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Biomedical subjects

K M Bell

Publications and source records attributed to K M Bell.

At least 37 records · Page 2Linked to original sources
PubMed1995

The influence of nitric oxide on tumour vascular tone.

Acetylcholine and sodium nitroprusside, which vasodilate via release of NO by endothelium-dependent and endothelium-independent mechanisms respectively, had little effect on tumour vascular resistance when administered to tissue-isolated tumours perfused in their normal state. However, under phenylephrine-induced vasoconstriction, sodium nitroprusside induced vasodilation whilst acetylcholine induced a small vasoconstriction. Phenylephrine itself induced an oscillatory change in tumour perfusion pressure. The nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine (L-NNA) caused a dose-dependent increase in vascular resistance in ex vivo perfused tumours which was greater than that in normal perfused hindlimbs. Systemic administration of L-NNA caused a 50% decrease in tumour blood flow which was a larger effect than in any of the normal tissues studied except spleen and skeletal muscle. Modification of NOS activity in tumours is a promising means for selective tumour blood flow modification. Investigation of endothelium-dependent versus endothelium-independent methods for modifying tumour blood flow may provide methods for further selectivity.

Acetylcholine↗
PubMed1995

Effect of endothelin-1 and sarafotoxin S6c on blood flow in a rat tumor.

The modification of tumor blood flow resulting from administration of endothelin-1 (ET-1) and sarafotoxin S6c (SX6c) was examined in female CBH rats. Blood flow in subcutaneous HSN tumors and normal tissues was measured by tissue uptake of 125I-labeled iodoantipyrine ([125I])IAP). A 75% increase in tumor blood flow was observed after 1 nM/kg ET-1, contrasting with flow in normal tissue, which was unaffected or reduced. The exception to this was the brain, in which blood flow was increased by 30%, resulting from a rise in mean arterial blood pressure (MABP) and the absence of vasoconstriction. Paradoxically, a significant drop in the tumor vascular resistance was observed after 1 nM/kg ET-1, whereas in all other tissues the vascular resistance was significantly increased. Vascular responses to SX6c differed from those observed with ET-1. At 1 nM/kg SX6c, blood flow in the tumor was increased to 175% of the control as a result of the increase in MABP, which was similar to ET-1. However, unlike ET-1, there was no associated vasodilatation. Vascular resistance was increased in all normal tissues with 1 nM/kg SX6c, corresponding to decreases in blood flow in the contralateral skin, skeletal muscle, and small intestine. This study therefore demonstrates that the vascular responses to ET-1 and SX6c are unique in the HSN tumor compared to normal tissues. This atypical response of the tumor vasculature may therefore be exploitable to improve the delivery of blood-borne anti-cancer agents in therapy.

Animals↗
PubMed1994

Primary juvenile fibromyalgia syndrome and chronic fatigue syndrome in adolescents.

Chronic fatigue syndrome (CFS) and primary juvenile fibromyalgia syndrome (PJFS) are illnesses with a similar pattern of symptoms of unknown etiology. Twenty-seven children for whom CFS was diagnosed were evaluated for fibromyalgia by the presence of widespread pain and multiple tender points. Eight children (29.6%) fulfilled criteria for fibromyalgia. Those children who met fibromyalgia criteria had a statistically greater degree of subjective muscle pain, sleep disturbance, and neurological symptoms than did those who did not meet the fibromyalgia criteria. There was no statistical difference between groups in degree of fatigue, headache, sore throat, abdominal pain, depression, lymph node pain, concentration difficulty, eye pain, and joint pain. CFS in children and PJFS appear to be overlapping clinical entities and may be indistinguishable by current diagnostic criteria.

Adolescent↗
PubMed1994

S-adenosylmethionine blood levels in major depression: changes with drug treatment.

INTRODUCTION: The relationship between plasma levels of S-adenosylmethionine (SAMe), an endogenous methyl donor, and clinical response were studied in patients with a DSM-III-R diagnosis of major depression. MATERIAL AND METHODS: A double-blind randomized protocol comparing oral SAMe with oral desipramine, involving a total of 26 patients, was employed. RESULTS: At the end of the 4-week trial, 62% of the patients treated with SAMe and 50% of the patients treated with desipramine had significantly improved. Regardless of the type of treatment, patients with a 50% decrease in their Hamilton Depression Scale (HAM-D) score showed a significant increase in plasma SAMe concentration. CONCLUSION: The significant correlation between plasma SAMe levels and the degree of clinical improvement in depressed patients regardless of the type of treatment suggests that SAMe may play an important role in regulating mood.

Adult↗
PubMed1992

Primary knee arthroplasty for distal femoral fractures in elderly patients.

We discuss the role of primary knee arthroplasty in supracondylar and intercondylar fractures of the femur in elderly patients with reference to 13 cases. This method of treatment is shown to be effective and to have good results. It is recommended for all type C and some type A supracondylar fractures in old people.

Aged↗
PubMed1992

Locked nailing of humeral shaft fractures. Experience in Edinburgh over a two-year period.

We report the results of locked Seidel nailing for 30 fractures of the humerus. There were frequent technical difficulties at operation especially with the locking mechanisms. Protrusion of the nail above the greater tuberosity occurred in 12 cases, usually due to inadequate locking, and resulted in shoulder pain and poor function. Poor shoulder function was also seen in five patients with no nail protrusion, presumably because of local rotator cuff damage during insertion. Our results suggest that considerable modifications are required to the nail, and possibly to its site of insertion, before its use can be advocated.

Adult↗
PubMed1991

Decreased seasonal mesor of platelet 3H-imipramine binding in depression.

Seasonal cycles of platelet 3H-imipramine binding were compared in 49 endogenous unipolar depressed patients and 20 normal volunteers. A significant sinusoidal component was detected in the Bmax of binding in both patients and controls with similar amplitudes and seasonal peaks. However, the yearly average (mesor) of the patient group was significantly lower (20.0%) than that of the normal controls. The results support earlier claims of a diminished platelet binding in endogenous depression and indicate that this decrease was still evident in the presence of a 48.2% (controls) to 65.8% (patients) seasonal variation. Control Bmax values were normally distributed about a best-fit mean (cosinor fit). In contrast, patient values appeared to be bimodally distributed with one mode that was similar to controls and one mode that was substantially lower. In general, psychiatric symptoms failed to distinguish between patients with high and low platelet binding and no correlation was found between Bmax and severity of illness (HAM-D).

Adolescent↗
PubMed1991

Pharmacokinetics, toxicity, and activity of intravenous dextran sulfate in human immunodeficiency virus infection.

Polysulfated polysaccharides are attractive candidates for antiviral drug development because of their potent in vitro activities against human immunodeficiency virus (HIV), herpesviruses, and other enveloped viruses. To determine the potential anti-HIV activity of a prototypical polysulfated polysaccharide, we administered the maximally tolerated dose of dextran sulfate by continuous intravenous infusion to 10 subjects with symptomatic HIV infection for up to 14 days. Since parenteral dextran sulfate is an anticoagulant, the infusion was adjusted to produce the greatest acceptable increase in activated partial thromboplastin time. Drug concentrations in plasma achieved with this protocol were up to 200-fold greater than the 50% inhibitory concentration for free HIV infectivity in vitro. Despite this, circulating HIV antigen (p24) levels increased in all eight subjects who received the drug for more than 3 days (median proportional increase, 73.5%; range, 32 to 130%); this increase was highly significant when it was compared with that in a large cohort of untreated historical controls (Fisher's exact test, P less than 0.001). Frequent decreases in infusion rate were required in all subjects to maintain a constant activated partial thromboplastin time; plasma dextran sulfate levels did not fall as the infusion rate decreased, suggesting a decline in estimated drug clearance over time. Continuous intravenous dextran sulfate was toxic, producing profound but reversible thrombocytopenia in all eight subjects who received drug for more than 3 days and extensive but reversible alopecia in five of these subjects. Because of its toxicity and lack of beneficial effect on surrogate markers, dextran sulfate is unlikely to have a practical role in the treatment of symptomatic HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Recurrent common peroneal palsy in association with the Ehlers-Danlos syndrome. A case report.

We report a patient with type III Ehlers-Danlos syndrome, presenting with recurrent footdrop, who had electrophysiologic evidence of a conduction block of the common peroneal nerve followed by complete resolution. We feel that this case supports the possible link between Ehlers-Danlos syndrome and multiple pressure sensitive neuropathy (tomaculous neuropathy), alluded to by Schady and Ochoa (1984).

Adult↗
PubMed1991

Eye protection for the surgeon.

The surgeon today is obliged to operate on an increasing number of patients who are classed as high risk. A study is presented which examines the extent of potential corneal contamination with blood or tissue fluids, during common orthopaedic operations. In all, 65% of goggles worn by surgeons during the study were contaminated. The greatest risk was associated with operations around the hip joint, which are among the commonest orthopaedic procedures. Increased contamination was associated with the use of power tools and irrigation. The contamination rate of the protective flaps at the side of the goggles was relatively low (5%) suggesting that ordinary spectacles, which are more convenient and comfortable than the standard issue goggles, would provide adequate protection during routine use.

Eye Protective Devices↗
PubMed1990

Effects of chronic imipramine treatment on subclasses of platelet 3H-imipramine binding sites and plasma cortisol.

A decreased density of platelet 3H-imipramine (3H-IMI) binding sites has been proposed as a putative trait marker of major depressive illness. However, subsequent studies have demonstrated that the number of such sites is increased so as to be more like normal controls upon chronic treatment with antidepressant drugs. In addition, there is some evidence to suggest that altered 3H-IMI binding may be secondary to elevated plasma cortisol levels which are common in depressed patients and which normalize with remission. The present study compares platelet 3H-imipramine binding, plasma cortisol levels, and clinical improvement of 10 endogenous depressed patients before and after 6 weeks of treatment with imipramine-HCl. Total high affinity 3H-IMI binding sites were further differentiated into two subclasses on the basis of their relative sensitivities to cyanoimipramine (CNIMI) inhibition. Treatment was associated with a significant increase (134%) in CNIMI resistant binding but a decrease (45.2%) in CNIMI sensitive binding. While the former was significantly correlated with posttreatment cortisol levels, no significant correlation was found between cortisol and CNIMI specific binding. Neither site appeared to be directly related to mood state. The significance of these findings to the evaluation of platelet binding as a trait dependent marker is discussed.

Adolescent↗
PubMed1990

Seasonal changes in cyanoimipramine specific platelet 3H-imipramine binding in depression.

Seasonal variations in cyanoimipramine (CNIMI) sensitive and CNIMI resistant subclasses of platelet 3H-imipramine (3H-IMI) binding sites were studied in depressed patients and normal volunteers. Sinusoidal rhythms of the binding of both subclasses were found in patients and controls with peak levels in mid-February. Patient values of CNIMI sensitive binding fluctuated about a yearly average that was 32% lower than the average of controls. Patient deviations from the normal pattern were apparently bimodally distributed, whereas those of controls were normally distributed. CNIMI resistant binding was also normally distributed in controls, but not in depressed patients, although patient mesor values were not lower than those of controls. Platelet binding was not correlated with the severity of illness as measured by the Hamilton Rating Scale for Depression, and individual symptoms failed to discriminate between patients with high and low Bmax values.

Adult↗
PubMed1989

Changes in platelet 3H-imipramine binding with chronic imipramine treatment are not state-dependent.

One month of imipramine treatment increased both the Kd and Bmax of platelet 3H-imipramine binding in 11 endogenous unipolar depressed patients. Continued treatment (13 weeks) of 5 patients subsequently lowered the Bmax values of 2 patients who had initially shown the largest increases, so that binding was no longer significantly elevated after 13 weeks. The observed changes in Kd but not in Bmax, could be explained by the carryover of tightly bound drug to the binding assay, although neither of the measures were correlated with plasma imipramine levels. Posttreatment Bmax (4 weeks) values were inversely related to plasma cortisol levels, although a weak but positive correlation was found before treatment. No significant change was found in plasma cortisol with treatment. Clinical responses were not related to cortisol or Bmax changes, although optimal improvement was associated with extreme values (high and low) of pretreatment Bmax. The present results, obtained with imipramine, and similar results obtained after nortriptyline and electroconvulsive shock by others, suggest that at least some antidepressants may induce transient changes in the Bmax of platelet binding that are independent of affective state.

Adolescent↗
PubMed1988

S-adenosylmethionine treatment of depression: a controlled clinical trial.

The antidepressant properties of S-adenosylmethionine, an endogenous methyl donor, were studied in inpatients who met the DSM-III criteria for major depression. Nine patients given intravenous S-adenosylmethionine and nine given low oral doses of imipramine were compared in a double-blind design for 14 days. The S-adenosylmethionine produced superior results by the end of the first week of treatment. By the end of the second week, 66% of the S-adenosylmethionine patients had a clinically significant improvement in depressive symptoms, compared to 22% of the imipramine patients. Side effects appeared to be fewer with S-adenosylmethionine than with imipramine during the last 5 days of the study.

Administration, Oral↗
PubMed1987

Expression of the insulin like growth factor II gene in the developing chick limb.

We have examined the expression of the insulin like growth factor II gene in the developing chick embryo. It was found that IGF II transcripts were present in abundant quantities in the eye and the heart as well as in the limb bud in the 4 day old chick embryo. A detailed analysis of the limb bud revealed that IGF II transcripts could be detected in the anterior and the posterior regions indicating that this gene is activated in segments covering the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) as well as in neighbouring tissue.

Animals↗
PubMed1986

The preliminary characterization of mitogens secreted by embryonic chick wing bud tissues in vitro.

Embryonic chick wing bud tissues secrete diffusible mitogens when cultured in vitro (Bell & McLachlan, 1985). These molecules may play an important role in limb development since media conditioned by morphogenetically active regions of the wing bud possess greater mitogenic activity than media conditioned by non-morphogenetic regions. These studies show that while the chick-derived growth factors were mitogenic for mouse-derived NIH 3T3, 10T1/2 and NR6 cells and chick limb bud cells, they did not stimulate DNA synthesis in 3B11, PC13 END, normal rat kidney or bovine endothelial cells. Furthermore, the effects of chick-derived mitogens were synergistically enhanced by insulin and PGF 2 alpha but remained unaffected by ECDGF, EGF, FGF and MSA. These findings indicate that embryonic chick limb bud cells synthesize and secrete growth factors which resemble in function other well-characterized growth factors and in particular PDGF.

Animals↗
PubMed1985

Stimulation of division in mouse 3T3 cells by coculture with embryonic chick limb tissue.

Two regions of the chick limb bud--the apical ectodermal ridge and the zone of polarizing activity--have been shown to influence cell division and pattern formation during normal development and following surgical manipulation. In this study, using a simple coculture system, together with autoradiography, we have shown that these morphogenetically active regions of the limb bud can stimulate quiescent 3T3 cells to initiate DNA synthesis to a significantly greater degree than comparable but morphogenetically inactive regions of the limb bud.

Animals↗