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Biomedical subjects

T Miller

Publications and source records attributed to T Miller.

At least 271 records · Page 15Linked to original sources

Genetic factors and host resistance in experimental pyelonephritis.

There have been no reports suggesting that a genetic component may affect host resistance to renal infection. In rats with experimentally induced unilateral pyelonephritis, consistent level of infection was achieved in the directly challenged (left) kidneys. Retrograde infection in the unmanipulated (right) kidneys was found to be strain dependent in these animals. Infection was readily established in the right kidneys of the AS2 and HO strains but not in the DA strain; however, infection was established in all unmanipulated kidneys of the DA X AS2 F1 hybrid, whereas eight of 10 kidneys from the DA X HO hybrid remained uninfected. These results suggest that host resistance to retrograde renal infection in the rat strains studied was genetically determined, although the relevant host factor(s) has not yet been identified.

Animals↗

Immunomodulatory interactions of suppressor cells, cell-mediated immunity, and cyclophosphamide in experimental pyelonephritis.

The recent observation that the administration of cyclophosphamide, an immunosuppressive agent, leads to the eradication of bacterial infection in experimental pyelonephritis seems paradoxical. However, cyclophosphamide is also an immunostimulator and, on the basis of its known characteristics, could enhance cell-mediated immunity either by modulation of suppressor cell activity or by depletion of infection-induced suppressor cells. This study examined these alternatives and the relation between suppressor cells, cell-mediated immunity, and cyclophosphamide administration. Cyclophosphamide enhanced the resistance of lymphocytes to the activity of suppressor cells but did not enhance cell-mediated immunity.

Animals↗

Effect of physiological manipulations on the chemotherapy of experimentally induced renal infection.

The belief that a favorable physiological milieu in the urinary tract may augment the effectiveness of antimicrobial agents used to treat urinary tract infections was examined by using an experimental model of Escherichia coli-induced renal infection in rats. The effect of manipulating urinary pH and flow on the antimicrobial activities of gentamicin, carbenicillin, ampicillin, nitrofurantoin and co-trimoxazole was assessed. In addition, a potential synergistic effect of the sequential administration of gentamicin and cephalothin in the eradication of renal infection was investigated. Although significant physiological alterations were achieved, these did not affect the efficacy of the antimicrobial agents studied, and therapeutic failures were common.

Ampicillin↗

Scarring as a factor affecting the eradication of microorganisms from the kidney in pyelonephritis.

The inability of antimicrobial agents to penetrate scarred renal tissue may explain some therapeutic failures. We examined the effect of scarring on antimicrobial therapy by using a unique animal model in which both kidneys were infected to the same degree but only one kidney was scarred. Scar formation could not explain the failure of ampicillin or nitrofurantoin to eradicate renal infection, but co-trimoxazole was less effective in the presence of tissue damage and scar formation than in their absence.

Ampicillin↗

Nuclear magnetic resonance imaging of a fibrosarcoma tumor implanted in the rat.

Fibrosarcoma tumor cells were implanted in the hind legs of 25 rats and studied from the first to the sixth week postimplantation. Nuclear magnetic resonance imaging detected all tumors and did not yield any false-positives in five control rats. The T1 relaxation values of tumors overlapped those of muscle, and the T2 values overlapped those of fat, but the combination of the two values allowed discrimination of each of the three tissues with no overlap. The difference in relaxation time between tumor and muscle could be accounted for on the basis of water content, which was approximately 14% higher in the tumors. This study confirms data from previous studies suggesting that nuclear magnetic resonance imaging is a highly sensitive modality, but that T1 and T2 values are not specific for individual pathologic conditions.

Adipose Tissue↗

Reliability of urinary monoamine and metabolite output measurements in depressed patients.

The authors measured urinary monoamines and their metabolite outputs in 12 unmedicated depressed patients. Output of 3-methoxy-4-hydroxy-phenylglycol and vanillylmandelic acid proved to be relatively stable from one sample to another. An average of at least two measures provided data with a meaningful reliability for normetanephrine, serotonin, and homovanillic acid output. Output of dopamine, norepinephrine, 5-hydroxyindoleacetic acid, and phenylethylamine was highly variable over time.

Depressive Disorder↗

Dysgenesis of testicular and streak gonads in the syndrome of mixed gonadal dysgenesis: perspective derived from a clinicopathologic analysis of twenty-one cases.

The clinical and pathologic aspects of 21 cases of mixed gonadal dysgenesis (MGD) were studied. The gonads in 15 patients consisted of a macroscopic testis and a streak gonad; six patients had variants, including two with bilateral testes and four with bilateral streak gonads or tumors. Functionally, the gonads were incompetent. Testes 1) failed to completely inhibit müllerian development, 2) failed to support full differentiation of mesonephric duct structures, 3) failed to adequately masculinize development of the external genitalia, or 4) often failed to mediate their own descent, resulting in asymmetry of the internal and external genitalia. None of the streak gonads mediated normal female adolescent development or fertility. Microscopic examination revealed that every gonad, regardless of its gross appearance, was morphologically abnormal. Although gonads with seminiferous tubules usually developed to a moderately advanced state, macroscopically resembling testes, the hilar zone remained architecturally disorganized; the cortex invariably lacked more than a rudimentary tunica albuginea or exhibited partial ovarian differentiation, sometimes even with a rare primordial follicle. Over time, the seminiferous tubules atrophied and hyalinized. Gonads that grossly resembled streak gonads were observed microscopically to be composed of a stroma resembling that of normal ovarian cortex. In patients more than several years of age, the entire complement of germ cells in streak gonads disappeared. It is suggested that patients with MGD be raised as females. Early removal of gonads will prevent the development of gonadoblastoma and dysgerminoma. If the uterus is retained and the patient is subsequently given exogenous estrogen, care should be taken to detect early any signs of the development of endometrial carcinoma or its precursor, to which these patients may be prone.

Adolescent↗

A liquid chromatographic assay for 5-hydroxytryptophan, serotonin and 5-hydroxyindoleacetic acid in human body fluids.

We describe the precision and accuracy of a liquid chromatographic method, which uses internal standards, 6-fluoroserotonin and 5-hydroxyindolecarboxylic acid, in quantitating serotonin and 5-hydroxyindoleacetic acid in human cerebrospinal fluid, plasma and urine. In addition, 5-hydroxytryptophan is measured in the cerebrospinal fluid. The limit of sensitivity of this method is 0.1 pmol/injection, the peak height/concentration ratio is linear in the concentration range of 0.1 pmol to 50 mumol/injection, and the coefficient of variation is of the order of 15% at the limit of sensitivity and below 10% at amounts above 0.5 pmol/injection. No endogenous monoamines or their metabolites interfere with the quantitation of the substances of interest in the body fluids studied.

5-Hydroxytryptophan↗

Characterization of the (rnunz) nude rat. Morphological characteristics of the lymphoid system.

A nude mutant (rnunz) arose spontaneously in a colony of Wistar albino rats (the wild-type strain) in Wellington, New Zealand. On gross examination no thymus could be found in the mediastina of young animals, whereas in older mutants lobules of fatty tissue mimicked the appearance of the thymus of the wild-type strain. Lymph nodes from the rnunz strain showed a marked lymphocyte depletion in the thymus-dependent para-cortical region of the node. Peyer's patches from the nude animals also showed a reduced density of small lymphocytes in the interfollicular zones. In the spleen, tissue from the reticular framework surrounding individual arterioles was sometimes completely empty of lymphocytes but the degree of depletion varied. Total leucocyte numbers in the rnunz strain were 28% lower than the wild-type strain. In 10 out of 13 animals T cells were less than 3% of the lymphocytes present (wild-type 35% T cells). The findings are in agreement with studies of the Rowett nude rat (rnu) and the nude mouse.

Animals↗

Characterization of the nude rat (rnunz). Functional characteristics.

Gross histopathological and morphological observations in an accompanying paper confirmed the absence of a thymus and thymus-derived lymphocytes in the New Zealand athymic nude mutant (rnunz). In the present studies an analysis of the cell-mediated immune status of the rnunz rat is reported. Lymphocyte transformation studies showed that lymphocytes from the rnunz strain did not respond to mitogenic stimulation with the T lymphocyte specific mitogen Concanavalin A. This confirmed the absence of potentially functional T lymphocytes suggested by the morphological analysis. Lymphocytes from the rnunz strain also failed to initiate a graft versus host response, and the absence of host versus graft response established the immune deficit in cell-mediated immunity in the intact animals. Additionally, the rnunz strain has been used as a reference point to determine the effectiveness of neonatal thymectomy and adult thymectomy with irradiation as a means of depleting the host of T cells.

Animals↗

Pyelonephritis: the relationship between infection, renal scarring, and antimicrobial therapy.

We studied the relationship between infection, renal scarring, and antimicrobial therapy in pyelonephritis by an experimental model of the disease. Our specific concern was to identify those aspects of the acute phase of infection associated with the induction of the inflammatory response. Our hypothesis was that the degree of the inflammatory response and the extent of the subsequent lesion in the kidney depended on the rate at which a critical number of microorganisms was reached in the kidney. We proposed that the rapid increase in bacterial numbers in the kidney was the stimulus initiating the inflammatory response and not the total number of microorganisms in the kidney. In the experimental investigation, we treated animals with induced renal infection at varying intervals after the establishment of infection, and we determined the effect of antimicrobial therapy on the bacteriologic, gross, and histopathologic features of the disease. The early events relating to the bacterial invasion of the kidney were important determinants but the hypothesis needed extending to account for the fact that antimicrobial agents, administered after bacterial numbers had reached a plateau, still reduced markedly the damage to the kidney. Two factors seem to be involved in the genesis of the pyelonephritic lesion. The first is the rate of acquisition of a bacterial population by a previously sterile organ, but an additional and important component is the total number of microorganisms in the kidney up to 4 days after challenge. Clinically, the results are relevant in that they demonstrate that renal scarring can be prevented or significantly reduced by prompt antimicrobial therapy.

Ampicillin↗

Nuclear magnetic resonance imaging of the abnormal live rat and correlations with tissue characteristics.

Nuclear magnetic resonance (NMR) images of live rats with sterile and pyogenic abscesses, hematomas, and various implanted and spontaneous neoplasms demonstrated good contrast differentiation between pathologic and surrounding normal tissues. This differentiation was maximal when both the T1 and T2 tissue relaxation times were used as criteria. Neoplasms have a broad range of T1 and T2 values and may be confused with abscesses or hematomas. Tissue rate constants (1/T1 and 1/T2) are mainly dependent on total water content, the exception being fat, which has a 1/T2 value much shorter than that expected on the basis of water content alone.

Abscess↗

Epithienamycins. II. Isolation and structure assignment.

At least six distinct beta-lactam antibiotics of the epithienamycin family are produced by a strain of Streptomyces flavogriseus MB 4638. Each of the six can be isolated in substantially pure form by column chromatography using Dowex 1, Amberlite XAD-2 and Biogel packings. The structures were established by comparison of the ultraviolet, proton magnetic resonance and mass spectral characteristics with those of thienamycin and its derivatives. All six compounds contain the carbapenem ring system which is also found in thienamycin. They differ from each other and from thienamycin by chemical modifications and/or stereoisomerism. Enzymatically deacetylated epithienamycin A has the properties of an isomer of thienamycin.

Anti-Bacterial Agents↗

Continuous measurement of transcutaneous oxygen tension of neonates under general anesthesia.

Neonates present unique challenges to the anesthesiologist because of their susceptibility to oxygen toxicity and because clinical assessment of the degree of an infant's hypoxia is more difficult than in the adult. Equipment is now available for the continuous noninvasive measurement of transcutaneous oxygen tension. We used this equipment to monitor nine different neonates undergoing ten surgical procedures requiring general anesthesia. We found that certain of the infants were above and below what we considered to be a safe range for the transcutaneous oxygen tension for a significant portion of the surgery. Additionally, the manipulations of the surgeon and anesthesiologists were seen to cause sudden and large fluctuations in the transcutaneous oxygen tension. By providing the anesthesiologist with continuous and immediate data on the cardiorespiratory status of the infant, transcutaneous oxygen monitoring makes itself a valuable addition to the equipment used in the intraoperative monitoring of the neonate.

Anesthesia, General↗