OTITIS EXTERNA

Otitis externa is a widespread condition which may occur in many different forms. Allergic reactions, bacteria, pathologic changes secondary to seborrheic dermatitis, and fungi, singly or in association with each other, are among the causative factors considered.In the treatment of this condition, the diversity of causative factors which may be present must be recognized and evaluated; after one factor has been eliminated, another often remains to be conquered. The apparent confusion of reports regarding etiology and treatment is in fact due to confusion regarding the fundamental nature of the condition. Good results usually can be obtained by careful evaluation of the factors in each case and adaptation of treatment to the circumstances.     

Pathophysiology and genetics of obesity

Obesity, a global problem, is a multifactorial disorder. The factors are environmental, metabolic and genetic and their interaction with each other regulates the body weight. Imbalance in either of the factors may be responsible for weight gain. With advancement of research techniques in the last decade, genetic studies have been undertaken for several different causative mutations involving obesity loci on different chromosomes. Monogenic and polygenic obesity has been observed however, polygenic forms are more common. So far more than 200 genes in mouse and more than 100 genes in humans have been identified which result in phenotypes that affect body weight regulation. In spite of this knowledge, the field of obesity has still not been explored extensively. There remain a lot of lacuna regarding causes and treatment of obesity. Challenges are still there to identify the exact cause of weight gain and the use of current knowledge for development of anti-obesity drugs targeted for body weight regulation. In this review, we have explained neuropathophysiologic regulation of feeding behaviour and some aspects of obesity-genetics especially with single nucleotide polymorphism of selected candidate genes and their functional aspects mainly in monogenic obesity.     

Interactions between age,sex, and hormones in experimental ischemic stroke

Age, sex, and gonadal hormones have profound effects on ischemic stroke outcomes, although how these factors impact basic stroke pathophysiology remains unclear. There is a plethora of inconsistent data reported throughout the literature, primarily due to differences in the species examined, the timing and methods used to evaluate injury, the models used, and confusion regarding differences in stroke incidence as seen in clinical populations vs. effects on acute neuroprotection or neurorepair in experimental stroke models. Sex and gonadal hormone exposure have considerable independent impact on stroke outcome, but these factors also interact with each other, and the contribution of each differs throughout the lifespan. The contribution of sex and hormones to experimental stroke will be the focus of this review. Recent advances and our current understanding of age, sex, and hormone interactions in ischemic stroke with a focus on inflammation will be discussed.     

THE SIGNIFICANCE OF INFECTION IN ALLERGIC DISEASE-Its Influence on Diagnosis and Management

The presence of infection in allergic disease produces a confused picture in which two different causative factors must be clearly separated by the physician if he is to treat the patient successfully. The effects of infection are not consistent. There are situations, as seen in infectious diseases, where symptoms of allergic disease are temporarily relieved and others where the infection may intensify or precipitate the allergic condition. It is likewise important to recognize the complications superimposed upon allergic disease by infection. In such cases, control of the infection is as dependent upon control of the allergy as it is upon antibiotics.     

THE SIGNIFICANCE OF INFECTION IN ALLERGIC DISEASE—Its Influence on Diagnosis and Management

The presence of infection in allergic disease produces a confused picture in which two different causative factors must be clearly separated by the physician if he is to treat the patient successfully. The effects of infection are not consistent. There are situations, as seen in infectious diseases, where symptoms of allergic disease are temporarily relieved and others where the infection may intensify or precipitate the allergic condition. It is likewise important to recognize the complications superimposed upon allergic disease by infection. In such cases, control of the infection is as dependent upon control of the allergy as it is upon antibiotics.     

Improved detection of rare genetic variants for diseases

Technology advances have promoted gene-based sequencing studies with the aim of identifying rare mutations responsible for complex diseases. A complication in these types of association studies is that the vast majority of non-synonymous mutations are believed to be neutral to phenotypes. It is thus critical to distinguish potential causative variants from neutral variation before performing association tests. In this study, we used existing predicting algorithms to predict functional amino acid substitutions, and incorporated that information into association tests. Using simulations, we comprehensively studied the effects of several influential factors, including the sensitivity and specificity of functional variant predictions, number of variants, and proportion of causative variants, on the performance of association tests. Our results showed that incorporating information regarding functional variants obtained from existing prediction algorithms improves statistical power under certain conditions, particularly when the proportion of causative variants is moderate. The application of the proposed tests to a real sequencing study confirms our conclusions. Our work may help investigators who are planning to pursue gene-based sequencing studies.     

Regulation of polypeptide growth factor synthesis and growth factor-related gene expression in the rat and mouse uterus before and after implantation

It is apparent that the uterus is a rich source of growth factors, the synthesis of which may be induced by female sex steroids. These growth factors appear to be involved in complex autocrine/paracrine regulatory circuits which in turn interact with steroid hormones. With the exception of CSF-1, however, detailed studies of the appearance of these growth factors and their receptors during pregnancy and under different hormonal regimens have yet to be performed. Furthermore, causative roles have not been established for any of these growth factors in uterine biology and pregnancy. In the near future we can expect that, by using in-situ techniques, the producing and responding cells will be identified. Cell culture models will also have to be established to investigate specific growth factor-induced functions. In the longer term, once more is known about the regulation of uterine growth factors, imaginative new experiments need to be designed, perhaps involving transgenic animals, to establish causative roles for growth factors in uterine biology.     

Relation between Aspects of Nutritional Disturbance and Menstrual Activity in Primary Anorexia Nervosa

A significantly high number of patients with anorexia nervosa are overweight immediately before the onset of the condition. This premorbid weight may be a feature of their constitution but is sometimes a more transitory phenomenon. Menstruation ceases early in the condition but usually within the context of significant weight loss. However, the subsequent amenorrhoea, related to factors that presumably may not begin to operate until several weeks later, may be a symptom which first draws attention to the condition.Treatment included the restitution of body weight to the matched population mean weight for each patient. This may be important, as the mean weight at which menstrual activity returned was not significantly different from the matched population mean weight. A further treatment aim, so far as nutrition was concerned. was restoration of regular and reasonable feeding behaviour, including adequate carbohydrate ingestion. It is suggested that these findings support the view that the nutritional disturbance in anorexia nervosa is an important factor affecting menstrual activity.     

The Obese Person as an Adolescent

Obesity constitutes a major health problem in the United States. Hypertension, atherosclerosis, coronary artery disease, diabetes and gout are often associated with obesity and may be a direct result of persistent obesity in adult life.Obesity frequently has its beginnings in childhood and adolescence. Unfortunately, obesity which develops in early life is a progressive problem. Eighty per cent of overweight children and adolescents will continue to be overweight as adults.¹² Furthermore, adults with a history of obesity in childhood are the most resistant to treatment.Recent studies have shown there is more than one body constitutional type among obese adolescents. Obese adolescents tend to eat less than non-obese controls. While obesity may be found to have many different causative factors, efforts to control this disease may be most successful in the area of primary prevention.     

Assessing the heritability of body condition in birds: a challenge exemplified by the great tit Parus major L. (Aves)

The definition and measurement of body condition are central to many ecological and evolutionary studies, yet the fundamental issue of whether variation in condition is inherited genetically remains unresolved. Furthermore, confusion has been caused through diverse uses of the word 'condition' itself. In this paper, we introduce the terms 'broad-sense condition' and 'narrow-sense condition' in an attempt to reduce this confusion. Because of the difficulty of measuring condition, field biologists use the mass relative to body size as a convenient index of condition. Such indices have also been used to estimate die heritability of condition. Using data from a wild great tit Parus major population, we demonstrate that a condition index may still contain residual variance that is due to body size. Hence, using a condition index to study the heritability of condition can give misleading results because that residual variance may itself be heritable. To avoid this problem, direct measures of condition, such as reserve tissues, should be used. We provide the first heritability estimates of direct measures of condition of full-grown birds in a wild population by the regression of mean offspring (both in winter, and when breeding) on mean parent (when breeding) values of two reserve tissues, fat and pectoral muscle, which are independent of body-size. A great tit's fat and muscle reserves in winter were significandy correlated with their respective values when the birds bred. However there was no evidence that the level of fat reserves in winter resembled those of the parents (when breeding), more than expected by chance. Slight resemblances between parents and offspring were detected for muscle in winter and for fat reserves when breeding. Muscle size in the breeding season provided stronger evidence for the inheritance of condition.     

A CONSIDERATION OF SOME FACTORS CAUSING DEATH IN THE OPERATING ROOM

Some of the causes of deaths in the operating room are related to anesthesia. In some cases death occurs because of lack of understanding of certain factors which are subject to control by the surgeon or the anesthetist.Simple comparisons of the rate of deaths from such causes in one hospital with the rate in another are meaningless because of the many variables involved. A better avenue to the knowledge that may prevent untoward deaths is exposition of the causes in each case. By this means the causative factors may be fully disclosed, emphasized, and guarded against.In this presentation the author has classified the causes of 46 operating room deaths that occurred in the Los Angeles County General Hospital in a period of 21 months, and has discussed the causes individually.     

Targeting gene-virotherapy of cancer

Due to concerns regarding the overlapping figures in this review that are identical to those contained in a reviewarticle that we have co-authored and published earlier,we retract the above paper we published in Cell Research.Weapologize for any confusion that may be caused by this matter,although we stand by the scientific contents containedin the Cell Research paper.     

Protein structure validation using a semi-empirical method

Current practice of validating predicted protein structural model is knowledge-based where scoring parameters are derived from already known structures to obtain decision on validation out of this structure information. For example, the scoring parameter, Ramachandran Score gives percentage conformity with steric-property higher value of which implies higher acceptability. On the other hand, Force-Field Energy Score gives conformity with energy-wise stability higher value of which implies lower acceptability. Naturally, setting these two scoring parameters as target objectives sometimes yields a set of multiple models for the same protein for which acceptance based on a particular parameter, say, Ramachandran score, may not satisfy well with the acceptance of the same model based on other parameter, say, energy score. The confusion set of such models can further be resolved by introducing some parameters value of which are easily obtainable through experiment on the same protein. In this piece of work it was found that the confusion regarding final acceptance of a model out of multiple models of the same protein can be removed using a parameter Surface Rough Index which can be obtained through semi-empirical method from the ordinary microscopic image of heat denatured protein.     

Comprehensive simulation on morphological and mechanical properties of trigger finger – A cadaveric model

Trigger finger has long been a common disorder in hand orthopedics. To clarify the unknown causative factors regarding the disease, numerous experiments were done on human cadavers, including tendon forces, tendon moment arm, mechanical properties of the pulley, gliding resistance, etc. However, most of these studies were conducted on normal fingers. As the etiology of trigger finger is still controversial on whether it is an outcome of tendon nodule or pulley scarring, in this study, a trigger finger model was built combining both the nodule created by silicone gel injection and pulley constriction by external compression. Indentation and gliding resistance tests were performed on cadaveric specimens to verify the model. Results showed that after silicone gel injection into the tendon, a significant increase in thickness was found. In addition, no significant difference was found in the toe region compressive modulus of the tendon after injection. Moreover, maximum, drop of gliding resistance and work of extension were all found to be significantly larger as the severity of triggering increased. Our results indicated we have developed a feasible cadaver model simulating trigger finger nodule which could be utilized for further experiments to elucidate other causative factors and biomechanical features of trigger finger in the future.     

Characterization of Burkholderia pseudomallei infection and identification of novel virulence factors using a Caenorhabditis elegans host system

The environmental saphrophyte Burkholderia pseudomallei is the causative agent of melioidosis, a systemic, potentially life-threatening condition endemic to many parts of south-east Asia and northern Australia. We have used the soil nematode Caenorhabditis elegans as a model host to characterize the mechanisms by which this bacterium mounts a successful infection. We find that C. elegans is susceptible to a broad range of Burkholderia species, and that the virulence mechanisms used by this pathogen to kill nematodes may be similar to those used to infect mammals. We also find that the specific dynamics of the C. elegans-B. pseudomallei host-pathogen interaction can be highly influenced by environmental factors, and that nematode killing results at least in part from the presence of a diffusible toxin. Finally, by screening for bacterial mutants attenuated in their ability to kill C. elegans, we genetically identify several new potential virulence factors in B. pseudomallei. The use of C. elegans as a model host should greatly facilitate future investigations into how B. pseudomallei can interact with host organisms.     

ASTHMA AND CARDIAC DYSPNEA—A DIFFERENTIAL DIAGNOSIS

There appear to be no infallible guides by which to differentiate between cardiac insufficiency and asthma as a cause of dyspnea, wheezing and coughing in elderly patients. Many of the symptoms of one condition are also symptoms of the other. Even the results of therapeutic trial cannot be relied upon to establish diagnosis, for drugs effective in treatment of heart disease may also help relieve asthma, and vice versa.Although there is no single factor that can be considered pathognomonic, there are certain symptoms and results of tests which are more strongly indicative of one condition than of the other. Careful evaluation of all factors, while it may not serve to establish unequivocal diagnosis, will provide a basis for judicious treatment of the patient.     

On the changing concept of evolutionary population stability as a reflection of a changing point of view in the quantitative theory of evolution

 Eighteen different terms, currently employed to define various concepts of evolutionary stability in population dynamics are mentioned in this paper. Most of these terms are used in different connotations and even different meanings by different authors. On the other hand, different terms are often employed by different authors to define quite the same concept. Twenty-five years ago there was only one, well-defined, concept of stability, universally recognized in the field. In this paper I will try to relate the recent confusion, concerning concepts of population stability, with a more serious, though not that well-recognized, confusion in the modern analytic approach to population dynamics and quantitative evolution. Concepts of population stability will be examined in relation to each other on the one hand and, on the other hand, in relation to two dichotomies regarding the dynamic processes to which they correspond: Short-term versus long-term processes and processes concerning phenotypic changes versus process concerning genotypic changes. A hopefully more consistent use of the current terminology is suggested. Received 15 August 1993; received in revised form 15 September 1994     

Sebaceous carcinoma in solid organ transplant recipients: The elegant path from epidemiology to etiology

Sebaceous carcinoma (SC) is a rare skin cancer associated with rapid progression and relatively poor survival, particularly in solid organ transplant recipients (SOTRs). Immunosuppressive regimens place SOTRs at substantially increased risk of a variety of skin cancers; recent research has shown a 25-fold increase in SC in the SOTR population, especially among lung recipients, older males, those with longer time since transplant, and patients undergoing induction therapy with thymoglobulin. The potential etiologic mechanisms underlying SC are multifaceted and complex. Immunosuppression creates a microcosm through which to view causative factors for carcinogenesis which has implications in elucidating mechanistic etiologies for SC far beyond the SOTR population, since not all cancers are more common in immunosuppressed patients. Research integrating the role of oncogenic viruses, underlying medical conditions, genetic risk factors, toxicity of prophylactic medications, drug-induced photosensitization, and T-cell deficiency/dysfunction is needed to better elucidate the factors underlying SC in immunosuppressed hosts. In this report, we integrate current research regarding SC in SOTR patients using the causal pie/sufficient-component cause model. In doing so, we provide a paradigm through which to view future research regarding the etiology of SC.     

Primate sexual swellings as coevolved signal systems

Many female catarrhine primates possess visually conspicuous organs that apparently function to increase the sexual interest of adult male conspecifics around the time the female is ovulating—i.e. sexual swellings. The hypothesized functional benefits for both sexes of these sexual swellings are reviewed (honest signaling; paternity confusion; paternity confidence and paternal investment; protection; incitement of precopulatory male-male competition; and postcopulatory sexual selection), as well as an additional hypothesis that has not yet been applied to this problem (sensory exploitation). Currently available evidence is presented that supports or fails to support each of these hypotheses. Predictions associated with broad groupings of these hypotheses, which could be tested in noninvasive field studies, are then presented. Ecological circumstances are discussed that could have led to differential mating success among female primates, and hence to sexual selection on females and directional evolution of sexual swellings. It is concluded that the available evidence does not support the paternity confidence-paternal investment hypothesis; that the paternity confusion hypothesis lacks empirical support, but could still be viable; and that insufficient data exists at present to rigorously test the other hypotheses. The ecological factors that may have led to differential reproductive success among females as a function of mating frequency or mate choice likewise require further empirical investigation.     

Asthma and cardiac dyspnea; a differential diagnosis

There appear to be no infallible guides by which to differentiate between cardiac insufficiency and asthma as a cause of dyspnea, wheezing and coughing in elderly patients. Many of the symptoms of one condition are also symptoms of the other. Even the results of therapeutic trial cannot be relied upon to establish diagnosis, for drugs effective in treatment of heart disease may also help relieve asthma, and vice versa. Although there is no single factor that can be considered pathognomonic, there are certain symptoms and results of tests which are more strongly indicative of one condition than of the other. Careful evaluation of all factors, while it may not serve to establish unequivocal diagnosis, will provide a basis for judicious treatment of the patient.