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Biomedical subjects

P Birch

Publications and source records attributed to P Birch.

At least 19 recordsLinked to original sources
PubMed2006

Experimental findings on the nasal tract resonator in singing.

SUMMARY: Many professional operatic singers sing the vowel /a/ with a velopharyngeal opening.(1) Here resonatory effects of such an opening are analyzed. On the basis of CAT scan imaging of a baritone singer's vocal tract and nasal cavity system, including the maxillary sinuses, acoustic epoxy models were constructed, in which velopharyngeal openings were modeled by different tubes. The sound transfer characteristics of this model were determined by means of sine-tone sweep measurements. In an idealized (iron tube) model, the VPO introduced a zero in the transfer function at the frequency of the nasal resonance. In the epoxy models, however, the resonances of the nasal system, and hence the zero, were heavily damped, particularly when the maxillary sinuses were included in the nasal system. A velopharyngeal opening was found to attenuate the first formant in /a/, such that the relative level of the singer's formant increased. A similar effect was observed in a modified epoxy model shaped to approximate the vocal tract of an /u/ and an /i/, although it also showed a substantial widening of the first formant bandwidth. Varying the size of the velopharyngeal opening affected the transfer function only slightly. It seems likely that singers can enhance higher spectrum partials by a careful tuning of a velopharyngeal opening.

Humans↗
PubMed2005

Bowel function following insertion of self-expanding metallic stents for palliation of colorectal cancer.

OBJECTIVE: Self-expanding metallic stents (SEMS) are an important addition to the treatment of large bowel obstruction. The aim of this study was firstly to assess bowel function following SEMS placement and secondly to identify any potential factors which might aid in the prediction of technical failure of stent insertion. METHODS: A review of all patients undergoing attempted SEMS placement for palliation of malignant left-sided colorectal obstruction over a four-year period (1st May 2000-30th April 2004) was performed. RESULTS: Twenty-one patients (12 male) with a median age of 76 years (range 48-92 years) were included, 11 with metastatic disease and 10 severe comorbidity. SEMS insertion was technically successful in 16 (76%) of 21 cases. Contrast successfully passed through the obstructing lesion in all 16 cases where SEMS placement was technically successful. It only passed through 1 of 5 cases where stenting was not possible (P = 0.0008, Fisher's Exact test). Complications included colonic perforation (1 case), stent migration (1 case) and tumour ingrowth requiring a second stent (1 case). Median survival after SEMS was 12 months (range 1-30 months), and 9 patients died during follow-up. Median bowel frequency following SEMS was 3.5 times per day (range 1-7). Eight patients always passed a liquid stool, 3 others regularly required laxatives and one further patient with poor function after stenting requested a defunctioning stoma. CONCLUSION: Failure of contrast to pass through the obstructing lesion may predict those cases where stenting will not be technically possible. Median survival following SEMS insertion is encouraging in this series, but bowel function is often poor. Expected bowel function should be discussed fully when consenting patients for a SEMS, particularly those with metastatic disease who are otherwise fit for resectional surgery.

Aged↗
PubMed2002

Paternal preconceptional irradiation, population mixing and solid tumors in the children of radiation workers (England).

OBJECTIVE: To investigate whether there was an increased incidence of solid tumors among offspring of male radiation workers at the Sellafield nuclear installation in Cumbria, northwest England and whether paternal preconceptional irradiation was associated with the risk of solid tumors. METHODS: A cohort study of 266,710 live births in Cumbria, 1950-1991, followed up to age 25 years on the end of 1991. RESULTS: Children of radiation workers had a non-significantly increased risk of solid tumors (RR= 1.5, 95% CI: 0.9-2.4, p = 0.09), determined largely by an increased risk of cancers excluding leukemias, lymphomas, brain, spinal and gender-specific tumors (RR= 1.9, 95% CI: 1.0-3.3, p = 0.05), which was partly explained by differing patterns of parental migration (adjusted RR= 1.7, 95% Cl: 0.8-3.2, p = 0.50). Within children of radiation workers there was no evidence of an increased risk with increasing paternal preconception dose of external radiation (hazard ratio per 100 mSv for all solid tumors=0.6, 95% CI: 0.1-1.8, p = 0.52). CONCLUSIONS: Any observed excess of solid tumors in children of radiation workers may be partly explained by population mixing. Fathers' occupational exposure to radiation before conception was not found to be risk factor for solid tumors in their children.

Adolescent↗
PubMed2000

Chronic neuropathic pain in treated leprosy.

The existence of chronic neuropathic pain in treated leprosy has received scant attention. We describe the clinical findings of 16 patients with multibacillary leprosy who had chronic stimulus-independent pain despite finishing their treatment. With confirmation, our results could be of importance in the establishment of "care after cure" programmes for patients with leprosy.

Adult↗
PubMed2000

Associations of clinical features in neurofibromatosis 1 (NF1).

Neurofibromatosis 1 (NF1), an autosomal dominant disease, exhibits extreme clinical variability. This variability greatly increases the burden for affected families and impairs our ability to understand the pathogenesis of NF1. Recognition of heterogeneity within a disease may provide important pathogenic insights, therefore we tested clinical data from three large sets of NF1 patients for evidence that certain common features are more likely to occur in some NF1 patients than in others. Clinical information on 4,402 patients with NF1 was obtained from three independent databases. We examined associations between pairs of clinical features in individual affected probands. We also examined associations between the occurrence of individual features in affected relatives. Associations were summarized as odds ratios with 95% confidence intervals. We found associations between several pairs of features in affected probands: intertriginous freckling and Lisch nodules, discrete neurofibromas and plexiform neurofibromas, discrete neurofibromas and Lisch nodules, plexiform neurofibromas and scoliosis, learning disability or mental retardation and seizures. We also found associations between the occurrence of Lisch nodules, macrocephaly, short stature, and learning disability or mental retardation as individual features in parents and children with NF1. Our observations suggest that, contrary to established belief, some NF1 patients are more likely than others to develop particular manifestations of the disease. Genetic factors appear to determine the development of particular phenotypic features.

Adult↗
PubMed2000

Growth in North American white children with neurofibromatosis 1 (NF1).

OBJECTIVE: To analyse the distributions of and generate growth charts for stature and occipitofrontal circumference (OFC) in neurofibromatosis 1 (NF1) patients. DESIGN: Cross sectional database survey. SETTING: The National Neurofibromatosis Foundation International Database (NFDB) includes clinical information on NF1 patients from 14 participating centres in North America. SUBJECTS: A total of 569 white, North American, NF1 patients, 55% female and 45% male. MAIN OUTCOME MEASURES: Stature and OFC measurements of NF1 patients were compared to age and sex matched population norms using z score standardisation and centile curves. RESULTS: The distributions of stature and OFC are shifted and unimodal among NF1 patients; 13% of patients have short stature (>/=2 standard deviations below the population mean) and 24% have macrocephaly (OFC >/=2 standard deviations above the population mean). CONCLUSIONS: Alterations of stature and OFC are not limited to NF1 patients with frank short stature or macrocephaly.

Adolescent↗
PubMed1999

King Solomon's miners--starvation and bioaccumulation? An environmental archaeological investigation in Southern Jordan.

Copper mining and smelting were important activities in various predesert wadis during the Iron Age, Nabatean, Roman, and Byzantine periods in southern Jordan and major spoil tips together with slag heaps remain as a legacy of such enterprises. Barley has grown in the area for a prolonged period and currently wild barley plants are affected by toxic cations, which reduce their yields. It is considered that such plants provide an adequate model to assess how similar plants would have performed, in terms of productivity, in the past. The population of miners/slaves, guards, etc., would have been subject to bioaccumulation of heavy metals, which conceivably would have led to detrimental effects on their health. Inhalation and ingestion of particulate pollutants cannot be discounted. It is argued that the population may have been further weakened as a consequence of food shortage, due to reduced plant productivity, as cereals are important foods for both humans and the animals upon which they are dependent. A sizeable mining community could only have been maintained by large-scale importation of food or a massive intensification of agricultural activity.

Agriculture↗
PubMed1998

The immunohistochemical detection of cripto-1 in benign and malignant human bladder.

The recently identified epidermal growth factor-related peptide cripto-1 has been previously implicated in the development of the malignant phenotype. The identification of gene products that can act as prognostic markers in bladder cancer would be value in determining the management of this heterogeneous group of patients. This study examines cripto-1 expression in benign and malignant bladder using immunohistochemical techniques. The expression of cripto-1 protein in benign and malignant bladder was examined in 45 bladder tumours (Ta/T1 n = 26, T2 n = 5, T3/T4 n = 14) and six benign controls. All 45 tumours showed positive cytoplasmic staining for cripto-1, including areas of carcinoma in situ. None of the six benign controls showed any evidence of positive cripto-1 staining. Twenty-three (60 per cent) bladder tumours had areas of papillary tumour that showed strong positive staining for cripto-1 as opposed to six (29 per cent) sections of histologically normal urothelium adjacent to tumour (P < 0.05). There was no association between cripto-1 staining and tumour grade, stage, or clinical outcome. Cripto-1 protein appears to be specifically expressed in malignant and benign adjacent urothelium of patients with bladder cancer. Its clinical significance, however, remains to be determined.

Aged↗
PubMed1997

The role of natural anti-Gal alpha 1-3Gal antibodies in hyperacute rejection of pig-to-baboon cardiac xenotransplants.

Xenoreactive natural antibodies in humans and higher primates are directed predominantly at Gal alpha 1-3Gal. These antibodies are thought to initiate hyperacute rejection of porcine organ xenografts. The contribution of anti-Gal alpha 1-3Gal antibodies to the xenoractive natural antibody repertoire and to the initiation of hyperacute rejection was tested in a pig-to-baboon cardiac xenograft model. Anti-Gal alpha 1-3Gal antibodies were depleted from baboons by extracorporeal absorption of anti-Gal alpha 1-3Gal antibodies from plasma using columns with a matrix bearing Gal alpha 1-3Galb1-4GlcNAc. Specific removal of anti-Gal alpha 1-3Gal antibodies was achieved prior to transplantation as demonstrated by immunoassay. Porcine hearts were then transplanted into these baboons and the outcome of the transplants was analysed. Immunofluorescence revealed little deposition of baboon antibodies in the grafts. The porcine hearts did not undergo hyperacute rejection even though complement activity was approximately 90% of baseline at the time of transplantation. These findings demonstrate that anti-Gal alpha 1-3Gal antibodies constitute a major fraction of xenoreactive natural antibodies in primate blood and that these antibodies contribute significantly to the pathogenesis of hyperacute xenograft rejection.

Acute Disease↗
PubMed1997

The effect of placing an aortic Wallstent across the renal artery origins in an animal model.

OBJECTIVES: To assess the effect on renal blood flow and renal function of placing a Wallstent (Schneider (Europe) AG) across the renal artery origins in an animal model. DESIGN: Laboratory animal study. MATERIALS AND METHODS: Six Large White pigs had Wallstents placed across the origins of one or both renal arteries. Preoperative jugular venous blood samples were submitted for blood count and urea and electrolyte estimation. The pigs were recovered for 6 weeks. At sacrifice the renal arteries and their origins were examined by aortography and direct pressure measurements were recorded from the renal arteries and both the stented and unstented portions of the aorta. Renal venous blood samples were submitted for blood count, urea and electrolyte and renin estimation while renal arterial blood samples were submitted to examination for red blood cell fragmentation. The aorta with contained stent, renal arteries and kidneys were submitted for histological examination. RESULTS: At sacrifice no renal arteries had occluded and the stent-covered origins appeared normal with no evidence of stenosis. This was confirmed histologically. There was no statistically significant difference between the arterial pressures measured in the stented and unstented portions of aorta and the renal arteries whether or not their origins had been covered by the stent. There was no statistically significant difference between the urea and electrolyte and renin levels of renal venous blood samples irrespective of whether or not the relevant kidney had a stent across its renal artery origin. Renal arterial blood samples showed no evidence of red blood cell fragmentation and histological examination of the kidneys showed no evidence of infarction or micro-emboli. Examination of the specimens by light and scanning electron microscopy demonstrated partial endothelialisation of the stents but the renal artery origins remained widely patent despite being crossed by at least one wire in all cases. CONCLUSIONS: It may be necessary to place stents across renal artery origins during endovascular repair of abdominal aortic aneurysms. It would appear that covering renal artery origins with a Wallstent has no effect on renal perfusion pressure or function in this short-term animal model.

Animals↗
PubMed1997

An association between optic glioma and other tumours of the central nervous system in neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) has a very heterogeneous phenotype. It is not currently possible to predict which patients will have mild disease and which will develop serious complications. Medical management of patients with NF1 might be improved if subgroups of patients who are at especially high (or low) risk for particular complications could be identified. We have begun an analysis of NF1 patients in the National Neurofibromatosis Foundation International Database (NNFFID) to identify possible associations between the occurrence of clinical features. A striking association has been observed between the presence of optic glioma and of other central nervous system (CNS) tumours in NF1 patients. This association is not dependent on the effect of age. No association is seen between optic glioma and non-CNS neoplasms. The association of optic glioma and other intracranial neoplasms in patients with NF1 suggests that there are fundamental pathophysiological differences between patients with and without optic glioma.

Age Factors↗
PubMed1996

Reduction in the level of Gal(alpha1,3)Gal in transgenic mice and pigs by the expression of an alpha(1,2)fucosyltransferase.

Hyperacute rejection of a porcine organ by higher primates is initiated by the binding of xenoreactive natural antibodies of the recipient to blood vessels in the graft leading to complement activation. The majority of these antibodies recognize the carbohydrate structure Gal(alphal,3)Gal (gal epitope) present on cells of pigs. It is possible that the removal or lowering of the number of gal epitopes on the graft endothelium could prevent hyperacute rejection. The Gal(alpha1,3) Gal structure is formed by the enzyme Galbeta1,4GlcNAc3-alpha-D-galactosyltransferase [alpha(1,3)GT; EC 2.4.1.51], which transfers a galactose molecule to terminal N-acetyllactosamine (N-lac) present on various glycoproteins and glycolipids. The N-lac structure might be utilized as an acceptor by other glycosyltransferases such as Galbeta1,4GlcNAc 6-alpha-D-sialyltransferase [alpha(2,6)ST], Galbeta1,4GlcNAc 3-alpha-D-Sialyltransferase [alpha(2,3)ST], or Galbeta 2-alpha-L-fucosyltransferase [alpha(1,2)FT; EC 2.4.1.691, etc. In this report we describe the competition between alpha(1,2)FT and alpha(1,3)GT in cells in culture and the generation of transgenic mice and transgenic pigs that express alpha(1,2)Fr leading to synthesis of Fucalpha,2Galbeta- (H antigen) and a concomitant decrease in the level of Gal(alpha1,3)Gal. As predicted, this resulted in reduced binding of xenoreactive natural antibodies to endothelial cells of transgenic mice and protection from complement mediated lysis.

Animals↗
PubMed1996

A new animal model for abdominal aortic aneurysms:initial results using a multiple-wire stent.

OBJECTIVES: The effect of a plain 48-wire self-expanding flexible stent (Wallstent-Schneider (Europe) AG) on abdominal aortic aneurysms has been studied in a new animal model. METHODS: Aneurysms were created by interposing fusiform segments of glutaraldehyde-tanned bovine internal jugular vein into the infrarenal aortas of 12 Large White pigs. The first six pigs were assessed after 6 weeks by ultrasonography and arteriography; they were then sacrificed for pathological examination. Endovascular placement of the stents, 2 weeks after aneurysm creation, was performed under arteriographic control in the next six pigs. These pigs were assessed by ultrasonography and arteriography 6 weeks after stenting; they were then sacrificed for pathological examination. RESULTS: At 6 weeks the aneurysms in the first group were pulsatile with partial endothelialisation and no mural thrombus. Placement of the stent in the second group was accomplished easily. Stenting resulted in an immediate reduction in wall pulsatility of all aneurysms and thrombosis of the excluded aneurysm sac occurred in three cases. In the other three cases the pulse pressure in the sac was reduced. In all cases there was a significant reduction in maximum aneurysm diameter when measured 6 weeks after stenting. CONCLUSIONS: A pulsatile, non-thrombogenic aortic aneurysm model approaching human dimensions has been successfully developed for the study of endoprostheses prior to their clinical use. Endovascular placement of a plain, multiple-wire Wallstent was associated with reductions in aneurysm pulsatility, pulse pressure within the sac and maximum aneurysm diameter over the study period. Stenting was associated with thrombosis of the excluded aneurysm sac in 50% of cases.

Animals↗
PubMed1996

Flow cytometric immunofluorescence assay for detection of antibodies to human immunodeficiency virus type 1 using insoluble precursor forms of recombinant polyproteins as carriers and antigens.

A new serological assay, the recombinant flow cytometric immunofluorescence assay (r-FIFA), was developed for the early detection of human immunodeficiency virus type 1 (HIV-1) antibodies by using recombinant insoluble forms of HIV-1 Gag-p45, Gag-gp41 chimeric protein, gp160, Po197 polyprotein as antigens and autologous carriers through flow cytometry. These recombinant proteins were expressed in insect cells by a baculovirus expression system. Eight anti-HIV-1 seroconversion panels, a low-titer anti-HIV-1 panel from Boston Biomedica Inc. (BBI), and three HIV-1 seroconversion specimens from the Provincial Health Laboratory of Ontario, Toronto, Ontario, Canada (PHL), were tested and analyzed by r-FIFA. In sensitivity comparisons between r-FIFA and tests licensed by the U.S. Food and Drug Administration, which were used to test all of the HIV-1 panels from BBI, detection of HIV-1 antibody by r-FIFA was on average greater than 20 days earlier than that by enzyme immunoassay. The sensitivity of r-FIFA has permitted the detection of HIV-1-specific immunoglobulin G (IgG), IgM, and IgA antibodies during seroconversion. A kinetic analysis of HIV-1 antibody production of r-FIFA has shown that either IgG or IgM, or both, can be detected, depending on the phase and type of the immune response in the HIV-1-infected individual. Both primary and secondary immune responses were observed during this period. The r-FIFA results suggest that implementation of r-FIFA may significantly reduce the "window" period from the time of infection to the time of seroconversion, with earlier detection of antibodies after initial infection. This would also make it possible for us to understand the immune response and the precise mechanisms of immunopathogenesis in the early period of HIV-1 infection.

AIDS Serodiagnosis↗
PubMed1995

Peripheral thrombolysis: state of the art.

Peripheral thrombolysis has become established in the last decade as an alternative method of treatment for acute limb ischaemia. New techniques of accelerated thrombolysis have expanded the indications to include almost all affected patients. Attention to detail and avoidance of known pitfalls, together with close cooperation between vascular surgeon and radiologist, ensure optimum results with minimum complications. A modern integrated lysis programme may vary from initial thrombolytic treatment for all patients with acute limb ischaemia to a selective policy of surgery and thrombolysis depending on the aetiology and severity of ischemia.

Extremities↗
PubMed1994

Non-specific effects of the tachykinin NK1 receptor antagonist, CP-99,994, in antinociceptive tests in rat, mouse and gerbil.

We have examined the antinociceptive activity of the potent and selective tachykinin NK1 receptor antagonist, CP-99,994, and its less active enantiomer, CP-100,263, in a variety of models in rat, mouse and gerbil. Administered systemically to gerbil or mouse CP-99,994 but not CP-100,263 stereo selectively inhibited a caudally directed biting and scratching elicited by intrathecal administration of the tachykinin NK1 receptor agonist, GR73632. In contrast, both CP-99,994 (ED50 = 3 (1-6) mumol.kg-1 s.c.) and CP-100,263 (4 (2-10)), were equipotent at inhibiting acetylcholine-induced abdominal constrictions in mice. Similarly, both enantiomers were also equipotent in reducing formalin-induced licking in gerbil (CP-99,994 (10.1 (5.7-18.6)), CP-100,263 (13.8 (7.8-27.1)) and rat (100 mumol.kg-1 s.c.). Finally, in the spinalised, anaesthetised rat, CP-99,994 dose-dependently and significantly inhibited the flexion reflex evoked by noxious pinch (5.0 (3.3-7.5) mumol.kg-1 i.v.), whereas the less active enantiomer, CP-100,263, was without significant effect when tested up to 30 mumol.kg-1. Our results demonstrate that in the spinal cord, CP-99,994 exhibits a tachykinin NK1 receptor mediated antinociceptive action.

Analgesics↗
PubMed1994

Influence of the chemical nature of side chain at beta 108 of hemoglobin A on the modulation of the oxygen affinity by chloride ions. Low oxygen affinity variants of human hemoglobin expressed in transgenic pigs: hemoglobins Presbyterian and Yoshizuka.

Hemoglobin A (HbA) and two low oxygen affinity variants of HbA, HbPresbyterian and HbYoshizuka, were produced in transgenic pigs and purified to homogeneity by ion-exchange chromatography. These two variants contain either lysine (HbPresbyterian) or aspartic acid (HbYoshizuka) instead of the normal asparagine residue at position beta 108 in HbA. Transgenic pigs expressed these variants at a level up to 11% and were healthy. Both HbPresbyterian and HbYoshizuka exhibited low O2 affinity (P50 of 21.2 and 18.9, respectively, compared with control HbA value of 11.8 in 0.1 M NaCl, pH 7.5) and retained normal cooperativity with Hill coefficients of 2.9 and 2.5, respectively. HbPresbyterian exhibited Bohr effect comparable with HbA. In contrast, HbYoshizuka had a diminished response to changes in pH. Thus the structural basis of reduced O2 affinity of these variants appears to be distinct: the consequence of mutation at beta 108 is a function of the chemical nature of the side chain. This is further confirmed by the sensitivity of the O2 affinity of the variants to the presence of Cl-. The O2 affinity of HbYoshizuka is insensitive to changes in Cl- concentration, whereas the O2 affinity of HbPresbyterian exhibited a pronounced and dramatic chloride effect. In fact, P50 of HbPresbyterian was identical to that of HbA at very low Cl- concentrations, and the P50 increased to >40 at 0.5 M Cl-. The chloride effect was completely abolished when HbPresbyterian was stabilized at the 2,3-diphosphoglycerate pocket by interdimeric cross-linking. Molecular modeling studies demonstrate that in HbPresbyterian, Cl- can bridge the epsilon-amino group of Lys beta 108 with either the guanidino group of Arg beta 104 or the epsilon-amino group of Lys alpha 99, resulting in the stabilization of the "T" structure. The utility of these low O2 affinity hemoglobins as cell-free oxygen carriers is discussed.

Allosteric Regulation↗