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Biomedical subjects

J C Allen

Publications and source records attributed to J C Allen.

At least 181 records · Page 10Linked to original sources
PubMed1985

Chemotherapy trials in recurrent primary intracranial germ cell tumors.

Gonadal germ cell tumors respond favorably to chemotherapy either at diagnosis or when they recur. Histologically similar tumors may arise in the CNS usually in the pineal or suprasellar regions. Although radiation therapy may produce a 5 year disease-free survival in excess of 60% in localized pure germinoma, germ cell tumors of other histology tend to recur. We have conducted 14 chemotherapy trials in 8 patients with recurrent CNS germ cell tumors using 3 different single agent and 2 multi-agent chemotherapy regimens. The histologic diagnoses of the patients were germinoma (4), endodermal sinus tumor (2), embryonal carcinoma (1), and mixed tumor - germinoma plus choriocarcinoma (1). There were 7 males and 1 female with a median age of 13 years. The primary tumor arose in the pineal region in 6 and was multicentric in 2. Seven patients had local recurrences and one developed an initial recurrence in the spinal canal. Three patients had CNS metastases at relapse and 2 had systemic metastases. Objective responses were documented in 7 of 14 trials (50%). Responses were observed with cyclophosphamide (80 mg/kg) in 3 of 4 patients for 2+, 3, and 5 mos, cisplatin (120 mg/m2) in 1 of 2 patients for 2+ mos, and the VAB 6 protocol (vinblastine, bleomycin, cyclophosphamide, actinomycin-d, cisplatin) in 3 of 5 patients for 5, 8, and 18 mos. The median duration of response was 5 mos. (2+-18). High doses of single chemotherapy agents such as cyclophosphamide and cisplatin as well as VAB 6 regimen have definite activity in recurrent CNS germ cell tumors, especially germinoma. Good palliation may be achieved with chemotherapy alone with acceptable morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Central chemical control of ventilation and response of turtles to inspired CO2.

The role of central chemosensors in the overall ventilatory response of freshwater turtles (Chrysemys scripta elegans) to the addition of CO2 in inspired gas was measured. Centrally mediated ventilatory responses were isolated in the unanesthetized animal by combining CO2 breathing and brain ventricular perfusion with mock cerebrospinal fluid (CSF) of varying acid-base status. Breathing 4.5% CO2 resulted in increases in both ventilatory frequency (f) and tidal volume (VT), with increases in VT providing most of the overall ventilatory change. Alterations in the acid-base status of the perfusate produced highly significant changes in f. VT changes were divorced from the acid-base status of the mock CSF perfusate. We therefore conclude that ventilatory changes in turtles, mediated by central chemosensors, are primarily affected by alterations in f. VT changes, associated with acid-base homeostatic mechanisms, are mediated by receptors outside the blood-brain barrier in these animals. On the basis of these data, we hypothesize that the increase in f observed when turtles breathe 4.5% CO2 is primarily mediated by the central chemosensors.

Acid-Base Equilibrium↗
PubMed1985

Metoclopramide: dose-related toxicity and preliminary antiemetic studies in children receiving cancer chemotherapy.

Prior studies in adults have shown that metoclopramide (MCP), when given in high intravenous (IV) doses (2 mg/kg), is a highly effective antiemetic for chemotherapy-induced vomiting. It is well-tolerated in older adults, but younger adults have an increased disposition to acute extrapyramidal reactions (EPRs). Before studying the efficacy of MCP as an antiemetic in children, we first had to establish the safe dose range. We performed a dose-increase MCP toxicity study in children receiving highly emetic chemotherapy such as cisplatin (120 mg/m2) or cyclophosphamide (greater than 900 mg/m2), beginning with a dose of 0.2 mg/kg and increasing the dose in nine steps to 3 mg/kg. MCP was given every two hours for four doses beginning one-half hour before chemotherapy. To reduce the incidence of EPRs, we added concomitant diphenhydramine. In MCP doses less than 2 mg, toxicity was minimal. In doses greater than or equal to 2 mg, 4/27 (15%) had EPRs and 9/27 (33%) had akathisia. Children who received two consecutive days of MCP had a higher frequency of EPRs. Metoclopramide (2 mg/kg) had promising antiemetic efficacy in a preliminary nonrandomized trial. Chemotherapy-experienced children vomited fewer than five times in 9/21 (43%) trials, and new patients vomited fewer than five times in 7/10 (70%) trials. MCP will become more useful as an antiemetic in children if better measures to prevent EPRs can be developed. Chemotherapy-induced emesis has the same negative implications in children as it does in adults and optimum antiemetic regimens can only be discovered by conducting randomized clinical trials in children.

Adolescent↗
PubMed1984

Radiation for medulloblastoma adjusted to prevent recurrence to the cribriform plate region.

In a recent survey of the recurrence pattern in 40 medulloblastoma patients treated at Memorial Hospital between 1970 and 1979, 15% of all recurrences were in the region of the cribriform plate, which is an area that is undertreated with commonly employed radiation therapy techniques. The authors, therefore, modified their technique to increase the dose in this area. They report on the initial results in 15 subsequent patients treated with this modification. Ten of the 15 patients had localized tumors (Groups I and II) and 8 of these patients are alive disease-free compared with 7 of 17 Group I and II patients treated between 1970 and 1979. Three of five patients with disseminated tumors (Groups III and IV) are alive disease-free compared with none in the previous series. Although the period of follow-up is relatively short (median, 32 months), the overall survival of patients with medulloblastoma seems to be improved with additional radiation to the region of the cribriform plate. No side effects attributable to this modification were observed. In the opinion of the authors, this modification should be used routinely in patients with medulloblastoma.

Adolescent↗
PubMed1984

Changes with hypertension and maturation in the response of stomach fundus to acetylcholine.

The purpose of these experiments was to compare the contractile response to ACh of stomach fundal strips from hypertensive (SHR) and normotensive (WKY) rats during the development of hypertension. The results indicate that the reactivity to ACh is the same in fundal strips from young SHR and WKY rats; however, with maturation strips from WKY rats undergo a reduction in responsiveness which does not occur in the SHR. Therefore, strips from older SHR rats are more reactive to ACh than are those from age matched WKY rats.

Acetylcholine↗
PubMed1984

Studies on human lactation. I. Within-feed and between-breast variation in selected components of human milk.

Within-feed and between-breast differences in the concentrations of sodium, potassium, chloride, calcium, magnesium, lipid, protein, lactose, glucose, urea nitrogen, creatinine, zinc, and copper were examined in milk samples from 10 women. The average lipid content doubled in the interval from the beginning of the feed to the end. The composition of the aqueous phase of milk, as determined by the major osmotically active constituents, did not vary significantly within the feed. For these components as well as for lipid a small mid-feed sample of milk gave the same mean composition as the pooled, pumped contents of one breast suggesting that such a sample is adequate for determination of milk composition in population studies. Sporadic, inconsistent differences in the composition of the milk from the right and left breasts were observed. It is suggested that mastitis may contribute to these differences. It is recommended that samples routinely be taken from both breasts and analyzed for sodium and chloride to rule out episodes of mastitis or other local phenomena which sporadically alter milk composition.

Adolescent↗
PubMed1984

Effect of vitamin D deficiency on mouse mammary gland and milk.

Lactational performance, milk composition, mammary calcium pools and serum calcium were examined in vitamin D-deficient lactating mice to determine whether the mammary gland is a target organ for vitamin D. CD1 mice were fed vitamin D-deficient or control diets containing 1.2% calcium and 0.5% phosphorus 8-12 weeks prior to breeding. Plasma calcium levels were within normal limits in all mice. Vitamin D deficiency was verified by lack of detectable serum 25-hydroxycholecalciferol. Deficient mice had fewer pups per litter than controls (7.1 +/- 0.5 vs. 8.4 +/- 0.3; P less than 0.05). Pups from vitamin D-deficient and repleted mothers grew at the same rate. Mammary tissue intracellular and extracellular calcium pools, measured by an efflux technique, did not differ in the two groups. Milk samples were collected by suction after injection of 0.1 IU of oxytocin i.p. or anaerobically by a surgical technique. Although protein, Na, K, ionized calcium and pH did not differ, milk from vitamin D-deficient mice had lower lactose (114.6 vs. 135.9 mM; P less than 0.02) and slightly lower calcium (66.8 vs. 75.4 mM; P less than 0.1) concentrations than controls. The data do not demonstrate any direct effects of vitamin D on mammary gland calcium metabolism.

Animals↗
PubMed1984

Depigmenting action of hydroquinone depends on disruption of fundamental cell processes.

The effect of the skin-depigmenting agent hydroquinone (HQ) on 2 melanotic and 3 nonmelanotic cell lines was studied. Significant differences in its effect on DNA and RNA synthesis were observed between cell lines. HQ caused inhibition of cellular metabolism in all cells tested, but the dose that caused 50% inhibition of tritiated thymidine incorporation was approximately 30 times lower for melanotic cells. Tritiated uridine incorporation was found to be 85 times more sensitive to HQ in the melanotic cells. These results suggest that HQ exerts its depigmenting effect by selective action on melanocyte metabolism rather than a specific effect on melanin synthesis. Further, the effects of UV irradiation on this system were investigated and found to be negligible, in spite of the stimulation of in vivo melanin synthesis by UV radiation.

Animals↗
PubMed1984

The effects of three differing anaesthetics on the immune response.

A clinical study was undertaken to investigate changes in the immune response in patients undergoing three differing anaesthetic techniques for inguinal hernia repair. No significant differences between anaesthetic groups were demonstrated in the haematological parameters. The value of mitogen stimulation tests was questioned in the clinical setting. The migratory component of neutrophil function was shown to be preserved following conduction anaesthesia compared to the other anaesthetic groups and its possible advantage noted.

Adult↗
PubMed1984

Adaptation of canine saphenous veins to grafting. Correlation of contractility and contractile protein content.

Saphenous veins are used extensively to replace stenotic coronary arteries. However, the contractile and biochemical adaptations of grafted veins are unknown. The three purposes of this work were to characterize the contractile properties of grafted veins, to determine whether altered contractile characteristics were associated with quantitative changes in actin, myosin and collagen, and to determine which changes were associated with the surgical procedure and which with placement in the arterial circulation. Canine saphenous veins were removed and returned to their original location (venous autograft), while others were used to replace a segment of femoral artery (arterial graft). The grafts were removed 1, 4, and 8 weeks later and compared with the contralateral saphenous vein. Both graft types exhibited an increase in sensitivity to norepinephrine but not to potassium chloride. The venous autograft exhibited a reversible reduction in myosin content and in maximum contractile response (force/cross-sectional area) to potassium chloride and norepinephrine. In contrast, the arterial graft exhibited increased wall thickness and content of all measured proteins and decreased maximum contractile response. The latter occurred even though there was an increase in the net production of actin and myosin. Expressing the maximum contractile response in terms of the myosin content did not normalize the contractile response. These results suggest that, except for the elevated sensitivity to norepinephrine, the vein is capable of recovering from the effects of surgery within 8 weeks; however, placement of the vein in the arterial circulation delays this recovery and initiates a hypertrophic response that includes an attenuation of contractile function.

Adaptation, Physiological↗
PubMed1983

Preradiation chemotherapy for newly diagnosed childhood brain tumors. A modified Phase II trial.

A poor-risk population of children with primary malignant central nervous system (CNS) tumors, other than gliomas, can be identified by their young age, by the presence of disease dissemination at diagnosis, and possibly by subtotal resection of the primary tumor. These children require at least neuraxis radiation therapy and possibly chemotherapy for disease control. Unfortunately, once neuraxis radiation is administered, tolerance of subsequent chemotherapy is limited. The authors have explored a multimodal treatment approach in 14 poor-risk patients initially consisting of a modified Phase II chemotherapy trial followed by neuraxis radiation. The diagnoses were medulloblastoma (5), pineoblastoma (3), cerebral primitive neuroectodermal tumor (3), germinoma (2), and choroid plexus carcinoma (1). Eleven patients had disseminated CNS disease, and two had bone marrow involvement at diagnosis. Nine patients received 2 courses of intravenous cyclophosphamide (80 mg/kg) alone over 8 weeks, and five others received three daily doses of intrathecal Ara-C (50 mg/m2) and oral hydroxyurea (40 mg/kg) with each course of cyclophosphamide. There were four complete responses (two dysgerminomas, one pineoblastoma, and one primitive neuroectodermal tumor), one partial response (medulloblastoma), and three mixed responses (two medulloblastomas, one pineoblastoma) to chemotherapy alone, for a response rate of 57%. Twelve patients subsequently tolerated the planned dose of neuraxis radiation. The median survival of all patients was 11 months, and seven of eight deaths were related to recurrent disease. The hematologic toxicity was appreciable, and one death resulted from gram-negative septicemia. Through the use of this type of Phase II trial, valuable information can be obtained on the response rates to specific chemotherapy agents administered prior to radiation. Although cyclophosphamide alone was an active agent in this context, these treatment regimens did not have an important affect on survival.

Age Factors↗
PubMed1983

Biochemistry of the polyamines.

The naturally-occurring polyamines exist in the free form, as N-acetyl derivatives and bound to protein. Their biosynthesis is subject to sensitive control, particularly of ornithine decarboxylase. This enzyme may be multifunctional and a key regulatory protein. Studies, principally with selective inhibitors, have elucidated the roles of polyamines in cell proliferation. Oxidized polyamines, in contrast, can be potent mitotic inhibitors. These effects are reviewed in terms of their chemistry and biochemistry. Their principal distinctions are that they can be made or degraded intracellularly, they can associate electrostatically with macromolecules by means of their spaced cationic groups, and these can be readily converted to covalent bonds.

Animals↗
PubMed1983

Brain metastases in children.

We reviewed the records of 31 children under the age of 21 years with parenchymal brain metastases diagnosed by CT scan (13 patients) or necropsy (18). Brain metastases were found in 18 of 139 (13%) children with solid tumors in whom complete postmortem examinations were done. Osteogenic sarcoma and rhabdomyosarcoma were the most frequent primary tumors causing brain metastases in patients younger than 15 years, and testicular germ cell tumor, from age 15 to 21 years. Evidence of intratumoral hemorrhage was found in 50% of autopsy cases. Pulmonary metastases were present in 28 of 31 (90%). The median interval from recognition of pulmonary metastases to the development of brain metastases was 10 months. No patient had evidence of brain metastases at diagnosis of the systemic cancer. In only one patient was the brain the only site of relapse. Following detection of brain metastases, the median survival was seven months in six patients who underwent surgery and whole-brain radiation therapy and four months in 15 given radiotherapy (3000 rads) alone. Patients with relatively radioresistant brain metastases may benefit from surgical excision or higher doses of radiation, or both.

Adolescent↗