Varicella-zoster vaccine: the bad news may be good.
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Biomedical subjects
Publications and source records attributed to J Mills.
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RATIONALE AND OBJECTIVES: To evaluate the use of a new thrombus-specific ultrasound contrast agent, MRX-408, in the ultrasonic detection of thrombus in arteriovenous (AV) fistulae. METHODS: Six purpose-bred mongrels with two AV fistulae each were imaged with gray-scale ultrasound 7 weeks after graft implantation before and after the intravenous bolus injection of MRX-408 (a GPIIb receptor-targeted ultrasound contrast agent). Pre- and postcontrast videotaped segments were randomized and reviewed by four radiologists blinded to the presence of thrombus in the grafts. RESULTS: After the use of MRX-408, there was improved visualization of thrombus within the grafts (P < 0.0001). This was due to the enhancement of the thrombus (P < 0.0001). The improved visualization and contrast enhancement were more marked in the grafts that contained thrombus nonhyperechoic to surrounding soft tissues. CONCLUSIONS: MRX-408 demonstrated better visualization of thrombus within AV fistulae. This was shown in both patent and occluded grafts. These results are encouraging and suggest that this contrast agent merits further development.
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A ventral marsupialisation technique is described which was used successfully to manage gastric dilatation-volvulus (GDV) in two large breed dogs. The procedure allowed the stomach to be completely and rapidly emptied and lavaged without peritoneal contamination. Drainage was maintained in the postoperative period for both dogs and the technique was expected to result in a permanent ventral gastropexy.
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We investigated twenty-one insulin-using patients, who had all been labelled as having insulin dependent diabetes mellitus (IDDM) or type 1 diabetes. Physicians have been erroneously using the term IDDM loosely to include all diabetics on insulin. The clinical criteria of the National Diabetes Data Group/WHO were used to reclassify these patients. Only thirteen were found to have IDDM and eight non-insulin dependent diabetes mellitus (NIDDM). Using fasting C-peptide values, only five of the thirteen with clinical IDDM truly had IDDM, the others might have maturity onset diabetes of the young (MODY) or diabetes in the young. Of the eight with clinical NIDDM seven had normal to high C-peptide values; the lone patient with low C-peptide values had diabetes diagnosed at age 64 years. We conclude that the clinical classification of diabetes mellitus may be inaccurate and that C-peptide evaluation improves the accuracy of the classification.
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OBJECTIVE: To investigate the general nutritional status of patients in Alexandra Hospital, Cape Town, and to determine whether dietary copper deficiency was causing anaemia in hospital patients. DESIGN: Descriptive and cross-sectional analytical studies. SETTING: A long-stay hospital for people with mental handicap. SUBJECTS: Information was obtained from the total hospital population. In addition, groups of 15 patients were selected from each of two specific wards, one with active and the other inactive patients. To determine whether copper deficiency was causing anaemia, a sample of 30 patients, divided into three groups (a hypochromic microcytic, a normochromic anaemic and a non-anaemic group) was studied. MAIN OUTCOME MEASURES: Body mass indices (BMI) and daily dietary intakes were compared with Recommended Daily Allowance (RDA) values. Serum copper and serum caeruloplasmin levels were used to detect possible copper deficiency. RESULTS: A considerable number of patients were found to be underweight (32% of males and 26% of females had BMIs < 20). A smaller number were obese (6% of males and 17% of females had BMIs > 30). Poor nutrition was more common in severely handicapped patients and those with acquired causes of their mental handicap. Subjects with Down syndrome were generally well nourished and occasionally obese. Poor dietary intakes of biotin, pantothenic acid, vitamin D and copper were encountered. The serum copper and caeruloplasmin values were found to be within normal limits. Patients with hypochromic, microcytic anaemia had higher serum copper and caeruloplasmin levels than those with normochromic anaemia and the control group. CONCLUSIONS: A number of nutritional problems among the inpatient population were found. Many were undernourished, while a smaller number of patients were overweight. In both the active and inactive wards macronutrient intakes were generally within normal limits. However, some micronutrient nutritional deficiencies were encountered. We were unable to establish that dietary copper deficiency was the cause of anaemia in our patients. Elevated serum copper and caeruloplasmin levels found in hypochromic, microcytic patients were thought to result from the existence of low-grade infection, associated with elevation of the acute-phase protein, caeruloplasmin.
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BACKGROUND AND METHODS: The Sydney Blood Bank Cohort consists of a blood donor and eight transfusion recipients who were infected before 1985 with a strain of human immunodeficiency virus type 1 (HIV-1) with a deletion in the region in which the nef gene and the long terminal repeat overlap. Two recipients have died since 1994, at 77 and 83 years of age, of causes unrelated to HIV infection; one other recipient, who had systemic lupus erythematosus, died in 1987 at 22 years of age of causes possibly related to HIV. We present longitudinal immunologic and virologic data on the six surviving members and one deceased member of this cohort through September 30, 1998. RESULTS: The five surviving recipients remain asymptomatic 14 to 18 years after HIV-1 infection without any antiretroviral therapy; however, the donor commenced therapy in February 1999. In three recipients plasma concentrations of HIV-1 RNA are undetectable (<200 copies per milliliter), and in two of these three the CD4 lymphocyte counts have declined by 9 and 30 cells per cubic millimeter per year (P=0.3 and P=0.5, respectively). The donor and two other recipients have median plasma concentrations of HIV-1 RNA of 645 to 2850 copies per milliliter; the concentration has increased in the donor (P<0.001). The CD4 lymphocyte counts in these three cohort members have declined by 16 to 73 cells per cubic millimeter per year (P<0.001). In the recipient who died after 12 years of infection, the median plasma concentration of HIV-1 RNA was 1400 copies per milliliter, with a decline in CD4 lymphocyte counts of 17 cells per cubic millimeter per year (P=0.2). CONCLUSIONS: After prolonged infection with this attenuated strain of HIV-1, there is evidence of immunologic damage in three of the four subjects with detectable plasma HIV-1 RNA. The CD4 lymphocyte counts appear to be stable in the three subjects in whom plasma HIV-1 RNA remains undetectable.
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The respiratory syncytial virus (RSV) G glycoprotein mediates attachment of RSV to cells via an unknown receptor. To study G glycoprotein function we have cloned two variants of the RSV G gene into a Semliki Forest virus (SFV) expression vector, a full length (rG) and soluble (srG) G glycoprotein variant. By immunofluorescence microscopy, rG was found to be predominantly membrane associated, while srG was mostly cytoplasmic. The rG (80-85 kDa) and srG (75-80 kDa) constructs produced heavily glycosylated proteins, however they were slightly smaller than the G glycoprotein expressed in RSV infected HEp-2 cells (85-90 kDa). The biological activity of purified srG was tested by its ability to bind to RSV permissive cells. Purified srG bound to HEp-2 cells and the amount bound increased linearly with the quantity added. Binding was not saturable with the small quantities of protein available. Binding of srG to HEp-2 cells was inhibited (67-68%) by MAb 30 and neutralising anti-G MAb 29. Nonpermissive SF9 insect cells bound 20-50 times less srG than HEp-2 cells. SFV expressed recombinant RSV G glycoprotein should be useful for studying interactions between the RSV G glycoprotein and cells.
Glutamate is the principal excitatory neurotransmitter in the mammalian brain. Several lines of evidence suggest that glutamatergic hypoactivity exists in the Alzheimer's disease brain, where it may contribute to both brain amyloid burden and cognitive dysfunction. Although metabotropic glutamate receptors have been shown to alter cleavage of the amyloid precursor protein, little attention has been paid to the role of N-methyl-D-aspartate receptors in this process. We now report that activation of N-methyl-D-aspartate receptors in transiently transfected human embryonic kidney 293 cells increases production of the soluble amyloid precursor protein derivative. Moreover, using both pharmacological and gene transfer techniques, we show that this effect is largely due to activation of the mitogen-activated protein kinase cascade, specifically the pathway leading to activation of extracellular signal-regulated protein kinase but not other mitogen-activated protein kinases. These observations further our understanding of the pathways that regulate amyloid precursor protein cleavage, and buttress the notion that regulation of amyloid precursor protein cleavage is critically dependent upon the mitogen-activated protein kinase cascade.
The recently developed technique of fibre optic respiratory plethysmography (FORP) has been modified to monitor the rapid, small amplitude movements of the chest wall during high-frequency oscillatory ventilation (HFOV). The FORP sensor is an expandable belt encircling the chest, in which is housed a fibre optic loop that alters its radius of curvature as a function of chest perimeter. These curvature changes cause variations in macrobending losses of light transmitted through the fibre, which are proportional to the chest perimeter. Dynamic measurement of transmitted light intensity can hence be used to monitor chest wall motion (CWM). For application to HFOV, the design of the FORP belt was altered to increase sensitivity and the materials were chosen to maximise macrobending effects induced by the CWM. FORP was tested in four piglets ventilated with HFOV, both in the normal and surfactant-deficient lung. Measurement of CWM was possible over the full range of tidal volumes and ventilation frequencies used during HFOV. In all cases, the measured frequency of the CWM fell within 3% of the applied ventilation frequency. In addition, the technique was sufficiently sensitive to detect changes in the amplitude of CWM in response to changes in applied tidal volume. It is anticipated that application of this new non-invasive measurement device will lead to an increased understanding of the dynamics of chest and abdominal wall motion during HFOV.
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Multiple lines of evidence suggest that increased production and/or deposition of the beta-amyloid peptide, derived from the amyloid precursor protein, contributes to Alzheimer's disease. A growing list of neurotransmitters, growth factors, cytokines, and hormones have been shown to regulate amyloid precursor protein processing. Although traditionally thought to be mediated by activation of protein kinase C, recent data have implicated other signaling mechanisms in the regulation of this process. Moreover, novel mechanisms of regulation involving cholesterol-, apolipoprotein E-, and stress-activated pathways have been identified. As the phenotypic changes associated with Alzheimer's disease encompass many of these signaling systems, it is relevant to determine how altered cell signaling may be contributing to increasing brain amyloid burden. We review the myriad ways in which first messengers regulate amyloid precursor protein catabolism as well as the signal transduction cascades that give rise to these effects.
Collectins are a family of calcium-dependent collagenous lectins that appear to be important in innate host defense. We investigated the ability of three human collectins, namely, lung surfactant proteins A (SP-A) and D (SP-D) and the serum mannose-binding protein (MBP), to bind to the surface glycoproteins of respiratory syncytial virus (RSV). SP-A was shown to bind to the F (fusion) glycoprotein but not to the viral G (attachment) glycoprotein, and binding was completely abrogated in the presence of EDTA. Neither SP-D nor MBP bound to either glycoprotein. SP-A also neutralized RSV in a calcium dependent fashion. These results support a role for SP-A in the defense of infants against infection with RSV and indicate a possible mechanism for its protective activity.
Philosophical counseling is a diverse and burgeoning type of mental health service delivery. Despite competing approaches to theory and practice, the field has largely strayed from an ethical critique of its methodology and counselor training requirements. This article outlines several ethical considerations and training recommendations that are proposed to bolster the quality and effectiveness of philosophical practice. As philosophical counseling gains increasing recognition in North America, recently established national organizations in philosophical practice may profit from revisiting their interim codes for professional conduct. Proposed training suggestions for counselor preparation my further assist institutions and board-regulated agencies in establishing competent and acceptable standards of client care.