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Biomedical subjects

A White

Publications and source records attributed to A White.

At least 73 records · Page 4Linked to original sources
PubMed2001

The case for uncontrolled clinical trials: a starting point for the evidence base for CAM.

Clinical research into the effectiveness of any therapy usually progresses in a series of steps that are aimed at providing evidence that will lead to improved patient care. One important early step is the uncontrolled trial. Uncontrolled trials serve several crucial purposes, including establishing firmly that there is a clinical effect worth investigating, identifying the most suitable patients and the most appropriate treatments, and providing information on how large the effect might be. They can be conducted relatively easily by practitioners in the course of their normal work, and are an excellent first step for anyone interested in clinical research. Such studies are not only satisfying, but develop skills in searching the literature and writing protocols, and promote rigorous thinking and attention to detail. The ultimate purpose of uncontrolled trials is to facilitate subsequent definitive studies that will help define the place of CAM in health care.

Clinical Trials as Topic↗
PubMed2001

Standards for reporting interventions in controlled trials of acupuncture: the STRICTA recommendations.

Acupuncture treatment and control group interventions in parallel-group randomised trials of acupuncture are not always precisely reported. In an attempt to improve standards, an international group of experienced acupuncturists and researchers devised a set of recommendations, designating them STRICTA: STandards for Reporting Interventions in Controlled Trials of Acupuncture. In a further consensus-building round, the editors of several journals helped redraft the recommendations. These follow the Consolidated Standards for Reporting Trials (CONSORT) format, acting as an extension of the CONSORT guidelines for the specific requirements of acupuncture studies. Participating journals are publishing the STRICTA recommendations and requesting prospective authors to adhere to them when preparing reports for publication. Other journals are invited to adopt these recommendations. The intended outcome is that interventions in controlled trials of acupuncture will be more adequately reported, thereby facilitating an improvement in critical appraisal, analysis and replication of trials.

Acupuncture Therapy↗
PubMed2001

Monoclonal antibodies to the carboxy-terminal Ea sequence of pro-insulin-like growth factor-IA (proIGF-IA) recognize proIGF-IA secreted by IM9 B-lymphocytes.

Insulin-like growth factor-I (IGF-I) circulates in human serum as a 7 kDa peptide but analysis of IGF-I cDNAs predicts two pro-hormone precursors (proIGF-IA and proIGF-IB) with distinct C-terminal E domains. The function of these precursors, and the E peptides generated on cleavage to mature IGF-I, is unknown, largely because of a lack of tools for distinguishing precursors from constituent peptides. We used a synthetic Ea peptide to develop monoclonal antibodies (MAbs) which can recognize the carboxy-terminal sequence of proIGF-IA. These were characterized using proIGF-IA generated by transfected HEK293 cells. The anti-proIGF-IA MAbs immunoprecipitated two peptides (19--21 and 14 kDa) which were also recognized by MAbs to mature IGF-I. The proIGF-IA MAbs could also detect peptides of 9 and 4 kDa predicted to be Ea peptides. Treatment with N -glycosidase proved the 19--21 kDa and 9 kDa bands to be glycosylated proIGF-IA and Ea peptide respectively. Using these antibodies, we have identified proIGF-IA secreted from the IM9 B-lymphocyte cell line. This work paves the way for studies on proIGF-IA and Ea peptide regulation and function.

Antibodies, Monoclonal↗
PubMed2001

Regulation of IGF bioavailability in pregnancy.

During pregnancy, insulin-like growth factors (IGFs) are important for growth of fetal and maternal tissues. One of the IGF binding proteins, IGFBP-1, is thought to regulate their activity within the local environment of the placenta. IGFBP-1 usually exists as a phosphorylated, high affinity species, which sequesters IGFs, thereby inhibiting their actions. This study has investigated the mechanisms that release IGF from IGFBP-1 at the maternal-fetal interface. Under basal conditions, human decidualized endometrium produces both non-phosphorylated (np) and phosphorylated (p) isoforms of IGFBP-1; however, in the presence of IGF-II, which is a trophoblast secretory product, npIGFBP-1 was preferentially produced. Furthermore, we found that trophoblast, presumably via placental alkaline phosphatase, can de-phosphorylate pIGFBP-1. Since npIGFBP-1 has decreased affinity for IGF-I, these effects should enhance IGF-I bioavailability. In addition, we found that decidual cells produce a protease, which cleaves IGFBP-1, but only when it is non-phosphorylated; [(125)I]-npIGFBP-1 is proteolysed into 14 and 17 kDa fragments which have markedly reduced affinity for IGF. We therefore propose paracrine modulation of IGFBP-1 at the maternal-fetal interface involving a multi-step process of de-phosphorylation and proteolysis; this will result in enhanced IGF bioavailability and is likely to represent an important mechanism for controlling fetal and maternal tissue growth.

Biological Availability↗
PubMed2001

The energetic cost of induced fit catalysis: Crystal structures of trypsinogen mutants with enhanced activity and inhibitor affinity.

The contribution of induced fit to enzyme specificity has been much debated, although with little experimental data. Here we probe the effect of induced fit on enzyme specificity using the trypsin(ogen) system. BPTI is known to induce trypsinogen to assume a trypsinlike conformation. Correlations are observed between BPTI affinity and the values of k(cat)/K(m) for the hydrolysis of two substrates by eight trypsin(ogen) variants. The slope of both correlations is -1.8. The crystal structures of the BPTI complexes of four variant trypsinogens were also solved. Three of these enzymes, K15A, DeltaI16V17/D194N, and DeltaI16V17/Q156K trypsinogen, are 10- to 100-fold more active than trypsinogen. The fourth variant, DeltaI16V17 trypsinogen, is the lone outlier in the correlations; its activity is lower than expected based on its affinity for BPTI. The S1 site and oxyanion hole, formed by segments 184A-194 and 216-223, are trypsinlike in all of the enzymes. These structural and kinetic data confirm that BPTI induces an active conformation in the trypsin(ogen) variants. Thus, changes in BPTI affinity monitor changes in the energetic cost of inducing a trypsinlike conformation. Although the S1 site and oxyanion hole are similar in all four variants, the N-terminal and autolysis loop (residues 142-152) segments have different interactions for each variant. These results indicate that zymogen activity is controlled by a simple conformational equilibrium between active and inactive conformations, and that the autolysis loop and N-terminal segments control this equilibrium. Together, these data illustrate that induced fit does not generally contribute to enzyme specificity.

Amino Acid Substitution↗
PubMed2001

Informed consent for acupuncture--an information leaflet developed by consensus.

Patients have the right to be fully informed about the likely benefits and risks of any proposed examination or treatment, and practitioners are obliged to obtain informed consent beforehand. Accurate information about the risks of acupuncture is available following publication of the results of two prospective surveys. At a joint meeting on the safety of acupuncture, members of the three largest UK professional bodies expressed a need to establish what information on risks patients should be given. A standard Information Leaflet was developed by consensus between thesc organisations, and is intended to be used as a stimulus for discussion of standard risks as well as any particular risks that might apply to individual patients. Additionally, it may be used as a form for written consent when this is required. To provide the context for using the Leaflet, the legal and ethical bases of informed consent for medical procedures are discussed.

Acupuncture↗
PubMed2001

Survey of adverse events following acupuncture (SAFA): a prospective study of 32,000 consultations.

Acupuncture is increasingly used, so it is important to establish whether its benefits outweigh its risks. Numerous case reports of adverse events show that acupuncture is not free of risk, but accurate data from prospective investigations is scarce. A prospective survey was undertaken using intensive event monitoring. Forms were developed for reporting minor events each month and significant events as they occurred. The sample size was calculated to identify any adverse events that occurred more frequently than once in 10,000 consultations. Acupuncturists were recruited from two professional organisations in the UK. Seventy-eight acupuncturists, all doctors or physiotherapists, reported a total of 2178 events occurring in 31,822 consultations, an incidence of 684 per 10,000 consultations. The most common minor adverse events were bleeding, needling pain, and aggravation of symptoms; aggravation was followed by resolution of symptoms in 70% of cases. There were 43 significant minor adverse events reported, a rate of 14 per 10,000, of which 13 (30%) interfered with daily activities. One patient suffered a seizure (probably reflex anoxic) during acupuncture, but no adverse event was classified as serious. Avoidable events included forgotten patients, needles left in patients, cellulitis and moxa burns. In conclusion, the incidence of adverse events following acupuncture performed by doctors and physiotherapists can be classified as minimal; some avoidable events do occur. Acupuncture seems, in skilled hands, one of the safer forms of medical intervention.

Acupuncture Therapy↗
PubMed2001

Haptoglobin, inflammation, and tumorigenesis in the MIN mouse.

We have determined that the MIN mouse, which is predisposed to adenomas of the small and large intestine, exhibits chronic inflammation characterized by the induction of haptoglobin (HP), as well as other acute phase proteins. Inflammation is initiated at about 40-70 days of age, and is maintained throughout the life of the animal. Delayed onset of inflammation brought on by dietary means is associated with a reduction in tumor number and longer life-span. Knockout mice that lack haptoglobin exhibit an increase in tumor number, indicating that the acute phase reactant suppresses tumorigenesis, perhaps through inhibition of the inflammatory response. The MIN mouse is, therefore, a useful model for studying the roles of HP and inflammation in tumorigenesis in vivo.

Adenoma↗
PubMed2001

Adrenocortical-pituitary hybrid tumor causing Cushing's syndrome.

We describe the first case of an adrenocortical-pituitary hybrid tumor causing Cushing's syndrome in a 17-yr-old boy. Adrenal vein sampling confirmed elevated secretion of both cortisol and ACTH precursors from a right adrenal mass, whereas pituitary ACTH levels, as determined by bilateral inferior petrosal sinus samples (IPSS), were unresponsive to CRH and equal to peripheral levels. There was no biochemical or histological evidence for a pheochromocytoma, but, rather, the tumor demonstrated lipid-rich clear cells characteristic of an adrenocortical adenoma. Immunohistochemical analysis revealed ACTH immunoreactivity and synaptophysin proteins in the tumor. Isolation of tumor cells by the novel technique of laser capture microdissection and subsequent RT-PCR showed expression of POMC messenger ribonucleic acid and cytochrome p450 enzyme messenger ribonucleic acid within the same cells. Finally, ultrastructural analysis provided ultimate proof for adrenocortical-pituitary hybrid cells exhibiting the characteristic vesicular mitochondria and abundant smooth endoplasmic reticulum of steroid cells and the typical secretory granules of corticotrophs within the cytoplasm of the same cells. The adrenocortical tumor expressed the pituitary transcription factor pituitary homeobox factor 1 and the steroidogenic factor 1. The intermingling of the centrally located ectodermally derived pituitary tissue with the mesodermally derived adrenocortical tissue in this adenoma suggests a hitherto unrecognized genetic and phenotypic plasticity within the hypothalamic-pituitary-adrenal axis.

Adenoma↗
PubMed2001

Patterning the optic neuroepithelium by FGF signaling and Ras activation.

During vertebrate embryogenesis, the neuroectoderm differentiates into neural tissues and also into non-neural tissues such as the choroid plexus in the brain and the retinal pigment epithelium in the eye. The molecular mechanisms that pattern neural and non-neural tissues within the neuroectoderm remain unknown. We report that FGF9 is normally expressed in the distal region of the optic vesicle that is destined to become the neural retina, suggesting a role in neural patterning in the optic neuroepithelium. Ectopic expression of FGF9 in the proximal region of the optic vesicle extends neural differentiation into the presumptive retinal pigment epithelium, resulting in a duplicate neural retina in transgenic mice. Ectopic expression of constitutively active Ras is also sufficient to convert the retinal pigment epithelium to neural retina, suggesting that Ras-mediated signaling may be involved in neural differentiation in the immature optic vesicle. The original and the duplicate neural retinae differentiate and laminate with mirror-image polarity in the absence of an RPE, suggesting that the program of neuronal differentiation in the retina is autonomously regulated. In mouse embryos lacking FGF9, the retinal pigment epithelium extends into the presumptive neural retina, indicating a role of FGF9 in defining the boundary of the neural retina.

Animals↗
PubMed2001

'Insuring' a correct differential diagnosis--a 'forensic' collaborative experience.

Mr. J was referred to a speech and language therapist (SLT) by a consultant psychiatrist. He had sustained an industrial accident which he claimed was responsible for a range of problems which included a speech and language problem. Some three years after his accident, he brought an action for damages arising out of the accident. His solicitor, on the recommendation of the consultant psychiatrist, contacted the SLT requesting his views as to whether Mr. J's speech difficulties were due to the injuries sustained and requesting recommendations for further treatment. The SLT saw Mr. J and concluded that he had problems at all communication levels, the greatest being an articulatory impairment. Some reports suggested a psychological basis for his problems and others, including the psychiatrists', suggested an organic basis.

Accidents, Occupational↗
PubMed2000

Caring for the critically ill patient. Current and projected workforce requirements for care of the critically ill and patients with pulmonary disease: can we meet the requirements of an aging population?

CONTEXT: Two important areas of medicine, care of the critically ill and management of pulmonary disease, are likely to be influenced by the aging of the US population. OBJECTIVE: To estimate current and future requirements for adult critical care and pulmonary medicine physicians in the United States. DESIGN, SETTING, AND PARTICIPANTS: Analysis of existing population, patient, and hospital data sets and prospective, nationally representative surveys of intensive care unit (ICU) directors (n = 393) and critical care specialists (intensivists) and pulmonary specialists (pulmonologists) (n = 421), conducted from 1996 to 1999. MAIN OUTCOME MEASURES: Influence of patient, physician, regional, hospital, and payer characteristics on current practice patterns; forecasted future supply of and demand for specialist care through 2030. Separate models for critical care and pulmonary disease. Base-case projections with sensitivity analyses to estimate the impact of future changes in training and retirement, disease prevalence and management, and health care reform initiatives. RESULTS: In 1997, intensivists provided care to 36.8% of all ICU patients. Care in the ICU was provided more commonly by intensivists in regions with high managed care penetration. The current ratio of supply to demand is forecast to remain in rough equilibrium until 2007. Subsequently, demand will grow rapidly while supply will remain near constant, yielding a shortfall of specialist hours equal to 22% of demand by 2020 and 35% by 2030, primarily because of the aging of the US population. Sensitivity analyses suggest that the spread of current health care reform initiatives will either have no effect or worsen this shortfall. A shortfall of pulmonologist time will also occur before 2007 and increase to 35% by 2020 and 46% by 2030. CONCLUSIONS: We forecast that the proportion of care provided by intensivists and pulmonologists in the United States will decrease below current standards in less than 10 years. While current health care reform initiatives and modification of existing practice patterns may temporarily forestall this problem, most anticipated effects are minor in comparison with the growing disease burden created by the aging US population. JAMA. 2000;284:2762-2770.

Aged↗