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Insulin resistance, hypertension, and coronary heart disease.

The goals of this review are two-fold: to examine the evidence in support of a role for insulin resistance and compensatory hyperinsulinemia in the pathogenesis of essential hypertension, and to evaluate the hypothesis that insulin resistance and its manifestations play major roles in the development of coronary heart disease in patients with essential hypertension. In both instances, only experimental results in human beings will be considered. Although it remains a scientific issue of great importance, the scope of this review precludes a discussion of the mechanistic link between insulin resistance/hyperinsulinemia and essential hypertension.

Coronary Disease↗

Long-term hormone therapy for perimenopausal and postmenopausal women.

BACKGROUND: Hormone therapy is widely provided to control menopausal symptoms and has been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of a Cochrane review first published in 2005. OBJECTIVES: To assess the long-term effects of prolonged use (at least one year) of hormone therapy on mortality, cardiovascular outcomes, cancer, gallbladder disease, fractures and cognition in perimenopausal and postmenopausal women. SEARCH METHODS: We used the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, three other databases and two trial registers, together with reference checking, citation searching and contact with study authors to identify the studies included in the review. The latest search date was 26 September 2024. SELECTION CRITERIA: We included randomised, double-blind trials in which peri- or postmenopausal women took hormone therapy or placebo for at least one year. We included various oestrogen formulations, with or without progestogens. We focused on studies assessing hormone therapy's effects on long-term clinical outcomes, including death, coronary events and cancer. Hormone therapy's efficacy in managing menopausal symptoms was beyond the scope of this review, and is assessed in other Cochrane reviews. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted data. We calculated risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, along with 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 24 studies - with two newly added in this update - involving 45,660 participants. We derived nearly 70% of the data from two well-conducted studies: the Heart and Estrogen/progestin Replacement Study (HERS 1998) and the large, multi-component Women's Health Initiative research programme, which included two hormone therapy arms (WHI 1998). Across all the studies, most participants were postmenopausal American women with one or more comorbidities. The mean participant age in most studies was over 60 years. Only one included study focused on perimenopausal women. We present full results for all included studies with available data in the main review. The results presented below are drawn from WHI 1998, in which the combined hormone therapy arm and the oestrogen-only arm were run concurrently, with women assigned to the appropriate trial based on their uterus status. One study with 16,608 postmenopausal women with an intact uterus compared combined continuous hormone therapy (conjugated equine oestrogen and medroxyprogesterone acetate) to placebo, and measured outcomes at an average of 5.6 years of follow-up. Based on this study, combined continuous hormone therapy probably makes little to no difference to the risk of a coronary event (RR 1.17, 95% CI 0.95 to 1.44; moderate-certainty evidence). It may increase the risk of stroke (RR 1.39, 95% CI 1.09 to 2.09; low-certainty evidence) and venous thromboembolism (RR 2.03, 95% CI 1.55 to 6.64; low-certainty evidence). Compared to placebo, combined continuous hormone therapy probably increases the risk of breast cancer (RR 1.27, 95% CI 1.03 to 1.56; moderate-certainty evidence) and probably makes little to no difference to the risk of lung cancer (RR 1.06, 95% CI 0.77 to 1.46; moderate-certainty evidence). It may increase gallbladder disease requiring surgery (RR 1.64, 95% CI 1.30 to 2.06; 14,203 participants; low-certainty evidence), and probably reduces the risk of all clinical fractures (RR 0.78, 95% CI 0.71 to 0.86; moderate-certainty evidence). One study including 10,739 postmenopausal women who had undergone a hysterectomy compared oestrogen-only (conjugated equine oestrogen) hormone therapy to placebo, and measured outcomes at an average of seven years' follow-up. Based on this study, oestrogen-only hormone therapy probably makes little to no difference to the risk of coronary events (RR 0.94, 95% CI 0.78 to 1.13), venous thromboembolism (RR 1.32, 95% CI 1.00 to 1.74) and breast cancer (RR 0.79, 95% CI 0.61 to 1.01), all with moderate-certainty evidence. It may make little to no difference to the risk of lung cancer (RR 1.04, 95% CI 0.73 to 1.48; low-certainty evidence). Oestrogen-only hormone therapy probably increases the risk of stroke (RR 1.33, 95% CI 1.06 to 1.67) and gallbladder disease requiring surgery (RR 1.78, 95% CI 1.42 to 2.24), and probably reduces the risk of all clinical fractures (RR 0.73, 95% CI 0.65 to 0.80), all with moderate-certainty evidence. We judged most included studies to have a low risk of bias for most domains. The overall certainty of evidence for the main comparisons was moderate. The main limitation was that only about 30% of women were 50 to 59 years old at baseline, the age group most likely to consider hormone therapy for vasomotor symptoms. AUTHORS' CONCLUSIONS: Long-term follow-up of women using hormone therapy suggests that the risk profiles vary between combined hormone therapy and oestrogen-only therapy. Oestrogen-only hormone therapy probably makes little to no difference to coronary events, and probably increases the risk of stroke and gallbladder disease. It probably makes little to no difference in the risk of breast cancer, and probably reduces the risk of all fractures. Combined hormone therapy may increase the risk of thromboembolism and probably increases the risk of breast cancer. These results should be interpreted with caution as they are based on one study using oral hormone therapy, which may not represent the risks of the hormone therapy currently used in clinical practice.

Humans↗

Catalytic, enantioselective, vinylogous aldol reactions.

In 1935, R. C. Fuson formulated the principle of vinylogy to explain how the influence of a functional group may be felt at a distant point in the molecule when this position is connected by conjugated double-bond linkages to the group. In polar reactions, this concept allows the extension of the electrophilic or nucleophilic character of a functional group through the pi system of a carbon-carbon double bond. This vinylogous extension has been applied to the aldol reaction by employing "extended" dienol ethers derived from gamma-enolizable alpha,beta-unsaturated carbonyl compounds. Since 1994, several methods for the catalytic, enantioselective, vinylogous aldol reaction have appeared, with which varying degrees of regio- (site), enantio-, and diastereoselectivity can be attained. In this Review, the current scope and limitations of this transformation, as well as its application in natural product synthesis, are discussed.

Aldehydes↗

Practical guides. II: Hospital pharmacy quality control services.

This article briefly reviews the evolution, scope and operation of hospital quality control (QC) services. Recent initiatives and developments are considered alongside the traditional 'core' QC/quality assurance (QA) work. Important new areas of work which could benefit from QC involvement are also discussed.

Guidelines as Topic↗

Peritoneal dialysis update 1994.

Each year there are over 400 papers published in the field of peritoneal dialysis. In this review I have touched on only a few highlights of some of the more active areas of investigation and development. The advances in controlling peritonitis rates with the Y-set have been dramatic and have resulted in peritonitis rates in many centers less than one episode per 24 patient months. Technique survivals have also improved with lower peritonitis rates. The enormous literature on new approaches to treatment and new understandings of host defenses are beyond the scope of this review. There are also many advances in peritoneal access. We now have many new types of catheters under investigation such as the Swan-Neck Missouri catheter and the Moncrief-Popovich catheter, with complete burial of the catheter until eventual externalization for CAPD training. There have been major advances in understanding the normal healing of exit sites and the early diagnosis and treatment of exit-site infections. All the extensive literature on catheter development in the management of exit sites will be reviewed elsewhere. I have focused primarily on an update of worldwide demographics, some of the new findings in peritoneal transport, the use of low-calcium solutions, experiences with EPO, new thinking about adequacy and nutrition, and finally, on recent comparisons of CAPD and hemodialysis.

Humans↗

Adverse effects of milk formula ingestion on the gastrointestinal tract. An update.

The large-scale use of cow's milk in infant feeding is less than one hundred years old. Much progress has been made by the manufacturers of proprietary formulas during this period to make their products safer. Although the current formulas provide an excellent "substitute" for the majority of infants, problems still remain, and it is necessary for every pediatrician and gastroenterologist to be aware of these. The purposes of this article are to review the adverse effects of nonhuman milk on the gastrointestinal tract, to examine the underlying mechanisms, and hopefully to stimulate further thought and research. Particular emphasis will be placed on hypersensitivity reactions, because there now appears to be a swing back to this diagnosis as a result of more sophisticated immunologic investigations. The arguments in favor of breast-feeding, the systemic biochemical differences resulting from different formulas, and the indications for specialized formula feeding are all beyond the scope of this review.

Animals↗

Development and progression of urothelial carcinoma.

Urothelial carcinomas are well known to feature multifocal development in the urinary tract, both synchronously and asynchronously. This phenomenon can be explained by either seeding of cancer cells in the urinary tract or field cancerization. As there are two characteristic morphological patterns of urothelial carinomas, papillary and nodular, published papers were here reviewed to understand the development and progression of urothelial carcinoma regarding multifocality due to seeding or field changes with reference to the type of urothelial carcinoma. From animal experiments using rats, mice and dogs treated with N-butyl-N-(4-hydoroxybutyl) nitrosamine, and from pathological observation of human cystectomy specimens on step-sectioning and molecular analysis, nodular carcinomas appear to either develop via papillary carcinomas or de novo. Clinical aspects of multifocal tumor development are outside of the scope of this review, although an understanding of the mechanisms underlying multifocality and the papillary/nodular morphological relationship is important to determine follow-up strategies for patients treated for primary urothelial carcinomas and for reconstruction of the urinary tract after cystectomy.

Animals↗

Cancer initiatives in developing countries.

The coming decades will bring dramatic increases in morbidity and mortality from cancer in the developing world. The burden of cancer is increasing globally, with an expected 20 million new cases per year in 2020, half of which will be in low- and middle-income countries. Despite an already overwhelming burden of health problems, developing countries must somehow address this cancer pandemic and their alarming share of cancer illness. Many large-scale and innovative worldwide initiatives have been launched in the fight against cancer. These programs represent colossal efforts to expand resources for health education among people and healthcare workers in developing countries and to increase awareness of cancer prevention. Many novel evidence-based and culturally-relevant programs are being implemented for screening and early prevention of common cancers. Several key initiatives are supporting clinical research, guideline development, oncology training, and appropriate technology transfer, such as access to electronic medical literature. Treatment programs are expanding access and quality of radiologic and pharmacologic therapies for cancer. These initiatives represent an unprecedented level of and cooperation among international agencies, governmental and nongovernmental organizations, international foundations, scientific societies, local institutions, and industry. This review examines the scope of need in response to the increasing burden of cancer in the developing world and major initiatives that have been created to respond to these needs.

Developing Countries↗

Early integration of retinal and extra-retinal information: recent results and hypotheses.

This review aims at highlighting and discussing some recent neurophysiological and psychological findings and hypotheses about early cortical integration of visual and extra-retinal information which is involved in the stability of visual perception in spite of the change of body orientation and distance to objects and eye movements. Within this framework, the possible role of some cortical and cortico-thalamic loops between earlier and later stages of visual processing is also emphasized. A complete study of multimodal processing is beyond the scope of this review.

Animals↗

Advances in real-time PCR: application to clinical laboratory diagnostics.

The polymerase chain reaction (PCR) has become one of the most important tools in molecular diagnostics, providing exquisite sensitivity and specificity for detection of nucleic acid targets. Real-time monitoring of PCR has simplified and accelerated PCR laboratory procedures and has increased information obtained from specimens including routine quantification and differentiation of amplification products. Clinical diagnostic applications and uses of real-time PCR are growing exponentially, real-time PCR is rapidly replacing traditional PCR, and new diagnostic uses likely will emerge. This review analyzes the scope of present and potential future clinical diagnostic applications of this powerful technique. Critical discussions focus on basic concepts, variations, data analysis, instrument platforms, signal detection formats, sample collection, assay design, and execution of real-time PCR.

Fluorescent Dyes↗

Altered renal handling of sodium in human hypertension: short review of the evidence.

A pathogenic role of the kidney in hypertension has been strongly supported by experimental studies by Guyton and Dahl since the 1960s. In the early 1980s, de Wardener and MacGregor proposed that in hypertensive patients the ability of the kidneys to excrete a sodium load could be genetically impaired. Since then, "sodium-sensitive" hypertension has been the object of numerous studies, mostly on animal models because of the difficulty to investigate the renal handling of sodium in humans. More recently, considerable progress in this field has been made thanks to the in vivo study of segmental renal tubular function by the clearance of lithium and to the growing knowledge of the genetics of renal tubular sodium transport systems. The scope of this review is to briefly review the most relevant information gathered by the investigation of segmental renal tubular sodium handling in humans as related to blood pressure regulation and hypertension. In aggregate, the results of these studies strongly support the association between altered renal sodium handling and high blood pressure and suggest a causal role of genetic, nutritional, metabolic, and neurohormonal factors. All of these factors, alone or in combination, may be able to impair the normal renal tubular sodium handling and influence blood pressure homeostasis. The paradigm of the pathogenic role of the kidney in hypertension is thus relentlessly shifting toward the definition of inherited as well as acquired renal tubular defects and molecular alterations, providing a plausible explanation for the alteration in blood pressure levels.

Blood Pressure↗

Consultation-liaison psychiatry: a psychosomatic service in the general hospital.

Consultation psychiatry, an outgrowth of the tenets of psychosomatic medicine that followed the departure from mental-hospital psychiatry to the general-hospital-based psychiatric units, is similar to those consultation services in other specialties available on medical-surgical wards. Its primary aim is to interpret the psychosocial phenomena of health and illness and to redirect the physician from disease- to patient-orientation and to a comprehensive approach. Its functions are diagnostic-therapeutic, instructional and research directed. The psychosomatic orientation is a sine qua non in the understanding of the psychosocial meaning of physical illness, its effect on psychic disability, the psychosocial adjustment of the patient and his family and his ability to adapt to illness and the hospital. An essential feature is the evaluation of the doctor-patient relationship, especially when severe illness requires serious interventions, including the consultation and its reciprocal effect upon the doctor-patient relationship. Liaison activity consists of interpretive-therapeutic mediation between the patient and the therapeutic team when strain endangers their satisfactory cooperation. The therapeutic activity must be short-term and so construed as not to interfere with the primary treatment. The instructional aspect is for the sake of the usual recipients of the service, as well as residents and students. Teaching the interview techniques, especially to students, should demonstrate the holistic approach, comprehensive diagnosis and the need of avoiding orthodox one-sidedness. This paper reviews briefly the scope and role of consultation psychiatry, compares its North American model with its status elsewhere and explores the resistances to it.

Adaptation, Psychological↗

Miniaturising the laboratory in emulsion droplets.

Biochemical and genetic assays can be both miniaturized and parallelized by compartmentalization in living cells. In vitro compartmentalization (IVC) offers an alternative strategy based on partitioning reactions in water droplets dispersed to form microscopic compartments in water-in-oil emulsions. The cell-like volumes of these compartments (as low as one femtolitre), the ability to freely determine and regulate their content and the large number of compartments (>10(10) per millilitre emulsion) have provided the basis for a range of new, ultra-high-throughput, cell-free technologies. This review describes the scope and potential of IVC in areas such as in vitro evolution of proteins and RNAs, cell-free cloning and sequencing, genetics, genomics, and proteomics.

Cell-Free System↗

The curve of the cervical spine: variations and significance.

OBJECTIVE: To review the literature regarding the curve of the cervical spine in normal and injured persons, emphasizing common variations in cervical curvature and their possible clinical significance. DATA SOURCE: A MEDLINE literature search of the English-language, human literature was performed using multiple search strategies relevant to radiography, posture, lordosis, injury, diagnosis and prognosis of the cervical spine (MESH: cervical vertebrae). Additionally, article bibliographies were searched for further relevant articles. No publication time limit was imposed. STUDY SELECTION: Articles were identified by the author as being directly relevant to the objective and scope of this review. DATA EXTRACTION: Data was extracted as presented in each original article. DATA SYNTHESIS: The articles reviewed indicate that a wide range of normal exists in the posture and configuration of the cervical spine. Although kyphotic angulation and straightening or reversal of cervical lordosis are commonly seen following trauma, they may be normal variants. Muscle spasm is a widely used explanation for these variations when seen in patients with pain or trauma. Kyphotic angulation is often associated with posterior ligamentous injury of a motion segment. Prognostic significance of these variations is claimed by some authors. CONCLUSION: There is little evidence to support the contention that altered cervical curvatures are of prognostic significance. Although kyphotic angulation is associated with anterior subluxation (hyperflexion sprain), it is not a reliable diagnostic criterion for that condition. It is reasonable to assume that straightening or reversal of a previously lordotic cervical curve is the result of muscular spasm, but more specific interpretation is not supported by the literature. More study is needed to characterize the specific dynamics and etiologies involved in the determination of cervical spine configuration.

Cervical Vertebrae↗

Neurophysiological measures in amyotrophic lateral sclerosis: markers of progression in clinical trials.

In this review we evaluate clinical neurophysiological methods, originally described for use in diagnosis that can be applied to measurement of change during the progress of amyotrophic lateral sclerosis (ALS). Such measurements are potentially important in clinical trials, and also in clinical practice. We have assessed methods for lower and upper motor neuron function, including conventional EMG, nerve conduction and F-wave studies, the derived Neurophysiological Index, motor unit counting methods (MUNE), and transcranial magnetic motor cortex stimulation. We have also addressed the validity of measurements of electromechanical coupling. Methods for measuring muscle strength are beyond the scope of this review. We conclude that MUNE, M-wave amplitude and the Neurophysiological Index are sufficiently reliable, sensitive, and relevant to the clinical problem of ALS, to be used in clinical trials in the disease. Transcranial magnetic stimulation is of limited value, but a combination of the measurements made as part of this technique may also be useful. We conclude that clinical neurophysiological techniques should now be used in measuring change in clinical trials in ALS.

Amyotrophic Lateral Sclerosis↗

Pituitary function in the acute phase response in domestic farm animals: cytokines, prostaglandins, and secretion of ACTH.

Contained in this report is a review of available data on pituitary cytokines in domestic species of agricultural importance. The concept is advanced that the pituitary gland is essential to appropriate generation of host defense mechanisms and thus should be considered among other tissues contributing to innate immunity. The functions of these intrapituitary cytokines, principally IL-6, are discussed in the context of potential regulation of the pituitary-adrenal axis (ACTH secretion) via intrapituitary PGE2 generation during the acute-phase response to infectious/inflammatory stimuli. Data from other species are cited as appropriate for comparative purposes and elaboration of proposed mechanisms. However, the scope of the review is not intended to comprehensively cover the vast literature on proinflammatory cytokines and prostaglandins generated peripherally and centrally during host responses to inflammatory stimuli.

Acute-Phase Reaction↗