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Biomedical subjects

J Brown

Publications and source records attributed to J Brown.

At least 577 records · Page 32Linked to original sources

Comparison of excretory urography and ultrasonography for detection of experimentally induced pyelonephritis in dogs.

Pyelonephritis was experimentally induced in 10 clinically normal dogs by nephropyelocentesis and introduction of Proteus mirabilis into the randomly chosen right or left renal pelvis. Dogs were examined by nephrosonography and excretory urography before and 2 weeks after infection. The major nephrosonographic findings of pyelonephritis were renal pelvic dilatation, usually with proximal ureteral dilatation, and a hyperechoic mucosal margin line within the renal pelvis, proximal portion of the ureter, or both. In addition, at least one or more of the following were observed: generalized hyperechoic renal cortex, focal hyperechoic areas within the medulla, and focal hyperechoic or hypoechoic cortical lesions. Interpretation of excretory urograms resulted in 3 false-negative and 1 false-positive conclusions, compared with the histologic findings. Interpretation of nephrosonograms resulted in 2 false-negative and no false-positive conclusions. Of the kidneys with histologic evidence of pyelonephritis, 73% were detected by excretory urography, whereas 82% were detected by nephrosonography. Nephrosonography appeared to be useful for detection of mild to moderate cases of acute pyelonephritis that may be be interpreted as such by excretory urography.

Animals↗

Osteotomy and intramedullary nailing for the correction of progressive deformity in vitamin D-resistant hypophosphataemic rickets.

We have reviewed the results of surgical treatment of vitamin D-resistant hypophosphataemic rickets (VDRR) and describe a technique of corrective osteotomy and intramedullary nailing. From 1978 to 1986, epiphysiodesis (n = 4) and osteotomy (n = 8) was performed in 6 children (mean age 13, range 10-16 years) for the correction of progressive lower limb deformity. Realignment and internal fixation of a pathological fracture of the femur was performed in an adult (aged 24). Epiphysiodesis resulted in recurrent deformity in all patients and reapplication of staples for loosening was required in three. Corrective osteotomies were secured with staples (n = 3), plates (n = 4), or plaster alone (n = 1) and were complicated by non-union in one patient, and recurrent deformity in two patients. Double-plating of the femoral fracture resulted in union but recurrent deformity. Compliance to treatment with phosphate and vitamin D was variable. In order to manage progressive recurrent deformity, we have performed corrective osteotomy and closed intramedullary nailing of the tibia (n = 2) and femur (n = 3) in 4 skeletally mature patients (mean age 31). All osteotomies united and no complications were encountered. Deformity has been corrected in all cases and all patients are satisfied with the outcome at least 2 years after surgery. We conclude that rigid methods of fixation spanning the whole length of the bone are required to maintain limb alignment in skeletally mature patients with VDRR. Since the quality of bone in VDRR is variable, experience with intramedullary techniques is essential. We stress the importance of appropriate medical therapy throughout the treatment of these patients.

Adolescent↗

Ethical considerations in the treatment of AIDS patients in the intensive care unit.

The treatment of patients with AIDS in the ICU presents the clinician with special challenges. The admission policies of ICUs are examined, and the authors suggest ways in which ethical difficulties may be minimized. A new concept of futility is suggested, which considers both the patient's holistic needs together with his or her immediate medical prognosis. Changes in the law regarding patient choice are discussed.

Acquired Immunodeficiency Syndrome↗

Saccades.

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Eye Movements↗

Elevated arterial blood pressure in cardiac tamponade.

BACKGROUND: In cardiac tamponade cardiac output falls, but peripheral vascular resistance increases, so that systemic blood pressure may be maintained at normal or near-normal levels. We recently observed a patient with cardiac tamponade whose blood pressure was markedly elevated. METHODS: To determine the frequency of elevated blood pressure in patients with cardiac tamponade and their hemodynamic characteristics, we studied 18 consecutive patients with cardiac tamponade from a variety of causes using right heart catheterization. RESULTS: Six of the 18 patients had systolic arterial blood pressures ranging from 150 to 210 mm Hg (mean [+/- SD], 176 +/- 26) and diastolic pressures ranging from 100 to 130 mm Hg (mean, 113 +/- 14). All six had previously been hypertensive. After pericardiocentesis there was a significant decrease in blood pressure (to 139 +/- 13 mm Hg systolic, P less than 0.05; and 83 +/- 6 mm Hg diastolic, P less than 0.01) and peripheral vascular resistance (from 2150 +/- 588 to 1207 +/- 345 dyn.sec.cm-5, P less than 0.01). Cardiac output increased in all six. The other 12 patients, 3 of whom had a history of hypertension, had significant increases in cardiac output and systolic blood pressure (from 119 +/- 13 to 127 +/- 7 mm Hg, P less than 0.05) after pericardiocentesis, whereas peripheral vascular resistance decreased. Both groups had similar degrees of cardiac tamponade, as indicated by measurements of cardiac output and intrapericardial, right atrial, and pulmonary-artery wedge pressures. CONCLUSIONS: Elevated blood pressure may occur in some patients with cardiac tamponade who have preexisting hypertension. Moreover, blood pressure may fall after pericardiocentesis in patients who have elevated blood pressure associated with tamponade.

Adult↗

Early and multifocal tumors in breast, salivary, harderian and epididymal tissues developed in MMTY-Neu transgenic mice.

Transgenic mice carrying various oncogenes driven by mammary gland specific enhancers develop mammary tumors usually arising in a stochastic way. The only exception is a mouse lineage (TG.NF) carrying an activated rat Neu oncogene driven by the murine mammary tumor virus long terminal repeat (MMTV-LTR) that gave rise to rapid and multifocal mammary tumors interpreted as a result of a single-step neoplastic transformation. The effect of the oncogene appeared to be specific for breast tissue, since salivary and Harderian glands as well as epididymis expressed high levels of Neu but only developed hyperplasia (Muller et al., Cell, (1988) 54, p. 105). Here we describe a transgenic mouse lineage for the MMTV-Neu, analysed up to third generation. Multifocal tumors involving mammary glands arose very rapidly in all females independently from pregnancy and in some males. Moreover, multifocal neoplasias occurred also in salivary and Harderian glands and in the epididymis at a very high rate. These data demonstrate that the Neu oncogene can induce tumors in all the tissues where it is expressed at high levels.

Animals↗

Activation of in situ glycolytic flux by bisphosphorylated compounds: studies in porous rat adipocytes.

By carefully permeabilizing eukaryotic cells such that intracellular enzymes are largely retained, an opportunity is created to explore the regulation of in situ flux. This is particularly important since the latter may not be accurately represented by kinetic measurements of isolated, solubilized enzymes from disrupted cells. In this study the action of fructose 2,6-diphosphate (F2,6DP) and other bisphosphorylated sugars which purportedly activate phosphofructokinase-1 (PFK-1; EC 2.7.1.11) were studied. Using porous adipocytcs and initiating flux with radiolabeled glucose 6-phosphate, the regulation of lactate production under both 0.1 and 1.0 mM ATP conditions by F2,6DP, glucose 1,6-diphosphate (G1,6DP), ribulose 1,5-diphosphate (R1,5DP), 2,3 diphosphoglycerate (2,3DPG), and mannose 6-phosphate (M6P) was examined. Studied at 1, 5, and 25 microM concentrations, F2,6DP and 2,3DPG significantly (and to the same extent) augmented glycolysis compared to control (at 0.1 mM ATP, the respective glycolytic rates--as % above control--at these three above-mentioned concentrations for F2,6DP were 60, 84, and 77%, whereas for 2,3DPG they were 84, 105, and 179%; at 1 mM ATP, the F2,6DP effect was 88, 99, and 121%, and for 2,3DPG it was 52, 89, and 96%). Stimulation by these compounds was less obvious at higher glycolytic flux rates (saturating amounts of G6P). Amongst this group, and only at 1.0 mM ATP, the sole other positive effector was 25 microM R1,5DP. The measured fat cell content of G1,6DP was 24 +/- 4 microM (n = 3); at this concentration no significant effect on glycolysis was observed. Examining the effects of 2,3DPG (25 microM) on proximal glycolysis (to triose phosphates) revealed there was a modest, but significant, 41% increase over basal; in contrast, under the exact same conditions, F2,6DP caused a 123% increase. Separate experiments also examined the effect of F2,6DP, 2,3DPG, and G1,6DP on glycolysis at 5 and 25 microM in the presence of a physiologic cytosolic ATP/ADP ratio and free cation concentrations. Under these conditions, F2,6DP and 2,3DPG remained pre-eminent in their stimulatory prowess, inducing 27-71% increases over control, while G1,6DP remained ineffectual. These studies support a locus of action of 2,3DPG on overall glycolysis which is distal to the triose phosphates. M6P was ineffective at all concentrations. In conclusion, F2,6DP is the pre-eminent in situ regulator of in situ adipocyte glycolysis, especially at higher ATP levels, although other sugars containing two phosphoryl groups may under certain conditions cause activation.

2,3-Diphosphoglycerate↗

Selenium status of Christchurch infants and the effect of diet.

OBJECT: New Zealanders, because of a soil deficiency, have a low intake of selenium. To determine the impact of this on the infant population in Christchurch. METHODS: we have measured red cell and plasma selenium and the selenoenzyme, glutathione peroxidase, in 70 infants less than 12 months old and related these to age and diet. RESULTS: the infant population as a whole had mean plasma levels of selenium and glutathione peroxidase of 33 micrograms/L and 97 U/L compared with adult values of 74 micrograms/L and 150 U/L. Infant red cell levels of 0.30 mu g selenium and 9.0 U glutathione peroxidase per g haemoglobin were similar to those in adults. The selenium status of most breast fed infants after birth remained similar to that of cord blood. Mean plasma selenium and glutathione peroxidase levels in formula fed infants were about half those of breast fed infants, and their red cell selenium was also significantly lower. These did not increase until solids were introduced into the diet. The status of the infants reflected their diet, with the concentration of selenium in formulae being 3.9-5.2 micrograms/mL compared with a mean of 13.4 micrograms/mL in breast milk. CONCLUSIONS: since infants in more replete selenium areas show a gradual rise in blood selenium parameters after birth, this study suggests that formula fed and some breast fed infants in Christchurch receive an inadequate selenium intake. Consideration should be given to supplementing infant formulae and perhaps also the diet of pregnant and/or breast feeding mothers.

Adult↗

Retention of fetal bones 8 years following termination of pregnancy.

We report on an unusual case where bone had been retained in the endometrium for a period of 8 years following termination, causing no symptoms except subfertility. Routine ultrasonography diagnosed the foreign body and this was removed by hysteroscopy assisted by ultrasound scanning. Pregnancy resulted after 6 months. A review of the literature is presented.

Journal Article↗

Seroprevalence of hepatitis C virus nucleocapsid antibodies in patients with cryptogenic chronic liver disease.

The serological responses to two different hepatitis C virus antigens were studied by enzyme-linked immunosorbent assay in a variety of chronic liver diseases and in healthy blood donors. The study population comprised 97 cases of cryptogenic chronic liver disease (40% with a history suggestive of parenterally transmitted non-A, non-B hepatitis and 60% without such a history), 87 cases of other well-characterized chronic liver diseases and 96 voluntary blood donors. The commercially available C100-3 assay and a new assay utilizing a 22 kD recombinant protein (c22) from the nucleocapsid region of the virus were used for antibody detection. Overall in the non-A, non-B hepatitis group, 77% were positive for anti-c22, 55% were positive for anti-C100-3 and 24% were negative by both tests. In the parenterally transmitted chronic liver disease group, 82% were positive for anti-C100-3 and 90% were positive for anti-c22 (not significant). In the cryptogenic chronic liver disease cases 36% were positive for anti-C100-3 and 67% were positive for anti-c22 (p less than 0.001). Only in one case (a patient with hepatitis B virus infection) was anti-C100-3 detected without concomitant anti-c22. None of the voluntary blood donors had detectable hepatitis C virus antibodies. The new enzyme-linked immunosorbent assay test for anti-c22 would appear to be a more sensitive indicator of chronic hepatitis C virus infection than the existing commercial test, suggesting a useful diagnostic role in both cases of cryptogenic chronic non-A, non-B hepatitis liver disease and for the screening of blood products for prevention of hepatitis after transfusion.

Base Sequence↗

Lysosomes as key organelles in the pathogenesis of prion encephalopathies.

The causation, structural origin, and mechanism of formation of spongiform lesions in transmissible encephalopathies are unknown. We have used immunogold electron microscopy to locate ubiquitin conjugates, hsp 70, and beta-glucuronidase (markers of the lysosomal compartment) and prion protein (PrP) in both control and scrapie-infected mouse brain. In scrapie-infected brain, lysosomes and lysosome-related structures (multivesicular and tubulovesicular dense bodies) are present in abnormally high numbers in neuronal cell processes. These structures contain PrP, together with the lysosomal markers ubiquitin conjugates, hsp 70, and beta-glucuronidase, which could also be identified spilling from tubulovesicular dense bodies into areas of early rarefaction in neuronal processes; we suggest that these areas of rarefaction are the precursor lesions of spongiform change. We advance the hypothesis that spongiform change is brought about by cytoskeletal disruption in neuronal processes caused by liberation of hydrolytic enzymes from lysosomes overloaded with the abnormal isoform of PrP (PrPsc). We suggest that the lysosomal system is probably acting as the bioreactor for processing of normal PrP to the abnormal isoform. The continuous production of increasing quantities of abnormal PrPsc in lysosome-related bodies will eventually cause disruption of the lysosomal membrane with destruction of the neuronal cytoskeleton and the initiation of vacuolation. Later, death of the cell will be associated with release of the PrPsc isoform into the extracellular environment. Repeated rounds of phagocytosis, lysosomal biogenesis of PrPsc, lysosomal membrane rupture, hydrolytic enzyme release, and neuronal lysis will lead to an exponential increase in cell damage and cell death.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunoreactivity to ubiquitin-protein conjugates is present early in the disease process in the brains of scrapie-infected mice.

Brains from mice infected with either the 87V or the ME7 strains of mouse-passaged sheep scrapie were taken at stages during the disease process and immunostained to show the localization of ubiquitin-protein conjugates. In both models, conjugates were seen as fine, dot-like structures; as coarser, granular lesions within or adjacent to neurones; and in areas surrounding plaques. The dot-like structures were visible at 28 days post-ME7 infection and at 55 days in 87V-infected mice. In both models, the extent of immunoreactive changes increased as the disease progressed and terminal infection was as described earlier by us (Lowe et al., J. Pathol 1990; 162: 61-66). The patterns of development of these features were distinctive in two ways: progression from region to region was observable and the density of the pathological lesions grew exponentially as the clinical symptoms appeared. The earliest pathological dot-like structures corresponded temporally with the earliest detection of PrPSC by Western blotting, and immunogold electron microscopic investigation of the dot-like lesions indicated that they were the multi-vesicular, lysosome-related, dense bodies that we have described previously in terminal disease (Laszlo et al., J Pathol 1992; 166: 333-341). Until now, ubiquitin-protein conjugates were seen mainly in inclusion bodies associated with the terminal stages of a range of human degenerative diseases. This study establishes that ubiquitin-protein conjugates accumulate in lysosome-related bodies very early and appear to be intimately related to the pathological processes in the animal disorders that we have studied.

Animals↗

Measurement of anti-HBc IgM levels using the Amerlite anti-HBc IgM assay.

The Amerlite anti-HBc IgM assay was evaluated as a tool for determination of antibody levels. With an assay time of 1 hour, the test showed a broad dose response range with high sensitivity and specificity. The software configuration of the analyser can be customized to suit specific research requirements.

Hepatitis B↗

The comparative activity of fosfomycin trometamol against organisms isolated from infected urines.

Five hundred urinary pathogens, collected from patients of general practitioners and hospital in-patients, were identified and tested for susceptibility to fosfomycin, ampicillin, cephalexin, nalidixic acid, nitrofurantoin, trimethoprim and sulfamethoxazole. Overall, 83% of the isolates were sensitive to fosfomycin, comprising 89% of the out-patient strains and 77% of the in-patient isolates. This degree of sensitivity was similar to that of cephalexin, nalidixic acid and trimethoprim, but higher than that observed with ampicillin, nitrofurantoin and sulfamethoxazole. Fosfomycin generally showed a broad spectrum of activity, but was less active than some other compounds against Klebsiella spp. and streptococci. More than 70% of strains resistant to ampicillin, sulfamethoxazole or trimethoprim were sensitive to fosfomycin indicating that cross resistance is not presently a problem.

Anti-Bacterial Agents↗