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Biomedical subjects

J Walters

Publications and source records attributed to J Walters.

At least 37 records · Page 2Linked to original sources

Human immunodeficiency virus-associated pericardial effusion: report of 40 cases and review of the literature.

BACKGROUND: Human immunodeficiency virus (HIV)-associated pericardial effusion is common. We present its clinical features, cause, and prognosis on the basis of a review of 40 cases at a single public hospital. METHODS: A retrospective study was conducted of 122 patients with pericardial effusion (of which 40 were HIV associated) admitted to Queens Hospital Center from January 1988 to April 1997. A review of the literature is also presented. RESULTS: Forty patients with HIV-associated pericardial effusion represent 33% of the 122 patients with pericardial effusion admitted during that period. The most common symptom of the 40 patients was dyspnea (75%). Echocardiogram detected small effusions in 18 (45%), moderate effusions in 10 (25%), and large effusions in 12 (30%). Sixteen (40%) patients had cardiac tamponade, in 15 of whom pericardiocentesis or pericardiostomy was performed. Causes of cardiac tamponade were Mycobacterium species in 3 (19%), Streptococcus pneumoniae in 1 (6%), Staphylococcus aureus in 1 (6%), Kaposi's sarcoma in 1 (6%), and unknown in 10 (63%). In comparison, causes of cardiac tamponade in 74 cases of acquired immunodeficiency syndrome in the literature were 45% idiopathic, 20% mycobacteria, 19% bacteria, 7% lymphoma, 5% Kaposi's sarcoma, 3% viruses, and 1% fungus. Thirteen of the 40 patients were lost to follow-up. Among the other 27, 11 (41%) were alive at 3 months and 5 (19%) at 1 year. Ten of the 27 patients had cardiac tamponade, of whom 5 (50%) were alive at 3 months and 3 (30%) at 1 year. CONCLUSIONS: HIV-associated pericardial effusion is the most common type of pericardial effusion in our inner city hospital. Causes are diverse. The development of pericardial effusion predicts a poor prognosis in HIV infection.

Adult↗

Alkaline conditions accelerate polymorphonuclear leukocyte apoptosis in vitro.

Apoptosis was monitored in polymorphonuclear leukocytes (PMNs) cultured under mildly acidic, neutral, and alkaline conditions. Within 3 h, 9.0% of the PMNs underwent apoptosis at pH 6.7, as did 12% at pH 7.2, 38% at pH 7.7, and 60% at pH 8.2. Inhibitors of serine proteases, caspase-1, or caspase-3 significantly inhibited PMN apoptosis at pH 8.2, suggesting an involvement by these enzymes.

Amino Acid Sequence↗

Postnatal development of bone mineral status during infancy.

OBJECTIVE: To determine postnatal development in bone mineral status and its relationship to anthropometric measurements and other physiologic variables during the first year. METHODS: Cross-section observational study of total body bone mineral content (TB BMC) and density (TB BMD) of 130 healthy infants (71 male and 59 female with 63 white and 67 African American) between 1 and 391 days. Whole body dual energy X ray absorptiometry (DXA) scans were performed on unsedated infants using a bone densitometer with pediatric platform. Scan analyses were performed with software version V5.64P. The ability of study independent variables to explain variance in bone mineral status was determined by multiple linear regression analysis. RESULTS: During infancy, average TB BMC increased by 389% and TB BMD increased by 157%. The best determinant of bone mineral status is body weight which accounted for 97% of TB BMC, 98% of TB area and 86% of TB BMD variation. Postnatal age and body length jointly added only 1%, < 1% and 2.5%, respectively, to the explained variation of these DXA measurements; race, gender and season all failed to reach statistical significance. CONCLUSION: In healthy infants, body weight is the dominant predictor of bone mineral status. The percent increase in TB BMC differs from increase in TB BMD. Normative data generated from this study would be useful in the identification of abnormal bone mineral status in infants.

Absorptiometry, Photon↗

Long-term outcome following case management after coronary artery bypass surgery.

Patient outcome following coronary artery bypass grafting (CABG) has come under increasing governmental, social, and economic scrutiny. To insure quality patient outcome after CABG, many new policies and programs have been instituted. One of these, case management, was developed as a tool for identification and quantification of patient clinical sequences and resource utilization. This present study examines the influence of case management on length of stay and patient outcome following CABG. One hundred forty randomized, retrospectively analyzed CABG patients from 1990, prior to case management, were compared against 140 age-and case-matched randomly controlled CABG patients from 1994 after case management was in place. Patients' demographics were similar. The outcome data showed that intensive care unit (ICU) use and total length of stay were significantly decreased. Furthermore, resource utilization as monitored by chest X-ray, electrocardiography, and laboratory testing were decreased as well. Finally, mortality was decreased despite an increase in risk-adjusted acuity of the patients. There appeared to be no effect of gender or age on the benefit derived from case management. These data demonstrate that the influence of case management is beneficial for resource utilization and patient outcome following CABG and that these types of patient care policy advancements should be encouraged.

Aged↗

Effect of hand dominance on bone mass measurement in sedentary individuals.

The aim of this study was to determine in healthy sedentary subjects the effect of hand dominance on side-to-side difference in bone area and bone mass for upper and lower extremities. Dual-energy X-ray absorptiometry (DXA) measurements of both forearms and hips were performed on 193 right-handed and 20 left-handed subjects as determined by self-report. Scan acquisition and scan analyses were performed by one investigator, but all scan pairs were independently assessed for symmetry of positioning and movement artifacts by three investigators. Results show that DXA measurements between sides may be highly correlated regardless of the symmetry of the scan pair. However, asymmetric DXA scan pairs may have more than twice the side-to-side difference found in symmetric DXA scan pairs at the hip. Side-to-side differences between subregions were greater than the differences between measurements at the total radius, ulna, or hip. For symmetric pairs of DXA scans, the dominant forearm has significantly higher bone area and bone mineral content (BMC). Bone mineral density (BMD) was significantly higher only in the ulna of the dominant forearm. However, the nondominant forearm has higher values than dominant forearm in at least one DXA measurement in >24% of the subjects. There were no significant differences in any DXA measurements between hips, and higher DXA measurements did not occur significantly more frequently at the hip corresponding to the dominant hand. We conclude that healthy sedentary subjects tend to have proportionally higher bone area and BMC in the dominant forearm that results in similar BMD between dominant and nondominant forearms. This relationship does not appear to be applicable to measurements at the hip. In addition, there is a significant proportion of subjects with higher bone area and BMC in the nondominant extremities. Thus, in sedentary subjects, the consistency in the use of same extremity and the consistency in scan acquisition techniques and scan analyses is of greater importance than the selection of an extremity based on hand dominance in DXA studies.

Journal Article↗

Dopaminergic neurons intrinsic to the primate striatum.

Intrinsic, striatal tyrosine hydroxylase-immunoreactive (TH-i) cells have received little consideration. In this study we have characterized these neurons and their regulatory response to nigrostriatal dopaminergic deafferentation. TH-i cells were observed in the striatum of both control and 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)-treated monkeys; TH-i cell counts, however, were 3.5-fold higher in the striatum of MPTP-lesioned monkeys. To establish the dopaminergic nature of the TH-i cells, sections were double-labeled with antibodies to dopamine transporter (DAT). Immunofluorescence studies demonstrated that nearly all TH-i cells were double-labeled with DAT, suggesting that they contain the machinery to be functional dopaminergic neurons. Two types of TH-i cells were identified in the striatum: small, aspiny, bipolar cells with varicose dendrites and larger spiny, multipolar cells. The aspiny cells, which were more prevalent, corresponded morphologically to the GABAergic interneurons of the striatum. Double-label immunofluorescence studies using antibodies to TH and glutamate decarboxylase (GAD67), the synthetic enzyme for GABA, showed that 99% of the TH-i cells were GAD67-positive. Very few (<1%) of the TH-i cells, however, were immunoreactive for the calcium-binding proteins calbindin and parvalbumin. In summary, these results demonstrate that the dopaminergic cell population of the striatum responds to dopamine denervation by increasing in number, apparently to compensate for loss of extrinsic dopaminergic innervation. Moreover, this population of cells corresponds largely with the intrinsic GABAergic cells of the striatum. This study also suggests that the adult primate striatum does retain some intrinsic capacity to compensate for dopaminergic cell loss.

Animals↗

The location of acidic fibroblast growth factor in the breast is dependent on the activity of proteases present in breast cancer tissue.

Acidic fibroblast growth factor (FGF1) and two of its receptors, FGFR1 and FGFR4, were localized in cryostat sections of normal, benign and malignant human breast tissue by immunohistochemistry. Without pretreatment, FGF1 staining was mainly seen in normal epithelial cells. However, polymerase chain reaction (PCR) analysis and immunoblotting of isolated normal epithelial and myoepithelial cells showed FGF1 mRNA and protein to be present in both cell types. Following incubation of frozen sections at 37 degrees C in phosphate-buffered saline, FGF1 staining was also revealed in myoepithelial cells and basement membrane adjacent to carcinoma cells. Treatment with protease inhibitors demonstrated that this effect was due to the activity of an endogenous protease. In contrast, FGF1 staining was found to be associated with the stroma adjacent to malignant cells only in the presence of protease inhibitors. FGFR1 and FGFR4 immunostaining was localized to both normal and malignant epithelial cells and to a lesser extent to myoepithelial cells. There was no difference in the staining intensity for the FGF receptors between normal and cancer samples. The change in location of FGF1 between normal and malignant tissues and the sensitivity of stored FGF1 to the action of endogenous proteases raises the possibility of both autocrine and paracrine roles for FGF1 in the normal and malignant human breast.

Animals↗

Down-regulation of a novel form of fibroblast growth factor receptor 1 in human breast cancer.

Monoclonal antibodies against two epitopes of FGFR-1 have been used to investigate FGFR-1 expression in the normal and neoplastic human breast. Different forms are detected in the different cell types constituting the normal breast. Moreover, breast cancer cells lack one form of FGFR-1. Western blot analysis showed 115-kDa and 106-kDa forms of FGFR-1 within the human breast. The 115-kDa band corresponds to the beta form of FGFR-1, whereas the 106-kDa band is truncated at the carboxyl terminus. The 106-kDa form of FGFR-1 is the major form present in breast fibroblasts and myoepithelial cells, whereas epithelial cells contain equal amounts of the 115-kDa and 106-kDa forms. Breast cancer cells, however, appear to contain only the 115-kDa form of FGFR-1. This expression pattern is reflected in malignant and non-malignant tissue samples. Using reverse transcription polymerase chain reaction (RT-PCR) analysis, we have shown that the 106-kDa FGFR-1 isoform is not the previously described alpha 2 receptor that arises from a 25-base pair insertion in the second kinase domain. It is probable that the 106-kDa FGFR-1 has different signalling properties to the full-length receptor, having lost at least one tyrosine at amino acid 766, which is required for phospholipase C activation. This form of FGFR-1 appears to be lost in all breast cancer cells analysed and its absence may have a bearing on malignancy.

Amino Acid Sequence↗

Long-term ventilation in children with severe central nervous system impairment.

Absent from the list of indications for long-term ventilation (LTV) is its use for children with severe central nervous system impairment, including those with severe mental retardation or in a permanent vegetative state. Over a two year period, we evaluated eight children with severe CNS dysfunction for whom long-term ventilation was being contemplated. Of these eight patients, three were in a permanent vegetative state and the remainder were severely neurologically impaired, with minimal cognition. The following recommendations were developed: (1) LTV for patients in a permanent vegetative state is inappropriate. (2) In a patient with severe neurologic disease, the process of informed consent must be viewed as dynamic; once the patient's condition is diagnosed, discussion should begin about the likely course of the disease (upper airway obstruction, respiratory failure, or both) and available treatment options. (3) Continued efforts must be made to resolve conflicts between healthcare professionals and surrogates concerning aggressive support of children with severe CNS dysfunction. Discussions should continue even after a decision to provide long-term ventilation is made. (4) Currently, requests by surrogates for LTV in patients with severe neurologic impairment are usually honored because of respect for family values. (5) Physicians and other healthcare professionals should develop an open and fair process for determining inappropriate care. (6) Once LTV is initiated, efforts to transfer the child to home or a long-term care facility should be made. Further life-saving support should be discouraged. (7) Irremediable patient suffering is reason to refuse a surrogate request for LTV. A patient's preservable existence might be so torturous, painful, or filled with suffering that continued medical intervention would be inhumane or abusive.

Adolescent↗

Anencephaly: where do we now stand?

In 1995 the American Medical Association's ethics council issued an opinion calling for the direct procurement of organs from anencephalic newborns, making them an exception to the "dead donor" rule. Such a firestorm erupted that the Council for Ethical and Judicial Affairs withdrew its opinion. Although the AMA has called for further research into possible "consciousness" in anencephalic newborns, present studies convincingly demonstrate that the brain stems of these infants are almost completely devoid of any evidence of even primitive functional organization. New studies indicate that cerebral absence causes unusual behaviors such as stiffening and hyperirritability that can be detected prenatally. Although widespread testing and screening in recent years has drastically reduced the number of anencephalic newborns, the discussion of use continues, raising ethical issues that pertain to other marginal patients such as those in persistent vegetative states. There are two schools of thought on the permissibility of using anencephalic newborns as organ sources: physicalism and personalism. Physicalism holds that all humans are so precious that no exceptions can be made regarding organ procurement, even in the case of anencephaly. Personalism sees moral worth related to one's potential or actual mental capacities, and because of anencephalic newborns' uniqueness, believes considerable liberties can be taken here. Most bioethicists are themselves in the personalist camp, but many have questions about changing the law to allow for a proposal such as the AMA Council's, because of the social impact of that change.

Anencephaly↗

Dual-energy X-ray absorptiometry studies of bone mineral status in newborn infants.

We studied bone mineral status using dual-energy X-ray absorptiometry (DXA) on 150 singleton newborn infants with birth weights 1002-3990 g and gestational ages (GA) 27-42 weeks. Eighty-five infants were preterm (< 38 weeks), and 79 infants were low birth weight (< or = 2500 g). In addition, we aimed to determined the predictive value of anthropometric measurements, race, and gender on variability in bone mineral status. Data were acquired using a whole body DXA scanner with a pediatric platform. Scan analyses were performed with software version V5.64P. Results showed a highly significant (p < 0.001 for all comparisons) correlation among the continuous independent variables, gestational age, birth weight, study weight, study bare weight, and study length, and between independent and each of the dependent variables, total body bone mineral content (TB BMC), TB area, and TB bone mineral density (TB BMD). The best single determinant of bone mineral status is body weight, accounting for 95% of TB BMC and TB area and for 86% of TB BMD variation. Body length was the only additional significant predictor of TB area. Inclusion of postnatal age (during the first week after birth), race, gender, or season, either individually or in combination, failed to improve bone mineral status explanation. By term (GA 38-42 weeks, birth weight 2700-3990 g), the mean TB BMC was 68.2 g, TB area 307.6 cm2, and TB BMD 0.221 g/cm2. We conclude that DXA can be performed even in small preterm infants during the newborn period. Our results can be used as a basis for further studies in physiologic and pathologic situations that might affect bone mineralization in infants.

Absorptiometry, Photon↗

Transcriptional and post-transcriptional regulation of GM-CSF-induced IL-1 beta gene expression in PMN.

Polymorphonuclear leukocytes (PMN) play an important role in inflammation, immune responses, and tissue repair by secreting interleukin- 1 beta (IL-1 beta). We investigated the regulation of IL-1 beta gene expression in human PMN treated with granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF induced IL-1 beta mRNA accumulation at 0.1 ng/ml and maximal induction was observed at 1 ng/ml. IL- 1 beta mRNA levels reached a maximum with 1-2 h after stimulation with GM-CSF and returned to baseline levels by 4-6 h. The time course of IL-1 beta mRNA induction by GM-CSF was more protracted than previously reported for PMN stimulated with tumor necrosis factor-alpha (TNF-alpha, 10 ng/ml). Nuclear run-on analysis indicated that GM-CSF, like TNF, increases IL-1 beta transcription. Kinetic studies with the RNA synthesis inhibitor, actinomycin D, showed that GM-CSF induces stable IL-1B mRNA. Cycloheximide enhanced the IL-1 beta mRNA accumulation by GM-CSF at the level of mRNA stabilization, but blocked IL-1 beta mRNA expression by TNF. Thus, GM-CSF increases IL-1 beta message accumulation in PMN at both the transcriptional and post-transcriptional levels by mechanisms that are different from TNF induction of IL-1 beta gene expression.

Cells, Cultured↗

The rising prevalence of HIV-1 infection in patients attending an inner city accident and emergency department.

The recently published findings of the unlinked anonymous HIV prevalence study in England and Wales showed unchanging HIV prevalence in groups such as homo/bisexual men, and declining rates in non-injecting heterosexual men attending genitourinary medicine clinics. However, this multicentre study did detect a significant rise in seroprevalence rates in pregnant women in England and Wales and sentinel groups within hospitals in London, warning that changing patterns of HIV infection might account for these variable results. In 1992-1993 a seroprevalence study of adult patients attending the accident and emergency department at St. Mary's Hospital in West Central London showed a rate of HIV-1 infection of 1 in 77. We have repeated the seroprevalence study over the same calendar months in 1994-1995 to gain further information about HIV positive patients attending the department and to see whether a change in the patterns of HIV infection in the population served by St Mary's Hospital had occurred.

Adult↗

Salmeterol tachyphylaxis in steroid treated asthmatic subjects.

BACKGROUND: Tachyphylaxis to the protection afforded by salmeterol to broncho-constrictor stimuli after regular use has been described in patients with mild asthma not receiving inhaled corticosteroids. The present study was performed to investigate whether airway tachyphylaxis occurs in symptomatic asthmatic subjects receiving inhaled corticosteroids, the group for whom salmeterol is recommended in clinical practice. METHODS: Thirty one adult patients with symptomatic chronic asthma who were receiving inhaled corticosteroids were randomised in a double blind manner and on a 2:1 basis to receive salmeterol 50 micrograms (n = 22) or placebo (n = 9) twice daily. Baseline forced expiratory volume in one second (FEV1) was measured during the run-in period, on day 0, and after four and eight weeks of regular treatment (following a 36 hour test drug washout period). Airway responsiveness to methacholine was measured one hour after administration of the test drug on these occasions. Diary cards were kept throughout the study and for a two week follow up period. RESULTS: Baseline FEV1 was not significantly different between the treatment groups or between visits. There was significant bronchodilatation one hour after salmeterol administration at 0, four, and eight weeks. No significant tachyphylaxis of the bronchodilator action of salmeterol was seen. Protection against methacholine induced bronchoconstriction reduced from 3.3 doubling dilutions after the first dose of salmeterol to two doubling dilutions after four and eight weeks of regular treatment. Symptom scores and "rescue" salbutamol use were significantly reduced during salmeterol treatment and daytime improvements were maintained into the follow up period. CONCLUSIONS: Inhaled corticosteroids did not prevent tachyphylaxis to the protection afforded by salmeterol to methacholine induced bronchoconstriction. The clinical significance, if any, of these findings remains to be defined.

Administration, Topical↗

Attitudes and knowledge about case mix reform among hospital staff in Australia.

This paper reports some of the findings of a national survey of staff in acute care hospitals about their knowledge of case mix and their attitudes towards it. Our findings suggest that, despite the range and scope of activities that have been pursued under the Australian Casemix Development Program (ACDP), knowledge of case mix among acute care hospital staff remains patchy. The evidence also shows that significant aspects of the DRG classification system and the uses to which it can be put are not accepted by many hospital staff, particularly medical staff. The paper concludes with a discussion of what some of these findings imply for future activity on case mix reform.

Allied Health Personnel↗