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Biomedical subjects

J Pearson

Publications and source records attributed to J Pearson.

At least 19 recordsLinked to original sources

Origin and molecular changes associated with emergence of a highly pathogenic H5N2 influenza virus in Mexico.

In October of 1993, there was decreased egg production and increased mortality among Mexican chickens, in association with serologic evidence of an H5N2 influenza virus. First isolated from chickens in May of 1994, after spreading widely in the country, the virus caused only a mild respiratory syndrome in specific pathogen-free chickens. Because eradication of the virus by destruction of infected birds posed major obstacles to the poultry industry in Mexico, we were able to conduct a "field experiment" to determine the fate of an avirulent virus after repeated cycles of replication in millions of chickens. By the end of 1994, the virus had mutated to contain a highly cleavable hemagglutinin (HA), but remained only mildly pathogenic in chickens. Within months, however, it had become lethal in poultry. Nucleotide sequence analysis of the HA cleavage site of the original avirulent strain revealed R-E-T-R, typical of avirulent viruses and unlike the K-K-K-R sequence characterizing viruses responsible for the 1983 outbreak in poultry in the United States. Both mildly and highly pathogenic isolates contained insertions and a substitution of basic residues in the HA connecting peptide, R-K-R-K-T-R, which made the HA highly cleavable in trypsin-free chicken embryo fibroblasts. Phylogenetic analysis of the HA of H5 avian influenza viruses, including the Mexican isolates, indicated that the epidemic virus had originated from the introduction of a single virus of the North American lineage into Mexican chickens. This sequence of events demonstrates, apparently for the first time, the stepwise acquisition of virulence by an avian influenza virus in nature.

Amino Acid Sequence

A six year prospective study of fibrinogen and other risk factors associated with mortality in stable claudicants.

A total of 333 patients with stable intermittent claudication at recruitment were followed up for 6 years to determine risk factors associated with subsequent mortality. Cardiovascular diseases were the underlying cause of death in 78% of the 114 patients who died. The strongest independent predictor of death during the follow-up period was the plasma fibrinogen level, an increase of 1 milligram being associated with a nearly two-fold increase in the probability of death within the next 6 years. Age, low ankle/brachial pressure index and a past history of myocardial infarction also increased the probability of death during the study period. The plasma fibrinogen level is a valuable index of those patients with stable intermittent claudication at high risk of early mortality. The results also provide further evidence for the involvement of fibrinogen in the pathogenesis of arterial disease.

Aged

Relationship between the location of osteoblastic alkaline phosphatase activity and bone formation in human iliac crest bone.

It is not feasible to use in vivo tetracycline double labeling to study bone formation in biopsies taken during the emergency fixation of fractures. We therefore compared the trabecular localization and extent of osteoblastic alkaline phosphatase (AP) perimeters with tetracycline and osteoid perimeters in iliac crest biopsies from 7 women with postmenopausal osteoporosis and 13 women without metabolic bone disease. Fresh biopsies were chilled to -70 degrees C, and triplicate serial unfixed undecalcified cryostat sections were cut and reacted for AP, stained for osteoid, or mounted unstained. At individual remodeling sites, the mineralizing perimeter (M.Pm) was measured as the extent of a double or single label accompanied by greater than or equal to 1 lamella of osteoid and greater than or equal to 1 lamella of mineralized matrix between the mineralization front and the adjacent label. Osteoid perimeters (O.Pm) and AP perimeters (AP.Pm) were also measured. In each biopsy there was good agreement between the location of AP and bone formation (kappa statistic, range 0.71-1.0). The overall sensitivity and specificity of AP as an indicator of the location of bone formation were 0.963 and 0.902, respectively. At the level of the basic multicellular unit, in those samples in which greater than 3 active BMUs were found, there was (1) significant positive correlation between the M.Pm and both AP.Pm and AP-positive O.Pm (except 1 patient) and (2) no significant difference between the M.Pm and AP-positive O.Pm (17 of 18 patients and 18 of 18 patients at the tissue level).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Placental biopsy in the third trimester of pregnancy.

Forty-two women with abnormal ultrasound findings after 27 weeks' gestation underwent a placental biopsy. In 39 cases, a karyotype was obtained from a direct preparation within 48 h, five abnormal karyotypes being detected (four trisomies and a triploidy). One confirmed placental mosaic was also detected. In one case, a small terminal deletion of chromosome 7 was not detected at the time due to the quality of the preparation. A karyotype can be obtained from a direct preparation in the third trimester in over 90 per cent of cases, the quality of the preparation allowing the reliable detection of abnormalities of chromosome number. We believe that this technique may be usefully, reliably, and safely employed in the third trimester of pregnancy by those with an interest in antenatal ultrasound diagnosis who do not have immediate access to a cytogenetics laboratory and who feel that cordocentesis is inappropriate for their situation.

Chorionic Villi Sampling

Interactions of the beta carboline abecarnil with the high pressure neurological syndrome in a primate model.

The neurophysiological interactions between the high pressure neurological syndrome (HPNS) and a new beta carboline, abecarnil, were studied in the non-human primate Papio anubis. Abecarnil is a partial agonist at the benzodiazepine site on the GABA/benzodiazepine receptor. Six animals were exposed on two occasions to pressures of 91 ATA in an environment of helium and oxygen. One exposure was pretreated with a total dose of abecarnil 1.0 mg/kg, the other with an equivalent volume of vehicle. Treatment with abecarnil prevented the severe signs of HPNS occurring between 51 and 91 ATA. Onset pressures of the various signs were unaffected. Some signs, e.g. myoclonus, became more frequent when abecarnil was used. A residual protective effect of abecarnil was present 4 weeks after the dose was given, active at pressures less than 71 ATA. Changes with pressure in the EEG were recorded primarily from the frontal cortex, but were also present in the parietal and occipital areas of the left cortex. Amplitude and frequency spectra were calculated and changes with pressure in the four conventional wavebands, plus two others, analysed. The most striking change was the prevention by abecarnil of the pressure-induced 100% increase in alpha wave amplitude in the frontal region. It is concluded that modulation of GABA transmission is important in controlling the expression of HPNS.

Animals

How comparable are healthy 60- and 80-year-old men?

A critical issue in cross-sectional aging studies is the comparability of subjects of different ages, particularly regarding health status. For example, it is typically assumed that healthy 60-year-old men are equivalent to healthy 80-year-old men when both age groups are selected using the same criteria. The 60-year-old, however, may not survive or be healthy at age 80. To examine this issue, 212 healthy 60-year-old men in the Baltimore Longitudinal Study of Aging were identified. By life table analysis, 30% were expected to survive and remain healthy to age 80. In this study, 61 healthy 60-year-old men were followed to age 80. When compared with 125 healthy 80-year-old men, they had more heart disease, cancer, stroke, arterial, digestive, and peripheral nervous system diseases. Twenty-seven of the 61 men (44%) actually continued to be healthy at age 80. At age 60, systolic pressure and total serum cholesterol were predictive of who would be healthy at age 80.

Age Factors

Regulation of iron absorption in iron loaded subjects with end stage renal disease: effects of treatment with recombinant human erythropoietin and reduction of iron stores.

The effects on iron absorption of variation in erythroid activity, haemoglobin and iron stores were studied in six anaemic dialysis-dependent subjects in whom iron stores were increased from previous red cell transfusions. Gastrointestinal mucosal uptake and whole body retention of oral iron were measured at the beginning of the study, after starting treatment with recombinant erythropoietin (but before significant increase in haemoglobin), after partial correction of anaemia, after further reduction of iron stores by repeated phlebotomy, and when erythropoiesis decreased from the discontinuation of treatment with erythropoietin. Between successive measurements, valid comparisons were made in five subjects. Correction of anaemia decreased whole body retention of iron through decreased mucosal uptake (P = 0.032). Further reduction in iron stores through repeated phlebotomy whilst the increase in haemoglobin was maintained by treatment with erythropoietin, tended to increase whole body retention of iron through an increase in mucosal transfer (P = 0.010). With initial enhancement of erythropoiesis in anaemic iron-loaded subjects there was no change in any measured component of iron absorption. However, after correction of anaemia and reduction of iron stores, a decrease in erythropoiesis was associated with decreased whole body iron retention in all subjects through decreased mucosal transfer (P = 0.028). The data suggest that anaemia upregulates mucosal iron uptake, and that erythroid activity upregulates mucosal transfer but that this latter effect may be counter-balanced by iron overload which downregulates mucosal transfer.

Adult

Thermogenesis after surgery: effect of perioperative heat conservation and epidural anesthesia.

Body temperature, respiratory gas exchange, and plasma catecholamines were determined before and after surgery in three groups [control (C), warmed (W), and epidural (E) who received local anesthetic at T4-S5 dermatomes during and for 24 h after surgery] of patients undergoing colonic surgery under general anesthesia. At the end of surgery, group W were nursed in an ambient temperature of 28-30 degrees C, whereas the others were at 20-23 degrees C for a period of 24 h. Core (Tc) and dorsal hand temperature decreased during surgery in both C and E (P less than 0.05) but not in W. After surgery, Tc increased similarly in C and E and by a smaller amount in W. Plasma catecholamine concentrations increased significantly in C and W but not in E (P less than 0.001), with the greatest response occurring in C. Postoperative oxygen consumption and carbon dioxide production exceeded preoperative values (P less than 0.01) in C but not in W or E. After surgery, plasma albumin fell and C-reactive protein increased similarly in all three groups. Thus body heat conservation or epidural blockade attenuates or abolishes the rise in plasma catecholamines and oxygen consumption postoperatively but does not prevent the increase in Tc or the acute phase protein response.

Anesthesia, Epidural

Changing issues of quality control: diploid and non-diploid cell lines.

Early viral vaccines were prepared from primary monkey kidney cell cultures. However, primary cell cultures can be highly variable and also present a risk of contamination by endogenous viruses. The development of human diploid cell lines for vaccine production provide greater assurance of consistency and freedom from contaminating viruses. Continuous cell lines present considerable advantages in the preparation of proteins for therapeutic use. The perceived risks associated with the use of these cell lines include those of retroviral contamination, oncogenic DNA and consistency of final product during the extended life in culture. Advances in molecular biologic and analytical chemistry procedures have enabled extensive characterisation not only of the cells, but also of the product itself. The degree of testing which can now be performed on the product, to ensure its safety and consistency, should lead to a reappraisal of testing regimes applied to the cells themselves.

Animals

Prospective assessment of the role of five tumour markers in breast cancer.

Retrospective analysis previously identified significant elevation of five tumour markers, carcinoembryonic antigen (CEA), ferritin, orosomucoid. C-reactive protein and erythrocyte sedimentation rate (ESR), in patients with systemic breast cancer and showed that changes in each of these markers individually correlated significantly with therapeutic response. In this study we have prospectively tested these findings. None of the five markers was significantly elevated in primary breast cancer compared to normal control or benign breast disease groups. They therefore appear to have no role either in screening or in the differential diagnosis of breast cancer. There was a significant elevation of all five markers in patients with systemic breast cancer (P less than 0.0001: analysis of variance) but sequential changes in CEA and ESR only correlated significantly with the UICC-assessed response. Prospective confirmation of the correlation between changes in serum CEA and ESR provides the basis for using these markers in the assessment of response to therapy in patients with systemic breast cancer.

Adult

The effects of the competitive NMDA receptor antagonist CPP on the high pressure neurological syndrome in a primate model.

Neurophysiological interactions between the competitive N-methyl-D-aspartate (NMDA) preferring receptor antagonist, CPP (3-((+-)-2-carboxypiperazine-4-yl)-propyl-1-phosphonate) and the high pressure neurological syndrome (HPNS) have been investigated in the non-human primate Papio anubis. Eight animals were exposed on two occasions to environmental pressures of 81 atmospheres absolute (ATA) in a hyperbaric chamber, using helium and oxygen. One exposure followed pretreatment with CPP (either 5 or 10 mg/kg i.v. plus 5 mg/kg/hr infusion), the other a saline control. Pretreatment with CPP delayed moderate signs of face tremor and myoclonus and abolished severe signs of whole body tremor and seizure activity. By 81 ATA, scores representing severity of HPNS were significantly reduced by CPP to a mean score, reflecting a level of just mild to moderate limb tremoring (P less than 0.001). Changes in the EEG were observed in channels associated with the frontal, parietal and occipital regions of the left cortex. Amplitude and frequency spectra were calculated and changes with pressure in the 4 conventional wavebands were analysed. The most striking change was the complete prevention by CPP of the 100% increase in the amplitude of alpha waves at 81 ATA in the frontal region (P less than 0.001). It is concluded that NMDA transmission has a major role in the expression of HPNS.

Animals

A novel technique for the administration of bronchodilator drugs formulated as dry powders to the anaesthetized guinea pig.

A technique is described for the administration of dry powder formulations of bronchodilator drugs to the anaesthetized guinea pig. The technique has been evaluated by comparing the efficacy of several bronchodilator drugs administered either as dry powders coformulated with a lactose carrier or as nebulized solutions. In each case, the dry powder formulation had comparable bronchodilator activity and duration of action to an equivalent dose administered as a nebulized solution. This technique offers a simple and inexpensive method for the rapid screening of bronchodilator drugs without the problems associated with aerosol administration.

Administration, Intranasal

Comparative analysis of murine T lymphocyte responses to cartilage proteoglycans.

Cartilage proteoglycans are large molecules consisting of several sub-regions each of which comprises homologous repeating subunits. Comparisons of murine primed popliteal lymph node responses to human cartilage proteoglycans in BALB and B10 congenic mice showed that the major histocompatibility complex (MHC) influences T cell responsiveness to this antigen. H-2k and H-2d were higher responders than H-2b. Responses were MHC class II-restricted, and human cartilage proteoglycans were cross-reactive with mouse cartilage proteoglycans for a BALB/c T cell line. The proportion of proteoglycan-specific T lymphocytes in BALB/c primed popliteal lymph nodes was about 45% lower in females than males. These results show that in mice both MHC haplotype and sex can determine T lymphocyte responsiveness to cartilage proteoglycans. If the same mechanisms apply in humans they could be important in determining the HLA-DR haplotype associations and the predilection of rheumatoid arthritis for females.

Analysis of Variance

Protein metabolism after abdominal surgery: effect of 24-h extradural block with local anaesthetic.

We have studied the effect of intraoperative and postoperative (24 h) extradural block with local anaesthetic on whole body protein turnover (stable isotope methodology) and urinary excretion of urea nitrogen, adrenaline, noradrenaline and cortisol in a group of well nourished elderly patients undergoing colorectal surgery who received a constant nutritional intake before (7 days) and after (4 days) surgery. One group (control, n = 8) received routine anaesthetic and surgical care. Patients in the test group (extradural, n = 9) received extradural bupivacaine, and sensory block (T4-S5) was maintained during and after surgery for a period of 24 h. Whole body protein breakdown and amino acid oxidation increased significantly after surgery in both groups (P less than 0.05), but the increase in protein breakdown in the extradural group was significantly less than that in the control group. Urinary excretion of urea nitrogen, adrenaline and noradrenaline increased in the control group after surgery, whilst the increase in the extradural group was very small. In contrast, urinary excretion of cortisol increased significantly in both groups after surgery. We conclude that extradural block maintained for 24 h after surgery significantly minimized postoperative protein breakdown without compromising whole body protein synthesis.

Abdomen

Ethical and legal responsibilities of the neurosurgeon: selected topics.

There are many ethical and legal implications in a variety of activities in the neurosurgeon's day-to-day practice. Awareness of and proper attention to these issues are a professional responsibility that should be attended to, to ensure that the practice of medicine is carried out efficiently and effectively, to maintain public confidence, and to try to avoid micromanagement by third parties. The authors discuss four such subjects of particular interest to them, namely: 1) reporting of certain diseases and conditions to authorities and third parties; 2) acting without the consent of the patient to prevent harm to him or her and/or others; 3) reporting problems with drugs and devices; and 4) the detection and treatment of colleagues impaired by alcohol, drugs, or mental or physical illness.

Confidentiality

Endothelial cells cultured from human umbilical vein release ATP, substance P and acetylcholine in response to increased flow.

Cultured human umbilical vein endothelial cells superfused with Krebs' solution were used to investigate release of ATP, substance P and acetycholine with shear stress. ATP was consistently released when the cells were exposed to increased flow rate; release was rapid, had declined by 1 min and occurred upon a second exposure. Release of substance P and acetylcholine was more varied; increased shear stress led to release of substance P from 4 out of 16 endothelial-cell columns, whereas acetylcholine was released in 4 out of 12 columns. This is the first time that unequivocal evidence has been presented for release of these neurotransmitter substances from vascular endothelial cells. These findings have important implications about the mechanisms of local regulation of vascular tone.

Acetylcholine