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Biomedical subjects

M Lewis

Publications and source records attributed to M Lewis.

At least 379 records · Page 21Linked to original sources
PubMed1987

Problems and pitfalls in the isolation of an endogenous Na+, K+-ATPase inhibitor.

Plasma from volume-expanded and salt-loaded hypertensive animals and from patients with essential hypertension has been reported to inhibit Na+, K+-adenosine triphosphatase (ATPase). Inhibition of the sodium pump in vascular smooth muscle caused by such a circulating factor could increase vascular tone and sensitivity to vasoactive agents, and thereby result in arterial hypertension. Numerous efforts in the past failed to isolate the putative factor from urine and plasma. Recent studies have suggested that the hypothalamus is an important source of an endogenous Na+, K+-ATPase inhibitor, but its isolation from the tissue extracts has been rendered difficult by the presence of other cellular constituents that cause artifactual interference with the assays and purification procedures. Using an alternative approach of isolating the inhibitor from culture medium, we found that dispersed fetal rat hypothalamic neurons in a capillary culture system release a heat-stable, peptidic, low-molecular-weight, active sodium transport inhibitor that causes a reversible increase in vascular tone, sensitizes vascular smooth muscle to the vasoactive effect of norepinephrine, and possesses several characteristics of the putative endogenous digitalislike factor. This inhibitor may be a chemical mediator linking kidney, brain, and cardiovascular system in the genesis of experimental volume-expanded and salt-loaded hypertension and human essential hypertension.

Animals↗
PubMed1987

Induction of transient hyperprolactinaemia in neonatal rats by direct or maternal treatment with the dopamine receptor blocker, sulpiride.

Prolactin was measured in the plasma of neonatal rats after iv and ip injection of the dopamine receptor blocking drug sulpiride, and after its ip injection to neonatal rats' nursing mothers. The sulpiride dose PRL response relationship in 10-25 day old neonatal rats was similar to that found in lactating rats, with a threshold sensitivity around 29 nmol sulpiride/kg body weight and a maximal response at about 2.9 mumol/kg. Absolute levels of PRL in the neonate (both peak and increment-over-basal) were, however, 90% lower than in adults. Treatment of lactating mothers with a maximally stimulatory dose of sulpiride (2.9 mumol/kg) twice daily for 4 days resulted in small but highly significant increases in neonatal PRL on days 1 and 2 but complete loss of response by day 4. These data demonstrate that there is a close similarity between the responses of maternal and neonatal rats to sulpiride and that transfer of the drug to the neonate via milk can induce neonatal hyperprolactinaemia. The subsequent loss of the neonatal PRL response on chronic exposure to sulpiride may indicate a degree of disturbance of hypothalamic dopaminergic mechanisms. In the clinical situation this would suggest that doses of dopamine receptor-blocking drugs used to enhance maternal milk production should be carefully chosen.

Animals↗
PubMed1987

Osteosarcoma: relation between extent of marrow infiltration on CT and frequency of lung metastases.

Thirty-seven patients with osteosarcoma were evaluated by CT of both the involved bone and the lungs. The ratio of the extent (E) of the involved marrow segment to the length (L) of involved bone (E/L) was correlated with the presence and subsequent development of pulmonary metastases. The marrow was evaluated by CT for the presence of tumor by measuring mean attenuation coefficients on serial axial scans. Three patient groups were identified: group 1 consisted of seven patients with lung metastases at presentation (mean E/L = 61%), group 2 consisted of 10 patients who developed lung metastases or recurrent tumor either during or after chemotherapy (mean E/L = 39%), and group 3 consisted of 20 patients who completed therapy and remained disease-free (mean E/L = 28%). All patients received chemotherapy in addition to surgical resection except for two patients in group 1. No patient with an E/L ratio greater than 50% remained disease-free for more than 14 months after the initial diagnosis. Fifty percent or greater involvement of the marrow cavity thus carries a particularly poor prognosis, and its absence or presence can be used as a significant prognostic aid in osteosarcoma.

Adolescent↗
PubMed1987

'Low-dose' corticosteroid prophylaxis against fat embolism.

The effect of 'low-dose' corticosteroids (9 mg/kg methylprednisolone), given after skeletal trauma, on the incidence of the fat embolism syndrome and isolated arterial hypoxemia was studied in 42 controls and 40 steroid-treated subjects. Fat embolism occurred in ten controls (23.8%) and one steroid-treated subject (2.5%) (p = 0.01). A further 44 subjects developed isolated hypoxemia. This was severe (PaO2 less than 50 mm Hg) in seven of 32 controls (21.9%) and one of 39 steroid-treated subjects (2.6%) (p = 0.01). The overall incidence of hypoxemia was 67.1%, affecting 33 controls (78.6%) and 22 steroid-treated patients (55%) (p less than 0.05). The degree of hypoxemia was severe (PaO2 less than 50 mm Hg) in 12 controls (28.6%) and two (5%) of the steroid-treated subjects (p = 0.005). No control subject died or required mechanical ventilation. One steroid-treated subject without fat embolism died of a fulminant infection. Although methylprednisolone in a relatively low dose provides protection against fat embolism and pulmonary dysfunction after skeletal trauma, the safety of this therapy requires further evaluation.

Adult↗
PubMed1986

Acute effect of 5-fluorouracil on cytoplasmic and nuclear dihydrofolate reductase messenger RNA metabolism.

Studies were completed in C3-L5178Y cells, in which the DNA-coding region for dihydrofolate reductase messenger RNA (DHFR-mRNA) is amplified, to determine the acute effect of 5-fluorouracil (FUra) on DHFR-mRNA metabolism. There was minimal to no effect of 100 microM FUra on total cytoplasmic DHFR-mRNA levels by 6 and 12 h and only a 25% reduction by 24 h. These results contrasted with the nuclear DHFR-mRNA levels which by 6 h following exposure to FUra increased by 80% in a dose-dependent manner. Furthermore, some of the increased nuclear DHFR-mRNA was found to be in a non-polyadenylated form. Under conditions to examine only RNA synthesized during the drug exposure, FUra was found to markedly enhance the level of newly synthesized nuclear DHFR-mRNA in a dose-dependent manner, while also producing an apparent dose-dependent reduction in the cytoplasmic DHFR-mRNA. RNA fractionated by 1.5% agarose-urea gel electrophoresis revealed two major cytoplasmic DHFR-mRNA species approximately 1.8 and 0.8 kilobases in size. Following a 24-h FUra exposure, a dose-dependent loss of the 0.8-kilobase DHFR-mRNA was observed. The combined results of these experiments indicate that FUra treatment reduces the ability of nascent DHFR-mRNA to relocate to the cytoplasm, suggesting either an inhibition of mRNA processing or nuclear-cytoplasmic transport.

Animals↗
PubMed1986

Characterization of the mechanical behavior of isolated papillary muscle preparations of the ferret.

The characteristics of isometric and isotonic contraction were studied in isolated papillary muscle preparations from the right ventricle of the ferret and compared with those previously reported for comparable preparations from cat and rat. The effects of stimulation rate, temperature, extracellular calcium concentration, caffeine, verapamil, and ouabain were measured. Afterloaded contractions and load clamps were used to study the mechanics of relaxation. The contractile characteristics of ferret papillary muscle preparation appear to be intermediate in many respects between those reported for cat and rat preparations.

Animals↗
PubMed1986

Social and cultural factors in pregnancy complications among Navajo women.

A population of 968 pregnant Navajo women was followed in a prospective study conducted from 1980 to 1983 at the Indian Health Service Hospitals in Gallup and Crownpoint, New Mexico. The purpose of the study was to examine social and cultural influences on obstetric and neonatal complications. The extent of traditional cultural practices and the availability of social support were ascertained in structured interviews completed during each woman's first prenatal visit. In a subsample of women, the occurrence of stressful life events was also measured during a final prenatal visit in the third trimester of pregnancy. Controlling for a variety of conventional risk factors and other potential confounders, traditional women sustained complications at a rate greater than twice that of the least traditional, most acculturated women (approximate relative risk = 2.1; p = 0.001). Social support and life events were modestly associated with maternal complications (approximate relative risk = 0.7, 0.8, respectively; p = 0.07), with poorer outcomes found among those with low social support and low numbers of life events. It is proposed that the relationship of maternal complications to all three sociocultural variables--traditionality, social support, and life events--may reflect the influences of social isolation on the course and outcomes of pregnancy.

Adolescent↗
PubMed1986

The impact of birth order on mother-infant interactions in preterm and sick infants.

Maternal-infant interaction patterns were observed for high-and low-risk, first-, and later-born infants at 3 months of age. The high-risk subjects included healthy preterm infants, sick preterm infants, and sick full-term infants. "Sickness" at birth was defined as respiratory distress or birth asphyxia. The low-risk group consisted of healthy full-term infants. The subjects were divided into first-born and later-born groups. Birth order was expected to interact with prematurity and illness in affecting maternal behavior. Multivariate analyses of variance indicated that this was the case; birth order had a significant impact among the high-risk but not the low-risk subjects. First-born preterm infants received more overall maternal stimulation than later-born preterms. Sick first-borns had more responsive mothers than sick later-born infants. The results suggest that high-risk later-born infants may be at greater risk as a result of both birth trauma and less optimal maternal interaction patterns.

Asphyxia Neonatorum↗
PubMed1986

The role of resident accessory cells in corneal allograft rejection in the rabbit.

Corneal grafts are more likely to be rejected when placed in a vascularized rather than in a normal host cornea. Using immunohistochemical techniques, normal rabbit cornea was found to contain measurable numbers of cells of hemopoietic origin, probably of either macrophage or dendritic lineage. After the deliberate induction of corneal inflammation and neovascularization, the number of these accessory cells was found to increase significantly. There was also a marked increase in the number of T cells present. Enzyme staining indicated a degree of heterogeneity in the infiltrate. The process of rejection of rabbit corneal grafts was found to occur earlier when additional infiltrating cells were present in either donor button or graft bed, and earlier still when the load of infiltrating cells was increased in both donor and recipient. We hypothesize that resident accessory cells of recipient origin may be implicated in graft rejection in vascularized, inflamed corneas.

Animals↗
PubMed1986

Some aspects of epidural block provided for elective caesarean section.

We present here clinical data from 993 patients who were destined to undergo elective Caesarean section under epidural analgesia. In 29 cases the attempt to provide an epidural was abandoned before the operation started. In regard to this, the importance of monitoring the fetal heart rate during initiation of the epidural is emphasised. In 10 cases general anaesthesia was induced after delivery, and in a further 108 cases supplemental analgesia was administered, either systemically, by inhalation or by an additional epidural top-up, after delivery. Satisfactory analgesia throughout the operation was achieved in 87.8%. In an appreciable proportion of cases the recommended maximum dose of bupivacaine, and the recommended maximum rate of bupivacaine administration, were exceeded without apparent complication. There was a tendency for the volume of Hartmann's solution infused intravenously before and during initiation of the epidural to be increased throughout the period under review (1971-85). The prevalence of hypotension diminished during that period. Characteristics of the data did not permit a close analysis of the main factors which could have led to an episode of maternal hypotension. However, it did appear that such an episode could be ascribed to too brief an interval between the first and second, or the second and third top-up doses. The frequency with which blood was transfused during operation was markedly lower than that noted in a concurrent series of elective sections conducted under general anaesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Epidural↗
PubMed1986

Nitrous oxide in early human pregnancy.

An analysis of the outcome of 375 cases (383 fetuses) of cervical cerclage and 58 other operations (59 fetuses) conducted under general anaesthesia, which included the administration of nitrous oxide, failed to reveal a single instance of which nitrous oxide could have been clearly indicted as a cause of fetal abnormality The incidence of inevitable abortion and of low birth weight babies in the series of cervical cerclage conducted under general anaesthesia was identical to that in a series conducted under regional analgesia (115 fetuses). This represents the first of a two-part test of the proposition that nitrous oxide should not be administered to women in the first or second trimester. Our interim conclusion is that the proposition is unacceptable.

Abnormalities, Drug-Induced↗
PubMed1986

Hypothalamic D2 receptors mediate the preferential release of somatostatin-28 in response to dopaminergic stimulation.

We have studied the effect of dopamine (DA) together with agonist and antagonist drugs of varying specificity on the release of immunoreactive forms of somatostatin (SS) from the perfused, adult rat hypothalamus in vitro. Levels of SS increased from 14.7 +/- 3.7 pg (mean +/- SE) under basal conditions to 137 +/- 23.0 pg after exposure to 10(-6) M DA. This dopaminergic effect was mimicked by the specific D2 agonists bromocriptine (10(-7) M) and LY 171555 (10(-6) M) but not by the D1 agonist SKF 38393A (10(-6) M). The stimulatory action of DA (10(-6) M) was blocked by the active (d) but not the inactive (l) isomer of butaclamol (10(-7) M). Similar blockade was achieved with the specific D2 antagonists metoclopramide (10(-8) M) and domperidone (10(-8) M), whereas the D1 antagonist SCH 23390 partially blocked the stimulation of DA but only when used at X100 greater concentration (10(-6) M). SCH 23390 (10(-8) M) did not affect the dopaminergic stimulation of SS release. HPLC characterization of the immunoreactive forms of SS yielded two peaks which corresponded to SS-28 and SS-14. The ratio of these forms varied significantly under different conditions. In the basal state the ratio of SS-28 to SS-14 was 1:4.4; in response to stimulation with DA, the ratio was 1:1.7 and in response to depolarization with 60 mM K+ the ratio was 1:3.1. In conclusion, the stimulatory action of DA on SS release is mediated via hypothalamic D2 receptors. Furthermore dopaminergic stimulation increases the molar ratio of SS-28 to SS-14 in the total immunoreactive SS which is released.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗