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Biomedical subjects

B Perkins

Publications and source records attributed to B Perkins.

16 recordsLinked to original sources

Elimination of glucagon-like peptide 1R signaling does not modify weight gain and islet adaptation in mice with combined disruption of leptin and GLP-1 action.

Leptin and glucagon-like peptide 1 (GLP-1) exhibit opposing actions in the endocrine pancreas. GLP-1 stimulates insulin biosynthesis, secretion, and islet growth, whereas leptin inhibits glucose-dependent insulin secretion and insulin gene transcription. In contrast, GLP-1 and leptin actions overlap in the central nervous system, where leptin has been shown to activate GLP-1 circuits that inhibit food intake. To determine the physiological importance of GLP-1 receptor (GLP-1R)-leptin interactions, we studied islet function and feeding behavior in ob/ob:GLP-1R(-/-) mice. Although GLP-1R actions are thought to be essential for glucose-dependent insulin secretion, the levels of fasting glucose, glycemic excursion after glucose loading, glucose-stimulated insulin, and pancreatic insulin RNA content were similar in ob/ob:GLP-1R(+/+) versus ob/ob:GLP-1R(-/-) mice. Despite evidence linking GLP-1R signaling to the regulation of islet neogenesis and proliferation, ob/ob:GLP-1R(-/-) mice exhibited significantly increased islet numbers and area and an increase in the number of large islets compared with GLP-1R(+/+) or (-/-) mice (P < -0.01 to 0.05). Similarly, growth rates and both shortand long-term control of food intake were comparable in ob/ob:GLP-1R(+/+) versus ob/ob:GLP-1R4(-/-) mice. Furthermore, leptin produced a similar inhibition of food intake in GLP-1R(-/-), ob/ob:GLP-1R(+/+), and ob/ob:GLP1R4(-/-) mice. These findings illustrate that although leptin and GLP-1 actions overlap in the brain and endocrine pancreas, disruption of GLP-1 signaling does not modify the response to leptin or the phenotype of leptin deficiency in the ob/ob mouse, as assessed by long-term control of body weight or the adaptive beta-cell response to insulin resistance in vivo.

Animals↗

Epidemic serogroup B meningococcal disease in Oregon: the evolving epidemiology of the ET-5 strain.

CONTEXT: In 1993, Oregon's incidence of serogroup B meningococcal disease began to rise because of a highly clonal group of strains designated enzyme type 5 (ET-5), the first such increase observed in the United States. OBJECTIVE: To evaluate the impact that the ET-5 strain has had on the epidemiology of meningococcal disease in Oregon. DESIGN AND SETTING: Epidemiologic analysis of surveillance data on Oregon meningococcal disease cases from 1987 through 1996 and multilocus enzyme electrophoresis typing of serogroup B isolates from June 1993 through April 1995 and from April through June 1996. PATIENTS: A total of 836 persons with invasive meningococcal disease. MAIN OUTCOME MEASURES: Disease frequency and clonality of strains. RESULTS: Serogroup B disease incidence rates more than doubled from the preepidemic period in 1987-1992 (1.0 case per 100000 population) to the recent epidemic period in 1995-1996 (2.2 cases per 100000). The age-specific incidence rate of serogroup B disease among those 15 through 19 years old increased 13-fold between the preepidemic period (0.5 case per 100000) and 1995-1996 (6.4 cases per 100000). However, the proportion of cases with meningococcemia and the case-fatality rate did not change. Of 99 Neisseria meningitidis isolates obtained from 1993-1995, 88 (89%) belonged to the ET-5 complex. Of these, 69 (78%) were a single clone, designated 301. Of 20 serogroup B isolates from 1996, 18 (90%) belonged to the ET-5 complex; 17 (94%) were the 301 clone. CONCLUSION: Serogroup B meningococcal disease incidence continues at high levels in Oregon with increasing predominance of the ET-5 clonal strains.

Adolescent↗

Evaluation of meningococcal meningitis vaccination strategies for the meningitis belt in Africa.

BACKGROUND: Although the meningococcal polysaccharide vaccine has contributed to the control of Group A meningitis in the "meningitis belt" of Africa, recurrent large outbreaks have led to questions regarding vaccination strategy. We evaluated current and hypothetical vaccination strategies for the region. METHODS: A model was formulated to analyze the effectiveness and costs of vaccine campaigns in response to outbreaks based on 7 years of weekly incidence data from Burkina Faso. Additional models analyzed the potential impact and costs of either a 1- or 4-dose routine scheduled delivery of meningococcal polysaccharide vaccine based on data reported to the World Health Organization from 16 countries during 1948 through 1996. Vaccine efficacy, vaccination coverage and economic data from literature reviews provided model assumptions. RESULTS: For Burkina Faso neither 1- nor 4-dose vaccination schedules would prevent >30% of meningitis cases compared with the 42% prevented through an outbreak response program of vaccinating districts, which reach an incidence of 15 per 100000 persons for 2 weeks. For the entire meningitis belt, routine coverage with the 1- or 4-dose schedule meningococcal vaccine would require 4.9 and 19.6 million doses annually, respectively, for an annual net cost of $4.4 to $12.3 million and prevent an average 10300 to 12600 cases (23 to 28%), assuming a long term vaccine efficacy of 50%. In addition an initial "catch-up" campaign costing up to $72 million to vaccinate the population from 1 to 30 years of age would be required before achieving that level of effectiveness. CONCLUSION: Given the relatively poor routine vaccination coverage in this region, current strategies of vaccination campaigns that achieve higher coverage would generally be more effective and less costly than the modeled routine scheduled programs, assuming that campaigns can be rapidly implemented. Until a better vaccine is available, countries in this region would be more efficient in improving the response times to outbreaks, perhaps through improved surveillance, and in bolstering existing vaccination infrastructures rather than embarking on strategies of questionable effectiveness.

Africa↗

Capsule switching of Neisseria meningitidis.

The different sialic acid (serogroups B, C, Y, and W-135) and nonsialic acid (serogroup A) capsular polysaccharides expressed by Neisseria meningitidis are major virulence factors and are used as epidemiologic markers and vaccine targets. However, the identification of meningococcal isolates with similar genetic markers but expressing different capsular polysaccharides suggests that meningococcal clones can switch the type of capsule they express. We identified, except for capsule, isogenic serogroups B [(alpha2-->8)-linked polysialic acid] and C [(alpha2-->9)-linked polysialic acid] meningococcal isolates from an outbreak of meningococcal disease in the U. S. Pacific Northwest. We used these isolates and prototype serogroup A, B, C, Y, and W-135 strains to define the capsular biosynthetic and transport operons of the major meningococcal serogroups and to show that switching from the B to C capsule in the outbreak strain was the result of allelic exchange of the polysialyltransferase. Capsule switching was probably the result of transformation and horizontal DNA exchange in vivo of a serogroup C capsule biosynthetic operon. These findings indicate that closely related virulent meningococcal clones may not be recognized by traditional serogroup-based surveillance and can escape vaccine-induced or natural protective immunity by capsule switching. Capsule switching may be an important virulence mechanism of meningococci and other encapsulated bacterial pathogens. As vaccine development progresses and broader immunization with capsular polysaccharide conjugate vaccines becomes a reality, the ability to switch capsular types may have important implications for the impact of these vaccines.

Bacterial Capsules↗

Pulmonary function in spinal muscular atrophy.

We present the first prospective study on pulmonary function in spinal muscular atrophy patients. Seventy-seven spinal muscular atrophy patients, ages 5 to 18 years, from three centers, were studied with regard to forced vital capacity, using height as a predictor. Patients were categorized into four motor function categories. The highest-functioning group had normal or near-normal values, and those who sat with support had the lowest values. Those with intermediate function had intermediate values. Forced vital capacity was studied longitudinally in 40 spinal muscular atrophy patients for 1.1 to 4.4 years. Eighty-eight percent of patients grew in height, but only 35% showed an increase in height-adjusted forced vital capacity percent. In those patients with the least function, 100% lost height-adjusted forced vital capacity over time. In those patients with the highest function, 57% lost height-adjusted forced vital capacity. In addition, the basic forced vital capacity, not correlated to height, decreased in 43% of cases. These pulmonary function alterations appear to be important determinants for function and survival in spinal muscular atrophy patients.

Adolescent↗

Botulinum A chemodenervation: a new modality in cerebral palsied hands.

Botulinum A chemodenervation of the Adductor Pollicis muscle for the treatment of the thumb-in-palm deformity in cerebral palsied hands is presented as a new therapeutic option. Early results of a clinical trial in five hemiparetic Cerebral Palsied (C.P.) children are assessed using a prospective nontrialist-biased study design based on an independent panel assessment of pre- and post-intervention photographic and videotaped records of hand function and appearance, in combination with grip dynamometry and goniometry. All cases are shown to improve in terms of both function and appearance with results approaching statistical significance (p = 0.06) when assessed by the Wilcoxon's matched-pairs signed rank test, despite the small study group. The modality is shown to be simple, safe and effective over the period reported (229 days). The benefit is sustained beyond the period of muscle paresis and ongoing long term follow-up will document the need for, and timing of, reinjection.

Botulinum Toxins↗

Spinal muscular atrophy: new thoughts on the pathogenesis and classification schema.

We have established the first prospective, collaborative study of spinal muscular atrophy, the second most common neuromuscular disease of childhood. One hundred and forty-one patients have been evaluated on at least four occasions over a 3-year period. The patients have been grouped by age of onset, as well as by function at the time of initial evaluation. The muscle strength of 96 patients aged 5 years or older was evaluated at 6-month intervals using a fixed myometry system. The new observations made are: (1) The present classification schema is not valid; for example, 49 patients with onset of weakness before 6 months of age (type I or Werdnig-Hoffmann disease), whose life span is said to be only 2 to 4 years, participated in the study and are 4 months to 31 years of age. (2) Thirty-seven patients were evaluated over an 18-month period. None lost strength during this time but four lost function. Although the period of observation was short, the results suggest that the loss of function in patients with spinal muscular atrophy might be explained by a process other than cell death that allows patient strength to be maintained and simultaneously prevents the motor unit from achieving its normal adult potential.

Adolescent↗

Levels of rifampin and ciprofloxacin in nasal secretions: correlation with MIC90 and eradication of nasopharyngeal carriage of bacteria.

To predict the efficacy of antibiotics in eliminating nasopharyngeal carriage of organisms such as Neisseria meningitidis, Haemophilus influenzae, and methicillin-resistant Staphylococcus aureus (MRSA), a novel approach for measuring drug concentrations in nasal secretions was developed. Five healthy individuals received four doses of rifampin and then, at a later date, ciprofloxacin. At 2, 5, and 8 h after the last dose, serum, saliva, and cold-stimulated nasal secretion samples were collected, and drug levels were analyzed by high-performance liquid chromatography. Nasopharyngeal levels of rifampin reached but did not substantially exceed 90% of the minimal inhibitory concentration (MIC90) for H. influenzae, exceeded the MIC90 for N. meningitidis, and were well above that for MRSA. Ciprofloxacin levels in nasal secretions far exceeded the MIC90 for meningococci and Haemophilus organisms but were below that for MRSA. These findings are consistent with the clinical studies showing that rifampin eliminates, in most instances, the nasal carriage of N. meningitidis and to a lesser extent H. influenzae. A single dose of ciprofloxacin has been shown to eradicate meningococci, yet a long course of treatment with this drug is not adequate for MRSA. On the basis of these results, clinical trials with ciprofloxacin to eliminate nasopharyngeal carriage of H. influenzae appear to be warranted.

Carrier State↗

Soft high tech.

Explore the source record for details and available documents.

British Columbia↗

Fast work on new addition saves money.

A hospital administrator and a design team worked with clearly established needs and constraints and have made it possible to complete a special care addition in 18 months.

Hospital Bed Capacity, 100 to 299↗