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Biomedical subjects

D Griffith

Publications and source records attributed to D Griffith.

At least 19 recordsLinked to original sources
PubMed2001

The Incontinence Impact Questionnaire and the Urogenital Distress Inventory: a revisit of their validity in women without a urodynamic diagnosis.

OBJECTIVES: We sought to assess validity of the Incontinence Impact Questionnaire (IIQ) and the Urogenital Distress Inventory (UDI) (long and short forms) in incontinent women previously urodynamically undiagnosed. STUDY DESIGN: Post hoc analysis of responses to the IIQ and UDI questionnaires were obtained from a trial on a urethral device in community-dwelling incontinent women. Internal consistency and validity were evaluated against the 1-hour pad test. RESULTS: Internal consistency (Cronbach's alpha) for the long forms was high for the IIQ and moderately high for the UDI, good for the IIQ-short, but poor for the UDI-short. Correlations with 1h pad test were low and non-significant for both versions. Correlation of the short with the long forms was high. CONCLUSION: In the community-dwelling population, without a urodynamic diagnosis, neither long nor short versions of the questionnaires correlate with the severity of the urinary incontinence as shown by the pad test. The validity of the current questionnaires in women without urodynamic diagnosis is questionable.

Adult↗
PubMed2001

Emerging areas of research reported during the CDC National Conference on Pfiesteria: from biology to public health.

Since its identification in 1996, the marine dinoflagellate Pfiesteria piscicida Steidinger & Burkholder has been the focus of intense scientific inquiry in disciplines ranging from estuarine ecology to epidemiology and from molecular biology to public health. Despite these research efforts, the extent of human exposure and the degree of human illness directly associated with Pfiesteria is still in the process of being defined. Unfortunately, during this same time Pfiesteria has also stimulated media coverage that in some instances jumped ahead of the science to conclude that Pfiesteria presents a widespread threat to human health. Political and economic forces also came into play when the tourism and seafood industries were adversely impacted by rumors of toxin-laden water in estuaries along the east coast of the United States. Amid this climate of evolving science and public concern, Pfiesteria has emerged as a highly controversial public health issue. In October 2000 Centers for Disease Control and Prevention sponsored the National Conference on Pfiesteria: From Biology to Public Health to bring together Pfiesteria researchers from many disparate disciplines. The goal of this meeting was to describe the state of the science and identify directions for future research. In preparation for the conference an expert peer-review panel was commissioned to review the existing literature and identify research gaps; the summary of their review is published in this monograph. During the meeting primary Pfiesteria researchers presented previously unpublished results. The majority of those presentations are included as peer-reviewed articles in this monograph. The discussion portion of the conference focused upon researcher-identified research gaps. This article details the discussion segments of the conference and makes reference to the presentations as it describes emerging areas of Pfiesteria research.

Animals↗
PubMed2000

SAR studies of anti-MRSA non-zwitterionic 3-heteroarylthiocephems.

SAR studies in a series of 3-heteroarylthio substituted cephalosporins established that high activity against methicillin-resistant Staphylococcus aureus (MRSA) can be achieved with various heteroaryl substituents. Early results showed that highly lipophilic 3-heteroarylthio substituents, which were necessary for anti-MRSA activity, caused high affinity of such cephems toward serum proteins. Our earlier published efforts described discovery of zwitterionic cephems MC-02,331 and RWJ-54428 (MC-02,479), where serum binding was reduced by employing basic, positively charged functionalities attached to the 3-heteroarylthio substituent. In order to avoid low solubility problems associated with most such zwitterionic cephalosporins a wide variety of non-basic heteroaryl substituents was tested (non-zwitterionic cephems are more easily formulated as water soluble sodium salts for intravenous administration). Considerable reduction in serum binding was obtained in some analogs while maintaining high anti-MRSA potency.

Animals↗
PubMed2000

Discovery of RWJ-54428 (MC-02,479), a new cephalosporin active against resistant gram-positive bacteria.

The discovery of RWJ-54428 (MC-02,479), a new cephalosporin displaying promising activity against sensitive and resistant Gram-positive bacteria, is described. Progressive structural modification from the previously reported 3-phenylthiocephem MC-02,331 afforded an overall increase in potency against MRSA while retaining other key properties such as acceptable solubility and serum binding. Evaluation of the in vitro potency and in vivo efficacy of a series of closely related compounds resulted in selection of RWJ-54428 (MC-02,479) for further studies.

Cephalosporins↗
PubMed1999

Autocatalytic processing of the streptococcal cysteine protease zymogen: processing mechanism and characterization of the autoproteolytic cleavage sites.

The autocatalytic processing of the streptococcal cysteine protease zymogen (proSCP) to active streptococcal cysteine protease (SCP) was investigated in vitro using purified protein from Streptococcus pyogenes strain B220. It was found that the autocatalytic maturation of the zymogen proceeds through the sequential appearance of at least six intermediates, five of which were characterized through a combination of N-terminal sequencing and MS. Intermediates were identified as resulting from cleavages after Lys26, Asn41, Lys101, Ala112, and Lys118. Time-course studies of the proSCP processing gave a sigmoidal activity profile and indicated that proSCP catalyses its own transformation, mainly via an intermolecular processing mechanism. A similar sequential appearance of intermediates was observed when inactive Cys192Ser proSCP was treated with native, enzymatically active SCP, thus demonstrating that the maturation can exclusively proceed by a bimolecular mechanism. It was shown that proSCP, but not mature SCP, immobilized on a Sepharose resin is capable of liberating itself from the column, indicating that the zymogen is also capable of intramolecular processing. In order to test whether the amino acid sequences at the processing sites could be used for developing new, specific substrates, 3-amino benzoic acid octapeptide derivatives based on all five characterized amino acid sequences from the autoprocessing cleavage sites were synthesized and tested for activity. The 3-amino benzoic acid derivatives have kcat/KM values ranging from 1200 to 7700.M-1.s-1, making them very good endopeptidase substrates for SCP.

Amino Acid Sequence↗
PubMed1998

Discovery of MC-02,331, a new cephalosporin exhibiting potent activity against methicillin-resistant Staphylococcus aureus.

A systematic approach toward building activity against methicillin-resistant staphylococci into the cephalosporin class of beta-lactam antibiotics is described. Initial work focused on finding the optimal linkage between the cephem nucleus and a biphenyl pharmacophore, which established that a thio linkage afforded potent activity in vitro. Efforts to optimize this activity by altering substitution on the pharmacophore afforded iodophenylthio analog MC-02,002, which although highly potent against MRSA, was also highly bound to serum proteins. Further work to decrease serum protein binding showed that replacement of the iodo substituent by the positively-charged isothiouronium group afforded potent activity and reduced serum binding, but insufficient aqueous solubility. Solubility was enhanced by incorporation of a second positively-charged group into the 7-acyl substituent. Such derivatives (MC-02,171 and MC-02,306) lacked sufficient stability to staphylococcal beta-lactamase enzymes. The second positive charge was incorporated into the cephem 3-substituent in order to utilize the beta-lactamase-stable aminothiazolyl(oximino)acetyl class of 7-substituents. These efforts culminated with the discovery of bis(isothiouroniummethyl)phenylthio analog MC-02,331, whose profile is acceptable with respect to potency against MRSA, serum binding, aqueous solubility, and beta-lactamase stability.

Animals↗
PubMed1997

Characterization of a rabbit model of staphylococcal osteomyelitis.

We previously described a rabbit osteomyelitis model that involved the direct introduction of Staphylococcus aureus into devascularized bone. To further evaluate the model, we performed experiments aimed at correlating the microbiological, radiographic, and histologic parameters involved in the development of experimental osteomyelitis. Using the strain UAMS-1, we achieved an infection rate of 75% with an inoculum as small as 2 x 10(3) colony-forming units. However, development of significant radiographic and histologic signs of disease required an inoculum of at least 2 x 10(4) colony-forming units. Radiographic signs were minimal 1 week after infection and progressed steadily to a maximum 3 weeks after infection. In contrast, histologic signs of disease were observed within 1 week and remained essentially unchanged throughout the 4-week evaluation period. Unlike the results obtained with UAMS-1, rabbits infected with the heavily encapsulated Staphylococcus aureus strain Smith diffuse exhibited little evidence of disease even when infected with 2 x 10(6) colony-forming units. The reduced virulence of strain Smith diffuse was surprising given its greatly enhanced virulence (relative to UAMS-1) in a murine peritonitis model of staphylococcal disease. These results suggest that UAMS-1 expresses virulence factors that are important in the pathogenesis of osteomyelitis and that some or all of these virulence factors are either absent or are not expressed in strain Smith diffuse. Most importantly, the results suggest that our model may be appropriate for the identification and characterization of these virulence factors.

Animals↗
PubMed1996

Cytomegalovirus involving gastrointestinal tract in renal transplant recipients.

Infection due to cytomegalovirus (CMV) is a substantial cause of mortality and morbidity among renal transplant recipients but the prognosis of the disease has changed dramatically since the introduction of ganciclovir (GAN). During a period of 5 years we treated 54 patients who developed CMV disease. From this group of patients we identified 7 patients with primary gastrointestinal tract (GIT) CMV disease who received treatment with GAN. Tissue diagnosis was made by endoscopy of the upper GIT (6 patients) or sigmoidoscopy (one patient) and histological examination. All patients improved after treatment with GAN; three patients required additional treatment for recurrent CMV disease and recovered, and 1 patient relapsed without GIT involvement (P = 0.014). Recurrent CMV disease was more severe (mean score of 15 in relapse compared to 7 in the first episode). We believe relapse to be more common and the disease to be more severe in the presence of GIT involvement suggesting that a longer duration of treatment with GAN may be required in this clinical manifestation of CMV disease.

Adolescent↗
PubMed1996

Facilitating the recovery of open heart surgery patients through quality improvement efforts and CareMAP implementation.

OBJECTIVE: To illustrate, using a literature review and CareMAPs, how care coordination and implementation of standard protocols can impact clinical outcomes for open heart surgery patients. METHODS: A CareMAP for open heart surgery patients was developed by a multidisciplinary team. To evaluate the effectiveness of CareMAP implementation and specific quality improvement efforts, a pilot study was done that focused on increasing activity levels, decreasing ventilator time, and decreasing the frequency of arterial blood gas sampling for a sample of 55 open heart surgery patients. A rapid recovery program was developed based on the results of this pilot study. A multidisciplinary continuous quality improvement team was developed to focus on three primary areas: ventilator weaning time, activity regimens, and early transfer to the open heart surgery step-down unit. Forty-nine open heart surgery patients were included in the initial program evaluation. RESULTS: The frequency of arterial blood gas sampling decreased from an average of 5.8 per patient to an average of 3.9 per patient. Postoperative length of stay also decreased by 1.3 days for diagnosis related group 106 patients, and 3.7 days for diagnosis related group 107 patients. Results of the pilot study demonstrated additional opportunities for improving the care of open heart surgery patients. Using the rapid recovery program, the average ventilator time decreased by 4.4 hours per patient. The average postoperative length of stay decreased to 4.7 days. CONCLUSIONS: Through the quality improvement process and through the use of CareMAPs and specific protocols, the recovery of open heart surgery patients was facilitated.

Analysis of Variance↗
PubMed1993

Respite care.

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Community Health Services↗
PubMed1993

Microwave sterilization of polyethylene catheters for intermittent self-catheterization.

A standard household 650 W microwave oven was used to sterilize polyethylene catheters of the type used for intermittent self-catheterization. The catheters were infected with Proteus sp. bacteria and microwaved at 650 W for periods of 2, 4, 6 and 8 minutes. The effect of microwaving was assessed by determining the resultant colony counts following catheter culture. It was determined that 6 minutes of microwaving were required to achieve sterility. It is suggested that use of a microwave oven is a reliable and cost-effective method of sterilizing polyethylene catheters for intermittent self-catheterization.

Catheterization↗