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Biomedical subjects

M Morris

Publications and source records attributed to M Morris.

At least 325 records · Page 18Linked to original sources
PubMed1990

Central serotonergic mechanisms in cardiovascular regulation.

This paper reviews the role of central serotonin-containing neurons in the control of blood pressure. Central serotonin nerves have their cell bodies in the brainstem in a number of discrete collections, from where they ascend to ramify throughout the brain, descend to terminate in the spinal cord, or send shorter projections terminating in medulla, pons, and midbrain. Activation of one important ascending serotonin pathway innervating the preoptic region of the hypothalamus causes an increase in blood pressure. Activation of a bulbospinal serotonin projection descending from the ventrolateral medulla (the B3 cell group) to terminate in the intermediolateral cell column (IML) also evokes a pressor response. This pressor response is independent of that elicited by stimulation of the ventrolateral medulla in the adjacent but separate area containing the C1 adrenaline cell group. The pressor action appears to depend on increased release of serotonin, as detected by microdialysis in the area of the IML, and to be mediated by serotonin receptors of the 5HT1 subclass, probably located on sympathetic preganglionic neurons. It is possible that neuroactive excitatory amino acids, such as glutamate or aspartate, and neuropeptides such as substance P, also play a part in the pressor response evoked by stimulation of the ventrolateral medulla in the area of the lateral B3 serotonin cells. This descending serotonin pathway also appears important in mediating the hypotensive action of the antihypertensive drugs methyldopa and clonidine.

Animals↗
PubMed1990

Recombinant human erythropoietin therapy in children maintained by haemodialysis.

Six children (aged 3 years 11 months to 15 years 9 months) with end-stage renal failure and anaemia (mean haemoglobin 7.1 g/dl, range 6.3-7.7 g/dl) on thrice-weekly haemodialysis were treated with recombinant human erythropoietin (rHuEPO), given as an intravenous bolus in an escalating dose regime after dialysis. All responded with an increase in reticulocyte count and haemoglobin concentration in a mean time of 11 weeks (range 9-13 weeks) and at a dose of 100 or 150 units/kg thrice weekly. The dose of rHuEPO was then adjusted to maintain the haemoglobin concentration within the lower half of the normal range for the child's age and sex. The mean haemoglobin after 12 weeks treatment was 10.9 g/dl (range 8.5-12.1 g/dl) and after 24 weeks, 10.5 g/dl (range 7.9-13.3 g/dl). Four children had no further need for blood transfusion and are thus no longer at risk of blood-borne infection, iron overload and sensitisation to HLA histocompatibility antigens. Serum ferritin fell in the three patients with evidence of iron overload; the three with low or normal iron stores at the onset of treatment maintained erythropoiesis with oral iron supplementation. HLA antibodies decreased in all patients. The only serious complication encountered was thrombosis of vascular access in one child. No child became seriously hypertensive or developed cerebral symptoms. The benefits of rHuEPO therapy for children with end-stage renal failure are potentially considerable and with careful monitoring, the risks low.

Adolescent↗
PubMed1990

Comparison of recombinant-interleukin-2-activated peripheral blood and tumor-infiltrating lymphocytes of patients with epithelial ovarian carcinoma: cytotoxicity, growth kinetics and phenotype.

We have compared the growth and tumor-directed cytotoxic efficacy of recombinant-interleukin-2-(rIL-2)-activated peripheral blood (PBL) and tumor-infiltrating lymphocytes (TIL) from patients with epithelial ovarian carcinoma. These studies demonstrated that TIL and PBL displayed similar levels of cytotoxicity and a broad range of target cell killing, as exemplified by their reactivity against autologous and allogeneic ovarian tumors as well as against tumor cell lines. No specificity of autologous tumor cell killing was manifested by TIL. Even though TIL of some patients showed higher proliferative activity (especially at the later times in rIL-2 culture) this was not a general phenomenon. In fact, in one case TIL did not proliferate at all, and in the other case the PBL proliferated more actively. While the cultures were composed primarily of CD3+ lymphocytes, the major cytotoxic cells displayed the CD56+ and CD16+ phenotype. Addition of OKT3 mAb to rIL-2 cultures resulted in an increased proliferative index, but showed only a minor effect on the cytotoxic potential of cultured lymphocytes. The therapeutic potential of rIL-2-activated TIL and PBL is discussed.

Antigens, CD↗
PubMed1990

Effects of temporary withdrawal from regular running.

Forty regular male runners were divided into two similar groups and studied for six weeks. One group continued normal running, but the other stopped running for the middle two weeks of the study. Questionnaires were completed at the end of each week. Symptoms of depression were greater in the withdrawn than in the control group at the end of the second week of withdrawal. Somatic symptoms, anxiety, insomnia and feelings of being under strain were greater in the withdrawn group after both the first and second weeks of withdrawal. The groups did not differ in the final two weeks, when running had been resumed. These effects strengthen the view that stopping regular physical exercise produces a 'withdrawal syndrome', and that exercise might therefore be regarded as addictive. The increase in depression may reflect a more gradual loss of the antidepressive effect of exercise training.

Adaptation, Psychological↗
PubMed1990

Radical wide excision and selective inguinal node dissection for squamous cell carcinoma of the vulva.

Limited resection of some vulvar cancers may provide cure rates equivalent to those obtained with radical vulvectomy and bilateral inguinal node dissection. Rapid recovery, fewer complications, and better functional result have been described as advantages to less extensive procedures. Since 1978, 32 patients with invasive squamous cell cancer of the vulva (depth greater than 1 mm) and clinically negative inguinal lymph nodes underwent radical wide excisions as primary therapy. Mean age at diagnosis was 61 years. Seventeen patients had T1 and 15 had T2 tumors. Resection of the primary lesion was tailored to lesion location and size, and dissection was carried to the deep perineal fascia. Twenty-two patients had unilateral superficial inguinal lymph node dissections, five with midline lesions had bilateral superficial dissections, and five had node samplings which included deep inguinal nodes. Depth of invasion ranged from 1.5 to 13.0 mm. Mean largest lesion dimension was 23 mm. Five-year lifetable survival for the entire group was 84%. Univariate analysis of potential prognostic variables showed no significant recurrence or survival differences for patient age (P = 0.56), symptom duration (P = 0.57), FIGO stage (P = 0.67), tumor grade (P = 0.20), tumor location (P = 0.26), depth of invasion (P = 0.56), or resection margin status (P = 0.63). Thirty-one percent of patients had perioperative complications, and 16% developed delayed complications. Mean hospital stay was 10 days. Three patients (10%) developed new or recurrent vulvar disease and underwent additional therapy. None have died of disease, although one is alive with persistent tumor. Radical wide excision and selective inguinal lymphadenectomy constitute a reasonable alternative to radical vulvectomy with bilateral inguinal node dissections for squamous tumors clinically limited to the vulva. Outcome may not be strongly influenced by lesion size or depth of invasion.

Adult↗
PubMed1990

Child sexual abuse: who goes home?

The purpose of this study was to ascertain the factors which influence custody change in cases of children who have been sexually abused. Of 180 children admitted to La Rabida Children's Hospital and Research center with a suspicion of having been sexually abused, 138 met the state's criteria for proven sexual abuse, and 30% of those children had a sexually transmitted disease. One-third of the children with proven abuse were under 4 years of age. Of the children with proven abuse, ultimately 40% had a custody change. Only an initial outcry of abuse was associated with an increased probability of a change in custody. A change in custody was not found to be related to the patient's age, sex, the perpetrator's relation to the child or access to the home, the presence of sexually transmitted disease, whether the child was also physically abused, or whether the child had had developmental delay. These data suggest an absence of any discernible guidelines in the juvenile court's decision concerning custody change of a sexually abused child.

Adolescent↗
PubMed1990

Neuropeptide gene expression in hypothalamic magnocellular neurons of normal and hypophysectomized rats: a combined immunohistochemical and in situ hybridization study.

Hypothalamic magnocellular neurons of the paraventricular and supraoptic nuclei contain several peptides and non-peptide putative neurotransmitters co-existing with vasopressin and oxytocin. However, the functional role of these substances is still unknown. In the present paper the temporal course of changes in the expression of vasopressin, oxytocin, galanin, cholecystokinin, dynorphin and tyrosine hydroxylase in magnocellular hypothalamic neurons of rats subjected to hypophysectomy was examined. Following different survival times the animals were processed either for immunohistochemistry with antibodies against the above mentioned peptides or for in situ hybridization with synthetic oligonucleotide probes complementary to the mRNAs encoding for the peptides. The results obtained showed a marked rise in vasopressin mRNA levels at two days followed by a decrease up to 36 days of survival. Oxytocin mRNA responded to the lesion with a transient decrease, with its lowest values between five and seven days. This was followed by a recovery which almost reached normal values at 36 days of survival. The results also showed a marked, transient activation of the synthetic pathway for galanin and cholecystokinin. The numbers of cells expressing these peptides were maximal between five and seven days, and the respective mRNA levels were significantly increased at these survival times. This was followed by a decrease in the amount of galanin- and cholecystokinin-like immunoreactivity as well as in the levels of their respective mRNAs. Dynorphin-like immunoreactivity showed a course similar to that of galanin and cholecystokinin in operated animals. However, the amounts of dynorphin mRNA were significantly increased at two days, but were followed by a reduction at five days and remained low throughout the different survival times tested. The experiments performed with the tyrosine hydroxylase antibodies and probe showed undetectable levels of the enzyme and its mRNA in normal and hypophysectomized animals. These results demonstrate that, in magnocellular hypothalamic neurons, expression of several peptides occur in differential ways after hypophysectomy. The possibility is discussed that these changes represent part of the mechanisms underlying the process of degeneration and regeneration known to occur in magnocellular hypothalamic neurons after hypophysectomy.

Animals↗
PubMed1990

Endogenous opioids modulate the cardiovascular response to mental stress.

The role of endogenous opioids in the cardiovascular response to mental stress was investigated in two controlled studies. In the first, cardiovascular, hormonal and psychological measures were made in a group of subjects before, during and after presentation of either a mental stress task or a non-stressful control task in the presence of naloxone (8 mg), an opiate antagonist, or an equal volume of saline. The study was carried out in random order and single(subject)-blind. Naloxone specifically enhanced the heart rate response to the stressful task but had no effect on blood pressure, plasma epinephrine or norepinephrine, or feelings of anxiety. Naloxone increased plasma cortisol and ACTH in both stressful and control tasks. A second, double-blind, study replicated the effect on heart rate. An endogenous opioid mechanism thus appears to inhibit the cardiovascular response to stress.

Adolescent↗
PubMed1990

Sleep-onset insomniacs have delayed temperature rhythms.

It was predicted from free running and ultradian cycle studies that sleep-onset insomniacs would have endogenous circadian rhythms that were phase delayed compared to good sleepers. Thirteen sleep-onset insomniacs and nine good sleepers were selected to differ only in their sleep-onset latencies as confirmed by polysomnography. their rectal temperatures were measured over a 26-h constant routine and analyzed with best-fit Fourier curves including 24-h fundamental and 12-h harmonic components. The temperature rhythm markers of the insomniacs' rhythms were approximately 2.5 h later than the respective phases of the good sleepers. The usual bedtimes of the insomniacs fell within the "wake maintenance zone" of their delayed temperature rhythm. The good sleepers had typical bedtimes several hours after their "wake maintenance zone" and closer to their body temperature minimum. It was suggested that manipulations to phase advance the insomniacs' rhythms would reduce their sleep-onset latencies. It was also predicted that early morning insomnia results from phase advanced circadian rhythms and that sleep maintenance insomnia results from an abnormal phase relationship between the 24-h temperature rhythm and 12-h sleep-alert rhythm.

Adult↗
PubMed1990

Differences in the central hypotensive actions of alpha-methyldopa and clonidine in the spontaneously hypertensive rat: contribution of neurons arising from the B3 and the C1 areas of the rostral ventrolateral medulla.

The rostral ventrolateral medulla (RVLM) is the proposed site of origin of bulbospinal excitatory vasomotor neurons, and this brainstem area gives rise to chemically distinct populations of neurons, including serotonin-containing neurons of the B3 group and epinephrine-containing neurons of the C1 group, which independently serve sympathoexcitatory functions. In the present study, we sought to establish (a) whether distinct and chemically specific pathways originating in the C1 or B3 regions are involved in the antihypertensive effects of alpha-methyldopa (methyldopa) and clonidine and (b) if so, whether these effects are related to an activation of alpha-adrenoceptors in these areas. Microinjections of methyldopa (6 nmol) or clonidine (5 nmol) were made in the C1 or B3 area in intact spontaneously hypertensive rats (SHR), pretreated with 5,7-dihydroxytryptamine (5,7-DHT) or with phentolamine. The microinjection of clonidine into both the B3 and the C1 area caused a rapid decrease in arterial pressure, whereas microinjection of methyldopa lowered the arterial pressure only after injection into the B3 area. Pretreatment with intracerebroventricular (i.c.v.) 5,7-DHT attenuated the hypotension produced by microinjection of clonidine into the B3 area, suggesting that this effect is mediated by serotonin-containing neurons. Central pretreatment with phentolamine reduced the hypotensive effects produced by injection of clonidine into either area and of methyldopa into the B3 region, consistent with previous suggestions that these central effects are mediated through alpha-adrenoceptors. These results suggest that both serotonin-containing and epinephrine-containing neurons contribute to the central action of clonidine, whereas the effects of methyldopa injection in RVLM appear to be mediated by serotonin-containing but not by epinephrine-containing neurons.

5,7-Dihydroxytryptamine↗
PubMed1990

The effect of sleep/wake state on nocturnal melatonin excretion.

Twenty-four hour patterns of urinary 6-sulphatoxymelatonin excretion were monitored in eight healthy adult subjects in two bed rest constant routines, one with normal nocturnal sleep and one with continuous wakefulness. The implementation of dim light "constant routines" enabled the effect of the sleep wake/state on melatonin to be tested without the confounding effects of body activity and normal room lighting. In both conditions 6-sulphatoxymelatonin excretion was significantly higher during the nighttime hours (2200-1000) than during the daytime hours (1000-2200) producing averages of 80% and 78.5% of the total 24 hour output in the sleep and wakeful conditions, respectively. The large differences between subjects in nocturnal melatonin excretion (38 to 150 nmol) were highly consistent between the two conditions. There were no differences between the nocturnal wakeful and sleep conditions in total nighttime melatonin excretion nor in the nighttime percentage of the 24 hour total melatonin excretions. Therefore, the sleep/wake state alone had no effect on nocturnal melatonin excretion. On the other hand, a significant correlation between the nighttime melatonin percentage and sleep length suggested the need to investigate further the relation between the amplitude of the melatonin circadian rhythm and sleep length and quality.

Adult↗
PubMed1990

National symposium on problems of presymptomatic testing for Huntington's disease, Cardiff.

Presymptomatic testing for Huntington's disease has given rise to several ethical problems relating to such issues as confidentiality, the privacy of the individual, the testing of minors and informed consent in connection with blood sample donation. A multidisciplinary conference of staff from genetic centres involved with presymptomatic testing was organised in Cardiff to discuss these and other problems. Recommendations on good practice are described under four headings: pre- and post-test counselling; confidentiality in relation to test results; collection and storage of DNA, and criteria for testing.

Confidentiality↗
PubMed1990

Regulation of plasma atrial natriuretic peptide by the central nervous system.

The anterior ventral region of the third ventricle (AV3V) is a major central site in the regulation of cardiovascular and renal function. To examine the role of the central nervous system in the regulation of atrial natriuretic peptide (ANP) secretion, the effect of lesions in this region on basal, volume-stimulated, and osmotic-stimulated plasma ANP was determined. Basal levels of plasma ANP were not different in sham- and AV3V-lesioned rats. Volume expansion with a continuous infusion of saline or with a bolus administration of saline increased plasma ANP in sham-lesioned rats. In AV3V-lesioned rats, continuous infusion of saline had no effect on plasma ANP, and a bolus administration of saline decreased plasma ANP. Osmotic stimulation with hypertonic saline increased plasma ANP in sham-lesioned rats but had no effect on plasma ANP in AV3V-lesioned rats. These results suggest that the central nervous system is involved in the regulation of ANP secretion and that altered ANP regulation may contribute to the cardiovascular and renal deficiencies in AV3V-lesioned rats.

Animals↗
PubMed1990

Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin.

Since 1984, we have treated 26 patients with malignant ovarian germ cell tumors with a combination of bleomycin, etoposide (VP-16), and cisplatin (BEP) at The University of Texas MD Anderson Cancer Center (UTMDACC). The median age of the patients was 19 years (range, 8 to 32). All patients underwent initial surgery (unilateral salpingo-oophorectomy in 14, unilateral salpingo-oophorectomy plus abdominal hysterectomy in one, and bilateral salpingo-oophorectomy with or without hysterectomy in 11 patients). Twenty patients had no residual disease, three had less than or equal to 2 cm (one each, dysgerminoma, mixed, and immature teratoma), and three had more than 2 cm lesions (two dysgerminomas, one endodermal sinus tumor). Fourteen patients had pure dysgerminoma (five, stage I; one, stage II; six, stage III; and two, recurrent), and 12 had nondysgerminomatous tumors (five, stage I; two, stage II; three, stage III; and two, recurrent). All four patients with clinically measurable disease had a complete response. All four patients who underwent second-look laparotomy had negative findings. Twenty-five patients (96%) remain in sustained remission 10.4 to 54.4 months from the start of chemotherapy. One patient died of progressive disease 14 months after beginning chemotherapy. We conclude that the BEP regimen has excellent activity and acceptable toxicity in patients with malignant ovarian germ cell tumors.

Adolescent↗
PubMed1990

Efficacy of local graft irradiation in preventing cadaveric renal transplant rejection: a prospective randomized trial.

Successful renal transplantation depends on the modification of the normal immunologic response. The earliest attempts at such modification involved the use of ionizing irradiation. The significant morbidity and mortality of total body irradiation led to its abandonment in favor of the safer technique of local graft irradiation. While still commonly used, the efficacy of this technique has never been evaluated in a prospective, randomized fashion. The present study is a prospective, randomized, double blinded evaluation of the efficacy of the addition of local graft irradiation to our immunosuppressive protocol. One hundred consecutive cadaveric renal transplants were randomized to receive either conventional immunosuppression alone or conventional immunosuppression plus local graft irradiation delivered in doses of 150 rads on the 1st, 3rd and 5th post-operative days. Patients were followed for a period of 2 years. No significant difference was demonstrated between the groups among any measured parameter. In conclusion, the addition of local graft irradiation in doses of 150 rads on d 1, 3, and 5 does not appear to offer any advantage over standard immunosuppressive therapy and its use cannot be recommended.

Adult↗
PubMed1990

Treatment of fallopian tube carcinoma with cisplatin, doxorubicin, and cyclophosphamide.

Primary carcinoma of the fallopian tube is uncommon and is often treated using regimens active in ovarian carcinoma. Evidence is scant that such therapies benefit patients with fallopian tube carcinoma. Between December 1979 and July 1988, we treated 18 patients who had adenocarcinoma of the fallopian tube with the combination of cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) administered intravenously on 1 day every 28 days. Histologic confirmation of fallopian tube carcinoma was obtained before entry in the study. Three patients had stage I disease, five had stage II, nine had stage III, and one had stage IV. Sixteen patients received the combination therapy as first-line treatment after cytoreductive surgery, and two patients received it for recurrent carcinoma. Seven patients had clinically measurable disease at the start of therapy. Two of these patients had a complete clinical response, two had stable disease, and three had progressive disease. Eight of the 15 patients with stages II-IV disease underwent second-look laparotomy; four had a complete response to therapy and four had a partial response, making the overall response rate 53%. The toxicity of the regimen was moderate. The median survival was 81 months. Patients with stages II-IV disease had a median survival of 43.9 months and a progression-free survival of 22.5 months. This regimen appears to be active in fallopian tube carcinoma and can result in response rates comparable to those reported for epithelial ovarian cancer.

Adenocarcinoma↗