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Biomedical subjects

M Jones

Publications and source records attributed to M Jones.

At least 757 records · Page 42Linked to original sources

Protamine induced arterial hypoxaemia: the relationship to hypoxic pulmonary vasoconstriction.

Protamine administration may induce arterial hypoxaemia in dogs and humans. However, the responsible mechanism has not been established. Protamine, as it is a pulmonary vasoactive substance, may interfere with normal hypoxic pulmonary vasoconstriction (HPV) and cause arterial hypoxaemia. This possibility was tested in dogs utilizing a one lung hypoxic model. One lung hypoxic ventilation decreased pulmonary blood flow in the hypoxic lung from 1022 +/- 96 ml X min-1 (mean +/- SEM) to 846 +/- 39 ml X min-1 (p less than 0.05) while increasing blood flow from 833 +/- 85 ml X min-1 to 1109 +/- 101 ml X min-1 (p less than 0.05) in the normoxic lung, resulting in 24 per cent effective diversion of blood flow. Protamine infusion, after heparinization, markedly elevated pulmonary vascular resistance in both lungs but preferentially in the normoxic lung (102 +/- 27 per cent increase in normoxic lung, 60 +/- 6.4 per cent increase in hypoxic lung) and significantly reversed the pulmonary blood flow shift induced by one lung hypoxic ventilation (effective diversion of blood flow was reduced to four per cent). Concurrently, arterial PO2 further decreased. Our results demonstrate that protamine interferes with effectiveness of pre-existing HPV and suggest that this mechanism, at least in part, may be responsible for arterial hypoxaemia observed after protamine infusion. The marked generalized pulmonary vasoconstriction with protamine appears to be the direct force that interferes with pre-existing auto-regulatory HPV. In addition to the well known haemodynamic effects of protamine, protamine infusion may also cause arterial hypoxaemia in those patients in whom HPV plays a significant role in maintaining arterial oxygenation.

Animals↗

Comparison of exponential and hyperbolic models of conduction through the atrioventricular node.

Conduction through the atrioventricular node (AVN) is assessed during electrophysiology study by relating the output to the input generated by an atrial extrastimulus. This extrastimulus scans electrical diastole of the heart to enable output to be plotted against input. Using this technique, we compared two mathematical models of the AVN, a rectangular hyperbola and a decaying exponential, respectively. The models were compared in 40 curves from 32 patients with only one AVN transmission pathway. Standard errors of the estimate were usually (25/40 trials) less with the exponential model, suggesting this the preferred algorithm for further development.

Adolescent↗

Prediction of gradients in fibrous subaortic stenosis by continuous wave two-dimensional Doppler echocardiography: animal studies.

The purpose of this study was to assess the accuracy of continuous wave, two-dimensional Doppler echocardiography for predicting pressure gradients across discrete subaortic stenoses. Twenty-three Newfoundland dogs with subaortic stenosis were studied by closed chest Doppler interrogation of aortic velocity from an apical view of the left ventricular outflow tract simultaneously with measurements of pressure gradient during cardiac catheterization. Continuous mode Doppler interrogation was used with two-dimensional echographic guidance (Irex model IIIB) to compare the Doppler-derived maximal velocity with the pressure gradient across the obstruction at rest and after provocation with amyl nitrite inhalation and isoproterenol infusion. The maximal velocities recorded by Doppler ranged from 98 to 539 cm/s and correlated with hemodynamic gradients ranging from 3 to 123 mm Hg (r = 0.92, SEE = 37 cm/s). Doppler velocities were converted to gradients using a simplification of the Bernoulli relation (gradient = 4 X maximal velocity2); the resulting Doppler-derived gradients also correlated closely with the catheterization-measured pressure gradients (r = 0.95, SEE = 7.1 mm Hg). The predictive capability of Doppler echocardiography for estimating the pressure gradient across fibromuscular subaortic obstructions in this group of dogs with a spectrum of disease similar to that found in human beings was validated. The results also indicate that Doppler methods may have clinical applications in patients with subaortic stenosis.

Amyl Nitrite↗

A developmental approach to the classification of birth defects.

Surgeons are accustomed to categorizing the birth defects they treat surgically according to morphology rather than pathogenesis. Commonly used classification systems fail to take into account the cause or developmental pathology of a given structural defect. Furthermore, surgeons often select operative procedures without considering the evolution of specific defects. Dysmorphology is a fairly new discipline that seeks a better understanding of the cause and pathogenesis of birth defects, not only to ensure optimum treatment but also to encourage prevention of birth defects.

Abnormalities, Multiple↗

Examination of an exponential model of conduction through the human atrioventricular node.

The atrioventricular node (AVN) has been modeled by relating output (A2H2 or H1H2) to input (A1A2) where A and H are atrial and His bundle electrograms during fixed rate atrial pacing (A1A1) or with an extrastimulus (A2). (Formula: see text) This study examined this model in 61 nonselected patients, specifically for AVN (in)stability and the possibility of multiple pathways. After programmed atrial stimulation at two basic cycle lengths of 600 ms and 462 ms, A1H1, A2H2 and H1H2 were digitized and plotted as a function of A1A2. Seven of 104 trials were rejected as SD. A1H1 was greater than 15 ms, suggesting AVN instability. Another 26 and 34 plots, respectively, of A2H2 and H1H2 were rejected because of inadequate data. In the remainder, goodness of fit of the single exponentials was tested statistically in three ways: R2, the runs test, and the Kendall rank coefficient test. Results were compared with an electrophysiologist who examined plots for one or more pathways (either discontinuous curves or slope change in a continuous curve). Single exponentials were successfully fitted (by runs test) in 44/71 and 34/63 of A2H2 and H1H2 plots, respectively, usually in accordance with the cardiologist. Discordance between computations and the cardiologist could be attributed to data scatter and lack of a sufficiently rigid stimulation protocol. The identification of bifurcation points in the presence of multiple pathways, particularly when manifest as a change in slope (approximately 6% of trials) rather than discontinuity of plots (approximately 20% of trials) remains an outstanding problem.

Adolescent↗

In vitro susceptibilities and beta-lactamase production of 53 clinical isolates of Branhamella catarrhalis.

We tested 53 clinical isolates of Branhamella catarrhalis recovered from patients with respiratory symptoms to determine the susceptibility of the isolates to 25 antimicrobial agents, including the newer beta-lactam antibiotics. Of the 53 strains, 46 (86.7%) were beta-lactamase producers. All the strains were susceptible to the majority of the new penicillins and cephalosporins. The combinations of amoxacillin-clavulanic acid and ticarcillin-clavulanic acid were also very active against the beta-lactamase-producing strains.

Anti-Bacterial Agents↗

In vitro activity of fosfomycin, alone and in combination, against methicillin-resistant Staphylococcus aureus.

We tested 148 strains of clinical isolates of methicillin-resistant Staphylococcus aureus against fosfomycin alone and in combination with methicillin, cefamandole, gentamicin, trimethoprim, and vancomycin. Fosfomycin inhibited 90% of the 148 methicillin-resistant S. aureus strains at a concentration of 4 micrograms/ml. Synergism was observed in 97 strains (66%) with fosfomycin-cefamandole and in 69 strains (46%) with fosfomycin-methicillin. The combinations of fosfomycin with vancomycin, gentamicin, and trimethoprim were indifferent in most strains.

Cross Infection↗

Mortality of men in the Rhondda Fach 1950-80.

In a 30 year follow up study of 8526 men aged 20 and over in the Rhondda Fach 99.9% of the population was traced. Generally, the results are similar to those found in a 20 year follow up of the same subjects. Miners and ex-miners had an excess mortality compared with non-miners, but within the former only those who had had categories B and C pneumoconiosis showed a raised mortality. Category A pneumoconiosis was not associated with any excess compared with other miners and ex-miners. Two further aspects of the data relating to gastric cancer and progressive massive fibrosis will be examined in later reports.

Adult↗

Diurnal variations in responsiveness of the hypothalamo-pituitary-adrenocortical axis of the rat.

Hypothalami, anterior pituitary gland segments and adrenal glands were removed from female Wistar-derived rats decapitated at various times of the day. Blood and tissue hormone concentrations were measured and the tissues challenged with appropriate stimuli in vitro. Both bioactive and immunoreactive corticotrophin-releasing factor (CRF) content of the hypothalami were significantly higher in the evening than in the morning, as was the basal release of bioactive CRF in vitro. The response of the hypothalami to serotonin or acetylcholine added in vitro did not change with time of day. Basal bioactive and immunoreactive adrenocorticotrophin (ACTH) release from the anterior pituitary gland was significantly increased in the evening, as was the response to synthetic ovine CRF in vitro. Plasma ACTH concentrations in intact rats given crude CRF (hypothalamic extract) in vivo were higher in the evening at all times after injection tested, but this difference was markedly reduced in animals with mediobasal hypothalamic lesions. Corticosterone released basally from adrenal glands in vitro was significantly increased in the evening and the response to added ACTH 1-24 was slightly enhanced. For adrenal glands removed from lesioned rats, the pattern was reversed, corticosterone release in vitro being lower in the evening for all doses of ACTH added. Similarly in vivo, in intact rats given ACTH 1-24, plasma corticosterone concentrations and corticosterone release in vitro from adrenal glands removed after the injection were higher in the evening. After the placement of basal hypothalamic lesions, the situation was reversed, the response to ACTH administration in vivo being greater in the morning.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Survival and functional results after valve replacement for aortic regurgitation from 1976 to 1983: impact of preoperative left ventricular function.

Recent studies suggest that preoperative left ventricular function may no longer be an important determinant of survival or functional results after operation for aortic regurgitation because of improved operative techniques. To assess the effect of left ventricular function on prognosis in the current surgical era, we performed echocardiographic and radionuclide angiographic studies in 80 consecutive patients undergoing valve replacement from 1976 to 1983. No patient had associated coronary artery disease. For all patients, 5 year survival was 83 +/- 5%, significantly better than the 62 +/- 9% 5 year survival in our patients operated on from 1972 to 1976. Preoperative resting left ventricular ejection fraction (p less than .001), fractional shortening (p less than .001), and end-systolic dimension (p less than .01) were the most significant predictors of survival (univariate life-table analysis). Five year survival was 63 +/- 12% in patients with subnormal ejection fraction (n = 50) compared with 96 +/- 3% in those with normal ejection fraction (n = 30). Patients with subnormal left ventricular ejection fraction and poor exercise tolerance or prolonged duration of left ventricular dysfunction (greater than 18 months) comprised the high-risk subgroup (5 year survival 52 +/- 11%). Patients in this subgroup also had persistent left ventricular dysfunction after operation, with greater left ventricular end-diastolic dimensions and reduced ejection fraction (both p less than .001) compared with patients with normal preoperative left ventricular ejection fraction or a brief duration of left ventricular dysfunction (less than 14 months). Cold hyperkalemic cardioplegia was used for myocardial preservation in 46 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Congenital hypernephronic nephromegaly with tubular dysgenesis: a distinctive inherited renal anomaly.

This paper describes a distinct, apparently inherited renal disorder we call congenital hypernephronic nephromegaly with tubular dysgenesis. The disorder is characterized by oligohydramnios, the Potter phenotype, and enlarged nonfunctional kidneys. Light microscopy demonstrates increased numbers of glomeruli, undifferentiated tubules, and interstitial fibrosis. Microdissection reveals short, immature nephrons that lack proximal convolutions, and abnormal vascularization of the glomerulus. Morphometric analysis demonstrates increased glomerular mass, primarily in the region of the corticomedullary junction, increased interstitial mass, and decreased tubular mass. The parameters that define this anomaly are presented, and the possible mechanisms of pathogenesis are discussed in relation to pathologic observations and current concepts concerning renal embryogenesis and differentiation. The recurrence of this anomaly in the male children of a consanguineous couple suggests an X-linked recessive mode of inheritance, although an autosomal-recessive mode of inheritance cannot be ruled out. This condition indicates that not all cases of the Potter phenotype can be considered to be sporadic.

Amniotic Fluid↗

Cuspal perforations caused by long suture ends in implanted bioprosthetic valves.

A description is presented of the gross anatomic, histologic, and scanning electron microscopic features of cuspal abrasions, perforations, and tears caused by excessively long ends of braided sutures in bioprosthetic cardiac valves implanted in the mitral position in sheep. These lesions are produced as consequences of contact between the ends of the sutures and the inflow surfaces of the bioprosthetic cusps, leading to a process of surface erosion that progresses to actual perforation of the cusps. The perforation has the appearance of a crater, the wider end of which faces the inflow surface and the walls of which are formed by broken ends of collagen fibrils. Suture perforations can extend to form tears that involve the free edge of the cusp and result in hemodynamically important regurgitation. Therefore, care must be taken to avoid leaving excessively long suture ends during the implantation of bioprosthetic cardiac valves.

Animals↗

The serologic response to Meth A sarcoma vaccines after cyclophosphamide treatment is additionally increased by various adjuvants.

We have shown previously that the serologic response of BALB/c mice to immunization with BALB/c sarcoma Meth A cells can be more effectively augmented by pretreatment with cyclophosphamide (Cy) than by the use of adjuvants. The serologic response was directed against a highly restricted cell surface antigen, closely related to or identical with the unique transplantation antigen characteristic for this tumor. In this paper, we report the results of our attempts to obtain additional augmentation by using Cy and adjuvants together. For these studies, the optimal Cy dose, interval between Cy and vaccine administration, and vaccine cell number were determined. Mice were injected with Cy 25 mg/kg i.p., and 3 days later, with viable irradiated (10,000 rad) Meth A cells subcutaneously, under conditions in which only few mice produced antibody. Sera were tested for antibody with reactivity against Meth A by complement dependent cytotoxicity (CDCX), which predominantly detects IgM, and by the protein A (PA) and anti-IgG assays, which detect IgG. Of the various adjuvants tested, only monophosphoryl lipid A (MPLA) and CP20,961 resulted in significantly increased titers of reactivity in both the CDCX and PA assays over that obtained when using Cy alone. Although the mean titers observed with CDCX ranged between 1/160 and 1/320, no titer above 1/40 was observed with the PA assay. The specificity of the CDCX reactivity detected by the assay for the Meth A antigen was ascertained by absorption analysis of selected sera by using a panel of BALB/c spleen and tumor cell lines grown in vitro or in vivo. PA titers were too low to permit absorption analysis, and the titers obtained in the anti-IgG assay were lower still. Attempts to augment the anti-Meth A IgG response or to convert the IgM response to IgG were unsuccessful. The combined approach described here (i.e., vaccination with irradiated syngeneic tumor cells plus MPLA in Cy-pretreated mice) was also shown to be effective in augmenting the serologic response against two additional murine leukemia virus-negative sarcomas that are known to be less immunogenic, CMS4 and CMS5. It appears, therefore, that this combined approach may be applicable to stimulating serologic responses against a variety of tumor cell surface antigens.

Absorption↗

Acute control of pulmonary regurgitation with a balloon "valve". An experimental investigation.

Operations for certain congenital cardiac lesions can produce pulmonary regurgitation. Pulmonary regurgitation contributes to right ventricular dysfunction, which may cause early postoperative morbidity and mortality. To ameliorate the problems of pulmonary regurgitation during the early postoperative period, we evaluated a method for its acute control. Complete pulmonary valvectomy was performed utilizing inflow occlusion in eight sheep. A catheter with a 15 ml spherical balloon was positioned in the pulmonary arterial trunk; its inflation and deflation were regulated by an intra-aortic balloon pump unit. Blood flow from the pulmonary arterial trunk and forward and regurgitant fraction were determined from electromagnetic flow transducer recordings. The regurgitant fraction with uncontrolled pulmonary regurgitation was 38% +/- 3% (forward flow = 42 +/- 5 ml/beat and regurgitant flow = 16 +/- 2 ml/beat). Inflation of the balloon during diastole was timed to completely eliminate pulmonary regurgitation. This balloon control of pulmonary regurgitation increased pulmonary arterial diastolic pressure from 12 +/- 1 to 17 +/- 1 mm Hg (p less than 0.0001) and decreased pulmonary arterial systolic pressure from 31 +/- 3 to 27 +/- 1 mm Hg (p = 0.06). Pulmonary arterial pulse pressure decreased from 19 +/- 3 to 9 +/- 1 mm Hg (p less than 0.003). Elimination of pulmonary regurgitation decreased right ventricular stroke volume (25 +/- 3 versus 42 +/- 5 ml/beat, p less than 0.0002) and resulted in a 46% reduction in right ventricular stroke work (5.0 +/- 0.6 versus 9.4 +/- 1.0 gm-m/beat, p less than 0.001) with no change in net forward pulmonary artery flow. Thus, acute pulmonary regurgitation can be controlled and this control improves overall hemodynamic status and decreases right ventricular work.

Animals↗