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Biomedical subjects

B Miller

Publications and source records attributed to B Miller.

At least 289 records · Page 16Linked to original sources
PubMed1988

Cellular pharmacology of N,N',N''-triethylene thiophosphoramide.

N,N',N''-triethylene thiophosphoramide (Thio-TEPA) is an alkylating agent whose antineoplastic activity has been known for nearly 30 years. Human plasma pharmacokinetic studies revealed the presence of TEPA, a Thio-TEPA metabolite which after 4 h achieved plasma concentrations equal to those of the parent compound. We studied the activity of both Thio-TEPA and TEPA against murine leukemia P388 cells in culture. We found that Thio-TEPA is approximately two-fold more active than TEPA in arresting cell growth (IC50 = 2.8 microM for TEPA and 1.5 microM for Thio-TEPA). In inhibiting [3H]thymidine incorporation, Thio-TEPA and TEPA have the same activity (IC50 = 2 microM for both compounds). Experiments in which drug was removed from cell cultures which were further incubated in drug-free media, revealed that the bulk of the cell damage occurs during the first 4 h of incubation. Cell cultures exposed to 0.5 microM Thio-TEPA for 22 h fully recovered their [3H]thymidine incorporation ability after 24 h of drug-free incubation. Cells exposed to 2.5 microM Thio-TEPA for 22 h partially recovered their ability to incorporate [3H]thymidine. Cells exposed to 10 microM Thio-TEPA for 22 h did not recover their ability to incorporate [3H]thymidine. Gas liquid chromatographic analysis of the media from incubated cells showed that the concentration of Thio-TEPA remained unchanged during the incubations and that TEPA was not present. In Thio-TEPA doses ranging from 0.1 microM to 100 microM, [3H]uridine and [3H]-leucine incorporation were less affected than [3H]thymidine incorporation. This may indicate that a longer observation time may be needed to allow the DNA damage to be expressed in terms of protein or RNA synthesis.

Animals↗
PubMed1988

Hemorheologic variables in breast cancer patients at the time of diagnosis and during treatment.

The increased risk of thrombosis seen in patients with malignancy also was recently confirmed in breast cancer patients undergoing hormonal or chemotherapeutic treatment. Besides changes within the coagulation system, alterations of hemorheologic variables have been implicated in the genesis of thrombosis. We evaluated plasma viscosity, erythrocyte aggregation, fibrinogen level, sedimentation rate, hematocrit concentration, and protein concentration in patients with breast cancer at the time of primary diagnosis and during follow-up with or without treatment. We then compared the results to a control group without malignant or infectious disease. Plasma viscosity and erythrocyte aggregation were significantly higher in patients with malignant disease, with a further increase at the time of dissemination. Plasma fibrinogen level was significantly higher only at the time of dissemination. The influence of therapy on hemorheologic variables was minor. Tumor volume was the most important factor. As individual values vary considerably and form a continuous spectrum, no cutoff line between normal and pathologic values can be defined. However, high values should induce further measures to diagnose metastatic disease. Second, these factors could explain the relative inefficiency of thrombosis prophylaxis in this patient group and suggest the addition of rheologically active drugs to the treatment regimen.

Blood Sedimentation↗
PubMed1988

Effects of cyclic mechanical stimulation of the cellular components of the heart: in vitro.

The response of the cellular components of the heart to cyclic mechanical stimulation is of particular importance because these cells are continually subjected to mechanical forces as a result of changes in blood volume and pressure. To directly investigate how mechanical tension affects these cellular components of the heart, an in vitro system that exposes the particular cell type (cardiac myocytes, endothelial cells, or fibroblasts) to a calibrated increase in cyclical linear stretch was developed. Cells were grown on silastic membranes coated with laminin and subjected to a 10% cyclical distention 10 times a minute for 72 h. Within 24 h of being exposed to the mechanical stretch, the cells became elongated and oriented perpendicular to the direction of the stretch. These results indicate that cyclical mechanical stimulation directly influences the cellular organization of the heart cells in vitro.

Animals↗
PubMed1988

Heart rate control in diabetic rabbits: blunted response to isoproterenol.

To study the effects of chronic diabetes on heart rate and adrenergic responsiveness we compared unanesthetized diabetic rabbits, 10-13 mo after alloxan monohydrate injection, to age-matched controls. There were no significant differences found between groups for body or heart weight. Both resting and intrinsic heart rate (the latter obtained after atropine sulfate and propranolol HCl) were similar. In addition, serum and left ventricular epinephrine and norepinephrine concentrations as well as left ventricular beta-receptor density and affinity were unchanged in diabetic animals. Heart rate responses to isoproterenol were blunted in diabetics at the three highest doses. Base-line mean blood pressure was modestly lower in diabetic rabbits, and parallel declines in pressure for both groups were observed in response to isoproterenol. The diminished heart rate response to isoproterenol in diabetic rabbits may be due to diminished myocardial sensitivity to catecholamines, possibly combined with altered baroreceptor reflexes. These experiments may provide an explanation for the blunted heart rate response to exercise described in human diabetics.

Animals↗
PubMed1988

A pathologic study of wild turkeys in Connecticut.

During the 1984 to 1986 spring hunting seasons in Connecticut, viscera from 300 hunter-killed wild turkeys and blood samples from live-trapped wild turkeys were examined in order to establish a health profile on the State's wild turkey population. Seven species of endoparasites were recovered from 224 (75%) of 300 birds: Metroliasthes lucida, Ascaridia dissimilis, Heterakis gallinarum, Syngamus trachea, Capillaria species, Trichomonas gallinarum, and Eimeria species. The most prevalent parasites were A. dissimilis (52%) and M. lucida (37%). Although some turkeys harbored high intensities of these two helminths, there were no associated gross or microscopic lesions nor body weight changes. The prevalence of S. trachea, H. gallinarum, Capillaria and Eimeria species, which are potential pathogenic parasites in domestic and wild turkeys, was very low (less than 3%). Blood samples from 19 live-trapped wild turkeys were negative for hemoprotozoa and antibodies to 15 common bacterial and viral agents. Serum samples from 82 birds were negative for Mycoplasma gallisepticum and Mycoplasma synoviae. The survey indicates that the wild turkey population of Connecticut presently has little evidence of common infectious diseases and minimal prevalence of potentially pathogenic parasites.

Animals↗
PubMed1988

[Percutaneous and implantable catheters in cancers of the upper respiratory and digestive tracts. Apropos of 600 cases].

For two years, 600 catheters (234 silicone catheters, 153 tunnelisation cuffed catheters and 188 total implantable systems) were place for chemotherapy in patients with head and neck cancer. Percutaneous catheters remain for 152 days and total implantable systems for 188 days. Total complications decrease with greater experience of physicians and using improved catheters.

Aged↗
PubMed1988

Late-onset schizophrenia. Studying clinical validity.

The authors compared clinical characteristics of 36 late-onset schizophrenic patients from four centers (hospitals in San Diego, Baltimore, Los Angeles, and Montreal). There was a preponderance of the paranoid type with bizarre delusions and auditory hallucinations, chronic course of illness, and response to relatively low doses of neuroleptics. A comparison of late-onset and younger schizophrenic patients revealed both similarities and differences between the two groups. The authors reviewed the relevant literature and discussed the implications for assessing the validity of the concept of late-onset schizophrenia. They believe that, although less common, late-onset schizophrenia is probably as valid an entity (or group of entities) as schizophrenia with onset before age 45.

Adult↗
PubMed1987

Neuropsychiatric aspects of multi-infarct dementia and dementia of the Alzheimer type.

Delusions, depression, and hallucinations were assessed in 30 patients with dementia of the Alzheimer type (DAT) and 15 with multi-infarct dementia (MID). The nature and prevalence of delusions did not distinguish DAT from MID: delusions were present at the time of examination in 30% of patients with DAT and in 40% of patients with MID, and had occurred at some time in the course of the illness in half the patients of each diagnostic group. Delusions were primarily paranoid in type and involved elementary misbeliefs concerning theft or infidelity. Depression was significantly more common in MID than DAT. Seventeen percent of patients with DAT had depressive symptoms; none with severe depression were identified. Four of 15 patients with MID exhibited major depressive episodes and 60% manifested depressive symptoms. Depression and delusions were not deducted in patients with severe dementia. Hallucinations occurred in both diagnostic groups but were not common: one patient with DAT and one with MID had auditory hallucinations, and three patients with MID had visual hallucinations.

Aged↗
PubMed1987

In the search for new anticancer drugs. XX: A comparison of the in vitro growth inhibition of P388 cells by TEPA and N,N;N',N'-bis (1,2-ethanediyl)-N''-(1-oxyl-2,2,6,6-tetramethyl-4- piperidinylaminocarbonyl) phosphoric triamide and congeners.

We tested the in vitro growth inhibitory activity of TEPA, and three analogs against P388 murine lymphocytic leukemia cells in culture. The analogs consist of spin-labeled TEPA and two reduced forms containing the NH and NOH groups instead of the nitroxyl function. Spin label TEPA was obtained by replacing one of the aziridine groups in TEPA with spin-labeled urea. In a concentration range of 10(-6)-10(-5) M, only the reduced analog containing the NH group was active. That is, to achieve a 50% inhibition of cell growth, a five-fold excess in concentration of this analog (IC50 = 10 X 10(-6) M) was needed as compared to the parent compound TEPA (IC50 = 2 X 10(-6) M). These results are in contrast with those obtained in vivo against the same leukemia cell line, indicating inherent discrepancies between in vivo and in vitro evaluation of antitumor agents.

Animals↗
PubMed1987

Vitreoretinal junction in infectious endophthalmitis in a primate eye.

A primate eye affected by postoperative infectious endophthalmitis was studied early in the course of the disease. Retinal perivasculitis, vitreoretinal adhesions along the inflamed vessels, and traction of the partially separated posterior vitreous on the retina at the adhesion sites were observed. It is suggested that such vitreoretinal junction pathology may be responsible for the development of retinal detachment in infectious endophthalmitis.

Animals↗
PubMed1987

Myocardial adaptation to chronic propranolol therapy in normal rats.

The intrinsic myocardial adaptation to chronic beta-blockade was explored in normal male Wistar rats. Propranolol was administered by subcutaneous infusion using osmotic minipumps for 3-4 wk (P group). Heart rate fell by approximately 100 beats/min. A second group of animals was similarly treated but had their pumps removed several days before study (P-R group). Heart rate rose, but remained below base line. Study of isolated ventricular papillary muscle from P, P-R, and age-matched controls (C group) revealed prolonged contraction duration in P and P-R groups, but no change in shortening velocity. A greater shortening of time to peak tension and time to one-half relaxation in response to norepinephrine was demonstrated in P and P-R groups. Acute in vivo or in vitro administration of propranolol had no effect on base-line mechanical performance. No changes in the Ca2+, actin-activated Mg2+ myosin adenosine triphosphatase (ATPase) activity, or myosin isoenzyme distribution were found. Free thyroxine levels were decreased in P but not P-R groups. These findings indicate that chronic propranolol therapy in normal rats slows contraction and relaxation without altering contractility. The greater shortening of contraction duration in response to norepinephrine is partly offset by the prolongation of the base-line contraction.

Adaptation, Physiological↗