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Biomedical subjects

M Patterson

Publications and source records attributed to M Patterson.

At least 91 records · Page 5Linked to original sources

Severity of beta-thalassemia due to genotypes involving the IVS-I-6 (T-->C) mutation.

Among individuals of Mediterranean or Middle Eastern descent, the IVS-I-6 (T-->C) mutation is one of the most common causes of beta-thalassemia. In this report, we describe the clinical phenotypes of a group of beta-thalassemia patients who are compound heterozygotes for the relatively mild IVS-I-6 (T-->C) beta-thalassemia mutation and more severe beta(+)- or beta (0)-thalassemia mutations. Although most of these patients are transfusion-dependent, the requirement for regular transfusions generally occurred late in childhood. A correlation between concomitant alpha-thalassemia and a mild transfusion-independent phenotype is not apparent, indicating the involvement of other ameliorating determinants.

Adult↗

Properties of calcium currents and contraction in cultured rat diaphragm muscle.

The characterization of calcium currents and contraction simultaneously measured in cultured rat diaphragm muscle cells was carried out in the present study. Whole-cell patch-clamp experiments were designed to further elucidate the mechanism of excitation-contraction (E-C) coupling in diaphragm which, though generally considered a skeletal-type muscle, has been reported to exhibit properties indicative of a cardiac-like E-C coupling mechanism. Normalized current/voltage (I/V) curves for two concentrations of external calcium (2.5 and 5 mM) were obtained from diaphragm myoballs. Both curves showed peaks corresponding to the activation of a T-type calcium current and a dihydropyridine-sensitive L-type calcium current. The normalized curve for the voltage dependence of the activation of contraction in diaphragm myoballs followed a typical Boltzmann-type relationship to the peak of contraction. Thereafter, the curve declined in a manner that was more pronounced in diaphragm compared to that measured in additional experiments using cultured rat limb muscle myoballs. This effect could be interpreted in terms of a more pronounced participation of the L-type current in E-C coupling in cultured diaphragm muscle. An increased likelihood of cultured diaphragm muscle to undergo depletion of sarcoplasmic reticular calcium stores during repetitive stimulation, or a heightened propensity for the voltage sensor for E-C coupling in diaphragm to enter the inactive state could also explain this effect. Maximal contractile activity was only slightly affected when the L-type current was blocked by externally applied cadmium (2 mM) or cobalt (3 mM), suggesting that a pronounced calcium-current-dependent component of contraction is unlikely in cultured diaphragm muscle. These results show that T- and L-type calcium channels are expressed in cultured rat diaphragm muscle cells and that, in contrast to cardiac muscle, the entry of calcium ions via L-type voltage-dependent calcium channels is not a prerequisite for contraction. Differences in the voltage sensitivity of contraction, observed at depolarized membrane potentials in cultured rat diaphragm and limb muscle cells, suggest that the voltage sensor for E-C coupling in diaphragm might more readily enter an inactivated configuration - possibly by a mechanism which is dependent on the concentration of external calcium.

Animals↗

A comparison of the mast cell and eosinophil responses of sheep and goats to gastrointestinal nematode infections.

The mucosal mast cell and eosinophil responses of goats and sheep to a mixed gastrointestinal nematode infection were compared. Groups of eight does and nine ewes, previously maintained on pasture and treated with anthelmintic when they were housed and five worm-free lambs were challenged with 10,000 Trichostrongylus vitrinus third stage larvae (L3) and 10,000 Teladorsagia circumcincta L3. Eleven days after challenge, the ewes had significantly (P < 0.001) lower burdens of abomasal and intestinal worms than the does or naive lambs, but significantly higher (P < 0.001) tissue concentrations of mast cell proteinase. Toluidine blue-stained sections indicated a paucity of mast cells in the does compared with the ewes, whereas the immunolocalisation of sheep mast cell proteinase revealed similar numbers of stained cells in the two species. This discrepancy was due to the relatively high proportion of globule leucocytes (77 and 91 per cent in the jejunum and abomasum, respectively) in the does compared with the ewes (7 and 24 per cent in the jejunum and abomasum, respectively). No differences were detected between the numbers of circulating or tissue eosinophils in the ewes and does.

Animals↗

A complex issue.

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Animals↗

Identification of a new high oxygen affinity hemoglobin variant: Hb Aurora [beta 139(H17) Asn-->Tyr].

A 73-year-old female of Dutch descent was referred for investigation of a high oxygen affinity hemoglobin variant. The beta-globin gene was amplified using the polymerase chain reaction. Direct nucleotide sequencing of the polymerase chain reaction amplified DNA revealed that she is heterozygous for a novel beta-globin gene mutation at codon 139, AAT-->TAT. The resulting hemoglobin variant has been designated Hb Aurora [beta 139 (H17) Asn-->Tyr].

Aged↗

DNA diagnosis of Hb S and Hb Caribbean (alpha 2 beta 2 91 Leu-->Arg) in a Jamaican family.

We describe a Canadian infant of Jamaican descent who presented with mild anemia. Hb electrophoresis revealed Hb S and an unknown Hb variant that migrated slightly faster than Hb S on cellulose acetate. Molecular studies of the family indicated that the proband is a compound heterozygote for Hb S and Hb Caribbean. Hb Caribbean has previously been characterized as a mildly unstable hemoglobin with low oxygen affinity, due to a Leu-->Arg substitution at amino acid residue 91. The present study establishes the molecular basis for Hb Caribbean (beta 91, CTG-->CGG) and confirms that Hb S/Hb Caribbean syndrome is not associated with serious clinical manifestations.

Adult↗

Hb E/Hb LeporeHollandia in a family from Bangladesh.

We describe a family from Bangladesh in which three children are compound heterozygotes for Hb E (alpha 2 beta 2, beta 26Glu Lys) and Hb Lepore (delta-beta fusion gene). PCR amplification and direct nucleotide sequencing established that the fusion gene is Hb LeporeHollandia, with the cross-over localized to a 40 bp window between codon 22 and IVS-1 nt 16 of the delta- and beta-globin genes. This unusual combination of mutations is associated with a relatively mild clinical phenotype, with all three affected siblings having microcytic anemia of moderate severity without the need for transfusions.

Bangladesh↗

Acute cocaine administration induces ventricular regional wall motion and ultrastructural abnormalities in an anesthetized rabbit model.

Whether acute doses of cocaine can induce left ventricular (LV) regional wall motion abnormalities in animals with otherwise normal coronary arteries is unknown. We studied rabbits receiving constant cocaine infusions (group I: 0.025 to 1.5 mg/kg/min, n = 10), multiple cocaine boluses (group II: 3-5 mg/kg each bolus, n = 10), or saline (group III; n = 8). In group I rabbits, short-axis LV area and diameter increased by 15% to 40% at 60 minutes compared to baseline and to controls (p < 0.01), but percentage of global area fractional shortening was unchanged. Eight rabbits in each of groups I and II, but no controls, developed LV regional wall motion abnormalities as detected by echocardiography: 15 (7 hypokinesis and 8 akinesis or dyskinesis) in the anteroseptal and 2 (hypokinesis) in the posterior LV wall. Among rabbits showing LV wall motion abnormalities, anteroseptal fractional shortening and % area reduction averaged > 20% less (p = 0.03 for area reduction) at 30 minutes versus controls. Only 50% of group I or II rabbits with LV anteroseptal wall motion abnormalities had intraventricular conduction disturbances. Radioactive microsphere flow studies (n = 6) 1 minute after a 4 mg/kg cocaine bolus revealed an equivalent decrease (10% to 20%, average) in septal and LV free wall perfusion (p value not significant). Electron microscopy revealed myocardial cell contraction band necrosis in 3 and sarcoplasmic reticular edema in 7 of 10 cocaine rabbits (unrelated to dose). We conclude that acute cocaine administration in rabbits frequently produces LV anteroseptal wall motion abnormalities even in the absence of differentially decreased perfusion or intraventricular conduction disturbances and produces ultrastructural abnormalities of the myocytes. These findings suggest a direct, nonuniform effect of cocaine on the LV myocardium.

Animals↗

Biosynthetic radiolabelling of excretions-secretions of adult male Onchocerca gibsoni.

Maintenance of adult male worms of the bovine filarial parasite Onchocerca gibsoni in vitro, in the presence of radioactive precursors, resulted in the time-dependent excretion-secretion of radiolabelled parasite macromolecules (ES). Molecules labelled with amino acids ([35S] methionine, [3H] leucine) covered a wide range of molecular weights, whereas labelling with [3H] glucosamine produced predominantly molecules of high molecular weight. Many of the products were recognized by antibodies in two serum pools from humans infected with Onchocerca volvulus. O. gibsoni ES may therefore provide a substitute source of material for studies on the ES of the less readily available human parasite.

Animals↗

Beta-thalassemia intermedia in a Lebanese child due to homozygosity for the -88 (C-->T) mutation.

We report a case of beta-thalassemia intermedia involving a 3-year-old male child of Lebanese descent. Molecular studies of the family showed that he is homozygous for the -88 (C-->T) beta (+)-thalassemia mutation. This mutation is the second most common cause of beta-thalassemia in Black populations, and has also been reported in Asian Indians. A review of Lebanese beta-thalassemia cases revealed considerable mutation heterogeneity and excess homozygosity due to consanguinity.

Adult↗

An orthopaedic theatre timings survey.

The efficient use of operating lists is important to clear waiting lists and because they are expensive to run (at 1988 prices, 151 pounds per hour). Of general surgical theatre session time, 49% is used for performing operations, but no survey of orthopaedic theatre sessions has been published. In light of this we surveyed 151 elective orthopaedic lists at three hospitals. Our aims were to determine the use of operating rooms and the reasons for inefficient use of time. We found 60% of elective list time was used for operating and 21% for turnover. No useful activity occurred during the remaining 19% of theatre time. An average start delay of 26.5 min and average early finish of 14.5 min contributed to this. Only 9/151 (6%) of lists started within 5 min of the scheduled time. Of unnecessary delays contributing to this, 63% involved anaesthetic staff and 24% theatre staff. Surgeons were implicated in 10% of start delays. There were less start delays if senior anaesthetic staff were present. During lists, turnover times were quicker if a consultant surgeon was present (P = 0.0022). We conclude that more efficient use of elective orthopaedic theatre sessions is possible and could be achieved if more detailed preparation was undertaken by the anaesthetic, theatre and surgical staff concerned. If a consultant surgeon is present the list is likely to proceed with fewer delays.

Anesthesiology↗

Postoperative bowel obstruction following laparoscopic surgery.

The rapid expansion of laparoscopic surgery has not been achieved without attendant complications, some of them unique. Visceral herniation into abdominal trocar entry sites is occasionally mentioned but seldom reported. We present three cases of postoperative bowel obstruction resulting from visceral herniation into trocar entry sites in different surgical settings, suggesting that this complication may be more common than is appreciated. Awareness of this clinical problem confirms the need for meticulous closure of larger abdominal trocar sites and should be considered when dealing with abdominal disorders following laparoscopic surgery.

Aged↗

Carrier detection and prenatal diagnosis of hemoglobinopathies in Ontario.

The province of Ontario has a total population of approximately 10 million people, with approximately 20% being of African, Southeast Asian, East Indian, Mediterranean, or Middle Eastern ancestry in whom the gene frequency for hemoglobinopathies is relatively high. In 1989, the Ontario Ministry of Health funded the establishment of the Provincial Hemoglobinopathy DNA Diagnostic Laboratory located at the McMaster University Medical Centre in Hamilton, Ontario. The Laboratory provides DNA analysis to identify the globin gene mutations in carriers and affected individuals, and performs prenatal diagnosis for severe hemoglobinopathies. Annually, more than 400 patient samples are referred to the Laboratory for investigation, of which 25-35 are fetal samples from pregnancies at risk for either homozygous alpha-thalassemia, beta-thalassemia major, or sickling disorders. We have detected more than 70 different globin gene mutations, including several mutations not previously reported in the literature. Here we present examples of the approaches used to detect globin gene mutations in a heterogeneous "at risk" population such as in Ontario, and discuss the impact of this service on patient care, genetic counselling, and the incidence of severe hemoglobinopathies in Ontario.

DNA↗

Markers of data quality in computer audit: the Manchester Orthopaedic Database.

This study investigates the efficiency of the Manchester Orthopaedic Database (MOD), a computer software package for record collection and audit. Data is entered into the system in the form of diagnostic, operative and complication keywords. We have calculated the completeness, accuracy and quality (completeness x accuracy) of keyword data in the MOD in two departments of orthopaedics (Departments A and B). In each department, 100 sets of inpatient notes were reviewed. Department B obtained results which were significantly better than those in A at the 5% level. We attribute this to the presence of a systems coordinator to motivate and organise the team for audit. Senior and junior staff did not differ significantly with respect to completeness, accuracy and quality measures, but locum junior staff recorded data with a quality of 0%. Statistically, the biggest difference between the departments was the quality of operation keywords. Sample sizes were too small to permit effective statistical comparisons between the quality of complication keywords. In both departments, however, the poorest quality data was seen in complication keywords. The low complication keyword completeness contributed to this; on average, the true complication rate (39%) was twice the recorded complication rate (17%). In the recent Royal College of Surgeons of England Confidential Comparative Audit, the recorded complication rate was 4.7%. In the light of the above findings, we suggest that the true complication rate of the RCS CCA should approach 9%.

Data Collection↗

Human embryonic zeta-globin chain expression in deletional alpha-thalassemias.

zeta-Globin chain expression in carriers of a number of deletional alpha-thalassemias is investigated by radioimmunoassay. In a few cases, zeta-globin mRNAs are also studied. zeta-Globin chains are detected in (--SEA/), (--MED/), and (--SPAN/) deletions, but not in six other deletional mutations. These results suggest that the DNA element capable of suppressing zeta-globin expression in adult erythroid cells is present within the (--SPAN/) deletion, while the DNA fragment between the 5' breakpoints of the (--SA/) and the (--SEA/) deletions may contain sequences necessary for augmenting zeta-globin expression in adult erythroid cells. Furthermore, zeta-globin chains are shown by an immunocytologic technique to be present in all circulating erythrocytes in carriers of the (--SEA/) and (--MED/) deletions. This simple immunocytologic test is highly sensitive and specific to detect adult carriers of either the (--SEA/) or (--MED/) deletions, and can be used for the detection of couples at risk of pregnancies involving fetuses with homozygous alpha-thalassemia.

Chromosome Deletion↗

A randomized double-blind study of neuroelectric therapy in opiate and cocaine detoxification.

Prior research on the use of transcranial neuroelectric stimulation suggested that the application of low-amperage, low-frequency alternating current via surface electrodes placed in the mastoid region could relieve the physiological signs and subjective symptoms of withdrawal and craving during opiate detoxification. These effects were reported without gradual tapering of the opiate or the addition of other medications. To test the efficacy of one particular form of neuroelectric therapy (NET), a double-blind, randomized, placebo-controlled study was conducted comparing active NET and placebo NET in the treatment of withdrawal and stabilization of 18 opiate-dependent and 25 cocaine-dependent subjects. Scores on scales for measuring substance withdrawal and craving for each abused substance, as well as the multiple dimensions of mood, were compared for degree of difference across the 10 days of treatment. There was an overall completion rate of 88%, with both cocaine and opiate groups reporting a comfortable detoxification and substantial improvement over the course of a 12-day hospitalization. There was no significant difference between the active or placebo groups, suggesting that placebo was as effective as active NET in reducing drug withdrawal or craving during cocaine and opiate detoxification. However, all placebo patients received 0.2 mA of current, which may have provided a degree of active current. Suggestions are offered for future research.

Adult↗