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Biomedical subjects

K Jones

Publications and source records attributed to K Jones.

At least 127 records · Page 7Linked to original sources

Accuracy of cyclosporin measurements made in capillary blood samples obtained by skin puncture.

International consensus guidelines suggest that cyclosporin should be measured in whole blood. In some instances it may be advantageous to collect capillary blood, by a finger or ear prick method. However, drug concentrations in skin-puncture blood may not necessarily correlate with those measured in venous blood. This study compared cyclosporin concentrations in blood collected from the fingertip or earlobe with blood collected by standard venipuncture. Patient preference for each of the blood collection methods was also assessed. Specimens were obtained from organ transplant patients receiving cyclosporin, using each of the three methods: venipuncture, finger prick, and earlobe prick. The samples were assayed using a specific radioimmunoassay and the results were compared. In the 102 sets of samples collected, the mean difference (+/- standard deviation) in cyclosporin concentration between finger prick and venipuncture and ear prick and venipuncture was 2.6% (+/- 9.5%) and 2.7% (+/- 12.1%), respectively, while the comparable median (IQR) differences were 1.9% (-3.4% to +6.6%) and -1.1% (-2.8% to +7.2%), respectively. A high degree of correlation was observed between finger prick and venipuncture or ear prick and venipuncture or ear prick and finger prick (r2 > 0.86). Of the three methods of blood collection, finger prick was the patients' preferred method (P < 0.01). These data suggest that capillary blood collected by skin puncture is suitable for use in cyclosporin blood monitoring and acceptable to patients.

Area Under Curve↗

Are infants with orofacial clefts at risk for insecure mother-child attachments?

OBJECTIVE: Several risk factors in the early lives of children with clefts are believed to interfere with their development of secure attachments to parents; however, this possibility has rarely been studied empirically. This study compared 12- and 24-month attachment classifications of infants with cleft palate (CP), infants with cleft lip and palate (CLP), and a comparison group of unimpaired infants (COMP). METHOD: Twenty-two CP infants, 24 CLP infants, and 61 matched COMP infants were assessed at 12 and 24 months of age in an urban children's hospital. At both visits, mothers and infants participated in the Strange Situation, which was videotaped and subsequently coded for patterns of attachment behavior. RESULTS: CP infants displayed a lower rate of 12-month attachment security than infants in the CLP or COMP groups. By 24 months, no diagnostic group differences in attachment classification were found. Stable 12- to 24-month attachment classifications were less likely in the CP group (36.3%) than in the COMP (62.3%) group. CP infants who were insecure at 12 months were more likely to become secure by 24 months than were CLP or COMP group infants. CONCLUSIONS: In contrast to previous theory and clinical speculation, the facial appearance of infants with CLP does not appear to affect the early mother-infant relationship adversely. The infancy period is marked by attachment instability for infants with CP, who demonstrated lower-than-expected rates of security at 12 months. However, these problems resolved in nearly all cases by 24 months of age. Most infants with clefts emerged from the first 2 years of life with secure maternal attachments.

Adult↗

Comparison of selected perceptual variables for backpacks with internal and external frames.

Differences in perceptions of comfort, exertion, balance, and heart rate were investigated with two types of backpack. Subjects were 20 male volunteers (M age = 24.3 yr., SD: 3.6, M height = 180.02 cm, SD: 8.0, and M weight = 86.46 kg, SD: 14.84). Following oral briefing and practice trials, each subject was fitted at random with either an internal- or external-frame backpack containing 18.2 kg. By random, cross-over design, subjects completed a 30-m simulated hiking trial consisting of 16 separate obstacles designed to resemble actual off-trail hiking. Trials were conducted in a controlled environment with the walking intensity regulated by a metronome. Upon completion of each trial, the subjects rated the experience on perceived comfort, balance and stability, and rating of perceived exertion. Heart rate was recorded immediately prior to and following each trial. Analysis yielded a significant difference only on rating of perceived exertion in favor of the internal-frame backpack. Under limited circumstances, these data suggest that both types of backpacks provide similar comfort and balance and stability; however, internal frames in backpacks may reduce perceived exertion during short, demanding hikes.

Adult↗

The mechanism of adverse events associated with terazosin: an analysis of the Veterans Affairs cooperative study.

PURPOSE: We determined the mechanism of adverse events associated with alpha1-blockers for treating benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We randomized 1,229 men with clinical BPH at 31 Veterans Affairs medical centers into equal treatment groups, including those who received placebo, terazosin, finasteride, and combined terazosin and finasteride therapy, respectively. Adverse events were captured at all study visits during our 1-year study. Our current review of adverse events is limited to patients randomized to the placebo and terazosin groups. We compared the incidence of orthostatic blood pressure change, postural symptoms and orthostatic hypotension in men who were normotensive and hypertensive at baseline, respectively. We also determined the association of changes in systolic blood pressure with the incidence of treatment related adverse events. RESULTS: The treatment related rates of dizziness, asthenia, postural hypotension and syncope were 19%, 6%, 6% and 1%, respectively. Of these adverse events only postural hypotension was associated with orthostatic blood pressure changes. The incidence of asthenia, dizziness and postural hypotension was not significantly greater in patients with a systolic blood pressure decrease of 5 or greater and less than 5 mm. Hg, respectively. CONCLUSIONS: Dizziness and asthenia are not associated with changes in blood pressure, suggesting that these treatment related adverse events associated with alpha1-blockers are not related to vascular events. Designing a subtype selective alpha1 antagonist that has less effect on blood pressure may not result in marked improvement in tolerability over commercially available alpha1-blockers.

Adrenergic alpha-Antagonists↗

Use of structural magnetic resonance imaging to predict who will get Alzheimer's disease.

We used magnetic resonance imaging (MRI) measurements to determine whether persons in the prodromal phase of Alzheimer's disease (AD) could be accurately identified before they developed clinically diagnosed dementia. Normal subjects (n = 24) and those with mild memory difficulty (n = 79) received an MRI scan at baseline and were then followed annually for 3 years to determine which individuals subsequently met clinical criteria for AD. Patients with mild AD at baseline were also evaluated (n = 16). Nineteen of the 79 subjects with mild memory difficulty "converted" to a diagnosis of probable AD after 3 years of follow-up. Baseline MRI measures of the entorhinal cortex, the banks of the superior temporal sulcus, and the anterior cingulate were most useful in discriminating the status of the subjects on follow-up examination. The accuracy of discrimination was related to the clinical similarity between groups. One hundred percent (100%) of normal subjects and patients with mild AD could be discriminated from one another based on these MRI measures. When the normals were compared with the individuals with memory impairments who ultimately developed AD (the converters), the accuracy of discrimination was 93%, based on the MRI measures at baseline (sensitivity = 0.95; specificity = 0.90). The discrimination of the normal subjects and the individuals with mild memory problems who did not progress to the point where they met clinical criteria for probable AD over the 3 years of follow-up (the "questionables") was 85% and the discrimination of the questionables and converters was 75%. The apolipoprotein E genotype did not improve the accuracy of discrimination. The specific regions selected for each of these discriminations provides information concerning the hierarchical fashion in which the pathology of AD may affect the brain during its prodromal phase.

Aged↗

Do psychosocial variables predict the physical growth of infants with orofacial clefts?

This study sought to determine whether psychosocial variables (parent-infant feeding interactions, infant temperament, maternal social support, family socioeconomic status) are important in predicting the physical growth of infants with orofacial clefts, after controlling for selected medical variables (infant health status, cleft diagnosis, and previous weight). Infant growth (weight-to-height zscores) was tracked for 2 years, and models were developed to predict growth at 3, 12, and 24 months. The authors also examined the growth trajectories of infants with different cleft types: cleft lip and palate (CLP) and cleft palate only (CPO). CPO infants showed some increase in their growth relative to the population mean over time, whereas the growth of CLP infants remained lower than the population mean at all time points. After controlling for medical variables, psychosocial variables collectively accounted for an additional 42% of the variance in infants' growth at 3 months of age, but they did not account for growth at 12 months and 24 months, largely due to the strong effect of previous growth. The authors tentatively conclude that psychosocial variables influence the early growth trajectory of infants with clefts, but subsequent growth becomes increasingly regulated by biological factors.

Child Development↗

Dialogues in the exam room: medical interviewing by resident family physicians.

BACKGROUND: Limited information exists about the application of the biopsychosocial model in medical practice. This study expanded our knowledge about the extent to which psychosocial content is included in medical interviews conducted by resident family physicians. METHODS: Interviews of 180 patients conducted by six second-year family practice residents were audiotaped and transcribed. Physician statements were analyzed and coded as social talk, physician-centered statements, patient-centered statements, and discussion of patient affect, family, health promotion, and patient education. RESULTS: The proportion of interviews in which specific physician interactions occurred were physician-centered statements: 100%, patient-centered statements: 66%, dealing with patient affect: 18%, information about family: 61%, initiation of health promotion: 33%, and initiation of patient education: 46%. Discussions of patient opinion/perception, patient affect, family information, and health promotion occurred most commonly during well-care visits and with female patients. CONCLUSIONS: In this sample of residents, providers extended the interview beyond a purely biomedical focus. However, the psychosocial focus often was brief and applied inconsistently across patients.

Adult↗

Simultaneous antagonism of interleukin-5, granulocyte-macrophage colony-stimulating factor, and interleukin-3 stimulation of human eosinophils by targetting the common cytokine binding site of their receptors.

Human interleukin-5 (IL-5), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-3 are eosinophilopoietic cytokines implicated in allergy in general and in the inflammation of the airways specifically as seen in asthma. All 3 cytokines function through cell surface receptors that comprise a ligand-specific alpha chain and a shared subunit (beta(c)). Although binding of IL-5, GM-CSF, and IL-3 to their respective receptor alpha chains is the first step in receptor activation, it is the recruitment of beta(c) that allows high-affinity binding and signal transduction to proceed. Thus, beta(c) is a valid yet untested target for antiasthma drugs with the added advantage of potentially allowing antagonism of all 3 eosinophil-acting cytokines with a single compound. We show here the first development of such an agent in the form of a monoclonal antibody (MoAb), BION-1, raised against the isolated membrane proximal domain of beta(c). BION-1 blocked eosinophil production, survival, and activation stimulated by IL-5 as well as by GM-CSF and IL-3. Studies of the mechanism of this antagonism showed that BION-1 prevented the high-affinity binding of (125)I-IL-5, (125)I-GM-CSF, and (125)I-IL-3 to purified human eosinophils and that it bound to the major cytokine binding site of beta(c). Interestingly, epitope analysis using several beta(c) mutants showed that BION-1 interacted with residues different from those used by IL-5, GM-CSF, and IL-3. Furthermore, coimmunoprecipitation experiments showed that BION-1 prevented ligand-induced receptor dimerization and phosphorylation of beta(c), suggesting that ligand contact with beta(c) is a prerequisite for recruitment of beta(c), receptor dimerization, and consequent activation. These results demonstrate the feasibility of simultaneously inhibiting IL-5, GM-CSF, and IL-3 function with a single agent and that BION-1 represents a new tool and lead compound with which to identify and generate further agents for the treatment of eosinophil-dependent diseases such as asthma.

Animals↗

The nasopharyngeal bacterial flora in infancy: effects of age, gender, season, viral upper respiratory tract infection and sleeping position.

The aim of the investigation was to determine the effect of age, gender, viral upper respiratory tract infection (URTI), season and sleeping position on the composition of the nasopharyngeal bacterial flora in infancy. Seventy-two babies, 38 male and 34 female, whose birthdates were evenly spread throughout the year were followed from birth to 18 months of age. From 0 to 6 months nasopharyngeal swabs were obtained once a month in periods without URTI and daily for 3 days during episodes of URTI. From 12 to 18 months of age nasopharyngeal swabs were obtained in the early morning alter an overnight sleep and later in the day after the baby had been up for over 2 h. Swabs were obtained in prone and supine sleepers with and without infection. In infants aged 0-6 months URTI had little effect on the nasopharyngeal bacterial flora, but there was a marked effect of age and less marked effect of season and gender. In particular Staphylococcus aureus carriage decreased with age, was most common in the winter months and the density of colonisation was greater in males than females. In infants aged 12-18 months the combination of prone sleeping with URTI and an early morning swab led to increased carriage of staphylococci, streptococci. Haemophilus influenzae and Gram-negative bacilli which are not normally part of the nasopharyngeal flora. These results are relevant to sudden infant death syndrome (SIDS). The combination of prone sleeping and URTI reproduces the nasopharyngeal flora seen in SIDS. Gram-negative bacilli isolated from SIDS cases should not be dismissed as post-mortem contaminants. The features of S. aureus make it a prime candidate for a pathogenic role in SIDS.

Aging↗

Sleeping position in infants over 6 months of age: implications for theories of sudden infant death syndrome.

The aim of this study was to determine the prevalence of prone and supine sleeping in infants aged 0-12 months and relate this to changes in the number of cases of sudden infant death syndrome (SIDS) since 1985. Seventy-two babies, 38 male and 34 female, were followed for the first 18 months of life with regular home visits and sleeping position was recorded. In addition, data on the number of cases of SIDS in England and Wales between 1985 and 1995 were analysed. All babies slept supine for the first 5 months of life, but once they could turn over in their cots (mean age 7.34 months, range 5-11 months) the majority slept prone. By 11 months of age, 53 regularly slept prone (73%), 95% CI +/- 19.8%), while 11 slept supine, three adopted the side position and five varied from night to night. The number of cases of SIDS in infants aged 7-11 months has fallen significantly (P<0.0001) in a period in which the prevalence of prone sleeping, in that age group, has not changed. The most plausible explanation for this paradoxical result is that supine sleeping in the first 5 months of life reduces the absolute risk of SIDS in the second 6 months of life even though most babies are then sleeping prone. It is suggested that reduced exposure to nasopharyngeal bacterial superantigens in babies sleeping prone might explain this effect.

Adult↗

Angiogenesis and hematopoiesis induced by Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6.

Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 [HHV-8]) is a herpesvirus linked to the development of Kaposi's sarcoma (KS), primary effusion lymphoma, and a proportion of Castleman's disease. KSHV encodes viral interleukin-6 (vIL-6), which is structurally homologous to human and murine IL-6. The biological activities of vIL-6 are largely unknown. To gain insight into the biology of vIL-6, we expressed vIL-6 in murine fibroblasts NIH3T3 cells and inoculated stable vIL-6-producing clones into athymic mice. vIL-6 was detected selectively in the blood of mice injected with vIL-6-expressing clones. Compared with controls, vIL-6-positive mice displayed increased hematopoiesis in the myeloid, erythroid, and megakaryocytic lineages; plasmacytosis in spleen and lymph nodes; hepatosplenomegaly; and polyclonal hypergammaglobulinemia. vIL-6-expressing NIH3T3 cells gave rise to tumors more rapidly than did control cells, and vIL-6-positive tumors were more vascularized than controls. Vascular endothelial growth factor (VEGF) was detected at higher levels in the culture supernatant of vIL-6-expressing cells compared with controls, and immunohistochemical staining detected VEGF in spleen, lymph nodes, and tumor tissues from mice bearing vIL-6-producing tumors but not control tumors. Thus, vIL-6 is a multifunctional cytokine that promotes hematopoiesis, plasmacytosis, and angiogenesis. Through these functions, vIL-6 may play an important role in the pathogenesis of certain KSHV-associated disorders.

3T3 Cells↗

Effect of finasteride and/or terazosin on serum PSA: results of VA Cooperative Study #359.

BACKGROUND: Medical management of benign prostatic hyperplasia (BPH) giving rise to lower urinary tract symptomatology (LUTS) has emerged as the mainstay for first-line therapy. Prostate-specific antigen (PSA) is the most important method of detecting prostate carcinoma. The effect of finasteride on PSA has been widely reported. Little data exist with respect to alpha-adrenergic blocking therapy in men treated for BPH. In the present investigation we set out to evaluate the effect of these two forms of therapy. METHODS: Patients enrolled in the VA Cooperative Study #359 trial were evaluated. This study evaluated men with moderate LUTS owing to BPH in four treatment groups: placebo (P), finasteride (F), terazosin (T), and combination of finasteride plus terazosin (C). Men were recruited at 31 VA medical centers and had a baseline in 52-week PSA determination at the respective sites. RESULTS: There was no significant difference in baseline PSA between four groups (mean range, 2.0-2.9 ng/ml). Statistically significant reduction in PSA levels was observed at 52 weeks in the F and C arms (P < 0.001), whereas significant increases were observed in the T and P arms (P < 0.01). Additionally, there was no significant difference in PSA response between the T and P arms. Thirty percent of men in the C or F arms had more than 40-60% reduction of PSA. In contrast, the majority of men on T or P had less than 40% change in PSA. Only 35% of men on F or C had the expected 40-60% reduction in PSA level. CONCLUSIONS: These data demonstrate no clinically significant effect of T on PSA level. The heterogeneity of PSA response to F may make monitoring patients for the development of prostate cancer problematic.

Adrenergic alpha-Antagonists↗

Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial.

OBJECTIVE: To assess neurological sequelae in patients with all grades of carbon monoxide (CO) poisoning after treatment with hyperbaric oxygen (HBO) and normobaric oxygen (NBO). DESIGN: Randomised controlled double-blind trial, including an extended series of neuropsychological tests and sham treatments in a multiplace hyperbaric chamber for patients treated with NBO. SETTING: The multiplace hyperbaric chamber at the Alfred Hospital, a university-attached quarternary referral centre in Melbourne providing the only hyperbaric service in the State of Victoria. PATIENTS: All patients referred with CO poisoning between 1 September 1993 and 30 December 1995, irrespective of severity of poisoning. Pregnant women, children, burns victims and those refusing consent were excluded. INTERVENTION: Daily 100-minute treatments with 100% oxygen in a hyperbaric chamber--60 minutes at 2.8 atmospheres absolute for the HBO group and at 1.0 atmosphere absolute for the NBO group--for three days (or for six days for patients who were clinically abnormal or had poor neuropsychological outcome after three treatments). Both groups received continuous high flow oxygen between treatments. MAIN OUTCOME MEASURES: Neuropsychological performance at completion of treatment, and at one month where possible. RESULTS: More patients in the HBO group required additional treatments (28% v. 15%, P = 0.01 for all patients; 35% v. 13%, P = 0.001 for severely poisoned patients). HBO patients had a worse outcome in the learning test at completion of treatment (P = 0.01 for all patients; P = 0.005 for severely poisoned patients) and a greater number of abnormal test results at completion of treatment (P = 0.02 for all patients; P = 0.008 for severely poisoned patients). A greater percentage of severely poisoned patients in the HBO group had a poor outcome at completion of treatment (P = 0.03). Delayed neurological sequelae were restricted to HBO patients (P = 0.03). No outcome measure was worse in the NBO group. CONCLUSION: In this trial, in which both groups received high doses of oxygen, HBO therapy did not benefit, and may have worsened, the outcome. We cannot recommend its use in CO poisoning.

Adult↗