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Biomedical subjects

J Anderson

Publications and source records attributed to J Anderson.

At least 451 records · Page 25Linked to original sources

Cytomegalovirus antibody detection in blood donors and mothers of very low birth weight neonates by using three serologic methods.

We compared three serologic methods for cytomegalovirus (CMV) antibody detection and determined the CMV antibody seroprevalence of blood donors and mothers of very low birth weight (less than 1250 g) neonates in the Greater Hartford region. CMV serology was determined for 577 healthy blood donors as well as for 147 mothers of premature infants. Plasma from blood donors and sera from mothers were tested by either latex agglutination (LA) or by an immunofluorescent antibody assay (IFA), and results were compared with those from an enzyme-linked immunosorbent assay (ELISA). Sensitivity and specificity for LA to ELISA were significantly better than for IFA to ELISA [sensitivity 79/81 (97%) vs 171/202 (85%), and specificity 90/94 (96%) vs 257/347 (74%), p less than 0.01]. These differences remained whether plasma or sera were tested. Borderline values explained only two (33%) of six LA-ELISA as well as only 70 (58%) of 121 IFA-ELISA discordance. CMV seroprevalence rate for the donor blood population was 38%, and for the mothers was 53%. The LA assay is superior to the IFA assay for CMV screening of blood donors and maternal populations.

Antibodies, Viral↗

Correlates of physician utilization of physical therapy.

A survey of 200 physicians explored the relationship between their beliefs in the efficacy of physical therapy (PT) and their use of PT for their patients with cerebral palsy (CP). Results show that utilization of PT is related to physicians' use of PT in general and is inversely related to the percentage of CP in physicians' patient loads, but is not related to their opinions of the value of PT services.

Attitude of Health Personnel↗

Dementia in Melton Mowbray--a validation of earlier findings.

In 1981 a survey of elderly persons aged 75 years and over who belonged to a general practice in Melton Mowbray, Leicestershire found a prevalence of moderate cognitive impairment of 4.7%. The criterion which determined the impairment was a score of 7 or under on the CAPE Information/Orientation (IO) sub-test. The prevalence rate has been considered to be much lower than in some key studies, notably the 13% reported in 1970 from Newcastle upon Tyne. Although rates based on cognitive scales are likely to give different results from those based on diagnostic assessment, the suggestion is that the IO sub-test is an insensitive screening instrument for dementia. Using results on the sensitivity and specificity of the CAPE IO sub-test (cut-point 8/9) to detect moderate or severe dementia as defined by clinical diagnosis using the Cambridge Mental Disorders of the Elderly (CAMDEX) schedule, the adjusted prevalence rates of moderate or severe dementia were found to be 3.4% in 1981 and 5.2% in 1988. Both these figures were lower than the observed rates scoring 8 or under on the IO sub-test, confirming that insensitivity of the IO sub-test was not the reason for the supposed low rate in Melton Mowbray in 1981. As the prevalence of dementia in those aged 75 years and over has been reported by other studies to range from 3% to 24%, it is more likely that high rates are due to screening instruments with low specificity.

Aged↗

Misclassification of dementia by the mini-mental state examination--are education and social class the only factors?

The 1988 Melton Mowbray Study of the Elderly comprised an initial screen with the Mini-Mental State Examination (MMSE) followed by a detailed clinical assessment using the Cambridge Mental Disorders of the Elderly Examination (CAMDEX) for all those scoring 21 and under on the MMSE, a one in two sample of those scoring 22 or 23 and a one in ten of the remainder. A total of 1579 subjects completed the initial screen with 438 subjects undergoing the CAMDEX assessment. Analysis of those subjects who were found to be free of dementia at the clinical assessment (n = 155) demonstrated that the very elderly, those from the manual social classes and subjects with visual impairments had an increased chance of being misclassified as demented by the MMSE. Low educational level and various measures of physical disability also showed a tendency to result in misclassification as falsely positive by the MMSE when viewed alone but these effects appeared to be due solely to their association with extreme age and/or manual social class.

Activities of Daily Living↗

DSM-III disorders from age 11 to age 15 years.

Although research into the continuity of disorder from childhood to adolescence is sparse, results from both longitudinal and cross sectional studies suggest that the prevalence of disorder increases for girls but may remain more stable for boys. In this paper, the methodologies of two assessment phases of the Dunedin longitudinal study have been equated to estimate the continuity of DSM-III disorder from ages 11 to 15. Although the overall prevalence of disorder doubled between the ages, this was primarily because of an increase in nonaggressive conduct disorder and major depressive episode. The sex ratios in disorder had largely reversed from a male predominance at 11 to a female predominance at 15. In terms of persistence, over 40% of those with disorder at age 11 were also identified at age 15. However, over 80% of those identified with disorder at 15 did not have a history of disorder at 11. Significant sex differences were also found in the continuity of internalizing and externalizing disorders, with externalizing disorders showing more continuity for boys, and internalizing for girls. Logistic regression models were employed to evaluate the roles family background, academic and social competence, and early histories of behavior problems may play in the determination of disorder continuity.

Adolescent↗

Cellular automaton model of ventricular fibrillation.

A theoretical analysis of ventricular fibrillation and the requirements for fibrillation are performed using a discrete element neighborhood (cellular automaton) model of ventricular conduction. The model is configured as a 2500 element rectangular grid on the surface of a cylinder. It is shown that vulnerability to fibrillation is strongly influenced by excited state duration which primarily determines the nature of the underlying reentry activity. As excited state duration is increased fibrillation changes from "coarse" macroreentrant activity to the more chaotic "fine" fibrillation sustained by multiple wavelets of microreentry. In general, defibrillation is achieved by a stimulus strong enough to depolarize the majority of relative refractory elements. The threshold for defibrillation is increased for the more irregular microreentrant fibrillation.

Computer Simulation↗

Immunophenotypic subclassification of chronic lymphocytic leukaemia (CLL).

To determine the significance of the immunophenotypic heterogeneity of B-cell chronic lymphocytic leukaemia (CLL), surface immunoglobulins (SIgs), mouse rosette assays (MR), and a panel of monoclonal antibodies for B cells, T cells and myeloid cells were performed on peripheral blood samples from 61 newly diagnosed cases. Four groups were observed: group I (SIg+, MR+, CD19/20+, CD5+, T antigen (Ag)-; 27 cases); group II (SIg+, MR+, CD19/20+, CD5+, T Ag+; 17 cases); group III (SIg+, MR+ CD19/20+, CD5-, T AG-; 12 cases); and group IV (SIg-, MR+, CD19/20+, Cd5+, T Ag-; 5 cases). Groups were compared according to French-American-British Cooperative Group subtypes, clinical and laboratory features, Rai staging, and survival. Typical CLL morphology (greater than 90% small lymphocytes) was present in 20/20 (100%) of group I cases and 23/27 (85%) group II, III and IV cases (P = 0.09). Expression of a myeloid antigen was seen in 5/27 group I cases (18%) and 1/16 group II cases (6%), but was not predictive of survival (P = 0.36). The CD5- group III had a lower haemoglobin level (P less than 0.0001), higher Rai stage (P less than 0.002), and poorer survival at 5 years (P less than 0.02) than the other groups. We conclude that at least four distinct immunophenotypic subgroups of B-cell CLL can be determined. Expression of myeloid or T-cell antigens does not appear to predict for patient survival; however, lack of CD5 antigen may be associated with more advanced stage of disease and poor patient survival.

Adult↗

Hypothesis for the control of clotting factor VIII inhibitory antibodies by decreasing potency of helper T-cell-recognized epitopes in factor VIII.

The study of the immunobiology of FVIII inhibitors may lead to new therapies for this potentially severe complication of haemophilia A and to new principles for the use of therapeutic proteins. In order to characterize the idiotype-anti-idiotype networks regulating FVIII inhibitors, we developed rabbit anti-idiotypic sera to 7 murine inhibitors and found at least 12 independent FVIII loci to which inhibitors could be raised. Rabbit antisera to the FVIII peptide, Ser1687-Thr1695, characterized one functional site to which about 46% of patients' inhibitor sera reacted. The multiplicity of inhibitor-recognized epitopes in FVIII makes it impractical, at the present time, to develop clinically useful specific anti-idiotypic therapies for FVIII inhibitors. Alternatively, one might induce genomic mutations in recombinant FVIII molecules to decrease immunogenicity of epitopes recognized by T helper cells. Methods to design such altered therapeutic proteins are presented, based on changing the longitudinal hydrophobic strip-of-helix which is in or near many T-cell-presented epitopes.

Animals↗

Central venous thrombophlebitis diagnosed by computerized tomography scanning.

A case is described in which computerized tomography scanning aided in a prompt diagnosis and assessment of an intravenous catheter-induced septic thrombus. Computerized tomography scanning detected gas bubbles within the thrombus, which extended from the right subclavian vein into the superior vena cava, and retrograde propagation of the thrombus into the right internal jugular vein. Computerized tomography scanning also helped in the assessment of the amount of deep tissue swelling present and the competence of the upper respiratory tract.

Adult↗

Western blotting analysis in patients with MS using human brain vessels as antigen.

Serum samples from patients suffering from multiple sclerosis, other neurological diseases and normal controls were screened by "western blotting" for antibody directed against proteins of human brain vessels purified from a post mortem brain. A small number of sera contained autoantibodies against some of the proteins of the brain vessels, particularly in patients suffering from MS, epilepsy and migraine. The significance of these results is discussed.

Antibody Specificity↗

Antipneumocystis activity of water-soluble lipopeptide L-693,989 in rats.

Water-soluble lipopeptide L-693,989 was evaluated for its antipneumocystis activity in rats. Rats from colonies with latent Pneumocystis carinii infections were immunosuppressed with dexamethasone for 6 weeks to facilitate the development of acute P. carinii pneumonia (PCP). After 6 weeks, the rats were maintained on dexamethasone and were treated twice daily for 4 days with various concentrations of L-693,989. At a dose of 0.15 mg/kg of body weight, the compound effectively eliminated 90% of the cysts in 4 days. Trophozoite forms of P. carinii were still present in these animals, as determined by using a P. carinii-specific DNA probe. A 3-week therapy study showed that the trophozoite load did not expand during treatment and that the trophozoites already present at the initiation of therapy appeared to persist. This may be a consequence of the stage specificity of the compound for cyst development and the severe immunosuppressive effects of dexamethasone on rats. When evaluated as a daily parenteral prophylactic agent, L-693,989 was effective in preventing the development of both P. carinii cysts and trophozoites, demonstrating its potential for use in prophylaxis and implying that the cyst stage of P. carinii is an obligatory step in trophozoite multiplication. The foamy exudate commonly associated with P. carinii infections was absent in the lungs of rats on prophylaxis. The compound was also evaluated via oral administration and was found to have a 90% effective dose of 32 mg/kg for therapy of acute infections and 5 mg/kg for daily prophylaxis.

Animals↗

Effect of pulsatile flow on microvascular resistance in adult rabbit lungs.

We have determined the effect of pulsatile flow on segmental vascular resistance in lungs from 29 adult rabbits. In group I (n = 4), II (n = 8), and III (n = 8) lungs were isolated. In group IV (n = 9) rabbits were anesthetized, their chests were opened, and lungs were studied in vivo. Group I and II lungs had steady-flow perfusion: group I with intact vasotonus and group II with papaverine treatment. Group III lungs (papaverine treated) were perfused for two consecutive 45-min periods with steady and pulsatile flow. In all isolated lungs and in lungs of five anesthetized rabbits, we measured pressures in subpleural 20- to 50-microns-diam arterioles and venules by use of the micropipette servo-nulling method. Measurement of distribution of blood flow in lungs of four anesthetized rabbits by use of radiolabeled microspheres revealed no abnormality of blood flow to the micropunctured lobe. We found that total and segmental vascular resistances were similar in group I and II lungs, with microvessels representing 55% of total resistance. In group III lungs, total resistance was 30% lower during pulsatile flow than during steady flow because of a lower microvascular resistance. Lungs in vivo (group IV) had a significantly lower total vascular resistance than isolated lungs and had a low fractional resistance in microvessels (approximately 28%). We conclude that, in isolated perfused adult rabbit lungs, vascular resistance is very high, particularly in the microvascular segment, and that pulsatile flow decreases microvascular resistance.

Animals↗

Regional differences in interstitial fluid albumin concentration in edematous lamb lungs.

We have determined regional lung interstitial fluid albumin concentration in lambs with hydrostatic pulmonary edema and correlated it with lung lymph and plasma albumin concentrations. In anesthetized lambs, we raised left atrial pressure to 25-30 cmH2O by obstructing the aorta and volume overloading the lambs with infusions of Ringer lactate solution (group I, n = 10) or sheep's blood (group II, n = 9). We measured lung lymph flow and concentrations of total protein and albumin in plasma and lymph. With micropipettes we also collected interstitial fluid from interlobular septal pools and peribronchial, periarterial, and perivenous liquid cuffs near the hilum for measurement of albumin concentration by the gel immunoelectrophoresis method. In both groups, lung lymph flow increased with left atrial hypertension, and the ratio of lymph to plasma protein concentration fell. For group I, plasma and lymph albumin concentrations during the phase of hydrostatic edema were 1.97 +/- 0.49 and 1.15 +/- 0.36, respectively; for group II, they were 3.77 +/- 0.42 and 2.43 +/- 0.39 g/dl, respectively. Lung wet-to-dry weight ratio averaged 6.0 in both groups. Albumin concentration was always lower in interstitial fluid than in plasma. In both groups, albumin concentration was similar in periarterial and peribronchial fluid cuffs (group I 1.19 +/- 0.6 and 1.36 +/- 0.79 g/dl, respectively; group II 2.87 +/- 1.05 and 2.33 +/- 0.58 g/dl, respectively) but was always greater than that in perivenous and interlobular septal pools (group I 0.61 +/- 0.21 and 0.67 +/- 0.23 g/dl, respectively; group II 1.76 +/- 0.49 and 1.55 +/- 0.52 g/dl, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

Incidence of dementia in Melton Mowbray: a proposed study and its problems.

This paper describes a proposed study to investigate the incidence of dementia in a population of over 75 year olds in Melton Mowbray, Leicestershire, England. The study population (n = 438) underwent a detailed psychiatric assessment using the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) as the second stage of a survey of the physical and mental health of the elderly begun in 1988. The CAMDEX assessment and the initial screening interview included information on the majority of potential risk factors for Alzheimer's disease and vascular dementias. Together with measures of incidence and risk factors, the proposed study aims to assess the effect of the decline in mental function of the elderly, on carers, family and health services and to suggest where improvements in planning and delivery of services might be made. A number of problems arise, particularly relevant for studies of the elderly, due to the frequent follow-ups necessary for incidence studies and these are discussed.

Aged↗

Glutathione localization and distribution after intratracheal instillation. Implications for treatment.

To gain insight into how glutathione given directly into the lung protects fasted mice against hyperoxic lung damage and to provide a framework for developing treatment strategies in patients, we determined the lung distribution and retention of intratracheally administered glutathione (GSH) and its fate after leaving the lung. Mice received an intratracheal injection of [3H]GSH with or without cold GSH and with or without liposomes. The distribution of the 3H label was equal in both lungs, but the left lung had a higher concentration because of its smaller size. The 3H label was cleared rapidly from the lung: only 1% remained at 24 h, and more than 50% of the label at that time was no longer attached to the GSH. Administration of GSH with liposomes increased the retention of GSH by 20 to 50%, but the amount remaining at 24 h was still only 1%. The increase associated with the liposomes was due to enhanced retention of the GSH encapsulated in the liposomes, not the much larger amount present free in the GSH-liposome mixture. Fasting and exposure to 100% oxygen had little effect on GSH retention. Some of the 3H label leaving the lung was excreted by the kidneys, a small amount was retained in the liver, and a large amount accumulated in the blood. Of the amount in the blood, about 60% was in red blood cells (RBC) and the rest in plasma. Much of the 3H label in RBC and lung at 24 h was no longer attached to the GSH, whereas most in the plasma and liver was.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Oxygen-induced lung damage. Relationship to lung mitochondrial glutathione levels.

Several reports suggest there is a relationship between lung glutathione (GSH) levels and susceptibility to oxygen-induced lung damage. However, studies of other organs and cells indicate that a better relationship may exist between mitochondrial GSH levels and oxidant damage. We determined whether there is a similar relationship in the lung using a well-characterized mouse model and a series of interventions that alter lung GSH levels and susceptibility to oxygen-induced lung damage. Mice were fasted or given buthionine sulfoximine (BSO, 20 mM), which reduce total lung GSH levels and increase susceptibility to oxygen-induced lung damage. Mice were also given glutathione monoethyl ester (GSH-ME) intraperitoneally (5 or 10 mM/kg/day for 2 days) or intratracheally (0.2 mM once) in an attempt to increase lung GSH levels. Fasting for up to 3 days and the administration of BSO for 7 to 10 days decreased total lung GSH levels (p < 0.001 for both) but not lung mitochondrial GSH levels. Intraperitoneal administration of GSH-ME increased mitochondrial GSH levels (p < 0.001 in both fed and fasted mice), but it had little effect on total lung GSH levels and no effect on susceptibility to oxygen-induced lung damage. Exposure to 100% oxygen increased mitochondrial GSH levels in both the fed and fasted mice to nearly the same extent (p < 0.001 for both). However, the fasted mice had lower total lung GSH levels compared with the fed mice (p < 0.05) and increased susceptibility to 100% oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Competitive ELISA for serodiagnosis of bluetongue: evaluation of group-specific monoclonal antibodies and expressed VP7 antigen.

The performance of 2 competitive enzyme-linked immunosorbent assays (C-ELISA) was compared with the reference C-ELISA I for the detection of antibodies to bluetongue virus (BTV). One of the assays (C-ELISA II) used a group-specific monoclonal antibody (MAb) to BTV, obtained from the American Type Culture Collection (8A3B-6) and tissue culture (TC)-derived BTV antigen (Ag), and the other assay (C-ELISA III) used BTV core protein VP7 (expressed in yeast) and the reference MAb (Pirbright Laboratory, 3-17-A3). Test sera were obtained by sequential blood samples from 22 calves, each inoculated with a different serotype (T) of BTV (South African [SA] T-1-T-16 and T-18-T-20 and USA T-11, T-13, and T-17). Sera were also obtained from 4 calves and 4 sheep inoculated with USA BTV T-10 and from several groups of calves exposed to single or multiple doses of epizootic hemorrhagic disease virus (EHDV) T-1-T-4 grown in TC (BHK-21) or suckling mouse brain (SMB). A total of 618 bovine and ovine field sera collected from BT-free and BT-endemic areas were also tested. The C-ELISA III was more sensitive than the C-ELISA II in the detection of anti-BTV antibody in sera from cattle and sheep early after infection with BTV. Seroconversion was demonstrated by the 3 C-ELISAs in all animals inoculated with BTV by 20 days postinfection (DPI), except in calves that received SA T-3 or USA T-13, which became positive at 40 DPI.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Aluminium administered in drinking water but not in the diet influences biopterin metabolism in the rodent.

To investigate the neurotoxic effects of aluminium (Al) Al was administered: 1) in the diet of the rat (30 mg Al/kg body weight for 6 weeks); 2) as a suspension of aluminium acetate in drinking water of the rat for 3 months and 3) in a long-term study in the mouse in which aluminosilicates were incorporated into a pelleted diet (1035 mg/kg of food over 23 months). In the latter treatment, increased Al was combined with a reduction in calcium and magnesium; a treatment designed to increase absorption of Al into the body. Administration of Al in the drinking water significantly reduced total brain biopterins and BH4 synthesis. However, no significant affect of Al in the diet on total biopterins or BH4 synthesis was found either in the rat or in the long-term study in the mouse. In addition, in the mouse no significant effects of the Al diet on levels of noradrenaline, serotonin, dopamine, 5-HIAA or CAT could be demonstrated. Hence, the occurrence of brain alterations may depend on the Al species present and the method of administration. Al salts in drinking water may increase brain tissue levels compared with the administration of a more insoluble species. Since alterations in biopterin metabolism are also a feature of Alzheimer's disease (AD) these results support the hypothesis that Al in the water supply may be a factor in AD.

Aluminum↗