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Biomedical subjects

A Moore

Publications and source records attributed to A Moore.

At least 73 records · Page 4Linked to original sources

Incidence rate and spatio-temporal clustering of type 1 diabetes in Santiago, Chile, from 1997 to 1998.

OBJECTIVE: To estimate the incidence rate of type 1 diabetes in the urban area of Santiago, Chile, from March 21, 1997 to March 20, 1998, and to assess the spatio-temporal clustering of cases during that period. METHODS: All sixty-one incident cases were located temporally (day of diagnosis) and spatially (place of residence) in the area of study. Knox's method was used to assess spatio-temporal clustering of incident cases. RESULTS: The overall incidence rate of type 1 diabetes was 4.11 cases per 100,000 children aged less than 15 years per year (95% confidence interval: 3.06 - 5.14). The incidence rate seems to have increased since the last estimate of the incidence calculated for the years 1986 - 1992 in the metropolitan region of Santiago. Different combinations of space-time intervals have been evaluated to assess spatio-temporal clustering. The smallest p-value was found for the combination of critical distances of 750 meters and 60 days (uncorrected p-value = 0.048). CONCLUSIONS: Although these are preliminary results regarding space-time clustering in Santiago, exploratory analysis of the data method would suggest a possible aggregation of incident cases in space-time coordinates.

Adolescent↗

Noninvasive in vivo measurement of beta-cell mass in mouse model of diabetes.

Pancreatic beta-cell mass (BCM) is a major determinant of the quantity of insulin that can be secreted. BCM is markedly reduced in type 1 diabetes because of selective autoimmune destruction of beta-cells. Accurate assessment of BCM in human diabetes is limited to autopsy studies, which usually suffer from inadequate clinical information; thus, the development of noninvasive means of BCM measurement could be important in intervention therapy. The goal of this study was to develop such noninvasive methods for measuring BCM featuring target-specific imaging probes and to investigate whether this technique is feasible, accurate, and predictive of BCM in normal and diabetic states. Using a beta-cell-specific monoclonal antibody IC2, modified with a radioisotope chelator for nuclear imaging, we showed that highly specific binding and accumulation to beta-cells occurs after intravenous administration of the probe, with virtually no binding to exocrine pancreas or stromal tissues. Furthermore, we observed a direct correlation between accumulation of the probe with BCM in diabetic and normal animals. Nuclear imaging of the animals that received an injection of the radioactive probe showed major difference in signal intensity between normal and diabetic pancreases. The results from this study set the route for further development of imaging probes for measuring BCM that would aid in diagnosis and treatment of diabetic patients in the clinic.

Animals↗

Patient monitoring using personal area networks of wireless intelligent sensors.

A wearable device for monitoring multiple physiological signals (polysomnograph) usually includes multiple wires connecting sensors and the monitoring device. In order to integrate information from intelligent sensors, all devices must be connected to a Personal Area Network (PAN). This system organization is unsuitable for longer and continuous monitoring, particularly during the normal activity. For instance, monitoring of athletes and computer assisted rehabilitation commonly involve unwieldy wires to arms and legs that restrain normal activity. We propose a wireless PAN of intelligent sensors as a system architecture of choice, and present a new design of wireless personal area network with physiological sensors for medical applications. Intelligent wireless sensors perform data acquisition and limited processing. Individual sensors monitor specific physiological signals (such as EEG, ECG, GSR, etc.) and communicate with each other and the personal server. Personal server integrates information from different sensors and communicates with the rest of telemedical system as a standard mobile unit. We present our prototype implementation of Wireless Intelligent SEnsor (WISE) based on a very low power consumption microcontroller and a DSP-based personal server. In future we expect all components of WISE integrated in a single chip for use in a variety of new medical applications and sophisticated human computer interfaces. Existing growth of wireless infrastructure will allow a range of new telemedical applications that will significantly improve the quality of health care.

Computer Communication Networks↗

Characterization of male and female wingbeat frequencies in the Anopheles quadrimaculatus complex in Mississippi.

Classifying individual mosquitoes of the Anopheles quadrimaculatus species complex to species has always been time consuming and complex, involving genetic analysis and profiling. We characterized the wingbeat frequencies of the 3 species of the Anopheles quadrimaculatus complex (An. quadrimaculatus, An. smaragdinus, and An. maverlius) that occur in Mississippi to determine if this character could successfully distinguish between individuals of the 3 species. Wingbeats of females varied from 320 to 480 beats/sec, but no significant differences in wingbeat frequencies were found among females from 3 populations of the 3 species. Wingbeats of males were higher than those of females (500-770 beats/sec), and the mean wingbeat frequency of An. maverlius was significantly different from the means of An. quadrimaculatus and An. smaragdinus, although overlap occurred at the individual level. Such overlap precludes use of wingbeat frequencies as an identification mechanism, and indicates that, at least for the An. quadrimaculatus complex, wingbeat frequencies are not involved in mate recognition.

Animals↗

No evidence for infection of human cells with porcine endogenous retrovirus (PERV) after exposure to porcine fetal neuronal cells.

BACKGROUND: Recent demonstration of human cell infection in vitro with porcine endogenous retrovirus (PERV) has raised safety concerns for new therapies that involve transplantation of pig cells or organs to humans. To assess better the specific risk that may be associated with the transplantation of fetal pig neuronal cells to the central nervous system of patients suffering from intractable neurologic disorders (Parkinson's disease, Huntington's disease, and epilepsy), we have performed studies to determine whether there is evidence for in vivo or in vitro transmission of PERV from fetal pig neuronal cells to human cells. METHODS: Ventral mesencephalon (VM) and lateral ganglionic eminence cells were isolated from fetal pigs and transplanted into patients with neurological conditions as part of clinical studies. Blood samples taken from patients at various time points posttransplant were tested for evidence of PERV. In vitro studies to test for PERV infection of human cells after cocultivation with either fetal porcine ventral mesencephalon or porcine fetal lateral ganglionic eminence cells were also performed. RESULTS: We found no evidence of PERV provirus integration in the DNA from PBMC of 24 neuronal transplant recipients. In addition, no PERV was released from cultured fetal porcine neuronal cultures, and there was no transfer of PERV from fetal pig neuronal cells to human cells in vitro. CONCLUSIONS: Our results demonstrate by both examination of transplant patient blood samples and in vitro studies that there is no evidence for transmission of PERV from porcine fetal neural cells to human cells.

Adult↗

Functional impairment of lens aquaporin in two families with dominantly inherited cataracts.

Opacities in the crystalline lens of eye appear with high frequency in the general population. Dominantly inherited cataracts with differing clinical features were found in two families carrying different point mutations in the gene encoding lens water channel protein AQP0 (major intrinsic protein, MIP). Families with E134G have a uni-lamellar cataract which is stable after birth, whereas families with T138R have multi-focal opacities which increase throughout life. To establish pathophysiological relevance of cataract formation, the Xenopus laevis oocyte expression system was employed to evaluate functional defects in the mutant proteins, E134G and T138R. Both substitutions cause loss of membrane water channel activity due to impaired trafficking of the mutant proteins to the oocyte plasma membrane. Although missense mutations in AQP1 and AQP2 proteins are known to result in recessive traits in vivo and in vitro, when E134G or T138R are co-expressed with wild-type AQP0 protein, the mutant proteins exhibit dominant negative behaviour. To our knowledge, these studies represent the first in vitro demonstration of functionally defective AQP0 protein from humans with congenital cataracts. Moreover, these observations predict that less severe defects in the AQP0 protein may contribute to lens opacity in patients with common, less fulminant forms of cataracts.

Amino Acid Sequence↗

Inhibition of IL-12 production in human monocyte-derived macrophages by TNF.

IL-12 is a pivotal cytokine that links the innate and adaptive immune responses. TNF-alpha also plays a key role in orchestrating inflammation and immunity. The reciprocal influence of these two inflammatory mediators on each other may have significant impact on the cytokine balance that shapes the type and extent of immune responses. To investigate the relationship between TNF-alpha and IL-12 production, we analyzed the effects of exposure of human monocyte-derived macrophages to TNF-alpha on LPS- or Staphylococcus aureus-induced IL-12 production in the presence or absence of IFN-gamma. TNF-alpha is a potent inhibitor of IL-12 p40 and p70 secretion from human macrophages induced by LPS or S. aureus. IL-10 is not responsible for the TNF-alpha-mediated inhibition of IL-12. TNF-alpha selectively inhibits IL-12 p40 steady-state mRNA, but not those of IL-12 p35, IL-1alpha, IL-1beta, or IL-6. Nuclear run-on analysis identified this specific inhibitory effect at the transcriptional level for IL-12 p40 without down-regulation of the IL-12 p35 gene. The major transcriptional factors identified to be involved in the regulation of IL-12 p40 gene expression by LPS and IFN-gamma, i.e., c-Rel, NF-kappaB p50 and p65, IFN regulatory factor-1, and ets-2, were not affected by TNF-alpha when examined by nuclear translocation and DNA binding. These data demonstrate a selective negative regulation on IL-12 by TNF-alpha, identifying a direct negative feedback mechanism for inflammation-induced suppression of IL-12 gene expression.

Biological Transport↗

Anticonvulsant drugs for acute and chronic pain.

BACKGROUND: Anticonvulsant drugs have been used in the management of pain since the 1960s. The clinical impression is that they are useful for neuropathic pain, especially when the pain is lancinating or burning. OBJECTIVES: To evaluate the analgesic effectiveness of anticonvulsant drugs compared to either placebo or other drugs in order to provide evidence-based recommendations for pain management in clinical practice and to identify a clinical research agenda. Adverse effects are also considered. SEARCH STRATEGY: Randomised trials of anticonvulsants in acute, chronic or cancer pain were identified by Medline (Silver Platter 3.0, 3.1 and 3.11) from 1966 to February 1994. In addition, 40 medical journals were hand searched (published between 1950 and 1990). Additional reports were identified from the reference list of the retrieved papers, and contacting investigators. Date of the most recent searches: 1994. SELECTION CRITERIA: Randomised trials reporting the analgesic effects of anticonvulsant drugs in patients, with pain assessment as either the primary or a secondary outcome. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers, and trials were quality scored. Numbers-needed-to-treat (NNTs) were calculated from dichotomous data for effectiveness, adverse effects and drug-related study withdrawal, for individual studies and for pooled data. MAIN RESULTS: Twenty trials of four anticonvulsants were considered eligible (746 patients). The only placebo-controlled study in acute pain found no analgesic effect of sodium valproate. Three placebo-controlled studies of carbamazepine in trigeminal neuralgia had a combined NNT for effectiveness of 2.6, for adverse effects 3.4, and for severe effects (withdrawal from study) 24. Three placebo-controlled studies of diabetic neuropathy had a combined NNT for effectiveness of 3, for adverse effects 2.5, and for severe effects 20. Three placebo-controlled studies of migraine prophylaxis had a combined NNT for effectiveness of 2.4, for adverse effects 2.4 and for severe effects 39. Phenytoin had no effect in irritable bowel syndrome, and carbamazepine little effect in post-stroke pain. Clonazepam was effective in one study of temporomandibular joint dysfunction. No study compared one anticonvulsant with another. Anticonvulsants fared poorly against other treatments. REVIEWER'S CONCLUSIONS: Although anticonvulsants are used widely in chronic pain surprisingly few trials show analgesic effectiveness. No trial compared different anticonvulsants. There is no evidence that anticonvulsants are effective for acute pain. In chronic pain syndromes other than trigeminal neuralgia anticonvulsants should be withheld until other interventions have been tried.

Acute Disease↗

Single dose paracetamol (acetaminophen), with and without codeine, for postoperative pain.

BACKGROUND: Patient surveys have shown that postoperative pain is often not managed well, and there is a need to assess the efficacy and safety of commonly used analgesics as newer treatments become available. Paracetamol (acetaminophen) is an important non-opiate analgesic, commonly prescribed, as well as being available for retail sale. This review seeks to examine the efficacy of paracetamol alone and in combination with codeine, and also considers adverse effects. OBJECTIVES: To assess the analgesic efficacy and adverse effects of a single dose of oral paracetamol (acetaminophen) alone and in combination with codeine for moderate to severe postoperative pain. SEARCH STRATEGY: Published trials were identified from: Medline (1966 to May 1996), Embase (1980 to 1996), Cochrane Library (Issue 2 1996) and the Oxford Pain Relief Database (1950 to 1994). Additional trials were identified from reference lists of retrieved studies. Date of most recent searches: July 1998. SELECTION CRITERIA: Inclusion criteria were: full journal publication, postoperative pain, postoperative oral administration, adult patients, baseline pain of moderate to severe intensity, double-blind design, and random allocation to treatment groups which compared paracetamol with placebo or a combination of paracetamol and codeine with either placebo or the same dose of paracetamol alone. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers, and trials were quality scored. Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of patients with at least 50% pain relief. This was used to calculate the relative benefit and number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief over 4 to 6 hours compared with placebo. Adverse effects were used to calculate relative risk and number-needed-to-harm (NNH). MAIN RESULTS: We found 40 trials of paracetamol against placebo (4171 patients), 22 trials of paracetamol plus codeine against placebo (1407 patients) and 12 trials of paracetamol plus codeine against the same dose of paracetamol (794 patients). In postoperative pain paracetamol 1000 mg had an NNT of 4.6 (3.8-5.4) for at least 50% pain relief when compared with placebo, and paracetamol 600/650 mg had an NNT of 5.3 (4.1-7.2). Paracetamol 600/650 mg plus codeine 60 mg had an NNT of 3. 6 (2.9-4.5). Comparing paracetamol plus codeine 60 mg with the same dose of paracetamol alone gave an NNT of 7.7 (5.1-17) for at least 50% pain relief. Adverse effects: Relative risk estimates for paracetamol 600/650 mg plus codeine 60 mg versus placebo showed a significant difference for 'drowsiness'/somnolence (NNH 11 (7.5- 0)) and dizziness (NNH 27 (15-164)) but no significant difference for nausea/vomiting. REVIEWER'S CONCLUSIONS: Paracetamol is an effective analgesic with a low incidence of adverse effects. The addition of codeine 60 mg to paracetamol produces additional pain relief even in single oral doses, but may be accompanied by an increase in drowsiness and dizziness.

Acetaminophen↗

Liver transplantation in a Jehovah's Witness with ankylosing spondylitis.

PURPOSE: Orthotopic liver transplantation is typically associated with large volume blood loss. Technological and pharmacological advances permit liver transplantation in patients who formerly were not candidates for this surgery because of strict limitations on blood product administration. We describe a liver transplant in a Jehovah's Witness with ankylosing spondylitis. CLINICAL FEATURE: A 49-yr-old Jehovah's Witness with ankylosing spondylitis and end stage liver disease secondary to sclerosing cholangitis underwent orthotopic liver transplantation. Recombinant human erythropoietin (4,000 IU sc every two days for four weeks, then 4,000 IU sc every week) established a normal hemoglobin concentration preoperatively (> 140 g x L(-1) compared with 120 g x L(-1) baseline). Intraoperatively, strategies for reducing risk of blood product transfusion included avoidance of hypothermia (T>35 degrees C), minimal blood sampling (four 1 ml samples), normovolemic hemodilution (two units), administration of Aprotinin (2 million units bolus dose followed by infusion of 500,000 u x hr(-1)), and return of blood (1,500 ml) scavenged from the operative field. Estimated blood loss was 2,200 mi. The preoperative and postoperative hemoglobin concentration was 147 g x L(-1) (hematocrit 0.45) and 123 g x L(-1) (hematocrit 0.37), respectively. No blood products were required and he was discharged three weeks postoperatively without complication. CONCLUSION: Technological and pharmacological advances allow patients to undergo surgery traditionally associated with large volume blood loss with reduced risk of blood product administration.

Blood Loss, Surgical↗

Science funding and infrastructures in Europe.

European science in crisis. Scared? Then read on; you should be. I argue that we cannot sit back for much longer and watch our best scientists emigrate to the USA for the most productive part of their career, and that European scientists should not tolerate a funding system that neither rewards an investigator's brilliance nor the innovative nature of their research. The EC Framework Programme is due for a face lift: scientists should wield the scalpel this time.

Europe↗

Transgenic Trifolium repens with foliage accumulating the high sulphur protein, sunflower seed albumin.

With the aim of increasing the rumen-protected level of the sulphur amino acids cysteine and methionine in Trifolium repens, we introduced the coding sequence of the sunflower seed albumin (SSA) into T. repens by Agrobacterium tumefaciens-mediated transformation. The SSA gene was modified such that the protein would be localised to the endoplasmic reticulum (ER). Four different T-DNA constructions all containing the SSA gene driven by either the promoter of a gene encoding the small subunit of ribulose bisphosphate carboxylase (Rubisco) from Arabidopsis thaliana (Assu), the promoter of the gene encoding the small subunit of Rubisco of Medicago sativa (Lssu), or the Cauliflower Mosaic Virus 35S promoter (CaMV35S), were transferred to T. repens cv. Haifa. Transgenic T0-plants and inter-transgenic hybrids were analysed for the level of SSA accumulation in the leaves by western blotting. The highest observed level of SSA accumulation was 0.1% of total extractable leaf protein. We observed that the promoter had a substantive effect on the level of SSA accumulation with Assu > CaMV35S > Lssu. Results from the inter-transgenic hybrids showed that the capacity to synthesise SSA was inherited. However the level of SSA accumulation in the leaves generally appears not to be additive with extra transgenic loci. During this work, we attempted to improve the efficiency of A. tumefaciens-mediated transformation of T. repens using the SAAT-method (Sonication Assisted Agrobacterium-mediated Transformation) on cotyledons of T. repens. T-DNA transfer was in general not enhanced by sonication compared to traditional A. tumefaciens-mediated transformation. Furthermore, Southern blot analyses of plants regenerated from the same cotyledon after A. tumefaciens treatment and under selection, indicated that multiple shoots were usually derived from the same transformation event. We concluded from these results that only one plant from each A. tumefaciens-treated cotyledon should be taken to avoid transgenic clones.

2S Albumins, Plant↗