Biomedical subjects

M J Edwards

Publications and source records attributed to M J Edwards.

At least 145 records · Page 8Linked to original sources

PubMed1996

Prevalence of third molars in dental practice attenders aged over 35 years.

There is a lack of information in the United Kingdom on the prevalence of third molars in older patients. The aim of this study was therefore to define the pattern of lower third molar retention in UK dental practice attenders aged 35 years and over. A random sample of 599 eligible patients from a rural dental practice were included in the study. Information was obtained from clinical notes and panoramic radiographs. Data collected included age, gender, presence or absence of lower third molars, number of teeth present in the lower arch and eruption status. Two hundred and sixty-four (44.1 per cent) had at least one lower third molar present (mean age = 57.1 years) while 335 (55.9 per cent) had no lower third molars (mean age = 50.2 years). The data suggest that a greater proportion of men than women retain at least one lower third molar although this finding was not statistically significant. Seventy per cent of retained lower third molars reported in the study were fully erupted. Sixty per cent were vertically placed. There was an association between age and number of teeth present (chi 2 = 38.85, 4DF, P < 0.05), older patients having fewer lower teeth. These data suggest that a large number of patients can expect to keep their lower third molars beyond the age of 35 years and that in many cases a conservative "wait and see' policy for lower third molars in the early twenties is appropriate.

Adult↗

PubMed1995

The effect of soluble tumor necrosis factor receptor-II on endotoxin-mediated hemodynamic instability.

Tumor necrosis factor-alpha (TNF-alpha), a central mediator in the hemodynamic response to injury and infection, is a primary mediator of endotoxin-induced hemodynamic instability. Two types of naturally occurring soluble TNF receptors circulate in human experimental endotoxemia and the recombinant proteins of both have been hypothesized as potential therapeutic agents antagonizing TNF-mediated effects of endotoxemia. The administration of recombinant sTNFr-I has been previously shown to attenuate the hemodynamic collapse of lethal bacteremia. In the current study, we investigated the role of recombinant sTNFR-II at low (0.5 mg/kg) and high (2.5 mg/kg) doses as a potential therapeutic agent for the inhibition of endotoxin lipopolysaccharide (LPS)-mediated hemodynamic instability. Eighteen male Sprague-Dawley rats were anesthetized and cannulated for continuous blood pressure monitoring and cardiac output measurement by thermodilution. Groups of animals received saline, LPS (1 mg/kg), or sTNFr-II (at 0.5 or 2.5 mg/kg) 15 min prior to LPS (1 mg/kg). Hemodynamic variables (blood pressure, cardiac output, heart rate) were monitored every 15 min for 2 hr. LPS caused a 30% decrease in mean arterial pressure by 60 min, which began to recover by 120 min. sTNFr-II was unable to prevent LPS-induced hypotension at low or high dose. Serum levels of immunoreactive TNF-alpha, undetectable in control animals, were significantly increased by sTNFr-II compared to LPS alone. Serum from animals treated with high-dose sTNFr-II showed significantly less TNF cytotoxicity than those treated with low-dose sTNFr-II, indicating that high doses of sTNFr-II are required for the inhibition of the bioactivity of TNF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Alpha-adrenergic receptor antagonism prevents intestinal vasoconstriction but not hypoperfusion following resuscitated hemorrhage.

Resuscitation (RES) after hemorrhage (HEM) results in persistent arteriolar constriction and hypoperfusion of the small intestine (SI) despite restoration of mean arterial pressure (MAP) and cardiac output (CO) to normal values. We postulated that increased adrenergic activity contributes to this vasoconstriction and impairment of flow. A loop of SI from decerebrate rats was exteriorized and suffused with Krebs' solution (37 degrees C, pH 7.4). In initial experiments, the effectiveness of alpha-adrenergic receptor antagonism by phentolamine (PHEN) was assessed. Subsequent groups received either topical PHEN (10(-6) M, n = 6) or saline (n = 6) in the suffusion and were then bled to 50% baseline (BL) MAP for 60 min and resuscitated to BL with shed blood/lactated Ringer's. Intravital microscopy and optical Doppler velocimetry were used to measure large (A1) and small, premucosal (A3) arteriolar diameters and RBC velocity; microvascular blood flow was calculated. MAP and transpulmonary CO were measured. During HEM, control animals developed A1 constriction and hypoperfusion with A3 arteriolar dilation. PHEN treatment prevented A1 constriction and enhanced A3 dilation but did not improve flow. Immediately after RES in controls, microvascular diameters and A1 flow returned to BL; however, over the 2-hr post-RES period there was progressive A1 and A3 vasoconstriction and hypoperfusion despite maintenance of BL MAP and CO. After RES in PHEN-treated animals, A1 flow returned to BL, but progressive hypoperfusion was only partially prevented. alpha-Adrenergic-mediated vasoconstriction contributes to intestinal hypoperfusion after HEM, but other mechanisms are also involved in microvascular responses during RES.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

PubMed1995

Hyperthermic isolated limb perfusion increases circulating levels of inflammatory cytokines.

Hyperthermic isolated limb perfusion is an established method of treatment for regionally advanced melanoma. Recent studies suggest that exogenously administered cytokines potentiate tumor response in patients with in-transit melanoma. We hypothesized that isolated limb perfusion induces an immunogenic response characterized by increased circulating levels of cytokines in the pump circuit, potentially contributing to the antitumor effect. We obtained blood samples from the perfusion circuit and systemic circulation at various intervals from patients undergoing isolated chemotherapeutic perfusion for melanoma. Samples were analyzed for serum cytokine profiles by enzyme-linked immunosorbent assay. When compared with baseline values, significant increases in serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor (TNF) occurred within the perfusion circuit during isolated limb perfusion (P < 0.05). In addition, there was a corresponding increase in IL-8 within the systemic circulation at the 60-min interval (P < 0.05), suggesting some degree of leakage from the isolated circuit due to the extremely high levels of IL-8 in the perfusion circuit. A transient but insignificant decrease in circulating levels of neutrophils was also observed during the perfusion process, which may be attributed to margination. Increased levels of cytokines IL-6, IL-8, and TNF occurred within the isolated circuit during hyperthermic limb perfusion and may contribute to tumor response seen in patients treated with isolated limb perfusion.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

The effects of oral pentoxifylline on interleukin-2 toxicity in patients with metastatic renal cell carcinoma.

Interleukin-2 (IL-2) mediates the regression of metastatic renal cell carcinoma, but clinical application has been limited by associated toxicities. Preclinical studies show that pentoxifylline (PTXF), a methylxanthine derivative, inhibits IL-2 toxicity while preserving anti-tumour efficacy. This study was designed to determine whether oral PTXF would alter IL-2-induced toxicities. Patients with disseminated renal cell carcinoma were treated with continuous infusion of 18 x 10(6) IU/m2/24 h for 4 days followed by 3 days without treatment, for 4 consecutive weeks. After a 2-week interval, the 4-week treatment cycle was repeated. All patients concomitantly received oral PTXF (2000 mg/24 h) in five divided doses. Despite the co-administration of PTXF, all patients demonstrated a spectrum and severity of toxicities consistent with previous reports of continuous infusion of IL-2 alone. There was considerably more nausea and vomiting associated with the administration of PTXF which improved on withdrawal of PTXF. Oral PTXF in IL-2 therapy did not show any substantiated benefit. Indeed, patients suffered more severe nausea and vomiting than if they had received IL-2 alone, resulting in the early termination of the trial.

Administration, Oral↗

PubMed1995

Emergency ambulance assistance in The Netherlands: is the Dutch situation optimal?

The system of prehospital trauma care in the Netherlands is the subject of great concern. Although many improvements have been achieved in the last decade, there are still some deficits. Legislation concerning the minimal level of education for ambulance attendants was recently upgraded to 'registered nurse', a standard which must be achieved by 1997. Standardization with regard to extrication techniques, equipment and methods of treatment in prehospital trauma care does not yet exist. Although aware of the fact that large regional differences exist throughout the USA, a system of care in accordance with the advanced trauma life support (ATLS) standard of the American College of Surgeons (ACS) and by means of prehospital and advanced trauma life support (PHTLS) given according to the standards of the National Association of Emergency Medical Technicians (NAEMS) was considered to be the 'golden standard'. Nineteen ground ambulance and two helicopter services in different states of the USA, working according to ACS/NAEMS standard, were visited to analyse the system of care, with special reference to (para)medical education, communication, logistics, and immobilization materials and techniques. In the Netherlands all 41 central post ambulance services (CPAs) were asked to return a questionnaire. This resulted in a 90% (37 out of 41) response. The deficits of the Dutch system of care related to the PHTLS/ATLS standard are pointed out, resulting in recommendations to improve the Dutch system. The requirements of the dispatcher are far inferior to the optimal situation, which, together with the lack of technical equipment, results in serious communication problems. The Dutch ambulance attendant education, in which in the present system the education level reaches 'registered nurse' in only 91% and specialized courses are not mandatory, should be upgraded to the PHTLS level of care.

Air Ambulances↗

PubMed1995

Agnathia (severe micrognathia), aglossia and choanal atresia in an infant.

A neonate is reported here, who was born with severe mandibular hypoplasia, complete absence of the tongue, unilateral choanal atresia, contralateral choanal stenosis and developed severe airway obstruction at birth. Arrested development of the ventral first branchial arch most likely underlies the clinical deficits. Most reported cases of agnathia have been lethal but the infant reported here has survived into infancy with a tracheostomy and feeding gastrostomy. Her clinical features, assessment and management are discussed.

Abnormalities, Multiple↗

PubMed1995

Pentoxifylline inhibits FMLP-induced macromolecular leakage.

The acute inflammatory responses to the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) and the effects of pentoxifylline (PTXF) on the responses in vivo were studied. We used intravital microscopy with rat cremaster muscle preparation to determine inflammatory responses of microcirculation. Macromolecular leakage from postcapillary venules was evaluated by quantifying the extravasation of fluorescein isothiocyanate conjugated to bovine serum albumin. FMLP induced a rapid increase in macromolecular leakage, an increase in leukocyte-endothelium adhesion, and a decrease in blood flow in the microcirculation. PTXF inhibited FMLP-induced responses in a dose-dependent manner but failed to block the histamine-dependent leakage induced by compound 48/80. In addition, diphenhydramine, a histamine-receptor blocker, did not affect the macromolecular leakage induced by FMLP. The cell-permeable adenosine 3',5'-cyclic monophosphate (cAMP) analogue N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate mimicked PTXF's effects on the microcirculation and also inhibited FMLP-induced macromolecular leakage. PTXF is known to inhibit phosphodiesterase and increase intracellular cAMP, which modulates functions of endothelial cells, smooth muscle cells, and neutrophils in vitro. Our findings suggest that FMLP induces acute inflammatory responses through activation of neutrophils, independent of endogenous histamine release, and that PTXF inhibits these responses through elevated intracellular cAMP.

Animals↗

PubMed1994

[Comparison of emergency ambulance assistance in The Netherlands and the U.S.; are conditions optimal in The Netherlands?].

OBJECTIVE: To inventory the difference in ambulance assistance in the Netherlands and the USA and to formulate recommendations to improve this assistance in the Netherlands. DESIGN: Study trip to the USA and enquiry. SETTING: USA and Central Post Ambulance Transportation (CPAs) in the Netherlands. METHOD: At 19 different ambulance and two helicopter services in the USA inventories were made of the training requirements, communication methods, logistics, methods of immobilization and extramural assistance. Questions on the same aspects were asked in an enquiry of 41 heads of Dutch CPAs. RESULTS: Thirty-seven questionnaires were returned. It appears that the American ambulance attendant is much better trained than his Dutch counterpart. In 81% of the Dutch ambulances this is compensated by presence of a qualified nurse. The requirements to be met by dispatchers vary in the two countries, but the American dispatchers work according to fixed protocols and special dispatcher training exists. In the Netherlands, communication is unnecessarily delayed by lack of equipment and because the ambulance attendants can only communicate with the hospital via the dispatcher. In the USA, the ambulance that is closest is always sent out, in 6 Dutch CPAs this is not the case. In the USA, use is being made according to protocol of better immobilization materials than those used in the Netherlands. CONCLUSION: The training requirements for ambulance attendants and dispatchers should be tightened up and dispatchers should be issued with protocols. In addition, the communication between the switchboard, the ambulance and the hospital and the means of immobilization used should be improved. Use of the scoop stretcher is considered inadvisable.

Clinical Protocols↗

PubMed1994

Hypertrichosis "cubiti" with facial asymmetry.

Hypertrichosis of the elbow region may be the only abnormality in hypertrichosis cubiti (hairy elbow syndrome). Only 6 cases have been reported; 2 Amish sibs also had additional short stature and, in the most recent case report, a patient had asymmetry of the face, generalized hypotonia, ptosis, epicanthic folds, highly arched palate, and delayed growth and development. The child reported here also had asymmetry of facial growth, ptosis, delayed speech development, and hypertrichosis in a patchy distribution which included the elbow regions, face, trunk, and thighs. There was no family history of hypertrichosis, and the karyotype of cultured fibroblasts was normal in the skin of an area of hypertrichosis. These patients appear to have a distinct condition compared to other hypertrichosis syndromes.

Elbow↗

PubMed1994

Clinical and linkage study of a large family with simple ectopia lentis linked to FBN1.

Simple ectopia lentis (EL) was studied in a large family, by clinical examination and analysis of linkage to markers in the region of FBN1, the gene for fibrillin which causes Marfan syndrome on chromosome 15. No patient had clinical or echocardiographic evidence of Marfan syndrome, although there was a trend towards relatively longer measurements of height; lower segment; arm span; middle finger, hand, and foot length in the affected members of the family, compared with unaffected sibs of the same sex. Analysis of linkage to intragenic FBN1 markers was inconclusive because they were relatively uniformative. Construction of a multipoint background map from the CEPH reference families identified microsatellite markers linked closely to FBN1 which could demonstrate linkage of EL in this family to the FBN1 region. LINKMAP analysis detected a multipoint lod score of 5.68 at D15S119, a marker approximately 6 cM distal to FBN1, and a multipoint lod score of 5.04 at FBN1. The EL gene in this family is likely to be allelic to Marfan syndrome, and molecular characterization of the FBN1 mutation should now be possible.

Adolescent↗

PubMed1994

Mixoploidy in humans: two surviving cases of diploid-tetraploid mixoploidy and comparison with diploid-triploid mixoploidy.

We report on 2 cases of diploid/tetraploid (2n/4n) mixoploidy in surviving females, 11 and 21 years old. Both individuals manifested severe mental retardation, reduced peripheral limb muscle bulk, asymmetric growth deficiency, seizure disorder, and skin pigmentary dysplasia. Previous lymphocyte karyotypes had been normal on 2 occasions, but when skin fibroblast karyotypes were done, 33% of the cells were tetraploid on the younger woman, and over 60% were tetraploid in the older woman (on 2 separate occasions). In both individuals, the distal limbs and digits were long and thin, with reduced small muscle bulk. The similarity in distal limb findings prompted reexamination of the younger woman's chromosomal constitution in skin fibroblasts. We concluded that the clinical findings in these cases are unique and similar, and we caution clinicians about uniformly dismissing tetraploidy as artifactual in amniocytes from normal patients, especially since this phenotype would be very difficult to detect, even with directed prenatal ultrasonography. We compare the 2n/4n phenotype with that in diploid/triploid (2n/3n) mixoploidy and note subtle differences which might be detected postnatally. These findings should be useful in guiding clinicians on when to request skin fibroblast karyotypes in mentally-deficient individuals with asymmetric growth deficiency and pigmentary skin variation.

Abnormalities, Multiple↗

PubMed1994

Scalp-ear-nipple syndrome: additional manifestations.

Scalp-ear-nipple (SEN) syndrome is a rare, autosomal dominant condition that causes aplasia cutis congenita of the scalp, alteration of the shape of the external ear, and hypoplasia of the nipple. Women in a new family, the fifth to be described, had virtually complete aplasia of the breast and a small skin dimple without any pigmentation instead of a normal nipple, although other affected women had normal breast and nipple development. Dental changes included widely spaced or missing secondary teeth; the ears were cupped or folded and stood out from the head, axillary apocrine secretion and axillary hair growth were reduced; and finger nails were brittle. There was no generalized abnormality of sweating. Some patients had partial syndactyly of the 3rd and 4th fingers, and complete cutaneous syndactyly of the 2nd and 3rd toes. and 3rd toes.

Abnormalities, Multiple↗

PubMed1994

Is diagnostic ultrasound safe? Current international consensus on the thermal mechanism.

OBJECTIVE: To describe the potential risk of heating during ultrasound examinations and to report the international consensus on the safety of ultrasound in medicine. DATA SOURCES AND DATA EXTRACTION: Literature on the biological effects of hyperthermia and ultrasound. CONCLUSION: The use of B-mode grey-scale imaging is not contra-indicated on thermal grounds. Some pulsed Doppler equipment has the potential to produce biologically significant temperature increases, specifically at interfaces between bone and soft tissue. Exposures resulting in temperatures less than 38.5 degrees C can be used without reservation.

Female↗

PubMed1994

Interleukin-8 suppresses the toxicity and antitumor effect of interleukin-2.

The clinical application of interleukin-2 (IL-2) for the treatment of certain human malignancies has shown promise. However, the use of IL-2 in immunotherapeutic protocols has been limited due to its associated toxicities. The administration of therapeutic doses of IL-2 results in a vascular leak syndrome with associated multiple system organ edema, hypotension, and respiratory, renal, and hepatic dysfunction. Previous studies suggest that the mechanism of these toxicities involves the activation of both immune effector cells and the microvascular endothelium with resultant leukocyte-vessel wall interaction, endothelial cell injury, and subsequent invasion of normal tissues by activated leukocytes. Recently it has been demonstrated that interleukin-8 (IL-8) will inhibit leukocyte adherence to an activated endothelium. Thus, we hypothesized that IL-8 would ameliorate IL-2-evoked detrimental effects. We also investigated the influence of IL-8 on IL-2-induced antitumor efficacy. Four groups of nontumored, female, C57BL/6 mice and four groups of C57BL/6 mice with pulmonary metastases from a 3-methylcholanthrene-induced fibrosarcoma (MCA-105) were treated every 6 hr for 4 days by intraperitoneal injections of IL-2 alone, IL-2 and IL-8, IL-8 alone, or an equal volume of saline which served as our control. Upon completion of therapy, we found that IL-8 suppressed many of the IL-2-induced effects including multiple organ edema, hepatic dysfunction, leukopenia, and lymphocytic infiltration of normal organs. When the number of pulmonary metastases were counted 20 days after the cessation of therapy. IL-8 was also found to significantly ablate the IL-2-elicited antitumor efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Interleukin-2-induced lymphocyte infiltration of multiple organs is differentially suppressed by soluble tumor necrosis factor receptor.

Interleukin-2 (IL-2) mediates the regression of metastatic cancer, but clinical application is restricted by associated toxicities. Previous studies implicate tumor necrosis factor (TNF) as an important mediator of certain IL-2-induced toxicities. We hypothesized that soluble TNF receptor (sTNFr), a TNF antagonist, would alter lymphocyte trafficking into normal tissues and ameliorate IL-2-induced toxicity. Four groups of C57BL/6 mice were treated for 4 days with intraperitoneal injections of 100,000 IU IL-2 alone, 100,000 IU IL-2 and 30 micrograms sTNFr combined, 30 micrograms sTNFr alone, or equal volumes of saline. Animal activity was graded and blood obtained for SGPT and SGOT. At necropsy, organs were harvested for wet:dry ratios as a measurement of organ edema. The lung, liver, and thymus were examined histologically for lymphocytic infiltration and graded on a scale of 1 to 5. IL-2-treated groups had a statistically significant increase in organ edema, lymphocytic infiltration into the lung and liver, liver enzyme elevation, and pancytopenia when compared with controls. Soluble TNFr significantly suppressed IL-2-induced pulmonary lymphocytic infiltration and associated serum lymphopenia without significant alteration of other IL-2-induced effects. These data implicate TNF as a mediator of the pulmonary lymphocytic infiltration and of lymphopenia that accompanies IL-2 therapy and further suggest that alternative mechanisms are involved in other IL-2-induced deleterious effects.

Animals↗

PubMed1994

Tumor necrosis factor causes microvascular protein leakage independently of neutrophils or mast cells.

Tumor necrosis factor-alpha (TNF-alpha) has been implicated as an important mediator in the development of multiple system organ failure after either severe injury or infection. Using the rat cremaster muscle, we previously showed that systemically administered TNF-alpha caused hypotension, tachypnea, and microvascular protein leakage in association with leukocyte-endothelial adherence. In the current study, we hypothesized that topical administration of TNF-alpha to the cremaster muscle would cause microvascular protein leakage independent of changes in hemodynamic parameters. In addition, histological methods were used to study the role of neutrophils and mast cells in the TNF-alpha-induced microvascular protein leakage. Topically applied low-dose (1 ng/ml) TNF-alpha caused microvascular leakage in the cremaster, without changes in central hemodynamic parameters, but high-dose TNF-alpha (10 ng/ml) did not cause protein leakage. Histological studies did not demonstrate evidence of either neutrophil adhesion or mast cell degranulation in topically applied TNF-alpha-treated cremasters compared to controls. These data suggest that TNF-alpha-induced macromolecular leakage is a dose-dependent phenomenon which can occur independently of neutrophils or mast cell degranulation.

Animals↗

PubMed1994

Interleukin-2 alters the positions of capillary and venule pericytes in rat cremaster muscle.

Interleukin-2 (IL-2) mediates regression of metastatic cancer, but its therapeutic efficacy has been limited by toxicities which occur secondarily to IL-2 induced macromolecular leakage from microvessels. Previous studies have indicated that pericytes function in an endothelial cell junction-dependent manner in lung capillaries and cremaster muscle venules, possibly to limit cellular and macromolecular leakage. The purpose of this investigation was to determine if pericyte positioning on skeletal muscle capillaries was junction-related, and if it was altered by IL-2. Anesthetized rats received intravenous injections of fluoroscein isothiocyanate conjugated to albumin. The cremaster muscle model of microcirculation was used in conjunction with intravital fluorescence microscopy to monitor changes in interstitial fluorescence which was used as an index of macromolecular leakage. IL-2 induced a progressive increase in interstitial albumin which started within 30 min of application and continued to increase until the end of the experiment at two hours. Cremaster muscle tissue was fixed and prepared for examination by transmission electron microscopy. A digitizing platter and morphometric software were used to quantify pericytes near vs away from endothelial cell junctions of capillaries and venules. In microvessels from animals in the control group, pericytes were randomly positioned on capillaries, and concentrated at endothelial cell junctions of venules. After treatment with IL-2, capillary pericytes were concentrated at junctions. Venular pericyte density also increased in endothelial junctional regions. IL-2 appears to alter the distribution of pericytes in the microcirculation, perhaps by induction of contraction.

Animals↗