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Biomedical subjects

R Miller

Publications and source records attributed to R Miller.

At least 199 records · Page 11Linked to original sources
PubMed1999

Identification of regions of arrestin that bind to rhodopsin.

Arrestin facilitates phototransduction inactivation through binding to photoactivated and phosphorylated rhodopsin (RP). However, the specific portions of arrestin that bind to RP are not known. In this study, two different approaches were used to determine the regions of arrestin that bind to rhodopsin: panning of phage-displayed arrestin fragments against RP and cGMP phosphodiesterase (PDE) activity inhibition using synthetic arrestin peptides spanning the entire arrestin protein. Phage display indicated the predominant region of binding was contained within amino acids 90-140. A portion of this region (residues 95-140) expressed as a fusion protein with glutathione S-transferase is capable of binding to rhodopsin regardless of the activation or phosphorylation state of the receptor. Within this region, the synthetic peptide of residues 109-130 was shown to completely inhibit the binding of arrestin to rhodopsin with an IC50 of 1.1 mM. The relatively high IC50 of this competition suggests that this portion of the molecule may be only one of several regions of binding between arrestin and RP. A survey of synthetic arrestin peptides in the PDE assay indicated that the two most effective inhibitors of PDE activity were peptides of residues 111-130 and 101-120. These results indicate that at least one of the principal regions of binding between arrestin and RP is contained within the region of residues 109-130.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1999

Failure of spinal cord oligodendrocyte development in mice lacking neuregulin.

Oligodendrocytes develop from a subpopulation of precursor cells within the ventral ventricular zone of the spinal cord. The molecular cues that direct this spatially and temporally restricted event seem to originate in part from structures ventral to and within the spinal cord. Here, we present evidence that the family of ligands termed neuregulins are necessary for the normal generation of mouse spinal cord oligodendrocytes. Oligodendrocytes mature in spinal cord explants from wild-type mice and mice heterozygotic for a null mutation in the neuregulin gene (NRG +/-) in a temporal sequence of developmental events that replicates that observed in vivo. However, in spinal cord explants derived from mice lacking neuregulin (NRG -/-), oligodendrocytes fail to develop. Addition of recombinant neuregulin to spinal cord explants from NRG -/- mice rescues oligodendrocyte development. In wild-type spinal cord explants, inhibitors of neuregulin mimic the inhibition of oligodendrocyte development that occurs in NRG -/- explants. In embryonic mouse spinal cord, neuregulins are present in motor neurons and the ventral ventricular zone where they likely exert their influence on early oligodendrocyte precursor cells.

Animals↗
PubMed1999

Impact of resident feedback on immunization outcomes.

OBJECTIVE: To investigate the effect on immunization levels of retrospective written feedback to residents regarding missed immunization opportunities. DESIGN: Randomized trial with control group. SETTING: Pediatric resident continuity clinic in an urban hospital-based primary care clinic. PARTICIPANTS: Thirty-two postgraduate level 2 and postgraduate level 3 pediatric residents. INTERVENTION: Monthly retrospective written feedback mailed to residents detailing their missed immunization opportunities and appointment failure rates over a 12-month period beginning in February 1997. MAIN OUTCOME MEASURES: The immunization level of 2-year-old children in the resident clinic was the main outcome of interest. Secondary outcomes included missed immunization opportunity rates and appointment failure rates. RESULTS: Postintervention immunization levels were 71.4% (95% confidence limits [CLs]: 63.2%, 78.7%) for patients from the intervention group and 68.5% (95% CLs: 60.8%, 75.4%) for patients from the control group. The immunization level for patients of both groups who had fewer than 2 visits during the second year of life was 47.2% (95% CLs: 38.2%, 56.3%). This compares with an immunization level of 78.1% (95% CLs: 66.0%, 87.5%) for patients from both groups who had 2 visits during the second year of life, and with an immunization level of 88.2% (95% CLs: 81.0%, 93.4%) for patients of both groups who had more than 2 visits during the second year of life (P<.001). CONCLUSIONS: In this setting, written retrospective feedback to residents was an ineffective strategy for improving immunization levels. Adequate follow-up during the second year of life is critical in achieving high immunization levels.

Adult↗
PubMed1999

The use of a side effect as a qualitative indicator of plasma chlorpromazine levels.

Chlorpromazine (CPZ) is widely used in South African hospitals. The purpose of this study was to determine whether any physiological parameter (side-effect) could be correlated with plasma concentrations of CPZ or its metabolites. In the absence of a blood level, such a correlation could serve as a qualitative indicator of the amount of chlorpromazine in the body. Such a marker can assist the psychiatrist with therapeutic decisions regarding poor compliance and the lack of response with the drug. Fifteen schizophrenic patients were included in this study and regression analysis was used to determine any correlation between CPZ, 7-hydroxychlorpromazine, Chlorpromazine-N-oxide, Nor1 chlorpromazine, Nor2 chlorpromazine, chlorpromazine sulfoxide, Nor2 chlorpromazine sulfoxide and blood pressure, pulse rate, sedation and finger tremor. No correlation was seen between blood pressure or pulse rate and plasma concentrations of CPZ or the metabolites. A good correlation was seen between sedation, 7- hydroxychlorpromazine (P=0.035) and chlorpromazine sulfoxide (P=0.016). The results suggest that as the levels of chlorpromazine sulfoxide increase, the probability of sedation increases, while increasing levels of 7-hydroxychlorpromazine have the opposite effect. A good correlation was also seen between finger tremor and chlorpromazine levels (P=0.035). These results suggest that there is a 50% probability that the patient would experience finger tremor when the plasma concentration of chlorpromazine is 46 ng/ml. This study demonstrated the potential for the use of sedation and finger tremor as qualitative indicators of the plasma concentration of CPZ and two metabolites. Further studies with larger patient numbers are warranted.

Adolescent↗
PubMed1999

Serum organochlorine pesticides and PCBs and breast cancer risk: results from a prospective analysis (USA).

OBJECTIVE: To prospectively evaluate relationships of organochlorine pesticides and polychlorinated biphenyls (PCBs) with breast cancer, we conducted a case-control study nested in a cohort using the Columbia, Missouri Breast Cancer Serum Bank. METHODS: Women donated blood in 1977-87, and during up to 9.5 years follow-up, 105 donors who met the inclusion criteria for the current study were diagnosed with breast cancer. For each case, two controls matched on age and date of blood collection were selected. Five DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] analogs, 13 other organochlorine pesticides, and 27 PCBs were measured in serum. RESULTS: Women in the upper three quartiles of hexachlorobenzene were at twice the risk of breast cancer compared to those in the lowest quartile. However, there was no evidence for a dose-response relationship, and the association was limited to women whose blood was collected close to the time of diagnosis. Women with higher serum levels of other organochlorine pesticides and PCBs showed no increased risk of breast cancer overall, although positive associations were suggested for PCB-118 and PCB-138 when blood was collected close to the time of diagnosis. CONCLUSIONS: Results of this study do not support a role for organochlorine pesticides and PCBs in breast cancer etiology.

Aged↗
PubMed1999

ICU admission in patients infected with the human immunodeficiency virus - a multicentre survey.

We conducted a retrospective study to assess the reasons for admission to the intensive care unit, and subsequent outcome, in patients infected with the human immunodeficiency virus (HIV). Four hospitals in the south of England participated, all with specialist HIV units. Data were collected on 127 patients admitted to ICU on 133 separate occasions between June 1993 and October 1997. The mean age on admission was 38 years (range 23-60 years). Ninety-four patients (70.7%) were documented HIV-positive before admission and 36 (27%) were diagnosed HIV-positive for the first time during admission; 36.1% were admitted with Pneumocystis carinii pneumonia. Overall ICU mortality was 33%, in-hospital mortality was 56% and the eventual mortality at the end of follow-up (March 1998) was 72%. Survival was highest in those admitted with respiratory HIV-related disease or HIV-unrelated illness. Associations with poor outcome included a prior AIDS-defining illness, a CD4 cell count of less than 100 cells.ml-1 and admission secondary to sepsis.

AIDS-Related Opportunistic Infections↗
PubMed1999

Lateral ligaments of the rectum: an anatomical study.

BACKGROUND: The lateral ligaments of the rectum are surrounded by confusion and misconception. Their identification before 'hooking them on the finger', clamping and ligating is considered in many surgical texts to be an essential step in mobilization of the rectum. By contrast, it is the experience of many colorectal surgeons that the mesorectum can be dissected out either by diathermy or sharp dissection alone. METHODS: Dissection in the mesorectal plane was performed on 28 cadaveric pelves. RESULTS: In ten of the pelves, no connective tissue structure crossed from the pelvic side wall to the rectum. The remaining 18 had only very insubstantial connective tissue strands crossing this space. A total of 17 middle rectal arteries were found, all of them unilateral. Fourteen of these vessels crossed the mesorectum independent of any structure, while the remainder were part of a neurovascular bundle with a connective tissue element. CONCLUSION: It is proposed that the 'lateral ligaments' of the rectum do not exist and that the term should be dropped from surgical texts. When present, the middle rectal artery is a small vessel, close to the pelvic floor. The entire rectum may be mobilized by sharp dissection without the need for clamping or ligation of any significant structure.

Aged↗
PubMed1999

Counselling about diagnosis and inheritance of genetic bleeding disorders: haemophilia A and B.

Genetic counselling remains an important part of comprehensive haemophilia care despite the improved outlook and quality of life for those who can obtain factor replacement concentrates. Eighty per cent of the world's population with haemophilia have limited or no treatment. It is vital that information about inheritance is made available to them. Genetic bleeding disorders impact on the daily life and psychological health not only of the affected individual, but on carriers and close family. Informed decisions about childbearing (when there is a risk of haemophilia) require knowledge about inheritance, antenatal diagnosis possibilities and consideration of selective abortion. Genetic counselling touches on sensitive issues related to childbearing, handicap and continuation of the family. Guilt, resentment and blame can be reduced if couples are enabled to gain insight into each others views and wishes in a neutral setting. Counsellors need technical knowledge, skills and clarity of purpose to carry out this task.

Adult↗
PubMed1999

Hepatitis C lookback programme: a single hospital experience.

As part of the national Hepatitis C (HCV) Lookback Programme, HCV-infected donors donating blood after September 1991 were identified and the fate of their previous donations received at a single hospital were traced; 123 of 160 implicated blood components were traceable and transfused. Only 19 recipients were alive and traceable and were tested for HCV. Nine of the 14 recipients (64%) of HCV-positive donations and 2 of 5 recipients (40%) of HCV-indeterminate donations had evidence of HCV infection. Neither the number of donor exposures nor the type of component was predictive of recipient HCV status. Three recipients have chronic active hepatitis. The Hepatitis C Lookback Programme successfully identifies some but not all cases of transfusion-transmitted HCV. Transfusion records, particularly in the medical case notes, should be substantially improved. Many of the traced recipients are young, so that identification of HCV is of great importance.

Adolescent↗
PubMed1999

Western blot analysis of bile or intestinal fluid from patients with septic shock or systemic inflammatory response syndrome, using antibodies to TNF-alpha, IL-1 alpha and IL-1 beta.

Septic shock or systemic inflammatory response syndrome (SIRS) often develops in patients following burns, traumatic injury, surgery or biliary obstruction. Although the inflammatory cytokines TNF-alpha and IL-1 have been strongly implicated in the development of these syndromes, treatment of patients by the systemic administration of inhibitors of TNF-alpha or IL-1 has shown limited effectiveness. Recent reports suggest that septic shock may be perpetuated by inflammatory cytokines secreted by the liver in response to bacterial translocation resulting from cytokine-induced gastrointestinal damage. The present study sought to demonstrate the presence of high levels of inflammatory cytokines in the bile or small intestine of patients suffering from septic shock or SIRS, with a view to the development of strategies for the reduction of gastrointestinal damage through intraduodenal administration of cytokine inhibitors. Western blot analysis of human bile or intestinal fluid using anti-TNF-alpha antibodies resulted in the detection of a number of bands in samples from patients with septic shock or SIRS. However, these proteins differed antigenically from human recombinant TNF-alpha (rTNF-alpha) and showed no activity in a biological assay for TNF-alpha. Antibodies to IL-1 alpha and IL-1 beta detected several strong bands, some of which appeared to be identical to recombinant IL-1 alpha and IL-1 beta. It is concluded that proteins resembling several known inflammatory cytokines are present in the bile and intestine of septic shock patients, but it is suggested that further work is required to determine the nature and function of these molecules.

Animals↗
PubMed1999

DNA profiling reveals remarkably low genetic variability in a herd of SLA homozygous pigs.

Inbred strains of rodents have become indispensable for a wide range of biological studies. It has generally been accepted that genetic uniformity is unlikely to be achieved before 20 generations of brother x sister matings discouraging attempts to inbreed larger mammals. Nevertheless, pigs, homozygous for the swine MHC haplotype SLA b/b, have been inbred at the Babraham Institute for almost thirty years and used for immunological studies. Since the herd had not been studied at the DNA level, DNA profiling at multiple hypervariable loci was performed and surprisingly little genetic polymorphism and extremely high inter-individual resemblance were observed reminiscent of that observed in inbred strains of mice.

Animals↗
PubMed1999

Glucose-induced increase in memory performance in patients with schizophrenia.

Previous investigations have found that increasing circulating glucose availability can increase memory performance in rodents, healthy humans, and individuals with dementia of the Alzheimer's type. In this study, patients with schizophrenia, healthy control subjects, and controls with bipolar affective disorder were tested using double-blind treatment with either 50 g anhydrous dextrose plus 4 mg sodium saccharin (for "taste") or 23.7 mg saccharin alone, followed by cognitive testing on a complex battery. At this glucose dose, verbal memory performance on a paragraph recall task was increased during the glucose condition relative to the saccharin condition in the patients with schizophrenia; this effect was not detected in either the psychiatric or normal controls. The results provide preliminary support for the hypothesis that memory performance can be improved in patients with schizophrenia by increasing circulating glucose availability and suggest the importance of further evaluation of therapeutic manipulations of glucose availability.

Adult↗
PubMed1999

A new noninvasive method to measure blood pressure: results of a multicenter trial.

BACKGROUND: Blood pressure (BP) monitoring with arterial waveform display requires an arterial cannula. We evaluated a new noninvasive device, Vasotrac (Medwave, Arden Hills, MN) that provides BP measurements approximately every 12-15 beats and displays pulse rate and a calibrated arterial waveform for each BP measurement. METHODS: Surgical and critically ill patients (n = 80) served as subjects for the study. BPs, pulse waveforms, and pulse rates measured via a radial artery catheter were compared with those obtained by the Vasotrac from the opposite radial artery. Data were analyzed to determine agreement between the two systems of measurement. RESULTS: Blood pressure measured noninvasively by the Vasotrac demonstrated excellent correlation (P<0.01) with BP measured via a radial arterial catheter (systolic r2 = 0.93; diastolic r2 = 0.89; mean r2 = 0.95). Differences in BP measured by the Vasotrac versus the radial arterial catheter were small. The mean+/-SD bias and precision were as follows: systolic BP 0.02+/-5.4 mm Hg and 3.9+/-3.7 mm Hg; diastolic BP -0.39+/-3.9 mm Hg and 2.7+/-2.8 mm Hg; mean BP -0.21+/-3.0 mm Hg and 2.1+/-2.2 mm Hg compared with radial artery measurements. The Vasotrac pulse rates were almost identical to those measured directly (r2 = 0.95). The Vasotrac BP waveform resembled those directly obtained radial artery pulsatile waveforms. CONCLUSIONS: In surgical and critically ill patients, the Vasotrac measured BP, pulse rate, and displayed radial artery waveform, which was similar to direct radial arterial measurements. It should be a suitable device to measure BP frequently in a noninvasive fashion.

Adult↗