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Biomedical subjects

J Holt

Publications and source records attributed to J Holt.

At least 37 records · Page 2Linked to original sources
PubMed2000

Characterization of a recombinant outer surface protein A (OspA) vaccine against Lyme disease.

Lyme disease, the most prevalent tick-borne disease in the United States, results from infection with Borrelia burgdorferi sensu stricto. Early studies of Borrelia burgdorferi sensu stricto identified outer surface protein A (OspA), a lipoprotein on the surface of spirochetes that could be the target of protective antibodies to this agent. Pasteur Mérieux Connaught has developed a Lyme vaccine, ImuLyme, using recombinant OspA protein (rOspA). Methods were developed to routinely assess the identity, quantity, structure, purity, biological activity, heterogeneity, stability, and potency of rOspA. In addition, several methods were performed on a series of lots to support the routine testing methods and further our understanding of the physicochemical characteristics of rOspA. These tests were electrospray mass spectrometry, circular dichroism, two-dimensional gel electrophoresis, amino acid analysis, peptide mapping with peptide sequencing, and the application of proteomic methodology to identify trace contaminant host cell proteins. The results of these methods indicate that the rOspA lots are composed of highly purified and properly processed and folded rOspA with trace amounts of E. coli host cell proteins.

Amino Acid Sequence↗
PubMed1999

Cellular mechanisms of neuropathic pain, morphine tolerance, and their interactions.

Compelling evidence has accumulated over the last several years from our laboratory, as well as others, indicating that central hyperactive states resulting from neuronal plastic changes within the spinal cord play a critical role in hyperalgesia associated with nerve injury and inflammation. In our laboratory, chronic constriction injury of the common sciatic nerve, a rat model of neuropathic pain, has been shown to result in activation of central nervous system excitatory amino acid receptors and subsequent intracellular cascades including protein kinase C translocation and activation, nitric oxide production, and nitric oxide-activated poly(ADP ribose) synthetase activation. Similar cellular mechanisms also have been implicated in the development of tolerance to the analgesic effects of morphine. A recently observed phenomenon, the development of "dark neurons," is associated with both chronic constriction injury and morphine tolerance. A site of action involved in both hyperalgesia and morphine tolerance is in the superficial laminae of the spinal cord dorsal horn. These observations suggest that hyperalgesia and morphine tolerance may be interrelated at the level of the superficial laminae of the dorsal horn by common neural substrates that interact at the level of excitatory amino acid receptor activation and subsequent intracellular events. The demonstration of interrelationships between neural mechanisms underlying hyperalgesia and morphine tolerance may lead to a better understanding of the neurobiology of these two phenomena in particular and pain in general. This knowledge may also provide a scientific basis for improved pain management with opiate analgesics.

Animals↗
PubMed1999

[Children with birth weight 1500 g or under from Nordland in the period 1978-1989].

All 271 liveborn infants with birthweight < or = 1,500 g born of mothers residing in Nordland county during 1978-89 were studied retrospectively. Mean birthweight was 1,083 g, mean gestational age 29 weeks and 21% of the children were growth retarded. 18% of the newborns were transported from local hospitals to a neonatal intensive care unit, most of them (82%) by the unit's transport team. The number of infants delivered by caesarean section increased during the study period. 103 children (38%) died before the age of four. 15 children (6%) died after the newborn period, mostly due to bronchopulmonary dysplasia (n = 8) and sudden infant death syndrome (n = 4). Mortality rate corrected for birthweight < or = 500 g, lethal malformations and sudden infant death syndrome was 32%. The proportion of liveborn children suffering from cerebral palsy was 4.8%. Although the mortality rate remained unchanged during the study period, the proportion of disabilities decreased.

Adolescent↗
PubMed1999

Negative correlation between oral malodour and numbers and activities of sulphate-reducing bacteria in the human mouth.

The majority of cases of oral malodour are thought to be due to bacterial activities in the mouth, but many of the bacterial species responsible have not been identified. Volatile sulphide compounds have been proposed as constituents of oral malodour. Therefore, the relation between intensity of odour and numbers of bacteria in the mouth that are sulphide-producing from sulphate was investigated. Numbers of such dissimilatory sulphate-reducing bacteria (SRB) and sulphide reduction rates were evaluated in samples from different oral sites in relation to measures of oral malodour. Results showed that sulphate-reducing bacterial numbers and activities were negatively correlated with malodour, as determined by organoleptic assessment and measurement with a sulphide-monitoring instrument, the Halimeter. The data indicate that sulphide produced by oral SRB may not be an important contributor to oral malodour. A rather poor correlation was observed between Halimetric and organoleptic values, indicating that these methods may measure different aspects of oral malodour intensity.

Adult↗
PubMed1999

Moral guidance, moral philosophy, and moral issues in practice.

Approaches to teaching ethics to nurses have been debated in literature for some years. Three issues in particular are commonly addressed: the intentions of such teaching; the value of examples and case studies; and the compatibility of philosophical approaches with the clinical reality experienced by students. It is argued here that moral guidance as a strategy is unacceptable, and that a basic introduction to philosophical methods is the key to effective learning of the skills required for autonomous analysis and decision making. A means for including the use of personal experiences and case study material is presented which relies upon the provision of a framework of analysis to facilitate structured thinking and the pursuit of justifiable arguments. The approach suggested is compatible with students' existing experiences and work-context, and enhances the integration of ethical reasoning into the multi-faceted totality of clinical practice.

Clinical Competence↗
PubMed1999

Atopic diseases in Sami and Norse schoolchildren living in northern Norway.

Among children in the western world, atopic diseases are a major cause of morbidity. However, several prevalence studies have indicated that the frequency of these diseases displays both geographic and ethnic variations. In 1995, we conducted a questionnaire-based, cross-sectional survey in northern Norway. Atopic diseases among 8676 schoolchildren, aged 7-13 years, including 491 children with Sami ethnicity, were studied. The role of ethnicity (Sami/white Caucasian) was determined by comparing the reported atopic disease rate in each of the respective groups. In the areas under investigation (the cumulative incidence, the point prevalence of asthma and allergic rhinoconjunctivitis and the cumulative incidence of atopic dermatitis), the Sami children scored higher than the white Caucasian Norwegian children. The relative risks (RR) in Sami children were: current asthma RR = 2.01 [95% confidence interval (CI) 1.48-2.73]; current allergic rhinoconjunctivitis RR = 1.51 (95% CI 1.14-1.99); lifetime atopic dermatitis RR = 1.39 (95% CI 1.18-1.63). We thus conclude that there is an association between Sami ethnicity and asthma and allergy among schoolchildren in northern Norway.

Adolescent↗
PubMed1999

Air transport of the sick newborn infant: audit from a sparsely populated county in Norway.

The aim of this study was to describe principal problems and to analyse transport times, stabilizing procedures, adverse events during transfer, outcome, effectiveness and the care of infants transferred by air from district general hospitals and maternity homes to a central hospital. Transfer times, equipment adverse events and clinical deterioration were recorded as they occurred. Data regarding clinical problems, diagnoses and outcome were collected retrospectively from hospital records. During the study period (1984-95) 275 infants (267 transports) were transferred by fixed-wing aircraft (233) or helicopter (34). Median time from request of transfer to arrival of the transport team (usually a neonatal nurse and a paediatrician) was 120 min, median stabilizing time 60 min. Ninety-six infants (35%) were intubated, 62 (22.5%) by the transport team. During 34 transports (12.7%), equipment-related adverse events occurred making six infants worse. Ten more infants deteriorated during transit. A significant correlation between birthweight and after-transfer temperature was recorded. After-transfer temperature for very low birthweight (<1500 g, VLBW) infants was significantly higher when the transport team attended the delivery than when they did not (35.9 degrees C vs 34.7 degrees C). All nine infants (3.2%) with after-transfer temperature <34.0 degrees C died, 15 infants (5.5%) died within 24 h after transfer and 20 (7.3%) died later. Adjusted OR for death among transported versus in utero transferred VLBW infants was 3.8 (1.4-10.4). Every effort should be taken to transfer VLBW infants in utero. If preterm deliveries at 26-28 weeks of gestation at district general hospitals is unavoidable, an early request for the neonatal transport team to be there at delivery is advisable. Transport of very immature infants <26 weeks gestational age is not recommended. An outreach educational program ("Team Pink Newborn") has been created. Staff training to combat hypothermia and regular inspection and control of the transport equipment by three neonatal intensive care nurses has now been implemented.

Air Ambulances↗
PubMed1998

[Can deliveries at risk be selected at smaller delivery units?].

In order to explore the possibility of converting a delivery unit at a small hospital to a maternity home, we examined the medical records of those women who delivered by Caesarean section, forceps or vacuum extraction at Lofoten hospital during 1995. How many of these women might it have been necessary to transfer to an obstetrical department if Lofoten hospital had been a maternity home caring for low risk deliveries (primipara and multipara)? Out of a total of 271 deliveries (primiparas 98), 49 women delivered by Caesarean section (n = 35), forceps (n = 5) or vacuum extraction (n = 9). Using risk assessment, 22 women (45%) would have been selected for antenatal transfer, and 20 (41%) for intrapartum transport. For seven women no transfer would have been possible. These women would have delivered locally by vacuum extraction. Primipara versus multipara had a relative risk of 2.8 for Caesarean section or assisted vaginal delivery. It is estimated that 8-9% of the women would be selected prenatally for planned delivery at a hospital unit and that 7-8% would be transferred in labour if primiparas delivered at the maternity home. If primiparas were excluded, the proportions would be 41% and 1-2% respectively. In 1997 the delivery unit at Lofoten hospital was temporarily converted to a maternity home for a period of two years.

Birthing Centers↗
PubMed1998

Very low birthweight infants: outcome in a sub-Arctic population.

OBJECTIVE: To evaluate the outcome for very low birthweight (VLBW) infants in northern Norway. SUBJECTS AND METHODS: All live born infants (n = 536) with birthweight < or = 1500 g born during 1978-89 to women residing in the northern health region of Norway were studied retrospectively. Data were from the Medical Birth Registry (MBR), hospital records and from follow-up recordings to 4 y of age at maternal and child health centres. Stillborn infants (n = 269) with birthweight < or = 1500 g during the same period were also registered. RESULTS: The annual incidence of live born VLBW infants (7.1/1000 live births) did not change, but the proportion of infants born alive before 26 weeks' gestation increased and the stillborn part decreased significantly. The Caesarean section (CS) rate, antenatal transfer and the use of a neonatal transport team increased significantly. Four hundred and seventy-five infants (89%) were considered viable at birth, 347 (65%) survived to 1 y and 343 (64%) to 4 y. The likelihood of survival was independently related to female gender. The trend for survival to 4 y of age did not increase significantly. Thirty children suffered from cerebral palsy (8.7% of survivors, 5.6% of live births) and the cerebral palsy rate for infants with birthweight 751-1000 g decreased. The proportion of survivors considered to be normal or mild disabled increased and the part suffering from moderate or severe disability decreased significantly. CONCLUSIONS: In spite of long distances and unfavourable climatic conditions VLBW infants can be adequately cared for in this sparsely populated region of Norway.

Arctic Regions↗
PubMed1997

[Phimosis can be treated with local steroids].

The effectiveness of topical steroid application in relieving phimosis was studied in 41 boys treated with a potent steroid ointment. 35 patients showed improvement initially but in 12 of them the phimosis recurred completely and in seven of them partly. There was significantly less recurrence in the patients who improved within one month. Most of the families were satisfied with the treatment. We recommend topical steroids as first treatment of choice for phimosis, when treatment is necessary.

Administration, Topical↗
PubMed1997

Divalproex: a possible treatment alternative for demented, elderly aggressive patients.

Elderly, demented people often exhibit behavioral dyscontrol. Divalproex appears to be safe and effective in the management of this presentation. Twelve cases treated with divalproex all responded with improved emotional control. Patients became less verbally and physically disruptive and much more socially appropriate. Divalproex was well tolerated in this population with none of the subjects experiencing significant medicinal side effects. This uncontrolled report suggests that divalproex should be considered as a pharmacotherapy for aggressivity in cognitively impaired, elderly people.

Aged↗
PubMed1997

Violence in medical facilities: a review of 40 incidents.

Workplace violence has become an increasing problem in the United States. This paper reviews 40 such incidents of non-patient violence occurring in medical facilities. Areas of study include categories of violence, weapons used, number of persons killed or wounded, precipitant for the violent act, and the presence of psychopathology. Additional variables such as suicide, drug and alcohol use, stalking, and hostage-taking are also examined. The results indicate that workplace violence in medical settings differs considerably from incidents in other work environments, particularly with respect to motivation, psychiatric diagnoses, weapons used, and stalking. Intervention and management strategies in health care institutions may, therefore, need to be modified in order to deal with violence. An examination of the data allows development of a profile for violence in medical settings and the identification of risk factors. Security issues for hospitals, clinics, and physician offices are also discussed.

Adult↗
PubMed1995

Studies of the interaction between titin and myosin.

The interaction of titin with myosin has been studied by binding assays and electron microscopy. Electron micrographs of the titin-myosin complex suggest a binding site near the tip of the tail of the myosin molecule. The distance from the myosin head-tail junction to titin indicates binding 20-30 nm from the myosin COOH terminus. Consistent with this, micrographs of titin-light meromyosin (LMM) show binding near the end of the LMM molecule. Plots of myosin- and LMM-attachment positions along the titin molecule show binding predominantly in the region located in the A band in situ, which is consistent with the proposal that titin regulates thick filament assembly. Estimates of the apparent dissociation constant of the titin-LMM complex were approximately 20 nM. Assays of LMM cyanogen bromide fragments also suggested a strong binding site near the COOH terminus. Proteolysis of a COOH-terminal 17.6-kD CNBr fragment isolated from whole myosin resulted in eight peptides of which only one, comprising 17 residues, bound strongly to titin. Two isoforms of this peptide were detected by protein sequencing. Similar binding data were obtained using synthetic versions of both isoforms. The peptide is located immediately COOH-terminal of the fourth "skip" residue in the myosin tail, which is consistent with the electron microscopy. Skip-4 may have a role in determining thick filament structure, by allowing abrupt bending of the myosin tail close to the titin-binding site.

Amino Acid Sequence↗