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Biomedical subjects

L C Wright

Publications and source records attributed to L C Wright.

At least 37 records · Page 2Linked to original sources
PubMed1992

The history of ventriculoscopy: where do we go from here?

With the availability of better endoscopes, improved lighting and increased instrumentation, the use of ventriculoscopy and ventriculostomy in the management of hydrocephalus is becoming increasingly more common. Neurosurgeons recognized the potential for endoscopic surgery early in this century, but were frustrated in many of their attempts at treatment due to the poor quality of the instruments available. Nevertheless, much progress has been made, and the stage was set for better results with modern instrument design. This paper reviews the history of endoscopes in neurosurgery and ponders the direction these instruments will take us in the near future.

Cerebral Ventricles↗
PubMed1992

Improvement of cortical morphology in infantile hydrocephalic animals after ventriculoperitoneal shunt placement.

As a sequel to our previous descriptions of the pathological changes induced by hydrocephalus in the infantile cerebral cortex, the study presented here has evaluated the effects of surgical decompression on cortical cytology and cytoarchitecture. Hydrocephalus was induced in 14 kittens by the intracisternal injection of kaolin at 4 to 11 days of age. Nine of these hydrocephalic animals received low-pressure ventriculoperitoneal shunts at 9 to 15 days after kaolin injection; these animals were monitored preoperatively and postoperatively by ultrasound and were killed at various postshunt intervals up to 30 days. Five normal or saline-injected animals served as age-matched controls. At the time of shunt placement, the ventricular index confirmed that all recipient animals had attained moderate or severe degrees of ventriculomegaly. Within 3 days after shunt placement, the size of the lateral ventricles had decreased to control levels and was accompanied by rapid and dramatic improvements in behavior and skull ossification. When the animals were killed, gross inspection revealed that about half of the animals exhibited mild to moderate ventriculomegaly, with cortical mantles 50 to 80% their normal thickness. Tissue from frontal (primary motor), parietal (association), and occipital (primary visual) cortical areas was processed for light microscopic analysis. Pyknotic or dark shrunken neurons, which are found typically in hydrocephalic brains, were observed only occasionally in the cortex of shunted animals. Gliosis and mild edema were prevalent, however, in the periventricular white matter. The laminae of the cerebral cortex could be identified in all shunted animals. In those animals with mild residual ventriculomegaly, the entire cortical mantle was somewhat compressed, as evidenced by an increased packing density of neurons. Furthermore, the somata of some neurons were disoriented. Overall, these results indicate that most of the morphological characteristics of the cerebral cortex are preserved after surgical decompression and suggest that ventriculoperitoneal shunts may prevent neuronal damage and/or promote neuronal repair.

Animals↗
PubMed1991

Comparison of search strategies on CD Plus/MEDLINE.

OBJECTIVE: To compare two strategies for searching MEDLINE using the CD Plus/MEDLINE program on compact disc. DESIGN: Comparison study. INTERVENTIONS: Two search strategies were designed and executed for each of two topics (patient recruitment to clinical trials and attitudes of patients, the public and health care professionals toward clinical trials). Strategy A: searches based on key words selected from the medical subject heading (MeSH) tree structure. Strategy B: searches based on MeSH terms most frequently used to index a known set of relevant articles. Defined search restrictions were then applied. The effects of the restrictions on the absolute number of citations retrieved and on the proportion of relevant citations were assessed. OUTCOME MEASURES: Number of articles retrieved, number of relevant articles, precision and recall of each search strategy and overlap between strategies. MAIN RESULTS: Strategy A produced more citations than strategy B (recruitment 147 v. 38, attitude 366 v. 57) but had more inappropriate citations (recruitment 75 v. 17, attitude 265 v. 25). Both strategies produced 73 relevant recruitment citations and 101 relevant attitude citations. In the recruitment search although the precision did not differ significantly between strategies A and B the difference in recall was significant (98.6% v. 28.8% respectively, p less than 0.0001). In the attitude search strategy A had a lower precision than strategy B (27.6% v. 56.1%, p less than 0.0001) but a much higher recall (100% v. 31.7%, p less than 0.0001). CONCLUSIONS: Strategy A would be more valuable to researchers doing extensive reviews, whereas strategy B would be useful for the busy clinician who simply wants a few appropriate references quickly and is willing to sacrifice comprehensive retrieval in the interest of efficiency.

Algorithms↗
PubMed1991

Protein kinase C phosphorylates the carboxyl terminus of the plasma membrane Ca(2+)-ATPase from human erythrocytes.

Purified Ca(2+)-stimulated, Mg(2+)-dependent ATPase (Ca(2+)-ATPase) from human erythrocytes was phosphorylated with a stoichiometry of about 1 mol of phosphate/mol of ATPase at both threonine and serine residues by purified rat brain type III protein kinase C. In the presence of calmodulin, the phosphorylation was markedly reduced. Labeled phosphate from [gamma-32P]ATP was retained on an 86-kDa calmodulin-binding tryptic fragment of Ca(2+)-ATPase but not on 82- and 77-kDa non-calmodulin-binding fragments. Similarly, fragmentation of the phosphorylated Ca(2+)-ATPase by calpain I revealed that calmodulin-binding fragments (127 and 125 kDa) retained phosphate label whereas a non-calmodulin-binding fragment (124 kDa) did not. The calmodulin-binding domain, located about 12 kDa from the carboxyl terminus of the Ca(2+)-ATPase, was thus located as a site of protein kinase C phosphorylation. A synthetic peptide corresponding to a segment of the calmodulin-binding domain (H2 N-R-G-L-N-R-I-Q-T-Q-I-K-V-V-N-COOH) was indeed phosphorylated at the single threonine residue within this sequence. The additional serine phosphorylation site was carboxyl terminal to the calmodulin domain. Phosphorylation by purified type III protein kinase C (canine heart) antagonized the calmodulin activation of the Ca(2+)-ATPase, particularly at lower Ca2+ concentrations (0.2-1.0 microM). By contrast, a purified but unresolved protein kinase C isoenzyme mixture from rat brain stimulated the activity of Ca(2+)-ATPase prepared in asolectin, but not glycerol, by more than 2-fold in the presence of the ionophore A23187, without increasing its Ca2+ sensitivity. The results clearly indicate that human erythrocyte Ca(2+)-ATPase is a substrate of protein kinase C, but the effect of phosphorylation on the activity of the enzyme depends on the isoenzyme form of protein kinase C used and on the lipid associated with the Ca(2+)-ATPase.

Amino Acid Sequence↗
PubMed1991

Pharmacokinetics of gentamicin after intravenous and subcutaneous injection in obese cats.

Six adult domestic shorthair obese cats were given 3-mg/kg gentamicin sulfate by rapid i.v. and by s.c. injection in a cross-over design. The plasma concentration-time data were analyzed using statistical moment theory with no assumption of a specific compartmental model. Means +/- SD for the half-life, which was calculated from the terminal slope of the log concentration-time curve, were 1.37 +/- 0.24 and 1.24 +/- 0.22 h following i.v. and s.c. injection, respectively. The apparent volume of distribution at steady state was 118.55 +/- 19.83 ml/kg, and total body clearance was 1.07 +/- 0.25 ml/kg/min. Bioavailability was 83.58 +/- 14.83% after s.c. administration. The calculated s.c. dose in obese cats to produce an average steady-state concentration of 4 micrograms/ml is 2.5 mg/kg every 8 h compared to 3 mg/kg in normal-weight cats.

Animals↗
PubMed1991

Tumour evolution in rats monitored by changes to serum and lipoproteins.

The biochemical, physicochemical and magnetic resonance (MR) properties of rat serum allow tumour evolution to be monitored. Serum from female Fischer rats injected with rat mammary adenocarcinoma cells contained a low-density lipoprotein (LDL)-like lipoprotein and decreased high-density lipoprotein levels compared with normal rat serum. Increases in secondary tumour burden coincided with enlarged LDL-like particles, altered MR properties and elevation of serum triglyceride. By fucosidase treating metastatic R13762 cells prior to injection, not only was metastatic capacity retarded, but serum lipoproteins were also altered. These physicochemical alterations suggest an intricate relationship between both primary and secondary tumour burdens and the serum lipoprotein profile.

Adenocarcinoma↗
PubMed1989

Elevated apolipoprotein(a) levels in cancer patients.

Elevated plasma lipoprotein(a) has been associated with an increased risk of cardiovascular disease. We report a significant elevation of total plasma apolipoprotein(a) levels in cancer patients compared with hospitalized control patients and normal healthy blood donors. Of the cancer patients studied, 48% had levels in excess of 350 mg/l compared to 20% in normal blood donors and 29% of hospitalized control patients. The elevation was more prevalent but less extreme than that reported in patients with cardiovascular disease. Density gradient centrifugation studies of plasma from cancer patients revealed the presence of apolipoprotein(a) at a density of 1.085 g/ml in the region where mRNA-containing proteolipids, neoproteolipids and malignancy-associated lipoproteins had previously been isolated.

Apolipoproteins A↗
PubMed1989

Vinblastine sensitivity of leukaemic lymphoblasts modulated by serum lipid.

The high-resolution proton magnetic resonance spectrum of leukaemic lymphoblasts is characteristic of neutral lipid in an isotropic environment. When such lymphoblasts are selected for resistance to the anticancer drug vinblastine, the intensity of this spectrum increases with increasing drug resistance. A reversal of this trend can be achieved by growing cells in delipidated serum, whereby lipid spectrum and drug resistance are diminished. However, both can be restored by subsequent regrowth in normal medium. Thus, although detectable genetic changes accompany the development of vinblastine resistance, the expression of these changes can be modulated by environmental lipid.

Cholesterol↗
PubMed1989

Management of posthemorrhagic hydrocephalus in the low-birth-weight preterm neonate.

Over a period of 34 months from 1987 to 1990 we inserted ventricular catheter reservoirs (VCR) into 20 premature low-birth-weight infants who had developed progressive, symptomatic posthemorrhagic hydrocephalus following grade III or IV intraventricular hemorrhages. The mean estimated gestational age was 27.7 +/- 5.3 weeks and mean birth weight was 1,041 +/- 699 g. The ventricular catheter reservoirs were placed on day of life 30.7 +/- 29.7 and tapped for a total of 3-34 days at varying frequencies and for varying volumes. Of the 20 patients, 4 died on days of life 25, 76, 88, and 187. There were two reservoir infections, both occurring in infants who eventually died. The 16 survivors have been followed from 2 to 24 months (adjusted age). Four (25%) remain shunt-free and 3 have undergone VCR removal. There have been two shunt infections in the 12 shunted patients; ten shunt revisions have been performed overall. At the time of last follow-up, 14 patients were old enough to undergo neurodevelopmental evaluation. Five patients (36%) were 'normal' on gross neurological screening examination, 5 (36%) had 'mild developmental delay' and 4 (28%) had 'significant developmental delay'. We feel these data support the continued use of ventricular catheter reservoirs in the management of posthemorrhagic hydrocephalus and offer hope that some of these patients might remain shunt-free and most will have a normal or mildly delayed neurodevelopmental outcome.

Brain Damage, Chronic↗
PubMed1989

Bioavailability of gentamicin in dogs after intramuscular or subcutaneous injections.

Healthy adult mixed-breed dogs, assigned to 2 groups of 6 dogs each, were given 3 mg of gentamicin sulfate/kg of body weight on 3 injection days 7 days apart. Group 1 was given gentamicin by rapid IV injection, by injection into the belly of the longissimus muscle at the first lumbar vertebrae (IM site 1), and by injection in the belly of the biceps femoris muscle (IM site 2). Group 2 was given gentamicin by rapid IV injection, by SC injection into the space over the cranial angle of the scapula on the midline (SC site 1), and by SC injection just caudal to the crest of the ilium (SC site 2). Pharmacokinetic values (mean +/- SD) from 12 dogs given gentamicin IV were 54.4 +/- 15.4 minutes for the effective half life, 2.29 +/- 0.48 ml/kg/min for clearance, and 172 +/- 25.4 ml/kg for volume of distribution at steady state. Bioavailability (93.92 to 96.65%) and peak plasma gentamicin concentration (9.43 to 10.89 micrograms/ml) were independent of injection site, but time to peak concentration when gentamicin was given at SC site 2 (43.33 minutes) was significantly (P less than 0.05) longer than that when gentamicin was given at IM site 1 (27.50 minutes). Absorption half-life was shorter after injections were given at both IM sites (8.9 and 9.8 minutes) than after injection was given at SC site 2 (18 minutes).

Animals↗
PubMed1988

Plasma membrane lipid composition of vinblastine sensitive and resistant human leukaemic lymphoblasts.

Plasma membranes purified 32- to 45-fold were isolated from leukaemic T-lymphoblasts, both sensitive and resistant to the Vinca alkaloid vinblastine. On development of drug resistance there was a very significant elevation of ether lipid content. 1-0-alkyl phospholipid increased by 200% with a smaller 30% increase in 1-0-alkenyl phospholipid. Cholesterol and phospholipid levels were also found to increase by 50% and 30% respectively, while the lipid to protein ratio increased by 60%. More modest changes were observed in the fatty acid composition of the membranes, with an alteration in the double bond index from 35.3 to 41.2. These lipid changes may have important implications in the changes to membrane permeability that develop with drug resistance.

Cell Line↗
PubMed1988

Inhibition of metastatic potential by fucosidase: an NMR study identifies a cell surface metastasis marker.

NMR spectroscopy is able to detect subtle changes to the surface chemistry of cells. We have previously shown that high-resolution 1H NMR methods can identify tumor cells with the capacity to metastasize, and we now report that the long T2 relaxation value (500-800 ms) observed in metastatic rat mammary adenocarcinoma cells is removed by treatment with fucosidase. Two-dimensional scalar-correlated NMR (COSY) spectra of fucosidase-treated cells show that a cross peak, consistent with scalar coupling between the methyl and methine groups on fucose and usually associated with malignancy and metastatic ability, is absent. Metastases were observed in only two out of ten rats injected subcutaneously with enzyme-treated cells compared to eight out of ten with untreated cells. NMR studies on isolated cellular lipids identified the long T2 relaxation value only in the ganglioside fraction. This fraction accounts for 51% of the total 14C-labelled fucose incorporated into the cells. We propose that fucogangliosides are an indicator of metastatic potential in rats. The observation that a cell surface metastasis marker has an NMR signal with a characteristically long relaxation value has important consequences for the future use of magnetic resonance imaging and spectroscopy in the cancer clinic.

Adenocarcinoma↗
PubMed1988

Hyperlipidemia as a biochemical basis of magnetic resonance plasma test for cancer.

An increase in the plasma levels of apoprotein B-containing lipoproteins is the basis of the magnetic resonance (MR) test for cancer. The narrow MR line width reported by Fossel and co-workers to be associated with the presence of malignant disease is due to a relative increase of very low density lipoprotein. In contrast, the plasma from healthy controls, which has a much broader spectrum, has a higher proportion of high density lipoprotein. However, plasma from patients with hyperlipidemia unrelated to cancer also show narrow MR line widths and are therefore a confounding variable. We used magnetic resonance spectroscopy (MRS) to assess the plasma from 253 patients with a range of lipid related diseases and cancer, and 28 controls. A significant difference (p less than or equal to 0.0005) of 10 Hz exists between the mean line width of the controls and hyperlipidemics without malignant disease. However, in patients with solid tumours a difference of 7 Hz (p less than or equal to 0.0005) in the mean values is recorded although there is an overlap of 6 Hz compared with the controls. Moreover the MRS method was not found to distinguish patients with lymphomas from the control population. The index was not found to be related to patient age or tumour burden.

Adult↗
PubMed1987

Proteolipid identified by magnetic resonance spectroscopy in plasma of a patient with borderline ovarian tumour.

Magnetic resonance spectroscopy (MRS) can identify abnormal lipoproteins in the plasma of patients with premalignant and malignant tumours. Proteolipid complexes, 8-11 nm and 25-28 nm in size, were isolated from the plasma of a patient with a borderline ovarian tumour. These complexes, which generated a characteristically long MRS T2 relaxation value (greater than 400 ms), were disrupted by ribonuclease. None of the conventional lipoproteins had a T2 value above 160 ms. Chemical analysis of the proteolipid complexes showed a 20% glycolipid component, and MRS identified a fucosylated molecule as the origin of the long T2 value. 9 months after resection of all tumour, a visible lipoprotein band, possibly lipoprotein (a), persisted in the plasma but neither the long T2 relaxation value nor the 8-11 nm or 25-28 nm particles were present. The long T2 relaxation value in the MRS profile, found in isolated proteolipid and unfractionated plasma and serum of other patients with carcinoma of the ovary and colon, provides a non-invasive method of assaying for cancer.

Adult↗
PubMed1986

A proteolipid in cancer cells is the origin of their high-resolution NMR spectrum.

High-resolution proton nuclear magnetic resonance studies show that the spectrum of a proteolipid complex, isolated from the serum of patients with malignant diseases, is directly comparable with that obtained from intact cancer cells and solid tumours. These NMR signals have previously been shown to reveal differences between cancer cells with various biological characteristics such as metastatic capacity and drug sensitivity. The proteolipid contains cholesterol, phospholipid, triglyceride, glycolipids, ether-linked lipids, and an apoprotein of unusual electrophoretic mobility. We have yet to confirm the presence of the mRNA reported by others. NMR spectroscopy could be used as a rapid method of identifying the presence of this proteolipid complex in human serum and aiding the diagnosis of malignant disease.

Female↗
PubMed1986

Cell surface involvement in cancer metastasis: an NMR study.

NMR spectroscopy is one of the few techniques which has the sensitivity to detect subtle changes to the surface chemistry of cells. It has previously been demonstrated that high resolution 1H NMR methods can distinguish tumour cells with the capacity to metastasis and this information appears to arise from a type of proteolipid in or attached to the plasma membrane. Here we report that the 1H NMR signal, which we have used to identify metastatic cells in rat tumours, is significantly reduced in intensity after cultured cells are treated with trypsin/EDTA. The long T2 relaxation value (greater than 350 ms) observed in metastatic cells is absent after enzyme treatment. 2D scalar correlated NMR (COSY) spectra of these treated cells show that a cross peak normally associated with malignancy and metastatic disease is markedly reduced. These findings indicate that the plasma membrane lipid particle which generates the high resolution spectrum is directly affected by trypsin/EDTA. Alterations to the cell surface properties were also demonstrated in vivo since reduced numbers of metastases were observed in animals injected with enzyme-treated cells. The correlation between the absence of a long T2 relaxation value and the diminished numbers of metastases in animals suggests that the plasma membrane particle is involved in the metastatic PROCESS.

Adenocarcinoma↗
PubMed1986

Assignment of methylene proton resonances in NMR spectra of embryonic and transformed cells to plasma membrane triglyceride.

Some biological characteristics of cancer cells and solid tumors are identifiable by the high resolution NMR relaxation behavior of their nonaqueous components. Chemical analysis and two-dimensional scalar correlated (COSY) NMR spectroscopy show these resonances arise from neutral lipid in the plasma membrane. Triglyceride is shown to be the main plasma membrane component giving rise to the NMR spectrum, while soluble nonmembrane components account for 90% of the remaining resonances in the spectrum of intact cells. The presence of triglyceride has been detected by chemical analysis in highly purified plasma membranes from two different cell lines. The COSY spectra of cancer cells are comparable with that obtained for the triglyceride-rich very low density human lipoprotein.

Adenocarcinoma↗