes or splenocytes of both types of chimeric mice generated Sendai virus-specific, self-MHC-or allo-MHC-restricted CTL. By applying the limiting-dilution technique, the CTL-precursor (CTL-P) frequencies of self-MHC-restricted and allo-MHC-restricted virus-specific T cells as well as of alloreactive T cells were determined. The data obtained revealed that independent of MHC differences between thymus and bone marrow, the frequencies of self-MHC-restricted and allo-MHC-restricted CTL-P were comparable, and in the same older of magnitude as those previously determined in conventionally reared mice. Self-MHC-restricted, virus-specific CTL-P were in a three- to fivefold excess over allo-MHC-restricted CTL-P. A segregation analysis revealed that clonally distinct CTL-P give rise to either self-restricted or allo-MHC-restricted, virus-specific CTL. Both sets were found not only in the spleen, but also in the thymus of chimeric mice, formally demonstrating the intrathymic differentiation pathway of self-MHC as well of allo-MHC-restricted CTL-P. These data reveal no major constraint of the thymic MHC on the capacity of T cells to recognize viral antigens either in the context of self-MHC or of allogeneic MHC products.
An in vitro acute-depletion protocol was used to detect trinitrophenyl (TNP)-specific, allo-major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) within thymocytes of inbred mice. After removal of alloreactivity, the negatively selected cells could be sensitized to become TNP-specific, allo-MHC-restricted cytotoxic T cells. A precursors frequency analysis revealed a three- to ninefold lower frequency of allo-MHC-restricted CTL precursors (CTL-P) as compared to self-MHC-restricted CTL-P. The specificity analysis of clonally distributed allo-MHC-restricted CTL-P excluded cross-reactivity as an explanation of allo-MHC restriction. These results provide direct evidence that thymic T cells are composed of a mixture of self-MHC- and allo-MHC-restricted immunocompetent T cells and that antigen-driven selection of precommitted T cells dictates the H-2-restriction phenotype, i.e., H-2 restriction is a consequence of priming.
Cultures of washed erythrocytes from rheumatoid arthritis patients and normal subjects were found to incorporated 14C-thymidine, suggesting the presence of an L-form. The extent of the incorporation by erythrocytes from rheumatoid patients was more variable than that by erythrocytes from normal subjects, and correlated negatively with IgG measurements and white cell counts performed on the patients' bloods, although not with the clinical activity of the patients.
Sixty-five samples of blood from patients with rheumatoid arthritis and 94 from control subjects were examined by multiple culture and monthly subculture for periods of up to 33 months to detect the revision stages of Bacillus licheniformis var. endoparasiticus (BLE), which exists as L-forms in blood. Isolation of BLE were obtained more often from the blood of control subjects than from rheumatoid patients during the first 6 months of incubation, when there was clustering of positive cultures within samples. Thereafter, the isolation rate was similar for the two groups and positive cultures were distributed randomly between samples. Isolation of diphtheroid intermediate reversion stages (phase A and B) occurred mainly during the first year of incubation, but isolations of the fully reverted sporing bacillus (phase C) increased in frequency with incubation time, particularly from cultures with a high rate of desiccation during prolonged incubation. The proportion of different phases of BLE amongst the isolates and the distribution of the phases with incubation time were similar for the rheumatoid-arthritis patients and the normal subjects.
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To analyze the developmental and functional interrelationship between cortical and medullary thymocytes, the peanut agglutinin-(PNA) binding capacity was used to separate thymocytes into PNA+ (cortical) and PNA- (medullary) thymocytes. Virtually, all positively selected PNA+ thymocytes (90% of the overall thymocyte population) expressed the Lyt 123 phenotype, whereas 90% of negatively selected PNA- thymocytes expressed Lyt 1 alloantigens, about 10% being Lyt 123 thymocytes. Provided, the requirement of Lyt 1 T helper cells was bypassed by Interleukin 2, a nonspecific mediator of T help, PNA+ Lyt 123 thymocytes mounted cytotoxic T cell responses comparable in magnitude to that of peripheral T cells. Their repertoire included antigenic disparities coded for by the complete MHC complex, H-2K, I-A, H-2D, mutational events at H-2K, as well as antigenic disparities expressed on TNP conjugated- and Sendai virus-infected syngeneic cells. PNA- Lyt 123 thymocytes represent a highly reactive pool of primary cytotoxic T lymphocyte (CTL) precursors for both alloreactive and H-2-restricted CTL responses. Since PNA- thymocytes include also Lyt 1 T helper cells, PNA- responder thymocytes are able to mount autonomously (CTL responses. Our data are first to provide direct evidence that Lyt 123 cells represent a common source of alloreactive and H-2-restricted CTL precursors in unprimed lymphocyte populations. Moreover, the apparent immunocompetence of cortical PNA+ thymocytes is now explained by their lack of T helper cells.
The rate of reversion from the L-form to the complete bacillus phase of Bacillus licheniformis var. endoparasiticus (BLE)was increased by a factor of c. x20, by growth in the presence of 1% diaminopimelic acid in a well plate, and c. x25 with a 1% hog gastric mucin spread on the plate surface. Saturated riboflavin solution and growth products of staphylococci in wells had a lesser effect. The revertants were subsequently stable when isolated in the absence of additive. The rate of reversion from a spheroplast to a diphtheroid phase was not significantly altered by these additives. These findings are of practical value in studies to distinguish between the BLE sporing bacillus and postulated phases of the organism that include diphtheroid and spheroplast L-forms and debated mycoplasma-like forms.
Electronmicrographs of sections show that the L-phases of Bacillus licheniformis var. endoparasiticus (Benedek) simulate the various types of micro-organism described by previous workers as associated with ostensibly noninfective conditions, notably cancer and arthritis; e.g., mycoplasmas, mycobacteria, corynebacteria and actinomycetes. The stages of the L-cycle, from spheroplasts through smaller and larger 'diphtheroid' bacteria to the fully reverted sporogenous bacillus, differ from one another mainly in their degree of reconstitution of the cell envelopes. Occurrence in 'diphtheroids' of nonresistant, cell-wall-deficient spore-like bodies, confirms their relationship with the true sporing bacillus stage. Large, swollen forms appear to be mother cells of minute stages.
Thirty-eight strains of the Gram-positive bacterium identified as Bacillus licheniformis var. endoparasiticus (Benedek), referred to as BLE, were isolated in various stages of reversion form the L-forms, from 28 out of 100 samples of whole blood or erythrocytes from normal healthy subjects, after prolonged incubation. Similar results were obtained from 100 samples from hospital patients with conditions not usually associated with blood infection. BLE was isolated from only one of 125 samples of plasma, including those separated from infected erythrocytes. Isolates from cultures incubated for up to 4 months were usually in the form of spheroplasts or diphtheroid bacilli; the fully reverted phase, resembling B. licheniformis, with the capacity to form endospores, was isolated occasionally from cultures aged 1--6 months, and it constituted about half the isolates recovered from cultures aged 6--25 months. BLE was isolated in subculture, and with the usual frequency, in previously unopened, primary cultures. It did not occur in 1200 subcultures of 150 control cultures made with autoclaved or irradiated blood cells; it was not detected in the environment of the laboratory or blood-sampling areas, or on the skin or in the respiratory passages of the operators and other persons associated with the laboratory, where typical, saprophytic B. licheniformis was very rare. It is concluded that this Bacillus species exists as an L-form, associated with the erythrocytes of a large proportion of normal persons, as previously recorded by several observers. Some of the morphological variants associated with the L-cycles have in the past been described as different organisms, for example L-forms of various bacteria or mycoplasmas, and the diphtheroid stage has been thought to belong to the genera Corynebacterium and Listeria. The sporogenous stage, although frequently described, has normally been discounted as a contaminant. These observations do not admit of any conclusion in respect of the claims that such bacteria may have a role in arthritis, cancer or other diseases.
The accuracy of predicting serum gentamicin levels based on a one-compartment open linear pharmacokinetic model was studied. Twenty-two patients accounted for 59 serum gentamicin levels which were measured by microbiologic assay and compared with predicted serum levels determined by pharmacokinetic calculation. Seventeen serum levels were collected at peak times, 15 at trough time and 27 at times between peak and trough. Forty-nine of the levels were obtained from patients with impaired renal function. Predicated gentamicin levels correlated well with measured serum levels (r = 0.85, p less than 0.001). Of the measured levels, 56% were within +/- 1 microgram/ml of the predicted levels. Of 49 levels collected from patients with impaired renal function, 59% were within +/- 1 microgram/ml of the predicted level. In 13 patients from whom multiple serum gentamicin levels were collected and predictions based on half-life or elimination rate obtained by fitting the first level, 83% of the measured levels were within +/- 1 microgram/ml of the predicted level. The one-compartment open linear pharmacokinetic calculations can be used to adequately predict serum gentamicin levels. In patients with changing or diminished renal function, pharmacokinetic predictions may not be accurate, and actual serum level determinations may be needed to monitor gentamicin therapy.
One hundred random urine specimens which were submitted for culture were planted using a calibrated loop within 2 h of collection and 2 and 4 h later after standing at room temperature. Colonies were counted after an 18- to 24-h incubation at 37 degrees C. Fifteen of the specimens demonstrated increases in counts exceeding 1 X log10; four increased from less than 10(5)/ml to greater than 10(5)/ml (three by the 4-h culture and a fourth by the 6-h culture), supporting the concept that delays of greater than 2 h in inoculating cultures may produce results which could cause errors in diagnosis.
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