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Biomedical subjects

G Howard

Publications and source records attributed to G Howard.

At least 289 records · Page 16Linked to original sources
PubMedDate not supplied

Risk factors for extracranial carotid artery atherosclerosis.

We related risk factors, cardiovascular symptoms, and coronary status to the extent of extracranial carotid atherosclerosis as measured by B-mode ultrasonography in 376 volunteers hospitalized for elective coronary angiography. In a first analysis, we correlated risk factors and cardiovascular symptoms with carotid atherosclerosis. Univariate analysis showed that relations between many continuous risk factors and carotid atherosclerosis were graded and consistent for men and women. Multivariate analysis identified 6 significant variables (age, hypertension, pack-years smoked, and inversely, plasma concentrations of high density lipoprotein cholesterol and uric acid, and Framingham Type A score) that together accounted for 35% of the variability in extent of carotid atherosclerosis. In a second multivariate analysis, addition of coronary status (presence or absence of coronary stenosis as evaluated by coronary angiography) to the roster of candidate independent variables produced a new equation that accounted for an additional 5% of the variability in carotid atherosclerosis extent. Although much of the variability in extent of carotid atherosclerosis remains unexplained, these data define an association between coronary and carotid atherosclerosis that depends partly on shared exposure of both arteries to the same risk factors. They are also consistent with the concept that as yet undiscovered risk factors and/or genetic (e.g., arterial wall) factors common to both arterial beds also contribute to the relation between coronary and carotid atherosclerosis in human beings.

Age Factors↗
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Xenon-133 inhalation method for regional cerebral blood flow measurements: normal values and test-retest results.

The purpose of this investigation is to determine the normal values for regional cerebral blood flow (rCBF) as determined by the xenon inhalation method of Obrist. Normal values for all rCBF parameters were measured in 15 healthy individuals. Our data are compared with the normal data obtained by other investigators. In addition, test-retest rCBF measurements were performed to determine the reproducibility of the method. Our results show that the method is highly reproducible when carried out in serial studies over a short period of time.

Adult↗
PubMedDate not supplied

Effect of aminophylline on cerebral infarction in the Mongolian gerbil.

The effects of aminophylline in Mongolian gerbils subjected to unilateral carotid ligation were studied. The drug was given in varying intraperitoneal doses at varying postoperative intervals and the animals observed for 5 days for clinical signs of stroke. Doses of 100 mg per kg caused early death and were discontinued. Doses of 50 mg per kg had no significant effect on morbidity, mortality, time until death, stroke incidence or lesion size, as compared to saline given as a control. Doses of 80 mg per kg caused a higher mortality, higher morbidity, and a shorter interval to death, but a smaller infarct. Thus, aminophylline did not have a protective effect against stroke in gerbils and was actually detrimental during the first 16 hours following the carotid ligation.

Aminophylline↗
PubMedDate not supplied

Re-engineering: managing radical change.

Faced with both a move to a new facility and the need for radical, cost-saving organizational change, the Ontario Cancer Institute/Princess Margaret Hospital turned to the principles of re-engineering. With the help of a consulting firm, the organization overhauled sufficiently to save $7.5 million, enough to finance the move, the transition and even the expansion of some services.

Cancer Care Facilities↗
PubMedDate not supplied

Application of membrane filtration for removal of diminutive bioburden organisms in pharmaceutical products and processes.

In this report, we present results of a recent investigation in our laboratories demonstrated the effect of process conditions and/or drug product composition on the ability of 0.2 micron and 0.22 micron sterilizing grade filters to fully retain Ralstonia (formerly Burkholderia, formerly Pseudomonas) pickettii. R. pickettii is a opportunistic pathogen widely distributed in nature as well as clinical specimens and there have been several reports of nosocomial infections due to intrinsic manufacture-related R. pickettii contamination in filter-sterilized parenteral fluids. This study documents the penetration of 0.2 micron nylon 66 and 0.22 micron modified PVDF sterilizing grade filters by R. pickettii (grown and challenged) in a drug solution under conditions that simulated a pharmaceutical filling operation. Penetration was not observed for every filter disc tested, and this may be explained, in part, by the stochastic nature (i.e., governed by the rules of probability) of the retention mechanisms involved. Scanning electron microscopy revealed significant changes in the microorganism's size and morphology as a result of exposure to the drug solution; these changes are consistent with those reported for bacteria subjected to nutrient deprivation. The SEM analyses of R. pickettii challenge suspensions in the drug solution showed that the average cell length decreased from 1.25 +/- 0.27 microns to 0.84 +/- 0.17 micron between zero and 24 hours. In addition, significant changes were observed in the size (length) distributions, with approximately 35% of the cells at 24 hours being smaller than any cell observed at the start of the challenge. These data suggest that the significant reduction in bioburden size and morphology that occurred as a result of exposure to the drug solution may play a role in the reduced ability of the 0.2 micron and 0.22 micron filters tested in this study to retain these organisms. Under the same test conditions where penetration of 0.2/0.22 micron filters was observed, 0.1 micron rated membrane filters qualified with both B. diminuta and Acholeplasma laidlawii mycoplasma consistently provided sterile effluent. Bacterial penetration of 0.2 (or 0.22) micron sterilizing grade filters was not observed under identical test conditions with either R. pickettii in a standardized solution (saline lactose broth) routinely used in challenge testing filters, or with the standard test organism, B. diminuta, in the drug solution. This study thus supports the renewed emphasis on both product- and process specific validation as well as routine bioburden monitoring expressed by regulatory agencies, and the use of enhanced bacterial removal efficiency 0.1 micron rated filters to provide enhanced sterility assurance in pharmaceutical processes.

Bacteria↗
PubMedDate not supplied

Retention of water-borne bacteria by membrane filters. Part III: Bacterial challenge tests on 0.1 micron rated filters.

Clear performance differences were observed between different 0.1 micron rated filters in terms of their microbial removal efficiency when challenged with naturally occurring waterborne bacteria from a water source. Penetration occurred with three 0.1 micron rated "sterilizing grade" filter types tested, from three different filter manufacturers, that did not have a specific high titer reduction claim for Acholeplasma laidlawii. Bacteria shown to penetrate these 0.1 micron rated filters were quite similar to those recovered downstream of 0.2.0.22 micron rated filters (described in Part II). All of the isolates identified via FAME analyses were common environmental or ubiquitous organisms, and some, such as Acidovorax sp. and Hydrogenophaga pseudoflava, have also been isolated from pharmaceutical water systems. In contrast, four different 0.1 micron rated "sterilizing grade" filter types from two different manufacturers, which had been qualified with both B. diminuta and A. laidlawii, consistently produced sterile effluents under similar test conditions. This study thus highlights the need for an industry or regulatory standard method of defining the microbial removal performance of 0.1 micron rated filters, and supports the use of functionally qualified 0.1 micron rated filters as sterilizing grade filters in pharmaceutical operations for enhanced sterility assurance.

Bacteria↗
PubMedDate not supplied

Retention of water-borne bacteria by membrane filters. Part I: Bacterial challenge tests on 0.2 and 0.22 micron rated filters.

The results of bacterial challenge tests conducted on several 0.2 and 0.22 micron rated "sterilizing grade" filter cartridge types with bacteria from a natural water source are presented. Eight different 0.2/0.22 micron rated "sterilizing grade" filter types from four different filter manufacturers, claimed to be capable of retaining Brevundimonas diminuta at a challenge level of 10(7) CFU/cm2, were tested. The filters tested included nylon 6.6 and polyamide filters from two manufacturers, modified or hydrophilic PVDF filters from two manufacturers, modified or asymmetric PES filters from three manufacturers, and cellulose acetate filters from a single manufacturer. Consistent bacterial penetration was observed, over the 18-24 h challenge period, for all twenty-five integral 0.2 and 0.22 micron rated filter cartridges tested, at challenge levels of about 10(1)-10(4) CFU/cm2, indicating that natural waterborne bacteria were more penetrative than B. diminuta. The observed penetration was thus qualitatively independent of filter media type or manufacturer. These results add to the growing body of evidence that shows 0.2 and 0.22 micron rated filters may not remove all microorganisms under all conditions. These results further establish that bacterial penetration of 0.2/0.22 micron rated filters is not limited just to (1) specific membrane types, or (2) extended duration challenges (>> 24 h), or (3) extremely high challenge levels, or (4) bacteria that can only exist in a penetrative state in an artificial laboratory setting.

Culture Media↗
PubMedDate not supplied

Retention of water-borne bacteria by membrane filters. Part II: Scanning electron microscopy (SEM) and fatty acid methyl ester (FAME) characterization of bacterial species recovered downstream of 0.2/0.22 micron rated filters.

The results of scanning electron microscopic (SEM) and fatty acid methyl ester (FAME) characterization of the bacterial species shown to penetrate conventional 0.2/0.22 micron rated "sterilizing grade" filters are presented. SEM data suggest that retention of bacteria by these filters appears to be strongly influenced by the morphology, and especially the width of bacteria and less so by length. When the bacterial cell width is small, less than 0.3 micron or so, the cell length does not appear to limit the ability to penetrate 0.2/0.22 micron rated filters. As the bacterial width increases, there is also a strong, almost exponential, decrease in the allowable length for penetration, with most penetrative cells tending to be coccoid beyond a width of 0.5 micron. Significant percentages of the bacteria (40-50%) that were observed downstream of these filters were larger than B. diminuta, the standard organism used to qualify 0.2/0.22 micron rated filters. The average sizes of natural waterborne bacteria that penetrated the filters tested were 20-40% larger in width, and 40-70% larger in length, compared to B. diminuta. These results indicate that size exclusion is not the sole mechanism governing bacterial retention. All isolates identified via FAME analyses were common environmental or ubiquitous organisms, and some, such as Acidovorax sp. and Hydrogenophaga pseudoflava, have also been isolated from pharmaceutical water systems. Most of the bacteria recovered downstream of 0.2/0.22 micron rated filters were gram negative, oxidase positive, motile, nonfermentors.

Bacteria↗
PubMedDate not supplied

Amyloidosis of the orbit and adnexae.

Five patients representing a spectrum of orbital and adnexal amyloidosis are presented. One patient with conjunctival amyloidosis did not have antecedent infection nor systemic disease (primary localized amyloidosis), while another patient with conjunctival amyloidosis had a long history of repeated attacks of bacterial conjunctivitis (secondary localized amyloidosis). The third patient presented with serial bilateral lacrimal gland amyloid without systemic disease (primary localized orbital amyloidosis). Another patient had intraorbital amyloid associated with metastatic deposits or immunoglobulin-producing lymphoma cells in the orbit (secondary systemic amyloidosis) and a fifth patient, with borderline Congo red staining for amyloid, was shown by electron microscopy to have macrophages with intracellular amyloid-like fibrils and extracellular crystalline material resembling immunoglobulin deposits. Amyloidosis has been clearly shown to be associated with immunoglobulins and plasma cells. Electron microscopic findings in our two cases of primary localized orbital amyloidosis leave unresolved the suggestion that mesenchymal cells, in addition to plasma cells, may be responsible for the production of amyloid. It should be emphasized for the clinician that amyloidosis of the conjunctiva and orbit is almost always a benign disease without systemic implications. On the other hand, amyloid of the skin of the eyelids, is a hallmark of generalized amyloidosis.

Adult↗
PubMedDate not supplied

Method for qualifying microbial removal performance of 0.1 micron rated filters. Part I: characterization of water isolates for potential use as standard challenge organisms to qualify 0.1 micron rated filters.

Although 0.1 microm rated filters intended for pharmaceutical sterilization applications have been commercially available for at least 15 years, there is no industry-wide standard for qualifying the microbial removal performance of these filters. In this article, we report on the bacterial challenge methodology used to screen four bacterial species for potential utility as a standard challenge organism to qualify 0.1 microm rated filters. These isolates were, in their natural state, demonstrated to penetrate 0.2/0.22 microm rated filters in prior studies. In the screening challenges described in this study, three out of these four candidates tested demonstrated consistent penetration of one 0.22 microm rated filter type tested (when cultured in a low nutrient medium under standard laboratory conditions). These included 6204-22 (FAME ID Acidovorax avenae citrulli), 6266-15 (FAME ID Comamonas acidovorans), and 6266-34 (FAME ID Hydrogenophaga pseudoflava). Of these, H. pseudoflava (6266-34) was chosen for additional experiments with other 0.2 microm rated filter membranes. In total, seventeen 0.2 and 0.22 microm rated filter discs, spanning five different "sterilizing grade" filter types from three different filter manufacturers were tested. H. pseudoflava penetration was observed for every filter tested. Under the same challenge conditions, H. pseudoflava was consistently retained by a 0.1 microm rated hydrophilic PVDF (polyvinylidenefluoride) filter with a specified high titer reduction claim for Acholeplasma laidlawii. In order to ensure selection of the most stable penetrative phenotype (i.e., select for nonrevertants), H. pseudoflava was subjected to three rounds of "filter cloning," and these results are described herein. The advantages of using H. pseudoflava for qualifying the microbial removal performance of 0.1 microm rated filters are also discussed.

Acholeplasma↗
PubMedDate not supplied

Method for qualifying microbial removal performance of 0.1 micron rated filters. Part II: preliminary characterization of Hydrogenophaga (formerly Pseudomonas) pseudoflava for use as a standard challenge organism to qualify 0.1 micron rated filters.

In this article, we report on the preliminary characterization of Hydrogenophaga (formerly Pseudomonas) pseudoflava for potential use as a standard challenge organism to qualify 0.1 microm rated filters. Filter-cloned H. pseudoflava (ATCC 700892) was easily cultured in a low nutrient broth (R2A broth) under standard laboratory conditions, reaching high titers of 10(8)-10(9) cfu/mL within 48-65 hours of incubation at 25+/-5 degrees C. Under these conditions, H. pseudoflava is a rod-shaped bacterium, averaging 0.25+/-0.03 microm by 1.65+/-0.35 microm, and appears to be smaller than Brevundimonas diminuta in width (0.31+/-0.03 microm), but somewhat longer in length (0.88+/-0.19 microm), which may partly explain the observed penetration. In total, thirty-five 0.2/0.22 microm rated filter discs, spanning five different "sterilizing grade" filter types from two different filter manufacturers were challenged with H. pseudoflava. In all cases, H. pseudoflava was shown to consistently penetrate every 0.2/0.22 microm rated filter disc tested. These tests also spanned three different challenge durations, including short-term challenges (30-40 minutes), and two different challenge fluids. The use of serial (double) 0.22 mm rated filters, which is a common industry practice to reduce the prefiltration bioburden to the final "sterilizing" filter, was also shown to be inadequate to fully retain H. pseudoflava under the challenge condition used. In contrast, two different 0.1 microm rated filter types functionally qualified with a specified high titer reduction claim for Acholeplasma laidlawii, were shown to consistently and fully retain H. pseudoflava, and retention by these two filter types was shown to be robust and independent of the challenge duration.

Acholeplasma↗
PubMedDate not supplied

Method for qualifying microbial removal performance of 0.1 micron rated filters. Part III: bacterial challenge tests on 0.2/0.22 and 0.1 micron rated filter cartridges with Hydrogenophaga (formerly Pseudomonas) pseudoflava.

We have previously reported on the preliminary characterization of Hydrogenophaga (formerly Pseudomonas) pseudoflava for potential use as a standard challenge organism to qualify 0.1 microm rated filters. This article reports on the retention efficiencies of a large panel of 0.2/0.22 microm and 0.1 microm rated filter cartridges for H. pseudoflava (ATCC 700892) versus the retention capabilities of the same filters for Brevundimonas diminuta (ATCC 19146). A total of thirty-two 0.2/0.22 microm rated filter cartridges, spanning nine different "sterilizing grade" filter types from four different filter manufacturers, were challenged with H. pseudoflava at challenge levels exceeding 10(7) cfu/cm2. H. pseudoflava was shown to penetrate every 0.2/0.22 microm rated filter tested, with log titer reduction (LTR) values ranging from 3.5 to 7.7 logs. H. pseudoflava was shown to be more penetrative than B. diminuta under the same challenge conditions. B. diminuta was fully retained by nineteen of the twenty 0.2/0.22 microm rated filters that were challenged with both organisms. In the case of 0.1 microm rated filters, eighteen filter cartridges, spanning five different filter types from three manufacturers were tested. H. pseudoflava was consistently retained by four out of the five filter types tested, with LTR values in excess of 11.5 to 12.2 logs. The 0.1 microm rated filter type that was penetrated by H. pseudoflava has been previously demonstrated to be not fully retentive for naturally occurring bacteria. The data show that H. pseudoflava penetrates 0.2/0.22 microm rated filters just as readily as B. diminuta penetrates 0.45 microm rated filters. In addition, titer reductions provided by 0.2/0.22 microm rated filters for H. pseudoflava are comparable to those reported for A. laidlawii mycoplasma, albeit under different conditions. This study demonstrates that H. pseudoflava meets all criteria for use as a standard organism for qualifying the microbial removal performance of 0.1 microm rated filters for enhanced sterility assurance.

Acholeplasma↗
PubMedDate not supplied

Early rheumatoid arthritis in African-Americans: the CLEAR Registry.

African-Americans have been under-represented in genetic studies of rheumatoid arthritis (RA) susceptibility and severity. Genetic and non-genetic factors influencing the radiographic severity of RA and its response to treatment are poorly understood, particularly in African-Americans. The Consortium for the Longitudinal Evaluation of African-Americans with early RA (CLEAR) Registry, a collaborative effort among four institutions in the southeast USA, will hopefully provide a useful resource to study these issues.

Adult↗
PubMedDate not supplied

Comparison of bacterial and endotoxin retention by charge-modified sterilizing grade filters during intermittent long-term use.

There has been growing concern in recent years about control of bacterial bioburden and endotoxin in pharmaceutical water systems by both the pharmaceutical manufacturers and the Food and Drug Administration (FDA). This concern exists not only for Water for Injection (WFI) systems, but for any water system used in the manufacture of a product which could be affected by the microbial bioburden. In hot WFI systems, bioburden control is assured by keeping the water in the recirculating loops at 80 degrees C. At points of use in these systems, the temperature fluctuates and can be below sanitization temperature for extended periods. On the other hand, in cold water systems [WFI and deionized (DI)], both bioburden and endotoxin control are more difficult. This study shows that sterilizing grade, positively-charged filters can provide absolute bioburden control. In addition, these filters effectively retain high levels of both purified and cell-associated endotoxins over a five month period under severe intermittent system use conditions in a model high-purity water system. This study suggests a solution to the concerns over long-term use of bacterially retentive filters in properly maintained high-purity water systems.

Endotoxins↗
PubMedDate not supplied

Virus retention by a hydrophilic triple-layer PVDF microporous membrane filter.

Retention of bacteriophages (phi 6, PR772, T1, and PP7) and mammalian viruses (poliovirus and influenza A virus) by a hydrophilic triple layer PVDF microporous membrane, the Ultipor VF grade DV50 membrane, was evaluated. Challenges of membrane discs or pleated filter cartridges were performed at concentrations of 10(6)-10(8) PFU/mL in one or more of the following carrier fluids: water, saline, gelatin (0.1%) in phosphate buffer, Dulbecco's Modified Eagle Medium (MEM), and MEM supplemented with 10% fetal bovine serum (MEM + 10). The data demonstrate a minimum log titer reduction (LTR) of 6 for viruses larger than 50 nm irrespective of the carrier fluid. Protein transmission levels of greater than 95% for IgG and albumin were achieved. For integral pleated filter cartridges, correlation between a nondestructive integrity test (using the forward flow integrity test method) and virus retention was demonstrated. The Ultipor VF grade DV50 filter can be applicable in the manufacture of biologicals and biopharmaceuticals, where high protein transmission and consistent viral titer reduction are desired.

Membranes, Artificial↗