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Biomedical subjects

B Ross

Publications and source records attributed to B Ross.

At least 37 records · Page 2Linked to original sources
PubMed2000

Metabolism and distribution of the virus-encoded serine proteinase inhibitor SERP-1 in healthy rabbits.

SERP-1 is a secreted myxoma virus-encoded 55-kd protein of the serine proteinase inhibitor ("serpin") family that strongly inhibits the mitosis of medial arterial smooth muscle cells, thus preventing stenosis in injured rabbit and rat arteries. We have measured the fractional catabolic rate (FCR) and compartmental distribution of 1251-SERP-1 after injection of various doses into the circulation of healthy rabbits. The FCR within the intravascular space decreased from 2.99 d(-1) to 2.39 d(-1) and the whole-body FCR decreased from 0.66 d(-1) to 0.51 d(-1) as the dose was increased 35-fold from 0.11 microg/kg to 3.8 microg/kg. The fractional distribution of SERP-1 between the intravascular (0.21), noncirculating vascular wall (0.09), and extravascular compartments (0.70) at equilibrium did not change significantly over this dose range. SERP-1 did not appear to selectively accumulate in any organ in any of 11 rabbits studied over a 6-day interval. In comparison to other rabbit plasma serpins, the behavior of SERP-1 in vivo most closely resembled that of heparin cofactor II.

Animals↗
PubMed2000

Long term response to gallstone treatment--problems and surprises.

OBJECTIVE: To re-evaluate after 5 years the results of a randomised trial of cholecystectomy and lithotripsy for the treatment of symptomatic gallstones. DESIGN: Late follow-up of a randomised controlled trial. SETTING: Teaching hospital, UK. SUBJECTS: 144 of the 179 patients originally randomised. INTERVENTIONS: Either elective open cholecystectomy under general anaesthesia or a maximum of 4 sessions of lithotripsy (up to 3000 shocks/session) on consecutive days with no anaesthesia or analgesia. RESULTS: Of the original 87 patients randomised to be treated by lithotripsy, 39 (45%) subsequently underwent cholecystectomy, most of them within 32 months of treatment ("crossover" group). Patients in both main groups had a pronounced reduction in the number of episodes of pain at 5 years and significant reductions in the mean severity scores both on VAS and the McGill rating. Those in the crossover group had the worst scores. Gastrointestinal symptoms improved in the two main groups, but again the crossover group did least well. Quality of life improved significantly over baseline in the two main groups, but was much poorer in the crossover group. CONCLUSIONS: Patients who had primary cholecystectomy were more likely to be free of pain than those treated by lithotripsy. Lithotripsy gave good symptomatic results in 55% of patients, and this was not dependent on clearance of stones. Patients who had a cholecystectomy after lithotripsy had the worst symptomatic results. It is difficult to identify patients who will not benefit from lithotripsy, but the presence of many coexisting symptoms may be an important predictor.

Adult↗
PubMed2000

A high-precision magnetoencephalographic study of human auditory steady-state responses to amplitude-modulated tones.

The cerebral magnetic field of the auditory steady-state response (SSR) to sinusoidal amplitude-modulated (SAM) tones was recorded in healthy humans. The waveforms of underlying cortical source activity were calculated at multiples of the modulation frequency using the method of source space projection, which improved the signal-to-noise ratio (SNR) by a factor of 2 to 4. Since the complex amplitudes of the cortical source activity were independent of the sensor position in relation to the subject's head, a comparison of the results across experimental sessions was possible. The effect of modulation frequency on the amplitude and phase of the SSR was investigated at 30 different values between 10 and 98 Hz. At modulation frequencies between 10 and 20 Hz the SNR of harmonics near 40 Hz were predominant over the fundamental SSR. Above 30 Hz the SSR showed an almost sinusoidal waveform with an amplitude maximum at 40 Hz. The amplitude decreased with increasing modulation frequency but was significantly different from the magnetoencephalographic (MEG) background activity up to 98 Hz. Phase response at the fundamental and first harmonic decreased monotonically with increasing modulation frequency. The group delay (apparent latency) showed peaks of 72 ms at 20 Hz, 48 ms at 40 Hz, and 26 ms at 80 Hz. The effects of stimulus intensity, modulation depth, and carrier frequency on amplitude and phase of the SSR were also investigated. The SSR amplitude decreased linearly when stimulus intensity or the modulation depth were decreased in logarithmic steps. SSR amplitude decreased by a factor of 3 when carrier frequency increased from 250 to 4000 Hz. From the phase characteristics, time delays were found in the range of 0 to 6 ms for stimulus intensity, modulation depth, and carrier frequency, which were maximal at low frequencies, low intensities, or maximal modulation depth.

Adult↗
PubMed2000

Incidence and prevalence of neurological disorders associated with HIV since the introduction of highly active antiretroviral therapy (HAART).

OBJECTIVE: To determine the change of incidence and prevalence of neurological disorders caused by the human immunodeficiency virus (HIV) and opportunistic infections in HIV positive patients under treatment since the introduction of highly active antiretroviral therapy (HAART). METHODS: The data of all HIV infected patients were retrospectively analysed, who were examined in the HIV outpatients clinic of the neurological department of the University Clinic Essen between 1995 and 1998 (n=563, total number of visits=735). Data from identified patients were divided into two groups according to the time of examination from 1995 to 1996 (334 visits) and from 1997 to 1998 (401 visits). The incidence and prevalence of neurological disorders were statistically compared between both time intervals. RESULTS: Significantly more patients received HAART in 1997-8 (p<0. 001) and mean CD4+ cell count was significantly higher in 1997-8 (p<0.001). The prevalence of HIV associated dementia and HIV associated polyneuropathy were significantly lower in 1997-8 (both: p=0.02) and the incidence of toxoplasma encephalitis decreased from 5.7% in 1995-6 to 2.2% in 1997-8 (p=0.015). Based on the small number of patients significant changes in HIV associated myopathy, progressive multifocal leukoencephalopathy, cryptoccocal meningitis, and cytomegalovirus-encephalitis could not be detected. CONCLUSION: The prevalence of the most frequent HIV associated neurological disorders and incidence of toxoplasma encephalitis decreased since the introduction of HAART. This may be due to the improvement of immunostatus by HAART as demonstrated by the higher CD4+ cell count in the later time interval. Direct antiretroviral effects within the nervous system may be considered causative as well. The prevalence and incidence of HIV associated neurological disorders and opportunistic CNS infections decreased after introduction of HAART.

Adult↗
PubMed2000

A pilot scheme for the development of evidence-based practice.

This article presents an evaluative account of a pilot scheme that aimed to introduce evidence-based practice in one NHS trust. The scheme was based on collaboration between staff in the quality assurance department and a nurse researcher based in a university. This collaboration enabled three designated staff to develop skills required for evidence-based practice and guide the production of information that could be disseminated to nurses throughout the trust. Evaluation demonstrated that participants had examined eight practice-based topics and devised protocols that could be applied to practice in a range of hospital and community settings throughout the trust. Evaluation also highlighted the importance of ensuring that members of other disciplines are aware of, and feel involved in, new developments even if they are not directly concerned with them.

Community Health Nursing↗
PubMed1999

Characterization of the interaction between the Wilson and Menkes disease proteins and the cytoplasmic copper chaperone, HAH1p.

Wilson disease (WD) and Menkes disease (MNK) are inherited disorders of copper metabolism. The genes that mutate to give rise to these disorders encode highly homologous copper transporting ATPases. We use yeast and mammalian two-hybrid systems, along with an in vitro assay to demonstrate a specific, copper-dependent interaction between the six metal-binding domains of the WD and MNK ATPases and the cytoplasmic copper chaperone HAH1. We demonstrate that several metal-binding domains interact independently or in combination with HAH1p, although notably domains five and six of WDp do not. Alteration of either the Met or Thr residue of the HAH1p MTCXXC motif has no observable effect on the copper-dependent interaction, whereas alteration of either of the two Cys residues abolishes the interaction. Mutation of any one of the HAH1p C-terminal Lys residues (Lys(56), Lys(57), or Lys(60)) to Gly does not affect the interaction, although deletion of the 15 C-terminal residues abolishes the interaction. We show that apo-HAH1p can bind in vitro to copper-loaded WDp, suggesting reversibility of copper transfer from HAH1p to WD/MNKp. The in vitro HAH1/WDp interaction is metalospecific; HAH1 preincubated with Cu(2+) or Hg(+) but not with Zn(2+), Cd(2+), Co(2+), Ni(3+), Fe(3+), or Cr(3+) interacted with WDp. Finally, we model the protein-protein interaction and present a theoretical representation of the HAH1p.Cu.WD/MNKp complex.

Adenosine Triphosphatases↗
PubMed1999

Common duct diameter as an independent predictor of choledocholithiasis: is it useful?

We have evaluated the value of ultrasonographic measurement of common duct diameter in isolation from other predictors of choledocholithiasis. A cohort of 223 patients who did not have a history of jaundice or pancreatitis and had normal liver function tests underwent pre-operative ultrasound of the common hepatic duct and then had elective (open) cholecystectomy with operative cholangiography. One hundred and ninety-one (86%) of all patients had a normal (< or = 5 mm) common duct and of these only 12 (6%) had common duct calculi. Of the 32 patients who had a common duct diameter greater than 5 mm on pre-operative ultrasonography, 12 (37.5%) patients had ductal calculi. A pre-operatively dilated duct on ultrasonography has a high chance of containing stones and should be considered as a strong indication for pre-operative bile duct imaging or operative cholangiography.

Adult↗
PubMed1999

Plasminogen II accumulates five times faster than plasminogen I at the site of a balloon de-endothelializing injury in vivo to the rabbit aorta: comparison with other hemostatic proteins.

In the rabbit blood stream, plasminogen circulates as two glycoforms, plasminogen I (PLG-I) and plasminogen II (PLG-II), in a molar ratio of 1:2.2. To compare their relative behaviors toward a site of vascular injury, radiolabeled samples of PLG-I and PLG-II were coinjected intravenously into NZW rabbits before inducing a de-endothelializing (balloon catheter) injury to the thoracic aorta. At various times (5 to 60 minutes) after injury, each rabbit was anesthetized and exsanguinated, the aorta was excised, and the radioactivity per centimeters squared of aortic intima-media (IM) was measured relative to that of blood at exsanguination. The uptake of iodine 125-labeled PLG-I and iodine 131-labeled PLG-II showed that the IM was essentially saturated by both glycoforms by 30 to 40 minutes after injury. Extrapolation of the flux rates to 1 minute after injury indicated that the uptake of PLG-II (2.4 pmol/min/cm2) exceeded PLG-I (0.5 pmol/min/cm2) almost five-fold. This result is consistent with an earlier report (Metabolism 1994;43:1430-7) that PLG-II is released by the liver and catabolized in vivo approximately five times faster than PLG-I. By molar comparison, the flux of total plasminogen (ie, PLG-I plus PLG-II) into the injured aorta wall in vivo was 2.4 times greater than that for prothrombin. Assuming both zymogens are converted to their respective proteases within the wound site, then approximately 2 to 3 molecules of plasmin are released for each molecule of thrombin in vivo. The possible significance of this plasmin:thrombin ratio is discussed in respect to the turnover of fibrin(ogen) within the site of vascular injury.

Animals↗
PubMed1999

The neuronal ceroid lipofuscinoses in human EPMR and mnd mutant mice are associated with mutations in CLN8.

The neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of progressive neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in various tissues. Progressive epilepsy with mental retardation (EPMR, MIM 600143) was recently recognized as a new NCL subtype (CLN8). It is an autosomal recessive disorder characterized by onset of generalized seizures between 5 and 10 years, and subsequent progressive mental retardation. Here we report the positional cloning of a novel gene, CLN8, which is mutated in EPMR. It encodes a putative transmembrane protein. EPMR patients were homozygous for a missense mutation (70C-->G, R24G) that was not found in homozygosity in 433 controls. We also cloned the mouse Cln8 sequence. It displays 82% nucleotide identity with CLN8, conservation of the codon harbouring the human mutation and is localized to the same region as the motor neuron degeneration mouse, mnd, a naturally occurring mouse NCL (ref. 4). In mnd/mnd mice, we identified a homozygous 1-bp insertion (267-268insC, codon 90) predicting a frameshift and a truncated protein. Our data demonstrate that mutations in these orthologous genes underlie NCL phenotypes in human and mouse, and represent the first description of the molecular basis of a naturally occurring animal model for NCL.

Amino Acid Sequence↗
PubMed1999

Uptake of heparin cofactor II and antithrombin into the aorta wall after a deendothelializing injury in vivo: comparison with the behaviors of prothrombin and fibrinogen.

The initiation of a denuding injury to the vascular endothelium rapidly leads to a deposition of platelets and fibrin at the site of injury. We have measured previously the responses of rabbit fibrinogen, prothrombin, and antithrombin to a deendothelializing balloon-catheter injury to the rabbit aorta in vivo. In this study, rabbit iodine 125-labeled HCII and iodine 125-labeled AT were coinjected intravenously into anesthetized rabbits 5 minutes before deendothelialization of the thoracic aorta. The rabbit was exsanguinated at 5 to 60 minutes after injury, the aorta was excised, and the accumulation of each radiolabeled protein in each layer of aorta wall was determined relative to the concentration of the respective native protein in circulating blood at exsanguination. The maximum flux rates into the aorta wall (i.e., platelet layer and intima-media) in the first minute after injury were calculated from the uptake data; approximately 2.8 molecules of AT accumulated for each HCII molecule. By comparison with previous measurements, the maximum flux rate of AT was similar to that of prothrombin. Further, the molar ratio of accumulated prothrombin/AT + HCII) in the aorta wall was 0.75. Detergent extracts of the injured aorta intima-media contained unreacted HCII and HCII complexes; the uninjured aorta contained only unreacted HCII. By contrast, high molecular weight AT complexes and unreacted AT were extracted from the uninjured, and in greater quantity from the injured, aorta wall. We conclude that, of the plasma antithrombins, AT accumulated more rapidly than HCII in vivo and appeared to be the more active inhibitor at the site of vascular injury. HCII may play a relatively minor role as an antithrombin and possibly only after injury.

Animals↗
PubMed1999

A massive epidemic of multidrug-resistant typhoid fever in Tajikistan associated with consumption of municipal water.

From 1 January through 30 June 1997, 8901 cases of typhoid fever and 95 associated deaths were reported in Dushanbe, Tajikistan. Of 29 Salmonella serotype Typhi isolates tested, 27 (93%) were resistant to ampicillin, chloramphenicol, nalidixic acid, streptomycin, sulfisoxazole, tetracycline, and trimethoprim-sulfamethoxazole. In a case-control study of 45 patients and 123 controls, Salmonella Typhi infection was associated with drinking unboiled water (matched odds ratio, 7; 95% confidence interval, 3-24; P<.001). Of tap water samples, 97% showed fecal coliform contamination (mean level, 175 cfu/100 mL). Samples taken from water treatment plants revealed that fecal coliform contamination occurred both before and after treatment. Lack of chlorination, equipment failure, and back-siphonage in the water distribution system led to contamination of drinking water. After chlorination and coagulation were begun at the treatment plants and a water conservation campaign was initiated to improve water pressure, the incidence of typhoid fever declined dramatically.

Case-Control Studies↗
PubMed1999

The preoperatively normal bile duct does not dilate after cholecystectomy: results of a five year study.

BACKGROUND: The common hepatic duct (CHD) is commonly believed to dilate after cholecystectomy but previous studies have either not measured CHD diameter preoperatively or the follow up period is short. AIMS: To measure CHD diameter before and after cholecystectomy. METHODS: Patients undergoing (open) cholecystectomy and operative cholangiography had ultrasonographic measurement of CHD diameter before, and three and six months, and one and five years after cholecystectomy. The normal duct diameter was considered to be 5 mm or less, with an observer error of +/-1 mm. RESULTS: Fifty nine patients with normal diameter ducts were studied. The majority (more than 95%) of patients did not have a dilatation of the CHD beyond 6 mm after cholecystectomy. The CHD appeared to increase as well as decrease with an overall trend towards a minor increase at five years. This was not statistically significant if the margin of error of 1 mm was taken into account. CONCLUSION: A preoperatively normal CHD does not dilate after cholecystectomy and may require further investigation in symptomatic patients.

Adult↗
PubMed1999

Two by two hour creatinine clearance--repeatable and valid.

AIM: The purpose of this study was to determine the repeatability and validity of 2 x 2 hour creatinine clearance, and the validity of creatinine clearances estimated by equations. PATIENTS AND METHODS: In 30 patients two 2 x 2 h and two 24-h creatinine clearances were performed on consecutive days. In addition, creatinine clearances estimated by 4 different equations were calculated. Two by two hour creatinine clearance provided a measurement of GFR as valid as 24-h creatinine clearance. RESULTS: We found, that 2 x 2 h creatinine clearance was well repeatable with a mean difference between 2 repeated measurements of 0.8 ml/min and low coefficients of repeatability of 14.5 ml/min. The validity of 2 x 2 h creatinine clearance, assessed by the mean difference between 2 x 2 and 24-h creatinine clearances, was 1.2 ml/min with tight 95% limits of agreement with a range from -8.1 to 10.5 ml/min. This high degree of repeatability and validity was present over the entire range of renal function (6-141 ml/min). As 2 x 2 h creatinine clearance is more simple and rapid than 24-h creatinine clearance, results are obtained on the same day and easy, but repeatable and valid day-to-day monitoring of renal function is possible. In addition, the two times two hour clearances allow for quality control. In contrast, estimated creatinine clearances show only poor validity. CONCLUSION: Because of the high degree of repeatability and validity, 2 x 2 h creatinine clearance may replace 24-h creatinine clearance as the standard method to determine renal function in clinical practice.

Adolescent↗
PubMed1999

Cytologic and DNA cytometric diagnosis and therapy monitoring of squamous cell carcinoma in situ and malignant melanoma of the cornea and conjunctiva.

OBJECTIVE: To investigate the diagnostic accuracy of exfoliative cytology of the cornea and conjunctiva and DNA image cytometry for quality control and monitoring of therapy for malignant neoplasms. STUDY DESIGN: Conjunctival or corneal smears from six cases clinically suspicious for malignant melanomas and eight suspicious for carcinomas in situ were investigated. Smears from 18 cases clinically nonsuspicious for neoplastic diseases served as negative controls. Repeated smears were obtained during and after local mitomycin C (MMC) therapy. RESULTS: In none of 18 nonsuspicious cases, cytology revealed abnormal cells. DNA cytometry showed nonaneuploidy in all of these. All smears from patients with histologically proven malignant melanomas (MM) and squamous cell carcinomas in situ revealed abnormal cells. Image cytometry demonstrated DNA aneuploidy in 66.6% of patients with MM and 80% with carcinoma. Sensitivity of cytology thus was 100% for both MM and carcinoma; specificity also was 100%. DNA measurements after MMC therapy revealed euploid polyploidization of nonneoplastic squamous cells. DNA cytometry provided an objective identification of tumor cell regression. CONCLUSION: Cytologic examination of corneal and conjunctival smears is a noninvasive tool with high diagnostic accuracy for detection of epithelial neoplasms. DNA image cytometry can serve for quality control and for objective monitoring of the effect of local chemotherapy.

Aneuploidy↗
PubMed1999

The procoagulant state of the VX-2 tumor in rabbit lung in vivo--relative accumulation of fibrinogen, prothrombin, plasminogen, antithrombin and heparin cofactor II within the tumor.

During their growth, many malignant solid tumors elicit a hemostatic response in the host. In this report, the fluxes of various rabbit plasma hemostatic proteins into pulmonary VX-2 tumors have been measured in vivo. VX-2 cells were contained within a small rabbit plasma clot which was injected intravenously into rabbits. At 28 d, each rabbit was injected intravenously with two radiolabeled (131I, 125I) proteins selected from fibrinogen, prothrombin, antithrombin-alpha, heparin cofactor II, or plasminogen-I or -II. After allowing the labeled proteins to circulate for 10-200 min, each rabbit was perfused with Krebs-Henseleit solution and the lungs excised. Solid tumors were isolated, weighed and measured for radioactivity content. A mean of 14 tumors/pair of lungs with a mean tumor weight of 0.3 g was obtained. Radioactivity per g of tumor was related to radioactivity/ml of blood at exsanguination for each protein at each time interval. Maximum flux rates were calculated (as pmol/g of tumor/min): Fibrinogen, 65.0; prothrombin, 53.0; antithrombin-alpha, 24.1; HCII, 17.2; plasminogen-II, 5.0; and plasminogen-I, 3.2. Using immunocytochemical staining, fibrin(ogen) was distributed heterogeneously within the VX-2 tumor, appearing largely in the perinodular region and in the necrotic core. From the net fluxes of these proteins, the profile of chronic hemostasis associated with the VX-2 tumor was shown to differ markedly from the hemostatic response that occurs after an acute vascular injury.

Animals↗
PubMed1998

Auditory afterimage: tonotopic representation in the auditory cortex.

The auditory afterimage is a sensation which occurs for several seconds after the exciting acoustic signal has been switched off, and which roughly corresponds to the inverse of the spectrum of the exciting signal. In contrast to the well-known visual afterimage, the physiological mechanism generating the auditory afterimage has been questionable so far. Neuromagnetic source imaging revealed that the source of cortical neural activity which coincides with the sensation of the afterimage is located in the auditory cortex and exhibits a tonotopic organization similar to that of the sustained response which occurs during continuous presentation of an acoustic stimulus. It is concluded that the neural processes leading to the generation of the two phenomena -sustained response and auditory afterimage - are similar.

Acoustic Stimulation↗
PubMed1998

Increased auditory cortical representation in musicians.

Acoustic stimuli are processed throughout the auditory projection pathway, including the neocortex, by neurons that are aggregated into 'tonotopic' maps according to their specific frequency tunings. Research on animals has shown that tonotopic representations are not statically fixed in the adult organism but can reorganize after damage to the cochlea or after training the intact subject to discriminate between auditory stimuli. Here we used functional magnetic source imaging (single dipole model) to measure cortical representations in highly skilled musicians. Dipole moments for piano tones, but not for pure tones of similar fundamental frequency (matched in loudness), were found to be enlarged by about 25% in musicians compared with control subjects who had never played an instrument. Enlargement was correlated with the age at which musicians began to practise and did not differ between musicians with absolute or relative pitch. These results, when interpreted with evidence for modified somatosensory representations of the fingering digits in skilled violinists, suggest that use-dependent functional reorganization extends across the sensory cortices to reflect the pattern of sensory input processed by the subject during development of musical skill.

Adult↗