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Biomedical subjects

J C Holmes

Publications and source records attributed to J C Holmes.

At least 37 records · Page 2Linked to original sources
PubMed1984

Target organ patterns of tumors in mice following the arterial dissemination of B16 melanoma cells.

The arrest of B16 melanoma cells and the subsequent development of tumors have been studied following left intraventricular injections (LVI) into mice of radiolabelled and unlabelled cells respectively; the proportions of cardiac output going to different target organs were also determined by LVI of radiolabelled microspheres. B16 cell arrest in the various target organs was as predicted by relative arterial blood supply, except in the lungs and liver where more radioactive counts were detected than could be accounted for in terms of initial arterial dissemination alone; and the numbers of counts remaining in all organs after 24 h were related to the numbers of counts initially obtained. When the incidence of tumor-bearing organs was related to the cell arrest patterns, the organs could be divided into two major distinct groups. Within both of these groups, the patterns of tumor incidence were correlated with cancer cell delivery. These results on a model system suggest that the two major hypotheses used to account for metastatic patterns are not mutually exclusive: the "soil" effect divides the target organs into the two major groups; however, within these groups the incidence of tumors is explicable in terms of the "mechanical" hypothesis.

Animals↗
PubMed1983

Liver-to-lung traffic of cancer cells.

Following the injection of B16 melanoma cells into the portal veins of mice, all animals developed liver tumors, but only 16% developed lung tumors. Portal vein injections of radiolabelled B16 and Walker 256 cancer cells into mice and rats, respectively, revealed that all of the cells were temporarily arrested in the liver and most were then slowly released. Bioassays indicated that of 8 X 10(4) B16 cells released from the liver over 24 h after portal vein injections of 10(5) cells, only approximately 1% were delivered to the lungs in a viable state. Experiments made with radiolabelled B16 cells showed that transit through either the liver or lungs following portal vein or tail vein injections, respectively, resulted in massive death of cancer cells. It is suggested that the death of most circulating cancer cells passing through the first organ encountered after leaving their primary tumor, serves to severely limit their further direct spread to other organs. It is therefore expected that metastases to these other organs would, to a large extent, be generated by cancer cells from metastases in the "first organs" as distinct from direct seeding from cancer cells released from the primary tumor. If the results of the present experiments have general application, they serve to emphasize the importance of metastasis of metastases in the natural history of the spread of cancer. In a previous publication (Weiss, 1980), studies of lung-to-liver traffic of cancer cells in rats revealed that, after tail vein injections, most Walker 256 cells were temporarily arrested in the pulmonary vasculature and then slowly released. A large proportion of the released cancer cells were dead or lethally injured on release from the lungs, and this "first organ processing" apparently accounted for the comparative rarity of extrapulmonary tumors following tail vein injections. In this communication, the concept of "first organ processing" of circulating cancer cells is further examined with respect to the liver-to-lung traffic of B16 melanoma and Walker 256 cells injected into the portal veins of mice or rats respectively. Both of these cell types grow well in the lungs following tail-vein injection.

Animals↗
PubMed1983

Do metastases arise from pre-existing subpopulations of cancer cells?

The hypothesis that metastases arise from pre-existing metastatic sub-populations of cancer cells with heritable metastasis-related characteristics, was tested by comparing the metastatic behaviour of cancer cells derived from pulmonary metastases with those from corresponding primary tumours, after implanting them subcutaneously in mice. In the case of KHT osteosarcomas and B16 melanomas, injected minces of metastases gave rise to more pulmonary metastases than cells derived from minces of the primary cancers generating them. However, in the case of 3LL and T241 cancers, the primary tumour minces gave rise to more pulmonary metastases than those derived from minced metastases. It is therefore concluded that the subpopulation hypothesis cannot be accepted as a general rule. When fragments of solid tumours were implanted into animals, no differences were detected between the metastatic behaviour of implants taken randomly from pulmonary metastases and the volume/age matched primary tumours generating them. These experiments thus provide no support for the hypothesis that metastases arise exclusively or predominantly from pre-existing metastatic subpopulations of cancer cells. Finally, implants of matched fragments from 3LL tumours of different volume and age, essentially produced no statistically significant differences in numbers of metastases. These observations do not therefore support the concept of a progressive evolution of subpopulations of cancer cells with heritable metastatic phenotypes during tumour growth.

Animals↗
PubMed1982

Metastatic inefficiency in mice bearing B16 melanomas.

When injected i.v. into mice, the F10 subline of B16 melanoma cells produced significantly more lung tumours over a 3-week period than cells of the F101.r-6 subline. However, in animals bearing intramuscular tumours produced by these sublines, the high pulmonary-colonization potential of the F10 cells was not realized, and no significant differences in natural pulmonary metastasis formation were observed in animals with untreated primary cancers, even when they progressed to the moribund state. Massage of i.m. tumours derived from the two sublines produced no change in metastasis and no changes in the numbers of cancer cells in the blood detectable by bioassay. In contrast, massage increased metastasis from tumours derived from an invasive BL6 subline and B16 wild-type cells and, in the case of the wild-type, the numbers of circulating cancer cells. In vitro experiments show that blood cells from non-tumour-bearing animals are toxic to both sublines; but less to F10 than to F101.r-6. In addition, after i.v. injection of radiolabelled cells, more of the F10 subline were retained in the lungs of recipients than the F101.r-6. In spite of these apparent metastatic advantages of the F10 subline following intravasation, the incidence of natural metastases from i.m. F10 and F101.r-6 tumours was similar, suggesting that substantially fewer F10 than F101.r-6 cells gained access to the circulation. Thus, the higher colonization potential of the F10 cells was not matched by its intravasation potential, since metastatic efficiency is determined by the least efficient step in the metastatic process.

Animals↗
PubMed1981

Calcium emboli to the retinal artery in calcific aortic stenosis.

It is generally appreciated in the cardiovascular literature that calcium emboli to a central retinal artery or its branches may be the presenting feature of otherwise uncomplicated calcific aortic stenosis. The ophthalmologic literature provides good evidence for this point. Over a 7-month period, four such cases have come to our attention. Other potential sources of emboli were excluded by standard noninvasive and invasive diagnostic techniques, and two patients underwent successful aortic valve replacement. Previous studies of calcific aortic stenosis have demonstrated postmortem histologic evidence of calcium emboli to various organs, for example, heart, kidney, or brain. Since these emboli are small, their occurrence is clinically silent. The retinal circulation is unique in that its occlusion by a calcium microembolus results in loss of vision, and this symptom may be a clue to the presence of calcific aortic stenosis.

Adult↗
PubMed1978

Hemodynamic effects of nitroprusside and hydralazine in experimental cardiac tamponade.

Cardiac tamponade is associated with decreased cardiac output and increased systemic vascular resistance. Thus, vasodilator drugs might lower systemic resistance and increase cardiac output. Three groups of dogs were studied during tamponade. Group I received nitroprusside only; group II received blood transfusion and then nitroprusside; group III received hydralazine. In group I, nitroprusside lowered right artrial pressure and systemic resistance; cardiac output was unchanged. In group II, transfusion raised right atrial pressure but not cardiac output. Then nitroprusside raised cardiac output significantly. Hydralazine decreased right atrial pressure less than nitroprusside but decreased vascular resistance and raised cardiac output. Both nitroprusside and hydralazine decreased systemic vascular resistance during tamponade, but only hydralazine raised cardiac output probably because of its lesser effect upon the capacitance vessels. Nitroprusside maintained cardiac output during tamponade despite lowered right atrial pressure but increased cardiac output only after transfusion.

Animals↗
PubMed1978

Tardy ulnar nerve palsy in children.

Tardy ulnar nerve palsy in the child is an infrequent occurrence. In 5 cases all occurring after injury about the elbow, the lesion involved not only lateral but also medial structures. The latency period from elbow injury to palsy was not always long and ranged from 2 months to 29 months. Possibly because of the age of the patients and short duration of the palsy, anterior transposition promoted prompt remission of symptoms and signs.

Adolescent↗
PubMed1978

Fusion for instability and potential instability of the cervical spine in children and adolescents.

Instability and potential instability of the cervical spine in the child and adolescent not presenting as emergencies may be due to many causes. We have reviewed 30 patients treated surgically over a seven year period and have grouped them under four general headings: isolated congenital anomalies of the cervical spine, postlaminectomy instability, traumatic instability with delayed presentation, and bony or ligamentous inadequacy secondary to miscellaneous conditions. The variety of conditions permits few generalizations. However, an overview of the entire group supports the concept that abnormal motion in an immature spine or the potential for such motion should be viewed cautiously by the orthopedist, for it may herald severe neurologic compromise. When compromise has occurred, the decision to intervene is made easier. Should only increased motion or the potential for such be present, the natural history of the lesion, if available, should be the guide to treatment. If the natural history of a cervical spine lesion is not available and structural integrity is compromised with abnormal motion present, fusion is advised. Appropriate patient counseling as to the lack of an alternative, with the exception of prolonged bracing to avoid the hazards of life, is essential in this group of individuals.

Adolescent↗
PubMed1976

Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs.

Eight patients had cardiac manifestations that were life-threatening in five while taking psychotropic drugs, either phenothiazines or tricyclic antidepressants. Although most patients were receiving several drugs, Mellaril (thioridazine) appeared to be responsible for five cases of ventricular tachycardia, one of which was fatal in a 35 year old woman. Supraventricular tachycardia developed in one patient receiving Thorazine (chlorpromazine). Aventyl (nortriptyline) and Elavil (amitriptyline) each produced left bundle branch block in a 73 year old woman. Electrocardiographic T and U wave abnormalities were present in most patients. The ventricular arrhythmias responded to intravenous administration of lidocaine and to direct current electric shock; ventricular pacing was required in some instances and intravenous administration of propranolol combined with ventricular pacing in one. The tachyarrhythmias generally subsided within 48 hours after administration of the drugs was stopped. Five of the eight patients were 50 years of age or younger; only one clearly had antecedent heart disease. Major cardiac arrhythmias are a potential hazard in patients without heart disease who are receiving customary therapeutic doses of psychotropic drugs. A prospective clinical trial is suggested to quantify the risk of cardiac complications to patients receiving phenothiazines or tricyclic antidepressant drugs.

Adrenergic Agonists↗
PubMed1976

Pericarditis caused by Histoplasma capsulatum.

Sixteen patients with pericarditis caused by Histoplasma capsulatum were studied. Fourteen were less than 30 years old, and no patient had an underlying illness or was receiving immunosuppressive therapy. All patients experienced a flu-like prodromal illness lasting from 2 weeks to 4 months. Pneumonitis or hilar adenopathy, or both, was found in 12; pleural effusion, uncommon in primary pulmonary histoplasmosis, was found in seven patients. Pericardial fluid, pleural fluid and bone marrow cultures yielded no growth. All patients demonstrated a fourfold or greater change in complement-fixing antibody titers. No patient had disseminated disease, and only one required treatment with ampholericin B. The illness ran a protracted course, and in six patients symptomatic pericarditis recurred. Ultimately all recovered. Ten patients were restudied 6 months to 12 years after recover. Only one patient had pericardial calcification, and none had constrictive pericarditis. This form of granulomatous pericarditis, unlike that caused by Mycobacterium tuberculosis, appears to carry a good prognosis.

Adolescent↗
PubMed1975

Blood viscosity and cardiac output in acute experimental anemia.

The significance of blood viscosity alterations during anemia was evaluated in dogs under morphine-chloralose anesthesia. In group I, anemia (mean hematocrit 18.1 +/- 1.3 vol %) was produced by exchange transfusion with clinical dextran (avg mol wt 70,000). In group II, anemia was produced (mean hematocrit 19.9 +/- 0.88 vol %) with 500,000 molecular weight dextran, thus preventing the decrease in blood viscosity in group I. The cardiac output increase in group I (93.4%) with low-viscosity anemia was significantly greater than in group II (43.3%) with unchanged blood viscosity. Group III animals were transfused with a clinical dextran-red cell mixture, and group IV animals received a 500,000 mol wt dextran-red cell mixture. In group III, blood viscosity and cardiac output did not change. In group IV, blood viscosity rose and cardiac output fell significantly. The results suggest that a change in blood viscosity exerts a significant effect upon cardiac output, especially during acute dextran-exchange anemia.

Anemia↗
PubMed1975

Influence of acute hypertension on aortic valve competence.

The effect of acutely induced hypertension on aortic valve competence was studied in anesthetized dogs. Aortic pressure was increased by infusion of methoxamine or mechanically; aortic valve competence was evaluated by aortogrphy and by indicator dye. The aortic valve was normally competent; aortic insufficiency appeared with increase of mean pressure by as little as 20-50 mmHg; 6 of 9 animals showed aortic incompetence when mean aortic pressure was elevated 45-70 mmHg, but the valve remained competent in 2 of 9 animals with mean pressure increments of 60-90 mmHg. The aortic root was appreciably less distensible than was the proximal descending aorta; this factor may limit the degree of aortic insufficiency in response to acute hypertension in the dog.

Animals↗