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Biomedical subjects

K Henderson

Publications and source records attributed to K Henderson.

At least 55 records · Page 3Linked to original sources

Organisation and gel contraction by human colonic carcinoma (HCA-7) sublines grown in 3-dimensional collagen gel.

The role of cell-matrix interactions in controlling phenotypic heterogeneity in human colonic carcinoma sublines has been investigated. Four cell lines (colony 1, colony 3, colony 6 and colony 30) previously isolated from a single human colonic carcinoma cell line, HCA-7, were grown in 3-dimensional collagen gels. In collagen, the growth of the 4 sublines ranged from well-organised glandular structures (colony 30) to elongated branching structures (colony 3). The capability of cells to organise into glandular structures in collagen correlated with the degree of differentiation observed in their xenografts. Certain sublines, most notably colony 3, were able to contract the collagen gel. Gel contraction could be partially inhibited by a function-blocking antibody directed to the alpha 2 integrin chain but not by an antibody directed to the alpha 3 integrin chain demonstrating a role for alpha 2 integrin in the contraction process. In addition, colony 3 cultures treated with the function-blocking alpha 2 antibody formed more compact structures with limited outgrowth, suggesting a role for alpha 2 integrin in cell migration. Gel contraction and cell migration in collagen gel was largely restricted to 1 subline, colony 3. The subsequent demonstration that alpha 2 integrin is involved in both of these processes suggests that integrin expression and function has a role in generating the phenotypic heterogeneity exhibited by these cell lines.

Collagen↗

Dietary calcium intake in 18-year-old women: comparison with recommended daily intake and dietary energy intake.

Average dietary calcium intake and energy intake of 113 18-year-old university students in Western Australia was examined. Four-day, weighted diet records, including 1 weekend day, were completed by the subjects. A large proportion of the students (68%) had an average daily calcium consumption below the 800 mg recommended by the National Health and Medical Research Council of Australia. A strong positive association was also found between dietary calcium and dietary energy intakes. Many young women on self-imposed energy reduction diets are at risk of a dietary calcium intake deficit at a time when it should be enhanced. These findings are significant for nursing practice as they indicate the need for further health education concerning the importance of dietary calcium in young women.

Adolescent↗

Endocrine and mucous differentiation by a cloned human rectal adenocarcinoma cell line (HRA-19) in vitro: inhibition by TGF-beta 1.

Colorectal epithelium is composed of absorptive, mucous and endocrine cells, all of which are considered to arise from a common stem cell located in the crypt base. However, the factors controlling the commitment to differentiate are poorly understood. This is partly due to the lack of in vitro model systems for the study of differentiation in colorectal epithelium. The HRA-19 cell line, established from a human rectal adenocarcinoma, has been shown to have multipotential characteristics with cloned HRA-19 cells able to differentiate into absorptive, mucous and endocrine cells when grown as xenografts. The lack of such differentiated cells in HRA-19 monolayers in vitro suggests that differentiation is controlled by extracellular matrix, stromal cells and/or soluble factors. Such observations show that differentiation in HRA-19 cells can be controlled by extrinsic factors and therefore provide a model system for studying control of differentiation in colorectal epithelium. Unfortunately, the restriction of differentiation to xenografts of the cell line limits the degree to which this differentiation can be manipulated. In this study, the possibility that HRA-19 cells could be induced to differentiate in vitro under appropriate conditions has been investigated. Endocrine and mucous cells were identified by immunocytochemistry with differentiation-related antibodies and histology of monolayers. Preconfluent HRA-19 cells grown in 10% foetal calf serum formed a well polarised monolayer with apical tight junctions and sparse microvilli, but cells with mucous or endocrine phenotypes were only very occasionally observed. However, endocrine and mucous cells could reproducibly be demonstrated in postconfluent monolayers grown in 1% foetal calf serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Bupivacaine versus bupivacaine plus fentanyl for epidural analgesia: effect on maternal satisfaction.

OBJECTIVE: To compare a combination of epidural fentanyl and bupivacaine with bupivacaine alone for epidural analgesia in labour and to evaluate factors in addition to analgesia that may influence maternal satisfaction. DESIGN: A prospective randomised pilot study. SETTING: Birmingham Maternity Hospital. SUBJECTS: 85 primiparous women who requested epidural analgesia in labour and their babies. INTERVENTIONS: Group 1 mothers were treated with bupivacaine conventionally, group 2 mothers with bupivacaine and fentanyl in a more complex way designed to provide satisfactory analgesia but with less troublesome side effects. MAIN OUTCOME MEASURES: Overall maternal satisfaction, maternal perception of epidural analgesia and its side effects, and aspects of mothers' psychological states during labour, quantified using 100 mm visual linear analogue scales; the frequency of normal and operative deliveries; and measurements of neonatal wellbeing. RESULTS: Satisfaction was higher in group 2 mothers (median group difference +3 mm, 95% confidence interval +1 to +5, p = 0.012): this was associated with more normal deliveries (difference between proportions 0.23, 95% confidence interval +0.03 to +0.42); greater self control (median group difference -7 mm, -17 to -2, p = 0.003); and reduced unpleasantness of motor blockade (-10 mm, -19 to -5, p less than 0.001), sensory blockade (-5 mm, -11 to -2, p = 0.002) and shivering (-5 mm, -18 to 0, p = 0.046) at the expense of mild itching (0 mm, 0 to 0, p less than 0.001). Group 1 mothers found restricted movements more unpleasant (-1 mm, -11 to 0, p = 0.006) and were more sleepy (-4 mm, -20 to 0, p = 0.032). The addition of fentanyl to bupivacaine reduced the requirement for local anaesthetic (-33 mg, -55 to -15, p less than 0.001) without compromising analgesia. No adverse effects in neonates were attributed to the use of fentanyl. CONCLUSIONS: The already high maternal satisfaction from conventional epidural analgesia can be improved; epidural fentanyl may be combined with bupivacaine to reduce operative deliveries and confer other advantages that may increase maternal satisfaction. Further investigations should be performed to determine the exact mechanisms of these findings and, in particular, to develop a safe method of delivering such analgesia to women.

Analgesia, Epidural↗

Effects of social isolation on brain catecholamines and forced swimming in rats: prevention by antidepressant treatment.

Post-weaning rats were housed alone or in groups for a period of 4 or 8 weeks. A portion of the animals received tricyclic antidepressant treatment, desipramine 20 mg/kg/day, during this period. Animals were then tested behaviorally by forced swimming. Isolation was associated with significantly longer durations of immobility during forced swimming. This was blocked by desipramine treatment. Desipramine treatment did not have a significant effect on the swimming durations of group-housed rats. Hindbrain and midbrain levels of catecholamines were subsequently measured and turnover rates estimated by administration of alpha-methyl-p-tyrosine or saline. Isolated rats had increased levels and decreased turnover of catecholamines. The increase in norepinephrine but not dopamine levels was blocked by desipramine, while antidepressant effects on turnover could not be tested with this method. Reduced social stimulation thus appears to be associated with reduced catecholamine release which may result in the accumulation of these transmitters in the central nervous system. Treatment with desipramine appeared essentially to compensate for reduced social stimulation, blocking isolation-induced noradrenergic neurochemical changes, while having few significant effects on control animals. This study may be helpful in furthering our understanding of how the interaction of organisms with their environment influence catecholamine systems and how antidepressants may act to restore function.

Animals↗

Upper-limb and lower-limb exercise training in patients with chronic airflow obstruction.

We designed a randomized controlled study to evaluate the benefit of upper-limb exercise training, alone and in combination with walking training, in patients with severe CAO. In an outpatient department supervised by a physiotherapist, we evaluated 28 patients with severe stable CAO (FEV1, 32 percent of predicted). Patients were randomly allocated to either a control (eight), upper-limb (six), lower-limb (seven), or combined (seven) exercise group. The upper-limb group trained with a circuit of upper-limb exercises, the lower-limb group by walking, and the combined group with both. Exercise was for one hour three times per week for eight weeks. Assessment before and after training included pulmonary function, mouth pressures, respiratory muscle endurance, maximal bicycle exercise test, maximal and submaximal arm ergometer, six-minute walking distance, and a scale of well-being (Bandura scale). Twenty-six patients completed the program. There was a significant improvement (Wilcoxon rank sum test) in the following: six-minute walking distance in the lower-limb (p less than 0.005) and combined (p less than 0.003) groups; arm ergometer in the upper-limb (p less than 0.005) and combined (p less than 0.04) groups; and the scale of well-being in the combined (p less than 0.005) group. There was no significant change in any other parameter measured. We conclude that exercise training improves exercise performance in severe CAO, that the training is specific for the muscle group trained, and that upper-limb exercises should be included in training programs for these patients.

Aged↗

Cardiovascular effects and modulation of noradrenergic neurotransmission following central and peripheral administration of neuropeptide Y.

Experiments have been conducted to evaluate the effect of neuropeptide Y (NPY) administered at three distinct levels of the nervous system: 1) the posterior hypothalamic nucleus, 2) the spinal cord, and 3) the vascular noradrenergic neuroeffector junction. It was observed that NPY produced varying cardiovascular effects at these three distinct sites of the nervous system. Microinjections into the posterior hypothalamic nucleus resulted in an increase in blood pressure, which was reduced by prior microinjection of a muscarinic or H1-histamine antagonist but not an H2-histamine antagonist. In addition to the involvement of histaminergic and cholinergic pathways, the pressor effect of NPY appears to result from an increase in sympathetic outflow. NPY was also seen to decrease the potassium-induced release of norepinephrine (NE) from slices obtained from the posterior hypothalamic nucleus. In contrast to what was observed in the hypothalamus, the intrathecal injection of NPY at a level of T4 or T10 in anesthetized or T10 in unanesthetized rats resulted in a depressor effect as well as a decrease in heart rate. Both an alpha 2- and beta-adrenoceptor antagonist reduced the NPY effect. The depressor effect of intrathecal NPY was attenuated in rats pretreated with reserpine as well as in Spontaneously Hypertensive rats (SHR). These data suggest that the effects of NPY are closely associated with sympathetic preganglionic neurons in the spinal cord. At the vascular noradrenergic neuroeffector junction, NPY decreased the nerve stimulation-induced release of NE while potentiating the contractile response. Moreover, NPY potentiated the increase in perfusion pressure of the perfused mesenteric arterial bed in response to angiotensin, vasopressin, or phenylephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Alterations in blood pressure of normotensive and hypertensive rats following intrathecal injections of neuropeptide Y.

The effect of the intrathecal administration of neuropeptide Y (NPY) on blood pressure and heart rate of anesthetized normotensive and hypertensive rats was studied. Neuropeptide Y was observed to produce a decrease in the blood pressure of Sprague-Dawley, Wistar Kyoto (WKY), DOCA-salt, and DOCA-sham control rats. The maximum percent decrease in blood pressure of Sprague-Dawley rats was 12.8 and 15.2% in response to 0.1 and 1.0 nmol NPY, respectively. Similar changes in heart rate were observed. The depressor effect of intrathecal NPY was attenuated by prior treatment with yohimbine and propranolol but not prazosin. The depressor effect of intrathecal NPY observed in normotensive and DOCA-salt hypertensive rats was not seen in the spontaneously hypertensive rat (SHR). The studies extend to the spinal cord the list of regions and tissues where NPY can produce physiological effects. It is concluded that the effects of NPY are closely associated with sympathetic preganglionic neurons in the spinal cord that the depressor effect of NPY involves alpha 2 and beta adrenoceptors, and that a loss of the depressor effect of NPY may contribute to the development or maintenance of hypertension in the SHR.

Adrenergic alpha-Antagonists↗

Spinal arteriovenous malformations: some diagnostic difficulties with illustrative cases.

Spinal arteriovenous malformations commonly present with progressive or step-like cord and conus dysfunction. Diagnosis is achieved by demonstrating abnormal vessels on the cord by means of high-quality myelography followed by selective spinal angiography. Diagnostic difficulties arise where screening myelography is equivocal or where angiography is negative in patients with suggestive myelographic findings. Negative investigation may not exclude a spinal arteriovenous malformation in patients with very suggestive clinical presentations. Occasionally reinvestigation after a period of follow-up or surgical exploration, even in the absence of a definite diagnosis, may be indicated.

Arteriovenous Malformations↗

Caudate hemorrhage.

We studied 12 patients with intracerebral hemorrhage in the head of the caudate nucleus. These cases accounted for 7% of a consecutive series of intracerebral hemorrhage. The clinical findings differed from more common varieties of supratentorial hemorrhage. All patients had acute onset of vomiting, headache, stiff neck, decreased level of consciousness, and behavioral changes in a pattern that simulated subarachnoid hemorrhage. Seven patients had gaze paresis and hemiparesis, with or without sensory loss. Two of these seven patients had, in addition, elements of Horner's syndrome. The prognosis for recovery was good. No patient had recurrent hemorrhage or persistent hydrocephalus.

Adult↗

Cytomegalovirus infection in pregnancy: preliminary findings from a prospective study.

8278 (56%) of 14 789 pregnant women who were screened for cytomegalovirus (CMV) antibodies at their first antenatal visit were seropositive. 42 (3 per 1000) infants screened were congenitally infected. 3 (7%) have serious handicaps, 14 (33%) have minor or transient problems, and 25 (60%) have so far had no problems. In 26 of the 42 mothers with infected infants CMV antibodies were present in the first antenatal blood sample. 28 (67%) of the infected infants were born to mothers who had experienced a primary infection in pregnancy and 7 (17%) to mothers who had experienced recurrent infection. In the remaining 7 (17%) it was not possible to determine the type of maternal infection. One handicapped infant was born after a probable recurrent CMV infection during pregnancy. These preliminary findings suggest that routine screening of pregnant women to detect evidence of primary CMV infection is not helpful.

Antibodies, Viral↗

Duplication 9q34 syndrome.

Phenotypic, karyotypic, and developmental homology between affected children of carriers of an inverted insertion (9) (q22.1q34.3q34.1) led to recognition of a new chromosome syndrome: dup 9q34. Individuals with dup 9q34 have slight psychomotor retardation, understand simple directions, and acquire a limited vocabulary. In childhood, many are hyperactive. Clinical features include low birth weight, normal birth length, and initial poor feeding and thriving. Musculo-skeletal systems are affected: there are joint contractures, long thin limbs, and striking arachnodactyly. There is abnormal implantation of the thumb, increased space between the first and second fingers, and excess digital creases. Marfan syndrome was a provisional diagnosis for several cases prior to cytogenetic analysis. Cardiovascular and ocular systems are minimally affected, erythema and heart murmurs occur, and ptosis and strabismus are frequent, but lens dislocation is not observed. Features at birth include: dolichocephaly, facial asymmetry, narrow horizontal palpebral fissures, microphthalmia, prominent nasal bridge, small mouth, thin upper lip with down-turned corners, and slight retrognathia. In older children, retrognathia is diminished and the nose becomes long and narrow. The new culture and chromosome banding techniques enable sorting of cases with the distal dup 9q phenotype into two groups. The cases with a longer dup 9q are more likely to develop with life-threatening congenital anomalies. The cases with the shorter dup 9q34 have a less severe long-term prognosis and will benefit, together with their parents, from special education. Female carriers of the inv ins(9) (q22.1q34.3q34.1) have about a 31% risk in each pregnancy to conceive a fetus affected by the dup 9q34 syndrome. A comparable figure is not yet available for male carriers.

Abnormalities, Multiple↗

An evaluation of dynamic pituitary function tests in patients with pituitary tumours.

In a prospective study of 26 patients with macroadenoma of the pituitary (14 secretory and 12 non-secretory), basal and stimulated pituitary hormone levels were used to detect hypothalamic dysfunction and to examine pituitary hormone secretion before and after hypophysectomy. Suprasellar tumour extention with hypothalamic compression occurred in 18 patients but was not consistently associated with hormonal tests indicative of hypothalamic dysfunction. In patients with secretory tumours, secretory activity was adequately assessed by basal hormone levels alone, which showed that surgery reduced hormone levels by a mean 85% in acromegaly and by a mean 55% in prolactinomas. Preoperatively, pituitary reserve of hormones not being hypersecreted was often normal, despite large tumour size and hypothalamic compression. Even after apparently complete pituitary removal at surgery, normal responses to stimulatory tests could sometimes be detected. Conventional dynamic tests are only of limited value in the assessment of hypothalamo-pituitary dysfunction in patients with large pituitary tumours and should not be used indiscriminately in such individuals requiring surgery.

Acromegaly↗