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Biomedical subjects

L Johns

Publications and source records attributed to L Johns.

At least 37 records · Page 2Linked to original sources
PubMed1995

Papaverine-sensitive vasospasm and arterial contractility and compliance after subarachnoid hemorrhage in dogs.

This study examined the relationship between papaverine-sensitive and -insensitive components of vasospasm, arterial contractility and compliance, and time after subarachnoid hemorrhage (SAH) in dogs. Eighteen dogs underwent angiography and then two intracisternal injections of blood. Angiography was repeated 4 (n = 5), 7 (n = 4), 10 (n = 4), or 14 (n = 5) days later. Papaverine, 100 to 200 mg, was infused into the basilar artery, and angiography was repeated. Four additional dogs had cerebral angiography only and served as controls. The basilar arteries were removed and studied pharmacologically. Significant vasospasm of the basilar artery was observed each time after SAH. Papaverine significantly reversed vasospasm at 4 and 7 days (88 +/- 6% and 63 +/- 11% of vasospasm reversed; analysis of variance, P < 0.05). The papaverine-insensitive component of vasospasm increased significantly with increasing time after SAH and with increasing severity of vasospasm. Arterial contractility and compliance decreased significantly with increasing time after SAH and were significantly related to the degree of papaverine-insensitive vasospasm but not to the severity of vasospasm. In conclusion, the majority of vasospasm early after SAH in dogs was caused by reversible vasoconstriction. The ability of papaverine to reverse vasospasm depended on the time after SAH and on the severity of vasospasm, a finding that may be important to the use of papaverine in humans. The pathological and biochemical basis for the association between papaverine-insensitive vasospasm and reduced arterial wall contractility and compliance remains to be determined.

Animals↗
PubMed1995

Nitric oxide synthase and guanylate cyclase levels in canine basilar artery after subarachnoid hemorrhage.

Endothelium-dependent vasodilation may be impaired during cerebral vasospasm following subarachnoid hemorrhage. Under normal circumstances nitric oxide (NO) released by endothelial cells induces relaxation of smooth muscle by activating the soluble form of guanylate cyclase within muscle cells. In this study the levels of both endothelial NO synthase, the enzyme that produces NO, and soluble guanylate cyclase were determined in canine basilar arteries in a double-hemorrhage model using Western blot immunoassays. Thirty dogs were assigned to three groups: Group D0, control; Group D2, dogs sacrificed 2 days after cisternal injection of blood; and Group D7, dogs given double cisternal injections of blood and sacrificed 7 days after the first injection. Constriction of the basilar artery was confirmed by arterial angiography. Portions of the affected arteries or the corresponding region in control animals were solubilized for sodium dodecylsulfate-polyacrylamide gel electrophoresis and Western blotting. A specific monoclonal antibody against endothelial NO synthase was used. The extract from basilar arteries showed two bands on the blots: 135 kD, characteristic of endothelial NO synthase, and 120 kD, which may be a degradation product of the enzyme. The densitometer values of the bands were presented as percentages of D0 control values. Although the total signal in the D7 group was less than that of the D0 control group (D2, 97% +/- 22%; D7, 78% +/- 40%), it was not statistically significant. The proportion of the 135-kD form decreased between Groups D0 and D7, but the difference was not significant. A single major band corresponding to the alpha-subunit of soluble guanylate cyclase was seen at 70 kD in the basilar artery extracts. The signals of D2 and D7 samples were 69% +/- 40% and 25% +/- 18%, respectively. There was a significant difference between D7 and D0 (p < 0.001). The reduced expression of soluble guanylate cyclase may be related to the impairment of endothelium-dependent vasodilation in vasospasm.

Amino Acid Oxidoreductases↗
PubMed1994

Blood supply to the spinal cord: anatomic and physiologic correlations.

Although the subject has been studied for many years, the clinician's understanding of the blood supply to the spinal cord is complicated by both confusing nomenclature and conflicting data. This review attempts to clarify prevailing thoughts on the arterial and venous structures in this clinically important area.

Arteries↗
PubMed1993

National Health Service breast screening programme results for 1991-2.

OBJECTIVES: To report the results of the NHS breast screening programme for the year March 1991 to April 1992. DESIGN: A report of statistics was derived from Körner (K62) returns and from the radiology quality assurance programme. MAIN OUTCOME MEASURES: Detection rates for breast cancer and small (< or = 10 mm diameter) invasive cancer, benign biopsy rates, and recall and acceptance rates. RESULTS: The acceptance rate for screening across the United Kingdom was 71.3%. The referral rate for further investigation was 6.2% (regional 4.3-9.0%). The breast cancer detection rate was 6.2 cancers per 1000 women screened (5.1-9.0) and the detection rate of invasive cancers < or = 10 mm was 1.4/1000 (1.0-2.3). 72% of screening programmes reached the target 70% acceptance rate, and 95% of programmes achieved a recall rate of less than 10%. 75% of programmes had a cancer detection rate of more than 5/1000, but only 32% had a detection rate for invasive cancers < or = 10 mm of more than 1.5/1000. CONCLUSIONS: Overall, the results of the screening programme for the year 1991-2 can be regarded as extremely satisfactory, given the size and complexity of the operation.

Aged↗
PubMed1993

Liver abnormalities associated with chronic mercury accumulation in stranded Atlantic bottlenose dolphins.

Eighteen stranded Atlantic bottlenose dolphins (Tursiops truncatus) examined postmortem were sampled for histologic study. All cases were examined for ferric ion and lipofuscin. Ages were determined from tooth growth layers. Electron microscopic (EM) examination and X-ray spectroscopy (EDAX) were performed. Chemical analysis for mercury was conducted on 12 of the animals by atomic absorption spectrophotometry. Nine animals were found to have excessive lipofuscin in both liver and kidney. Four of these nine animals also exhibited active liver disease (fat globules, central necrosis, lymphocytic infiltrates) whereas, of the animals without the excessive pigment, only one animal had an active liver lesion. EM and EDAX showed electron-dense amorphous material presumably within lysosomes to be Hg with no deposits on mitochondrial or nuclear membranes noted. Age relationship to portal pigment deposition was positive. Liver mercury concentrations ranged from 0.01 to 443 micrograms/g of wet weight with all animals having liver pigment yielding values of or above 61 micrograms/g, whereas all animals lacking pigment had values of or below 50 micrograms/g. The evidence suggests that the excessive pigment accumulation is related to toxic effects of Hg and presents as increased active liver disease.

Age Factors↗
PubMed1990

Leaky intra-acinar arteries in rat lungs perfused with hydrogen peroxide.

We have investigated the effects of H2O2 (150 or 300 microM) on the ultrastructure and permeability of the pulmonary endothelium in rat lungs perfused for 60 min with buffered Hanks' bovine serum albumin medium. In one group of experiments, we examined the effect of H2O2 on the uptake and transport of cationized ferritin (CF) by endothelial cells in intra-acinar arteries, alveolar capillaries, and interlobular veins. The influence of the oxidant on endothelial adsorptive endocytic processes was assessed by measuring the density of ferritin particles in luminal vesicles, multivesicular bodies, and basal lamina. In a second group of experiments, we examined the effects of H2O2 on the fine structure and permeability to electron-dense macromolecules of arterial, microvascular, and venous endothelium. For this purpose, at the end of the 60-min perfusion with H2O2, CF was perfused to identify leaky vessels. We found that H2O2 caused a dose-dependent inhibition of transcytosis of CF in all vascular segments. At the lower dose of H2O2, inhibition of transcytotic activity was not associated with structural injury to the vascular endothelium or with elevation of wet-to-dry ratios. At the higher oxidant dose, inhibition of transcytosis was associated with leaky arterial endothelium and elevation of wet-to-dry ratios (6.44 +/- 0.12 vs. 5.64 +/- 0.16, P less than 0.02). The effects of H2)2 were prevented by adding catalase to the perfusate. The selective loss of structural integrity and leakiness of the arterial endothelium were diminished but not completely abolished by perfusing the oxidant retrograde from the venous side.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Selective contracting in California: an update.

Six years of selective contracting for health services in California provide strong evidence that the policy works to depress inflation in hospital inpatient costs and revenues, shift inpatient care to outpatient settings, and spread the PPO health benefit option throughout the state. These responses occur against a backdrop of rapid increases in population and aging and continuing declines in inpatient utilization. The policy has yet to affect excess capacity or capital expansion, and possibly even encourages the latter. There is still no good evidence of effects on quality of care, nor, due to a number of new negative influences, is there likely to be.

Ambulatory Care↗
PubMed1988

Inhibition of adsorptive endocytosis and transcytosis in pulmonary microvessels.

In isolated perfused rat lungs we have examined the effect of inhibition of receptor-mediated endocytosis and of intracellular acidic compartments activity on adsorptive and fluid-phase uptake and transport of macromolecules by capillary endothelium. Cationized and native ferritin were used as electron-dense tracers of adsorptive and fluid-phase transport, respectively. Luminal endothelial vesicles were labeled with tracers at 4 degrees C for 2 minutes and the density of ferritin particles in endothelial multivesicular bodies and in the capillary basement membrane, after a 60-minute chase with tracer-free perfusate at 37 degrees C, was determined by electron microscopic morphometry. Fluid-phase transport of native ferritin in 60-minute perfusions at 37 degrees C was also investigated. Adsorptive endocytosis was inhibited in chase experiments with hypertonic (800 mOsm) perfusate. Endothelial acidic compartments activity was decreased by adding either dextran sulfate or chloroquine to the chase media. We found that hypertonic solutions, dextran sulfate, and chloroquine inhibit cationized ferritin accumulation in multivesicular bodies and in the extravascular space. Hypertonic buffer or dextran sulfate have no effect on native ferritin uptake and transport in either pulse-chase or continuous perfusions. Since adsorptive or receptor-mediated mechanisms play a role in the transendothelial movement of plasma proteins, and other plasma constituents, our findings suggest a general role of the endothelial acidic compartments in modulating microvascular permeability to macromolecules.

Animals↗
PubMed1987

The sympathetic nervous system and atherosclerosis.

Morphometric and chemical changes in the arterial wall were studied after 12 months of diet-induced atherosclerosis in rhesus monkeys treated with either bilateral surgical thoracic sympathectomy or propranolol. There was a marked reduction in the progression of atherosclerosis in the carotid arteries and a moderate reduction in the disease found in the thoracic aorta of monkeys treated initially with a sympathectomy, in comparison to control monkeys fed an atherogenic diet alone. Propranolol at a dose of 40 mg/12 hrs also seemed to reduce the progression of atherosclerosis in the carotid arteries and thoracic aorta, although the differences were less dramatic. There were minimal differences in the extent of atherosclerosis in the abdominal aorta or femoral arteries of animals in either treatment group as compared with the control group. Similarly, the chemical composition of these same major vessels showed no significant differences. Therefore, in the face of severe atherogenic stimuli, chemical or surgical sympathectomy may be useful in controlling atherosclerosis in specific arterial beds.

Animals↗
PubMed1986

Binding and uptake of native and glycosylated albumin-gold complexes in perfused rat lungs.

We have examined, by electron microscopy, the effect of glycosylation on binding, uptake, and transport of albumin-gold complexes in capillaries of isolated perfused rat lungs. Lungs were perfused for 2 min at 4 degrees with native and glycosylated albumin-coated gold particles. After the excess probe was washed out for 5 min the lungs were fixed immediately or perfused for 30 and 60 min at 37 degrees with a isoosmotic buffer before fixation. The localization and density of the probes over different microvascular endothelial compartments were determined by electron microscopy. We found that both native and glycosylated albumin were bound to the surface of the pulmonary microvascular endothelium, preferentially over the stomatal diaphragms of luminal smooth-walled vesicles. In both BSA and glycosylated BSA perfusions at 37 degrees, most of the probe was internalized and accumulated in lysosomes and only a few gold particles were observed in the extravascular compartment even after 60 min perfusion. However, binding, internalization, and transport of the protein-gold complexes was enhanced by nonenzymatic glycosylation of albumin.

Animals↗
PubMed1986

Effect of 100% O2 on passage of uncharged dextrans from blood to lung lymph.

Since charge as well as size may influence the passage of plasma proteins from blood to lung lymph, we used uncharged dextrans as tracers to study the effects of hyperoxic lung injury on the molecular sieving properties of the pulmonary microcirculation in unanesthetized sheep. Polydisperse [3H]dextran was infused intravenously into five sheep before and after the animals breathed 100% O2 until lymph flow increased threefold (66-84 h). Lymph-to-plasma concentration ratios (L/P) were determined for [3H]dextran fractions of graded molecular sizes (1.6-8.4 nm effective radius) from samples obtained during the infusions. Before hyperoxia the blood-lymph barrier was highly restrictive to transport of [3H]dextrans above 5.0 nm in radius; steady-state L/P for these molecules averaged 0.03 or less. After the sheep breathed 100% O2, [3H]dextrans as large as 8.4 nm radius appeared in the lymph. Posthyperoxia, the L/P were significantly increased relative to prehyperoxia base-line values for every [3H]dextran fraction larger than 2.0 nm radius (P less than 0.05). In contrast, neither the L/P for albumin or total protein changed significantly. At autopsy, electron microscopy showed widespread damage to the endothelium of the alveolar capillaries with infrequent gaps between endothelial cells. In two control sheep, inhalation of compressed air for 96 h had no effect on lymph flow or L/P for the [3H]dextrans. We conclude that O2 poisoning reduced the selective sieving of uncharged dextrans across the blood-lymph barrier of the lungs and allowed larger dextrans to enter the lymph. These larger molecules may have leaked from the pulmonary microcirculation via disruptions in the continuity of the endothelial lining.

Animals↗
PubMed1985

Selective contracting in California: early effects and policy implications.

California is the first state to enable its Medicaid program and private insurance firms to negotiate with providers for prices to be paid for health services. Initial findings from a two-year study sponsored by the National Governors' Association indicate few problems with Medicaid contracting. Hospital contracts are widely dispersed at prices highly favorable to the state, there has been little documented dislocation of patients or physicians into a two-tier system, and there is no evidence of reduction in quality of care. State savings are estimated at $165 million for the first year of the program. Selective contracting in the private sector, by contrast, has moved more slowly than anticipated, owing to a number of unforeseen barriers.

Blue Cross Blue Shield Insurance Plans↗
PubMed1985

Selective contracting in California: experience in the second year.

Now entering its third year of implementation, selective contracting for health services in California continues to benefit the Medicaid program and is taking hold in the private sector. The number of hospitals under contract with Medicaid has increased to 274, and the state budget for inpatient services in FY 1984-1985 is projected to increase by only 1%. Operational preferred provider organizations (PPOs) in the state now approximate 50. Hospitals are contracting with private payers at prices averaging 10%-20%, and as high as 40%, below customary charges. PPO premiums are stated to be 10%-20% below indemnity rates. No measurable diminution of quality or access for Medicaid patients has yet been demonstrated. Selective contracting and its attendant competitive incentives have changed provider behavior and continue to dominate state health policy.

California↗