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Biomedical subjects

J S Roberts

Publications and source records attributed to J S Roberts.

At least 19 recordsLinked to original sources
PubMed1999

Phase I safety and antigenicity of TA-GW: a recombinant HPV6 L2E7 vaccine for the treatment of genital warts.

A phase I double-blind, randomized, placebo-controlled study was carried out in healthy subjects to assess the safety and immunogenicity of TA-GW, a recombinant HPV6 L2E7 fusion protein vaccine for the treatment of genital warts. Forty-two healthy male volunteers were randomised to receive three intramuscular injections of either 0, 3, 30 or 300 microg of recombinant L2E7 adsorbed onto Alhydrogel. Two vaccination schedules were compared: weeks 0, 1 and 4 (accelerated schedule) and weeks 0, 4 and 8 (classical schedule). Subjects were monitored for adverse events throughout. Immunogenicity was assessed by measuring L2E7 specific in vitro T cell proliferative responses, production of IFNgamma and IL-5 and serum antibodies. Dose-dependent and long-lived T and B cell immune responses were elicited by TA-GW with both vaccination schedules. In conclusion, TA-GW is both safe, well-tolerated and immunogenic. The results allow the selection of the 300-microg vaccine formulation and accelerated vaccination schedule for phase II trials in patients with genital warts.

Adult↗
PubMed1999

Phase IIa safety and immunogenicity of a therapeutic vaccine, TA-GW, in persons with genital warts.

A fusion protein vaccine consisting of human papillomavirus 6 L2E7 with Alhydrogel was developed for the treatment of genital warts. Twenty-seven subjects with genital warts received 3 immunizations over 4 weeks in an open-label study. The vaccine was well-tolerated, and all subjects made serum IgG antibodies, predominantly IgG1, against L2E7. Nineteen of 25 tested persons made antigen-specific T cell proliferative responses to L2E7, and peripheral blood mononuclear cells when cultured with L2E7 in vitro produced both interferon-gamma and interleukin (IL)-5, although IL-5 predominated after the final vaccination. Five subjects completely cleared warts within 8 weeks. Subjects whose warts were not cleared by 8 weeks were offered conventional therapy. Recurrence of warts was not seen in any of the 13 persons whose warts cleared by vaccine alone or with conventional therapy. While these preliminary results of the use of this therapeutic immunogen are encouraging, proof of efficacy will require randomized double-blind trials.

Adult↗
PubMed1999

Telescoping of landmark events associated with drinking: a gender comparison.

OBJECTIVE: The literature suggests that women exhibit "telescoped" development of (i.e., faster progression to) alcoholism, with fewer years drinking than men. The purpose of this study was to use data gathered in the course of a large clinical trial to further examine this issue. METHOD: Subjects in this retrospective study were from a pool of 1,307 men and 419 women enrolled in Project MATCH, a multisite alcohol treatment matching study. MATCH subjects were recruited from both outpatient and aftercare settings over a 2-year period. Age-of-onset for landmark events in the development of alcoholism were determined from self-report and clinical interviews given at baseline entry into the study. Gender differences in age-of-onset variables were assessed within both outpatient and aftercare settings. Gender differences in progression times between successive landmarks were also examined. Differences were tested with both multivariate and univariate ANOVA techniques. RESULTS: Women generally began getting drunk regularly at a later average age than men (26.6 versus 22.7 years, p< or =.001), began experiencing their first drinking problems at a later average age than men (27.5 versus 25.0 years, p< or =.001) and exhibited loss of control over their drinking at a later average age than men (29.8 versus 27.2 years, p< or =.001). However, these gender differences were most pronounced for older individuals and attenuated for younger subjects. Women also progressed faster than men, on average, between first getting drunk regularly and first encountering drinking problems (0.9 versus 2.3 years, p< or =.001) and between first loss of drinking control and onset of worst drinking problems (5.5 versus 7.8 years, p< or =.001). Women also exhibited shorter average progression times between first getting drunk regularly and first seeking treatment (11.6 versus 15.8 years, p< or =.001), although this effect was negligible for younger subjects. CONCLUSIONS: Telescoping is a relatively robust phenomenon in treatment-seeking alcoholics and indicates that women are more likely to progress faster through the landmark events in the development of alcoholism than are men.

Adult↗
PubMed1998

The effect of drinking intensity and frequency on serum carbohydrate-deficient transferrin and gamma-glutamyl transferase levels in outpatient alcoholics.

Whereas heavy alcohol consumption is known to elevate serum carbohydrate-deficient transferrin (CDT) and gamma-glutamyl transferase (GGT) levels, the contribution of drinking pattern to these effects is not completely understood. We present data on 423 men and 146 women evaluated 1 year after treatment in a large-scale alcoholism treatment study (Project MATCH). Relationships between drinking frequency (number of days drinking), intensity (drinks per drinking day), and blood levels of CDT and GGT were analyzed by using response surface regression models and thin-plate spline-smoothing techniques. Both models indicated differences between CDT- and GGT-drinking pattern relationships in men and, also, a difference between men and women in CDT drinking-pattern relationships. For men, CDT levels appeared to respond primarily to frequency of drinking, whereas GGT was influenced primarily by drinking intensity. For women, both CDT and GGT were influenced more by drinks per drinking day (intensity) than by number of days drinking (frequency). The data confirm both the independent nature of these biological markers of alcohol consumption and gender differences in alcohol-induced CDT response reported previously.

Adult↗
PubMed1998

Efficacy and complications of percutaneous pigtail catheters for thoracostomy in pediatric patients.

OBJECTIVE: To describe the efficacy of percutaneous pigtail catheters in evacuating pleural air or fluid in pediatric patients. DESIGN: A case series of children with percutaneous pigtail catheters placed in the pediatric ICU between January 1996 and August 1997. SETTING: Urban pediatric teaching hospital in Seattle, WA. METHODS: A retrospective chart review. RESULTS: Ninety-one children required 133 chest catheters. Most patients were infants with congenital heart disease (80%). One hundred thirteen of the catheters (85%) were placed for pleural effusion, with 20 tubes (15%) placed for pneumothorax. Efficacy of drainage of pleural fluid was significantly greater in serous (96%) and chylous (100%) effusions compared with empyema (0%) or hemothorax (81%). Evacuation of pneumothorax was achieved by a pigtail catheter in 75% of patients. Resolution of pleural air or pneumothorax was significantly greater in patients < 10 kg compared with larger children. Complications due to placement of the pigtail catheters included hemothorax (n=3, 2%), pneumothorax (n=3, 2%), and hepatic perforation (n= 1, 1%). There were also complications arising from the use of the catheters, including failure to drain, dislodgment, kinking, loss of liquid ventilation fluid, empyema, and disconnection in 27 of 133 catheters (20%). Significantly more complications during catheter use occurred in patients <5 kg than in larger children. CONCLUSIONS: Percutaneous pigtail catheters are highly effective in drainage of pleural serous and chylous effusions, somewhat less efficacious in drainage of hemothorax or pneumothorax, and least efficacious in drainage of empyema. Infants and smaller children had higher rates of resolution of pleural air and fluid from placement of a pigtail catheter than larger children. Complications from catheter placement were uncommon (5%) but serious, whereas complications associated with continued use of the catheters were more common (20%) but less grave. Strict attention to anatomic landmarks and close monitoring may reduce the number of complications.

Adolescent↗
PubMed1998

Colloid volume expanders. Problems, pitfalls and possibilities.

Colloid solutions have been developed and used over the past 70 years as expanders of the intravascular space, based on an understanding of Starling's law. Increasing osmotic pressure with colloidal products has remained an attractive theoretical premise for volume resuscitation. Indeed, colloids have been shown to increase osmotic pressure in clinical practice; however, the effects are short-lived. Lower molecular weight colloids exert a larger initial osmotic effect, but are rapidly cleared from the circulation. Larger molecules exert a smaller osmotic pressure that is sustained longer. The main drawback to colloid therapy lies in pathological states with endothelial injury and capillary leak, precisely the clinical scenario where colloids are commonly given. The colloid solution may leak into the interstitium and remain there exerting an osmotic gradient, pulling additional water into the interstitium. There are 4 general types of colloid products available for clinical use. Albumin is the predominant plasma protein and remains the standard against which other colloids are compared. Albumin, pooled from human donors, is in short supply and remains expensive. Dextrans have been used to prevent deep venous thrombosis and to lower blood viscosity during surgery. Hetastarch has been widely used as a plasma volume expander. It provides equivalent plasma volume expansion to albumin, but has been shown to alter clotting parameters in studies (prolonging the activated partial thromboplastin time and prothrombin time). Although severe coagulopathies have been reported in sporadic cases, hetastarch has not been shown to increase postoperative bleeding compared with albumin therapy, even in large doses (3 L/day). Despite some theoretical advantages compared with crystalloid therapy, colloid administration has not been shown to decrease the risk of acute lung injury or to improve survival. Specific indications for colloid products include hypoproteinaemic or malnourished states, patients who require plasma volume expansion who are unable to tolerate larger amounts of fluid, orthopaedic and reconstructive procedures requiring prevention of thrombus formation and leukapheresis.

Colloids↗
PubMed1997

Acute lethal toxicity following passive immunization for treatment of murine cryptococcosis.

Passive immunization with monoclonal antibodies (MAbs) specific for the major capsular polysaccharide of Cryptococcus neoformans alters the course of murine cryptococcosis. During studies of passive immunization for treatment of murine cryptococcosis, we noted the occurrence of an acute, lethal toxicity. Toxicity was characterized by scratching, lethargy, respiratory distress, collapse, and death within 20 to 60 min after injection of antibody. The toxic effect was observed only in mice with a cryptococcal infection and was reduced or absent in the early and late stages of disease. The clinical course and histopathology were consistent with those for shock. There was considerable variation between mouse strains in susceptibility to toxicity. Swiss Webster mice from the Charles River colony were most susceptible, followed by C3H/He, BALB/c, and C57BL/6 mice. DBA/2 mice and Swiss Webster mice from the Simonsen colony were resistant. Acute toxicity was mimicked by injection of preformed complexes of MAb and purified polysaccharide. The toxic effect was also produced by injection of MAbs into mice that were preloaded with polysaccharide. The toxic effect was not blocked by treatment of mice with chloropheniramine or anti-tumor necrosis factor alpha antibodies or by depletion of complement components via pretreatment with cobra venom factor. Toxicity was reduced by treatment of mice with high doses of epinephrine, dexamethasone, or chlorpromazine. Finally, the toxic effect was completely blocked by treatment of mice with the platelet-activating factor antagonist WEB 2170 BS or by pretreatment of mice with the liposome-encapsulated drug dichloromethylene diphosphonate, a procedure which depletes macrophages from the spleen and liver.

Animals↗
PubMed1996

Quantifying the clinical significance of drug-drug interactions: scaling pharmacists' perceptions of a common interaction classification scheme.

OBJECTIVE: To develop a precise, interval level scale of the clinical significance of drug-drug interactions that reflects the professional judgments of practicing pharmacists. PARTICIPANTS: A convenience sample of 63 practicing pharmacists representing hospital (clinical and staff) and retail (chain and independent) practice settings. METHOD: Pharmacists judged the similarity among 15 interaction categories that have been commonly used to classify drug-drug interactions. A multidimensional scaling technique produced a spatial representation (i.e., a psychological map) of the structure inherent in those similarity judgments. Pharmacists' ratings of clinical significance were projected onto that same spatial representation using a multiple regression procedure, and the resulting information was used to develop a scale of clinical significance. RESULTS: The clinical significance scale developed from pharmacists' judgments was substantially different from a comparison scale published in a popular reference. The new scale was more precise than the comparison scale, and it also approximated an interval level of measurement. The judgments used to produce the new clinical significance scale were not reliably influenced by pertinent demographic characteristics of the sample. CONCLUSIONS: Inconsistencies between published clinical significance scales and the professional judgments of practitioners could affect patient care to the degree that a summary measure of clinical significance affects a practitioner's response to a potential drug-drug interaction. The clinical significance scale developed in this study has good measurement characteristics and reflects the professional judgments of practicing pharmacists. Use of the new scale is recommended on these grounds, although further assessment of its generality is warranted.

Drug Interactions↗
PubMed1995

Pregnancy, lactation, and menopause: how physiology and gender affect the toxicity of chemicals.

We explore ways in which biological events and nonbiological gender factors in women's lives can mediate the toxicity of chemicals to women. We examine the physiologic changes that accompany pregnancy, lactation, and menopause in order to discuss how these changes might influence the target organ dose and distribution of toxic chemicals within women's bodies. We suggest that the interactions between divalent metals and calcium metabolism and those between lipophilic chemicals and fat metabolism could modulate the toxicity of metallic and lipophilic toxins in women over the course of a lifetime. These hypotheses need careful research consideration.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1994

Efficacy of Haemophilus influenzae type b conjugate vaccine PRP-T.

Efficacy of the Haemophilus influenzae type b (Hib) conjugate vaccine PRP-T (Pasteur-Merieux) was evaluated in a controlled community intervention study in the Oxford region, UK. PRP-T was offered to infants from May 1, 1991 in three of the region's eight districts and from July 1, 1991, in a fourth district. It was given by separate injection in addition to the standard diphtheria, tetanus, and pertussis vaccine according to an accelerated 2, 3, and 4 month schedule without a booster dose in the second year of life. By October 1, 1992, more than 90% of infants in vaccine districts had received at least one dose of PRP-T. None of the infants given three doses had developed Hib infection, whereas 11 infections occurred in the control population (vaccine efficacy 100%, 95% CI 80-100%). Intention-to-treat analysis also showed a high estimate of efficacy for the vaccine (90%, 50-99%). Follow-up of study children until November 1, 1993, has shown only 1 vaccine failure in an infant, and no invasive infections in those older than 1 year (average age 22 months). PRP-T vaccine had high protective efficacy with an accelerated immunisation schedule. Furthermore, the vaccine appears to remain protective through the second year of life without a booster dose. These findings provide encouragement for use of PRP-T in the Expanded Programme of Immunisation.

Child, Preschool↗
PubMed1994

Measuring, managing, and improving quality in the end-stage renal disease treatment setting: committee statement.

The Institute of Medicine (IOM) committee that organized the conference reported in this issue of the journal on assessing quality of care and quality of life, wishes to emphasize that it regards the task of measuring quality as one that can be approached systematically, albeit with caution. Outcomes of end-stage renal disease (ESRD) care by dialysis and transplantation (and variations of outcomes among treatment units) and related processes of care need to be measured in ways useful to clinicians. In addition to clinical measures of outcome, the committee also favored giving greater attention to functional outcomes and health-related quality of life. The interest in maintaining and improving quality in the treatment setting reflects an underlying need to encourage its systematic assessment on a sustained basis, with appropriate weight devoted to practical issues.

Humans↗
PubMed1994

Linking outcomes measurement to continual improvement: the serial "V" way of thinking about improving clinical care.

BACKGROUND: Outcomes measurement, process improvement, and continual improvement all have been used to improve quality in health care. However, the mutually complementary approaches have been used primarily in isolation from each other. The "Serial V" ("Vee") concept attempts to integrate these approaches to provide a fuller assessment and practical approach to quality improvement. METHODS: Outcomes measurement is used primarily to identify variations in care and possibly to determine corrective actions that may minimize those variations. Process improvement focuses on breaking down the components of a specific process of health care delivery, identifying or reworking problem areas in the process, then rebuilding the process. Continual improvement involves pinpointing a particular area for improvement, proposing specific changes, testing the instituted changes, and evaluating the success of such changes. The Serial V concept is an integrative strategy that incorporates aspects of all three approaches to create a comprehensive way to evaluate, institute, and reflect on change aimed at improvement. While this way of thinking appears complex at first glance, a practical worksheet that details each step in the process can be used to begin the clinical improvement work. Use of the Serial V approach, which unites measurement of outcomes, analysis of the clinical process, and repeated pilot tests to improve outcomes in real-world clinical settings, will accelerate improvement in health care outcomes and eliminate unnecessary costs.

Clinical Protocols↗
PubMed1993

Cell migration in cultured cerebral cortical slices.

In order to investigate the cellular mechanisms of migration and lamination in the mammalian cerebral cortex, we have cultured living slices of the developing telencephalon and tracked the migration of newly generated cortical neurons. Slice cultures made from neonatal ferret cortex were maintained in roller tubes and survived well for several weeks in vitro. Cells generated on Postnatal Day (P) 0 or 1 were labeled with the thymidine analog 5-bromo-2-deoxy-uridine (BrdU), and their movements were tracked during the subsequent culture period. At the beginning of the culture period, labeled cells were found almost exclusively in the proliferative zones of the cerebral wall, the ventricular and subventricular zones. Over the first week in culture, there was a dramatic movement of labeled cells out of the proliferative zones and into the cortical plate, the final destination of neocortical neurons. Comparison of the patterns of cell movement in cultured slices with that in intact littermate controls revealed that the initial migration of labeled cells into the cortical plate is similar in cultured slices and normal animals. The primary difference between migration in slice cultures and in vivo is that after longer times in culture, cells that migrate into the cortical plate fail to form the tightly clustered laminae characteristic of cells in the intact brain. Labeled cells are instead distributed more widely throughout the cortical plate and other regions of the cerebral wall. Thus, at least during the initial period of migration, cultured slices provide an experimentally manipulable system in which cell migration can be directly observed in a histotypically normal environment.

Animals↗
PubMed1990

Influenza vaccine and anticoagulation control in patients receiving warfarin.

The effects of a trivalent split virion influenza vaccine on anticoagulation control were prospectively evaluated in a sample of well-controlled warfarin recipients. Vaccine-induced changes in prothrombin time ratios were not detected during one month of follow-up after immunisation. The results are supported by the findings of other studies conducted in this country and the USA, which have all refuted the conclusions of early reports that suggested a possible interaction between warfarin and influenza vaccine.

Aged↗