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Biomedical subjects

J Ward

Publications and source records attributed to J Ward.

At least 91 records · Page 5Linked to original sources
PubMed2000

Hepatocellular carcinoma in the cirrhotic liver: double-contrast MR imaging for diagnosis.

PURPOSE: To measure the sensitivity and accuracy of double-contrast magnetic resonance (MR) imaging for the diagnosis of hepatocellular carcinoma (HCC) in the cirrhotic liver. MATERIALS AND METHODS: Twenty-seven patients with MR features of dysplastic nodules and/or HCC were examined. T2-weighted spin-echo and T1-weighted gradient-echo imaging was performed before and after superparamagnetic iron oxide (SPIO) administration and immediately followed by T1-weighted gradient-echo imaging at 10, 40, and 120 seconds after bolus injection of a gadolinium-based contrast material. Nonenhanced, nonenhanced plus SPIO-enhanced, and nonenhanced plus SPIO-enhanced plus gadolinium-enhanced images were reviewed. Alternative-free response receiver operating characteristic (ROC) methodology was used to analyze the results, which were correlated with histopathologic findings after transplantation in 15 patients and at biopsy in 12. Lesions visualized with all three techniques were characterized as a dysplastic nodule or HCC, and ROC analysis was performed. RESULTS: For all observers, SPIO-enhanced MR imaging (mean accuracy, 0.76) was more accurate than nonenhanced MR imaging (mean accuracy, 0.64) (P <.04), and double-contrast MR imaging (mean accuracy, 0.86) was more accurate than SPIO-enhanced imaging (P <.05). Both types of lesions were correctly characterized with all three techniques, although observer confidence for lesion characterization was greatest with double-contrast MR imaging. CONCLUSION: Double-contrast MR imaging significantly improves the diagnosis of HCC compared with SPIO-enhanced and nonenhanced imaging (P <.01).

Adult↗
PubMed2000

Transepithelial resistance can be regulated by the intestinal brush-border Na(+)/H(+) exchanger NHE3.

Initiation of intestinal Na(+)-glucose cotransport results in transient cell swelling and sustained increases in tight junction permeability. Since Na(+)/H(+) exchange has been implicated in volume regulation after physiological cell swelling, we hypothesized that Na(+)/H(+) exchange might also be required for Na(+)-glucose cotransport-dependent tight junction regulation. In Caco-2 monolayers with active Na(+)-glucose cotransport, inhibition of Na(+)/H(+) exchange with 200 microM 5-(N,N-dimethyl)- amiloride induced 36 +/- 2% increases in transepithelial resistance (TER). Evaluation using multiple Na(+)/H(+) exchange inhibitors showed that inhibition of the Na(+)/H(+) exchanger 3 (NHE3) isoform was most closely related to TER increases. TER increases due to NHE3 inhibition were related to cytoplasmic acidification because cytoplasmic alkalinization with 5 mM NH(4)Cl prevented both cytoplasmic acidification and TER increases. However, NHE3 inhibition did not affect TER when Na(+)-glucose cotransport was inhibited. Myosin II regulatory light chain (MLC) phosphorylation decreased up to 43 +/- 5% after inhibition of Na(+)/H(+) exchange, similar to previous studies that associate decreased MLC phosphorylation with increased TER after inhibition of Na(+)-glucose cotransport. However, NHE3 inhibitors did not diminish Na(+)-glucose cotransport. These data demonstrate that inhibition of NHE3 results in decreased MLC phosphorylation and increased TER and suggest that NHE3 may participate in the signaling pathway of Na(+)-glucose cotransport-dependent tight junction regulation.

Acids↗
PubMed2000

Intrathecal baclofen for management of spastic cerebral palsy: multicenter trial.

Intrathecal baclofen infusion has demonstrated effectiveness in decreasing spasticity of spinal origin. Oral antispasticity medication is minimally effective or not well tolerated in cerebral palsy. This study assessed the effectiveness of intrathecal baclofen in reducing spasticity in cerebral palsy. Candidates were screened by randomized, double-blind, intrathecal injections of baclofen and placebo. Responders were defined as those who experienced an average reduction of 1.0 in the lower extremities on the Ashworth Scale for spasticity. Responders received intrathecal baclofen via the SynchroMed System and were followed for up to 43 months. Fifty-one patients completed screening and 44 entered open-label trials. Lower-extremity spasticity decreased from an average baseline score of 3.64 to 1.90 at 39 months. A decrease in upper extremity spasticity was evidenced over the same study period. Forty-two patients reported adverse events. Most common reports were hypotonia, seizures (no new onset), somnolence, and nausea or vomiting. Fifty-nine percent of the patients experienced procedural or system-related events. Spasticity in patients with cerebral palsy can be treated effectively by continuous intrathecal baclofen. Adverse events, although common, were manageable.

Adolescent↗
PubMed2000

Introduction of a new NHS electric-powered indoor/outdoor chair (EPIOC) service: benefits, risks and implications for prescribers.

OBJECTIVE: To determine problems associated with electric-powered indoor/outdoor wheelchairs (EPIOCs) and the benefits perceived by their users. DESIGN: Hospital-based cohort study of all patients referred over a 19-month period. SETTING: Regional Wheelchair Service for North West London serving nine district wheelchair services. SUBJECTS: Of the 174 subjects referred, 10 withdrew their application or were found to be unsuitable at screening, 164 were assessed and 124 were prescribed chairs. One hundred and thirteen subjects were interviewed by telephone four months after provision of the chair. MAIN MEASURES: Demographic and diagnostic data; current chair usage; self-reported accidents and component faults were compared with those recorded in the unit records; new activities embarked on since delivery; and benefits reported for main carers. RESULTS: Seventeen 'mishaps' were reported by 15 users including tipping from chairs (6) and falls during transfers (3). Three probably reflected mechanical failure. Component failure was found in 39% of EPIOCs, mostly affecting control boxes (22), frames (10) and footrests (10). New activities were undertaken by 56 (50%) users, usually shopping and visits to friends/family. Eighty-five per cent of users felt that the chairs made life easier for their informal carers through increased independence, reducing transfers and reduced need for 'pushing'. CONCLUSIONS: The component failures and self-reported accidents (some potentially dangerous) have implications for the NHS, manufacturers, prescribers and users. EPIOCs enhance the independence of severely physically disabled individuals in the community and assist carers by lessening dependence and enhancing social interaction. This study demonstrated the need for follow-up of EPIOC users and chairs.

Accidents↗
PubMed2000

Three nursing home outbreaks of Norwalk-like virus in Brisbane in 1999.

We report on three nursing home outbreaks of gastroenteritis in Brisbane in 1999. The presence of Norwalk-like virus (NLV) genogroup 2 was demonstrated by reverse transcription polymerase chain reaction (RT-PCR) in all three outbreaks. Common findings of these investigations were rapid spread of the illness within the institutions and difficulties in identifying a common source. Nursing home populations are vulnerable and it is important for each institution to have infection control policies in place so outbreaks can be managed promptly. This includes the exclusion of ill staff for 48 to 72 hours after recovery from illness. Genogrouping of NLV by RT-PCR can take several days so control measures will generally have to be instituted before results become available.

Adult↗
PubMed2000

Enhanced surveillance for meningococcal disease in Queensland in 1999.

Enhanced surveillance of invasive meningococcal disease commenced in Queensland in 1999. There were 93 cases, an incidence of 2.8/100,000 population. Most (87%) cases were laboratory confirmed, but 12 per cent were probable cases without laboratory confirmation. The highest age-specific attack rates were in the under 1, 1 to 4 and 15 to 24 year age groups. Most of the serologically characterised isolates were group B (70%), followed by group C (24%). There were 12 deaths, resulting in a case fatality rate of 13 per cent. Those who died were more likely to have group C than group B disease (OR 5.04, CI 1.05-25.14). Only 14 per cent of cases that saw a general practitioner (GP) prior to hospitalization received parenteral antibiotics, 23 per cent of the 35 cases referred to hospital by a GP received pre-hospital parenteral antibiotics and 33 per cent of cases were notified to health authorities within 24 hours of hospital admission. Thirty per cent were notified two or more days after hospitalization, delaying the start of public health action. Enhanced surveillance has demonstrated a need to promote the use of pre-hospital parenteral antibiotics by GPs and a need to encourage more timely reporting of cases to health authorities.

Adolescent↗
PubMed1999

Negative regulation of macrophage activation in response to IFN-gamma and lipopolysaccharide by the STK/RON receptor tyrosine kinase.

IFN-gamma primes macrophages for antimicrobial activity, increased killing of intracellular pathogens, and Ag processing and presentation to lymphocytes by cooperating with a second signal (provided by LPS or endogenous TNF-alpha) to promote increased proinflammatory cytokine production, NO production, and MHC class II expression. Macrophage-stimulating protein (MSP) suppresses NO production by activated peritoneal macrophages in vitro. Furthermore, targeted deletion of the receptor for MSP, stem cell-derived tyrosine kinase receptor (STK/RON), resulted in increased production of NO by activated macrophages both in vitro and in vivo. Here we demonstrate that expression of STK in RAW264.7 cells resulted in suppression of NO production following IFN-gamma+/- LPS stimulation in the presence of MSP, reflecting a decrease in the levels of inducible NO synthase (iNOS) mRNA and protein, which was confirmed by decreased trans-activation of an iNOS reporter. The iNOS expression is regulated by the coordinate activity of the inducible transcription factors STAT-1, IFN response factor-1, and NF-kappaB. The presence of the STK receptor did not significantly alter the expression of the IFN-gamma receptor, STAT1 phosphorylation, or the up-regulation of IFN response factor-1 expression following IFN-gamma stimulation. However, nuclear translocation of NF-kappaB following stimulation of RAW cells with IFN-gamma and LPS was reduced in the presence of the MSP/STK signaling pathway. These results suggest that the negative regulation of macrophage responses by MSP/STK occurs at least in part via inhibition of costimulatory signals, resulting in NF-kappaB activation, that cooperate with IFN-gamma to promote activation.

Animals↗
PubMed1999

Combined vaccination of Haemophilus influenzae type b conjugate and diphtheria-tetanus-pertussis containing acellular pertussis.

After the introduction of effective Haemophilus influenzae type b (Hib) conjugate vaccines, clinical practice has driven the development of combination vaccines comprising Hib conjugates with the infant diphtheria-tetanus-pertussis (DTP) vaccines. However, when such combinations contain an acellular pertussis component (Pa), the antibody response to Hib is lower than that with separate injections and doubts have been raised about their efficacy. We believe that such concerns are unwarranted, since the serological correlates of efficacy previously applied for Hib polysaccharide vaccines seem inappropriate for Hib conjugates. Furthermore, our own studies have shown that the lower antibody responses are not associated with impaired function of the antibodies induced, nor, and possibly more importantly, with the induction of immune memory against Hib. Therefore, with the proviso that careful clinical surveillance of Hib disease is maintained, we encourage the introduction of DTPa-Hib combinations to facilitate the inclusion of Hib into the already crowded childhood immunisation schedule.

Bacterial Capsules↗
PubMed1999

Heterotopic endochondrial ossification with mixed tumor formation in C3(1)/Tag transgenic mice is associated with elevated TGF-beta1 and BMP-2 expression.

Transgenic mice which express the simian virus 40 large T-antigen (Tag) under the regulatory control of the hormone responsive rat C3(1) gene develop unusual lesions of heterotopic bone growth associated with mixed tumor formation arising from eccrine sweat glands found only in the foot pads of mice, ischiocavernosus muscle adjacent to bulbourethral glands and occasionally the salivary and mammary glands. These lesions are very similar to mixed tumors arising in several types of human cancers. Based upon electron microscopic examination and immunocytochemical analyses of cellular differentiation markers, the mixed proliferative lesions in this transgenic mouse model begin with the Tag-induced proliferation of epithelial and myoepithelial cells. The proliferation of these two types of cells results in hyperplasia and adenomatous transformation of the epithelial component, whereas the proliferating myoepithelial cells undergo metaplasia to form chondrocytes which deposit extracellular matrix, including collagen fibers. Cartilage develops focally between areas of epithelial proliferation and subsequently ossifies through a process of endochondrial bone formation. The metaplasia of myoepithelial cells to chondrocytes appears to require the inductive interaction of factors produced by the closely associated proliferating epithelial cells, including members of the TGF-beta superfamily. We demonstrate that TGF-beta1 protein accumulates in the extracellular matrix of the lesions, whereas RNA in situ hybridization reveals that BMP-2, another strong inducer of heterotopic bone formation, is overexpressed by the proliferating epithelial cells during the development of ectopic bone. The formation of sarcomatous tumors within the mixed tumors appears to be androgen-dependent and more frequent in mice lacking a normal allele of p53. This process of cartilage and bone induction may mimic epithelial-mesenchymal interactions which occur during embryonic bone formation. These transgenic mice may provide new insights into the processes of ectopic endochondrial bone formation associated with mixed tumor formation and serve as a useful model for human heterotopic bone disease.

Actins↗
PubMed1999

Surveillance for AIDS-defining opportunistic illnesses, 1992-1997.

PROBLEM/CONDITION: Acquired immunodeficiency syndrome (AIDS)-defining opportunistic illnesses (OIs) are the major cause of morbidity and mortality among persons infected with human immunodeficiency virus (HIV). As a result of new treatments that reduce mortality for persons with AIDS, the number of persons living with AIDS is increasing, and the incidence of AIDS is decreasing. In 1997, an estimated 271,245 persons were living with AIDS in the United States and thus were at high risk for OIs. In 1997, an estimated 21,909 HIV-infected persons died with AIDS, nearly all as a result of OIs. REPORTING PERIOD COVERED: Aggregate data and trends for 1992-1997 were examined to determine a) the frequencies at which OIs occurred first; b) the incidence of OIs; c) the percentage of persons among those who have died who had had a given OI during their course of AIDS, and d) the frequency of prescriptions for antiretroviral therapy and prophylaxis for Pneumocystis carinii pneumonia (PCP) and for Mycobacterium avium complex disease (MAC). DESCRIPTION OF SYSTEM: Data were analyzed from the Adult/Adolescent Spectrum of HIV Disease (ASD) sentinel surveillance project, a prospective medical record review of HIV-infected persons aged > or = 13 years conducted in 11 U.S. cities. ASD data were standardized to national AIDS surveillance data for 1992-1997 by age; race; sex; country of birth; year of AIDS diagnosis; HIV exposure mode; and for incidence calculations, by CD4+ T-lymphocyte distribution. RESULTS: The incidence declined significantly for each of 15 of the 26 specific AIDS-defining OIs (p<0.05). PCP was the most common AIDS-defining OI to occur first (PCP was the first OI to occur for 36% of HIV-infected persons), the most common incident AIDS-defining OI (274 cases per 1000 person-years), and the most common AIDS-defining OI to have occurred during the course of AIDS (53% of persons who died with AIDS had PCP diagnosed at some time during their course of AIDS). Of persons with CD4+ T-lymphocyte counts <500 cells/microL, the number with prescriptions for triple combination therapy increased from zero in 1992 to 40% in 1997, and 80% of persons had a prescription for any antiretroviral therapy in 1997. Of persons with CD4+ T-lymphocyte counts <200 cells/microL, the percentage with prescriptions for PCP prophylaxis remained stable from 1992 through 1997 (range: 75% to 80%). Of persons with CD4+ T-lymphocyte counts <50 cells/microL, the percentage with prescriptions for MAC prophylaxis increased from 9% in 1992 to 44% in 1997. INTERPRETATIONS: The incidences of many OIs are decreasing primarily because of advances in HIV-related therapy. However, OIs are still occurring, especially when patients access care late during the course of disease. Even after accessing care, persons may develop OIs because of lack of prescription for prophylaxis, antiretroviral drug resistance, or poor adherence to therapy. During 1992-1997, most patients in need of PCP prophylaxis received a prescription for it; however, even in 1997, most patients in need of MAC prophylaxis did not receive a prescription for it. ACTIONS TAKEN: These surveillance data are used by persons involved with developing guidelines for preventing OIs to determine the importance of and trends in OIs and preventive therapy. CDC is developing population-based approaches for surveillance of HIV disease progression, OIs, and therapies with the goal of making these data available in more geographic areas to help assess public health and health-care programs.

AIDS-Related Opportunistic Infections↗
PubMed1999

Role of maintenance treatment in opioid dependence.

Methadone maintenance treatment (MMT) involves the daily administration of the oral opioid agonist methadone as a treatment for opioid dependence-a persistent disorder with a substantial risk of premature death. MMT improves health and reduces illicit heroin use, infectious-disease transmission, and overdose death. However, its effectiveness is compromised if low maintenance doses of methadone (<60 mg) are used and patients are pressured to become prematurely abstinent from methadone. Pregnancy and psychiatric comorbidity are not contraindications for MMT. As an alternative to MMT, other oral opioid agents (eg, naltrexone, buprenorphine) may increase patient choice and avoid some of the more unpleasant aspects of MMT. The public-health challenge for the future is to develop and continue to deliver safe and effective forms of opioid maintenance treatment to as many opioid-dependent individuals as can benefit from them.

Humans↗
PubMed1999

MR imaging of the liver and spleen: a comparison of the effects on signal intensity of two superparamagnetic iron oxide agents.

We compared the effects of two superparamagnetic iron oxide (SPIO) contrast agents, ferumoxides and SHU-555A, in MR imaging of the liver and spleen. Thirty-six patients with known malignant lesions of the liver underwent T2W turbo spin-echo (TSE) and T1WGRE FLASH opposed-phase imaging before and after SPIO injection on a 1.0 T MR system. Post-ferumoxides images were obtained in 18 patients 90 min after infusion of 15 micrommol Fe/kg of the agent. In 18 other patients SHU-555A was administered as a rapid bolus at a dose of 7.0-12.9 micrommol Fe/kg. T1WGRE FLASH images were obtained immediately, 30 s and 480 s and T2WTSE images 10 min after injection. Signal intensity of the liver, spleen, and malignant liver lesions before and after SPIO was measured with operator-defined regions of interest. The effects of ferumoxides and SHU-555A were measured as the percentage signal intensity change (PSIC) and in the malignant liver lesions additionally as changes in lesion-to-liver contrast-to-noise ratio (deltaDCNR). On T2W TSE images, there was no significant difference between the two agents in signal loss of liver parenchyma (p > 0.05). The signal loss in the spleen produced by ferumoxides was greater than with SHU-555A (p < 0.05). Both SPIO agents produced a significant increase in the CNR of malignant liver lesions. Delta CNR was slightly greater with ferumoxides than with SHU-555A (p < 0.05). On T1WGRE FLASH images, a slight decrease of liver SI induced by both agents was found on late post-SPIO images. No significant difference of liver PSIC between the two SPIO agents was noted on T1W images. The SI of spleen was significantly increased with both agents on T1W images and no difference in PSIC of spleen was noted (p > 0.05). The T1 and T2 effects produced by ferumoxides and SHU-555A were comparable in the liver although ferumoxides produced a stronger T2 effect in the spleen.

Contrast Media↗
PubMed1999

Uteroglobin is essential in preventing immunoglobulin A nephropathy in mice.

The molecular mechanism(s) of immunoglobulin A (IgA) nephropathy, the most common primary renal glomerular disease worldwide, is unknown. Its pathologic features include hematuria, high levels of circulating IgA-fibronectin (Fn) complexes, and glomerular deposition of IgA, complement C3, Fn and collagen. We report here that two independent mouse models (gene knockout and antisense transgenic), both manifesting deficiency of an anti-inflammatory protein, uteroglobin (UG), develop almost all of the pathologic features of human IgA nephropathy. We further demonstrate that Fn-UG heteromerization, reported to prevent abnormal glomerular deposition of Fn and collagen, also abrogates both the formation of IgA-Fn complexes and their binding to glomerular cells. Moreover, UG prevents glomerular accumulation of exogenous IgA in UG-null mice. These results define an essential role for UG in preventing mouse IgA nephropathy and warrant further studies to determine if a similar mechanism(s) underlies the human disease.

Animals↗
PubMed1999

Developmental surface dysgraphia: what is the underlying cognitive impairment?

The purpose of this study was to investigate the cognitive causes underlying spelling difficulties in a case of developmental surface dysgraphia, AW. Our results do not support a number of possibilities that could be the cause of AW's poor orthographic lexicon, including difficulties in phonological processing, phonological short-term memory, configurational visual memory, and lexical semantic memory. We have found instead that AW performs poorly in tasks that involve detection of the order of adjacent letters in a word or the order of adjacent units in strings of consonants or symbols. Finally, he performs poorly in tasks that involve reconstructing the order of a series of complex visual characters (Japanese and Hindi characters) especially when these are presented sequentially. We advance the hypothesis that AW's poor spelling and good reading skills stem from an underlying pattern of cognitive abilities where a very good visual configurational memory is coupled with a poor ability to encode serial order. This may have resulted in a holistic word-based reading strategy, which, together with the original problem of encoding order, may have had detrimental effects for the acquisition of spelling.

Adult↗
PubMed1999

Brain stem blood flow, pupillary response, and outcome in patients with severe head injuries.

OBJECTIVE: Acute pupillary dilation in a head-injured patient is a neurological emergency. Pupil dilation is thought to be the result of uncal herniation causing mechanical compression of the IIIrd cranial nerve and subsequent brain stem compromise. However, not all patients with herniation have fixed and dilated pupils, and not all patients with nonreactive, enlarged pupils have uncal herniation. Therefore, we have tested an alternative hypothesis that a decrease in brain stem blood flow (BBF) is a more frequent cause of mydriasis and brain stem symptomatology after severe head injury. We determined the relation of BBF to outcome and pupillary response in patients with severe head injuries. METHODS: One hundred sixty-two patients with a Glasgow Coma Scale score of 8 or less underwent stable xenon computed tomographic blood flow determination at the level of the superior colliculus, and this blood flow was correlated with pupillary features, intracranial pressure, computed tomographic scan pathology, and outcome. RESULTS: A BBF of less than 40 ml/100 g/min was significantly associated with poor outcome (P < 0.009). In patients with bilaterally nonreactive pupils, the BBF was 30.5+/-16.8 ml/100 g/min, and in those with normally reactive pupils, the BBF was 43.8+/-18.7 ml/100 g/min (P < 0.001). Intracranial pressure and the presence of a brain stem lesion observed on the computed tomographic scan did not correlate with BBF, pupillary size, or reactivity. Unfavorable outcome at 12 months was directly related to age (P = 0.062) and inversely related to pupillary responsiveness (P = 0.0006), pupil size (P = 0.005), and BBF of less than 40 ml/100 g/min (P = 0.009). CONCLUSION: These findings suggest that pupillary dilation is associated with decreased BBF and that ischemia, rather than mechanical compression of the IIIrd cranial nerve, is an important causal factor. More important, pupil dilation may be an indicator of ischemia of the brain stem. If cerebral blood flow and cerebral perfusion pressure can be rapidly restored in the patient with severe head injury who has dilated pupils, the prognosis may be good.

Adolescent↗