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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 397 records · Page 22Linked to original sources
PubMed1999

Monocyte chemotactic protein-1 (MCP-1) accelerates the organization and resolution of venous thrombi.

PURPOSE: Organization, recanalization, and contraction are common to wound healing and thrombus resolution. Monocytes are essential to wound healing and are also found in venous thrombi. We measured endogenous levels of the monocyte chemotactic protein-1 (MCP-1) in naturally resolving venous thrombi and determined the effect of injecting MCP-1 into newly formed thrombus. METHODS: Endogenous MCP-1 levels were estimated in rat blood, thrombi, and the adjacent vessel wall after thrombus formation, in cohorts of eight animals at 1, 7, and 14 days. In another group (n = 10), 1 microgram of MCP-1 was injected into newly formed thrombi. Carrier was injected into the thrombi of control animals (n = 10). Thrombi and adjacent vein walls were obtained for histology at 7 days. Thrombi were given an arbitrary organization score based on erythrocyte and extracellular matrix content, which was assessed by means of computerized and observer analysis. Specimen weight, thrombus area, and cellular and monocyte content were measured. RESULTS: Endogenous MCP-1 increased between days 1 and 7 in the thrombus (1-day median, 1.1 ng/g wet wt; 1-day range, 0.8 to 1.4 ng/g wet wt; 7-day median, 5.4 ng/g wet wt; 7-day range, 1.5 to 7.4 ng/g wet wt; P <.0001) and vein wall (1-day median, 1.5 ng/g wet wt; 1-day range, 0.8 to 4.3 ng/g wet wt; 7-day median, 3.3 ng/g wet wt; 7-day range, 2.7 to 8.3 ng/g wet wt; P <. 05). At 14 days, thrombus was incorporated in the vein wall, and total MCP-1 levels remained high (median, 3.9 ng/g wet wt; range, 1.1 to 7.4 ng/g wet wt). Less MCP-1 was found in the thrombus than the adjacent vessel wall at day 1 (P <.05), but there was no difference at day 7. MCP-1 could not be detected in the blood. MCP-1 injection into thrombus increased the computer (P =.016) and observer (P =.004) organization scores, reduced the thrombus area (from median, 3. 4 mm(2), and range, 1.5 to 5.7 mm(2), to median, 0.2 mm(2), and range, 0.02 to 2.6 mm(2); P =.048), and increased the surrounding vessel wall monocyte content (P =.008). Specimen weights of treated animals were lower than those of control animals (P <.02). CONCLUSION: Venous thrombus MCP-1 levels increase during natural resolution. MCP-1 treatment increased the organization and resolution of thrombi. MCP-1 may therefore be of therapeutic use.

Animals↗
PubMed1999

A model of in vivo human venous thrombosis that confirms changes in the release of specific soluble cell adhesion molecules in experimental venous thrombogenesis.

PURPOSE: The mechanisms of venous thrombogenesis have been studied by using animal models and cells in culture. The results from these systems may not, however, be relevant to the human condition. The aim of this study was to develop a method by which thrombus could be safely produced in a human vein in vivo. The model that was developed was used as a means of studying the changes in soluble adhesion molecule expression in human venous thrombogenesis. METHODS: An autologous thrombin extract was used to generate experimental thrombi in the disconnected portion of the long saphenous veins of 30 patients who were undergoing routine bilateral varicose vein surgery. The contralateral vein was perfused with thrombin extract diluent buffer to act as the control. The concentration of soluble P-, E- and L-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule-1 were measured by means of specific enzyme-linked immunosorbent assays in samples of blood taken from veins in which thrombus had formed and in contralateral control veins. RESULTS: Thrombosis invariably formed when at least 100 IU of thrombin activity was administered. Thrombus formation was independent of the time that the thrombin extract was allowed to remain within the emptied vessel. Thrombosis never developed in control vessels that were similarly treated with the buffer used to dilute the thrombin extract. Experimental thrombi were composed mainly of red cells, with layers of fibrin next to platelet and leukocyte packages. These findings are similar to those observed in samples of established human venous thrombi. There were small but significantly higher levels of the adhesion molecules, soluble P-selectin, and vascular cell adhesion molecule-1 in blood taken from veins in which experimental thrombi had formed, compared with controls (P =.015 and.007, respectively; Wilcoxon signed rank test). Serum levels of soluble L-selectin, E-selectin, and ICAM-1 were not affected by thrombosis. CONCLUSION: This model is safe and reproducible. It produces thrombi with a morphology similar to that described for established human deep venous thrombi. The model may be appropriate for the study of the early changes that occur during human venous thrombogenesis and may also be of value in testing the efficacy of novel antithrombotic agents.

Cell Adhesion Molecules↗
PubMed1999

A calorimetric investigation into the interaction between paracetamol and polyethlene glycol 4000 in physical mixes and solid dispersions.

The solubility, heat of solution and dissolution rate of paracetamol and polyethyelene glycol 4000 (PEG 4000) systems have been studied in order to clarify the nature of the interaction between the two components during dissolution of solid dispersions. The logarithmic solubility of paracetamol demonstrated a non-linear increase with concentration of PEG 4000, while linear relationships between heat of solution in water and concentration were seen for both individual components. However, the heat of solution of paracetamol was found to decrease with increasing concentrations of PEG 4000. Similarly, the heats of solution in water of physical mixes and solid dispersions prepared using two manufacturing protocols were found to be lower than the theoretical values calculated from those corresponding to the individual components. Drug release studies showed a marked increase in paracetamol dissolution rate when prepared as a solid dispersion, with behaviour consistent with carrier controlled dissolution observed at low drug contents which was ascribed to enhanced dissolution of the drug into the diffusion layer of the PEG 4000. The implications of the understanding of this mechanism for the choice of carrier and manufacturing protocol for solid dispersion products is discussed.

Acetaminophen↗
PubMed1999

Dose response study of subarachnoid diamorphine for analgesia after elective caesarean section.

Subarachnoid diamorphine provides excellent analgesia after elective caesarean section but the optimum dose is still uncertain. We therefore investigated the effects of three regimens of subarachnoid diamorphine. Forty parturients were assigned to one of four groups. A control group received no diamorphine in their subarachnoid bupivacaine and three study groups received 0.1 mg, 0.2 mg or 0.3 mg diamorphine added to 12.5 mg hyperbaric bupivacaine 0.5% in a semi-blind randomised design study. All women received a 100 mg diclofenac suppository at the end of the caesarean section and were provided with morphine patient controlled analgesia (PCA) postoperatively. The patients were assessed for pain, morphine usage and side-effects at 2, 4, 8 and 24 h after the subarachnoid injection. Postoperative visual analogue scores for pain and PCA morphine consumption were significantly lower, and mean time to first use of morphine was significantly longer in the 0.3 mg diamorphine group. The mean (SD) dose of PCA morphine used over 24 h was 39.4 (14.7), 25.6 (16.5), 21.6 (15.9) and 3.1 (3.6) mg, and mean time to first use of morphine was 1.6 (0.5), 3.0 (1.4), 3.4 (2.4) and 14.1 (9.4) h, in the 0, 0.1 mg, 0.2 mg and 0.3 mg groups respectively. Side-effects of pruritus, nausea and vomiting were dependent on the dose of spinal diamorphine but did not require treatment in any patients. We conclude that 0.3 mg subarachnoid diamorphine provides significantly better postoperative pain relief than the smaller doses with an acceptable increase in side-effects.

Clinical Trial↗
PubMed1999

Antibodies raised by gastrimmune inhibit the spontaneous metastasis of a human colorectal tumour, AP5LV.

Both precursor forms of gastrin and mature amidated gastrin peptides can enhance proliferation of colorectal tumours and may regulate growth in an autocrine manner. The purpose of this study was to evaluate the effect of neutralization of precursor and amidated gastrin on primary and secondary in vivo growth of a human colorectal tumour. The human colorectal cell line, AP5LV, when injected into the muscle layer of the abdominal wall of severe combined immunodeficient (SCID) mice, grows as a well-vascularized primary tumour and metastasis to the lung. AP5LV expressed the precursor gastrin forms; progastrin and glycine-extended gastrin and gastrin/CCKB receptors, as assessed by immunocytochemistry. Gastrimmune is a gastrin immunogen in which the amino terminus of the gastrin-17 molecule is linked to diphtheria toxoid and induces antibodies which neutralise the amidated and glycine-extended forms of gastrin-17. Rabbit antiserum, raised against Gastrimmune, was administered intravenously into SCID mice bearing AP5LV tumours. Control animals were treated with antiserum raised against diphtheria toxoid only. Antibodies raised against Gastrimmune significantly limited the growth of primary AP5LV tumours, as assessed by median cross-sectional area (controls = 244 mm2; antibody-treated = 179 mm2; P = 0.033). In addition Gastrimmune-induced antiserum limited the growth of lung metastasis as assessed by nodule number (controls = 3.5; antibody-treated = 1.0; P = 0.0001) and nodule cross-sectional as assessed by image analysis (controls = 11.9 mm2; antibody-treated = 3.75 mm2; P = 0.0064). In conclusion in vivo neutralization of gastrin forms, which may potentially be fueling growth by an autocrine pathway, inhibited both primary growth and, to a greater degree, lung metastasis of a human colorectal tumour cell line. Immunization against tumour-associated gastrin forms may provide an effective therapy for advanced colorectal cancer.

Animals↗
PubMed1999

Primary renal tumours in cats: 19 cases (1992-1998).

A search from databases of four veterinary colleges and one private referral practice between January 1992 and April 1998 provided 20 cases diagnosed with primary renal neoplasia. Review of these cases revealed 19 primary renal tumours, excluding lymphoma. Of the 20 histologically reviewed cases, the diagnosis was amended in eight. There were 13 renal carcinomas (11 tubular and two tubulopapillary), three transitional cell carcinomas, one malignant nephroblastoma, one haemangiosarcoma and one adenoma. The haemangiosarcoma is, to our knowledge, the first reported case of this tumour type as a primary renal tumour in the cat. Most cats were presented for non-specific clinical signs such as anorexia and weight loss. One cat presented with tumour-associated polycythaemia which has not, to our knowledge, been reported previously. The metastatic rate for cats with complete staging was 64%, and 100% for transitional cell carcinomas.

Adenoma↗
PubMed1999

A unique case of ventricular isomerism?

Isomerism of the atriums has often been described with various complex cardiac malformations. As far as is known, a case of 'ventricular isomerism' has never been recorded. Described is a specimen where, on the basis of morphological criterions, there are two right ventricles.

Aorta, Thoracic↗
PubMed1999

Sea buckthorn products: manufacture and composition.

Sea buckthorn (Hippophae rhamnoides) is a unique plant currently being domesticated. The fruit is the main component of value, although the leaves are occasionally made into sea buckthorn tea. The two main sources of valuable products are derived from the berries, juice from the fleshy tissue and seed as a single seed from each berry. The juice provides a nutritious beverage, high in suspended solids and very high in vitamin C and carotenes. The juice may contain an oil phase trapped within the suspended solids, or the oil may be removed as pulp oil and provided separately. The pulp remaining after juice removal provides for extraction of "sea buckthorn yellow", a pigment that has potential use as a food coloring material. The seed is a source of seed oil, which is very unsaturated and shows promise, because of its light absorption and emollient properties, as an ingredient in cosmetics, phytopharmaceuticals, or UV skin protectant preparations. It may be prepared by conventional extraction techniques or by supercritical carbon dioxide extraction. The manufacture of the main products derived from sea buckthorn is described, including several examples from the patent literature. The available compositional data for the main products are tabulated to form a comprehensive source of information on the manufacture and composition of sea buckthorn products.

Ascorbic Acid↗
PubMed1999

Development and phonetic differentiation of speech movement patterns.

It is often hypothesized that speech production units are less distinctive in young children and that generalized movement primitives, or templates, serve as a base on which distinctive, mature templates are later elaborated. This hypothesis was examined by analyzing the shape and stability of single close-open speech movements of the lower lip recorded in 4-year-old, 7-year-old, and adult speakers during production of utterances that varied in only a single phoneme. To assess the presence of a generalized template, lower lip movement sequences were time and amplitude normalized, and a pattern recognition procedure was implemented. The findings indicate that speech movements of children already converged on phonetically distinctive patterns by 4 years of age. In contrast, an index of spatiotemporal stability demonstrated that the stability of underlying patterning of the movement sequence improves with maturation.

Adult↗
PubMed1999

Crystal structure of hemopexin reveals a novel high-affinity heme site formed between two beta-propeller domains.

The ubiquitous use of heme in animals poses severe biological and chemical challenges. Free heme is toxic to cells and is a potential source of iron for pathogens. For protection, especially in conditions of trauma, inflammation and hemolysis, and to maintain iron homeostasis, a high-affinity binding protein, hemopexin, is required. Hemopexin binds heme with the highest affinity of any known protein, but releases it into cells via specific receptors. The crystal structure of the heme-hemopexin complex reveals a novel heme binding site, formed between two similar four-bladed beta-propeller domains and bounded by the interdomain linker. The ligand is bound to two histidine residues in a pocket dominated by aromatic and basic groups. Further stabilization is achieved by the association of the two beta-propeller domains, which form an extensive polar interface that includes a cushion of ordered water molecules. We propose mechanisms by which these structural features provide the dual function of heme binding and release.

Animals↗
PubMed1999

A radiation hybrid map of the rat genome containing 5,255 markers.

A whole-genome radiation hybrid (RH) panel was used to construct a high-resolution map of the rat genome based on microsatellite and gene markers. These include 3,019 new microsatellite markers described here for the first time and 1,714 microsatellite markers with known genetic locations, allowing comparison and integration of maps from different sources. A robust RH framework map containing 1,030 positions ordered with odds of at least 1,000:1 has been defined as a tool for mapping these markers, and for future RH mapping in the rat. More than 500 genes which have been mapped in mouse and/or human were localized with respect to the rat RH framework, allowing the construction of detailed rat-mouse and rat-human comparative maps and illustrating the power of the RH approach for comparative mapping.

Animals↗
PubMed1999

The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways.

Many damage-sensing neurons express tetrodotoxin (TTX)-resistant voltage-gated sodium channels. Here we examined the role of the sensory-neuron-specific (SNS) TTX-resistant sodium channel alpha subunit in nociception and pain by constructing sns-null mutant mice. These mice expressed only TTX-sensitive sodium currents on step depolarizations from normal resting potentials, showing that all slow TTX-resistant currents are encoded by the sns gene. Null mutants were viable, fertile and apparently normal, although lowered thresholds of electrical activation of C-fibers and increased current densities of TTX-sensitive channels demonstrated compensatory upregulation of TTX-sensitive currents in sensory neurons. Behavioral studies demonstrated a pronounced analgesia to noxious mechanical stimuli, small deficits in noxious thermoreception and delayed development of inflammatory hyperalgesia. These data show that SNS is involved in pain pathways and suggest that blockade of SNS expression or function may produce analgesia without side effects.

Afferent Pathways↗
PubMed1999

Prospective study of a laparoscopically placed, adjustable gastric band in the treatment of morbid obesity.

BACKGROUND: Surgical control of morbid obesity should benefit from a minimally invasive approach and the ability to adjust the degree of gastric restriction. METHODS: The Lap-Band adjustable gastric banding system was evaluated prospectively in a consecutive series of 302 patients, and data on perioperative outcome and weight loss pattern at up to 4 years of follow-up are presented. Some 302 patients (89 per cent women; mean age 39 years, mean weight 124 kg) were entered into the study. Laparoscopic placement was used in 277 patients. Previous gastric stapling surgery was the principal reason for an elective open approach. RESULTS: The incidence of significant early complications was 4 per cent and included two perforations of the stomach after open placement. The mean length of stay after laparoscopic placement was 3.9 days and only one complication (infected reservoir site) occurred in these patients. The principal late complication of prolapse of the stomach through the band occurred in 27 patients (9 per cent). Significant modification of technique and patient care has enabled reduction of this complication in the latter part of the series. Mean(s.d.) excess weight loss was 51.0(17) per cent at 12 months (n = 120), 58.3(20) per cent at 24 months (n = 43), 61.6(2) per cent at 36 months (n = 25) and 682(21) per cent at 48 months (n = 12). CONCLUSION: The Lap-Band is an effective method for achieving good weight loss in the morbidly obese at up to 4 years of follow-up. Laparoscopic placement has been associated with a short length of stay and a low frequency of complications. The ability to adjust the setting of the device to achieve different degrees of gastric restriction has enabled progressive weight loss throughout the period of study.

Adolescent↗
PubMed1999

Experimental techniques and models in the study of the development and treatment of abdominal aortic aneurysm.

BACKGROUND: It is still unclear what initiates aneurysmal dilatation and what determines whether or not an aneurysm will continue to expand and rupture. Early detection and operative repair of an abdominal aortic aneurysm (AAA) still remains the only effective means of reducing the high mortality rate associated with the condition. Endovascular techniques are being developed in an attempt to reduce the mortality rate associated with elective repair. A variety of animal models and experimental techniques have been described in the investigation of the pathophysiology of AAA and in the development of improved endovascular surgical and pharmacological therapies. This article discusses these models and techniques, their advantages and some of the problems encountered in extrapolating experimental findings to the human condition. METHODS: This review is based on a search of the Medline database from 1966 to March 1998 using recognized key words and text words. A further search was then conducted on references quoted within selected relevant publications. RESULTS AND CONCLUSION: Treatment of rodent aortas with intraluminal elastase or periaortic calcium chloride creates reproducible aneurysms that have certain similarities to the human pathology; such aneurysms have been favoured in the investigation of the pathophysiology of aneurysm expansion. However, these models lack several of the prominent features of the human lesion, such as atherosclerosis and intraluminal thrombosis. The development of gene knockout mice may lead to a more analogous aneurysm formation, with associated atherosclerosis. Many large animal models have been used in the development of endovascular techniques but, in general, these do not mimic the human pathophysiology and fail to predict medium- and long-term complications.

Animals↗
PubMed1999

Role of laparoscopic ultrasonography in the management of patients with oesophagogastric cancer.

BACKGROUND: Laparoscopy and laparoscopic ultrasonography (lapUS) have been shown to improve the staging of patients with oesophagogastric cancer but there remains doubt as to whether most benefit follows laparoscopy alone and how much is contributed by the addition of lapUS. METHODS: The role of lapUS in surgical decision making was evaluated prospectively in a consecutive series of patients with oesophagogastric cancer following conventional radiological assessment. The results of the lapUS findings over and above the laparoscopic findings were documented in order to identify the additional benefit of lapUS. RESULTS: After initial conventional assessment 41 patients were considered unsuitable for surgery and treated by palliation, with a further 25 patients proceeding to surgery without laparoscopy. Of the 93 patients who underwent laparoscopy, 18 were shown to have irresectable disease and avoided further surgery; a further seven avoided inappropriate surgery by the addition of lapUS. The open-close laparotomy rate was reduced from five of 25 in patients who did not undergo laparoscopy to nine (12 per cent) of 75 by the introduction of laparoscopy and to two (3 per cent) of 68 with the addition of lapUS. CONCLUSION: Laparoscopy alone prevented unnecessary surgery in 18 (19 per cent) of 93 patients with oesophagogastric cancer and the addition of lapUS identified a further seven patients (8 per cent) in whom unnecessary surgery was avoided.

Adenocarcinoma↗
PubMed1999

Short communication: developmental control of Xa21-mediated disease resistance in rice.

The rice resistance gene Xa21 confers resistance against the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo). The molecular genetic mechanism controlling the integration of the Xa21-mediated disease resistance response with the developmental program in rice is under study in this model system. Reproducible means of infecting plants at certain developmental stages were designed based on the timing of full expansion of the leaf. Xa21-resistance progressively increases from the susceptible juvenile leaf 2 stage through later stages, with 100% resistance at the adult leaf 9/10 stage. We found that Xa21 expression is independent of plant developmental stage, infection with Xoo, or wounding. Expression of the Xa21 gene transcript is not correlated with expression of Xa21 disease resistance indicating that the developmental regulation of Xa21-resistance is either controlled post-transcriptionally or by other factors.

Gene Expression↗