Disease

This paper examines what it is for a condition to be a disease. It falls into two sections. In the first I examine the best existing account of disease (as proposed by Christopher Boorse) and argue that it must be rejected. In the second I outline a more acceptable account of disease. According to this account, by disease we mean a condition that it is a bad thing to have, that is such that we consider the afflicted person to have been unlucky, and that can potentially be medically treated. All three criteria must be fulfilled for a condition to be a disease. The criterion that for a condition to be a disease it must be a bad thing is required to distinguish the biologically different from the diseased. The claim that the sufferer must be unlucky is needed to distinguish diseases from conditions that are unpleasant but normal, for example teething. Finally, the claim that for a condition to be a disease it must be potentially medically treatable is needed to distinguish diseases from other types of misfortune, for example economic problems and legal problems.     

POSTURAL VERTIGO AND POSITIONAL NYSTAGMUS

Oscillation of the eyes of a patient when the head is placed in a certain position is objective evidence to support a complaint of postural vertigo—dizziness when the head is tilted forward or upward or turned to one side or the other. Since positional nystagmus may be difficult to evoke and may be elicited at one time and not at another, it is important to make repeated tests, lest a causative lesion be overlooked.Vertigo in such cases may be caused by pathologic change in the eighth peripheral nerve or in the central vestibular pathways. Sometimes no organic disease is observable even though positional nystagmus validates a complaint of vertigo. In such instances the patient should be assured that he does not have a progressive disease and be advised against activity in which dizziness would be hazardous.     

The use of amplified fragment length polymorphism (AFLP) in the isolation of sex-specific markers

Sex identification is a problem in research and conservation. It can often be solved using a DNA test but this is only an option if a sex-specific marker is available. Such markers can be identified using the amplified fragment length polymorphism (AFLP) technique. This is usually a taxonomic method, as it produces a DNA fingerprint of 50-100 PCR bands. However, if male and female AFLP products are compared, sex-specific markers are confined to the heterogametic sex and can rapidly be identified. Once a marker is found, AFLP can be used to sex organisms directly or the marker can be sequenced and a standard PCR test designed.     

Dysplasia of the hip; a factor in the development of static osteoarthropathy

Dysplasia of the hip is associated with a shallow acetabulum. It may be present and unrecognized until middle age when arthritic changes develop as a result of repeated microtraumata. By that time the process is irreversible. It can be recognized in infancy by roentgenographic study of the hips, and corrective measures can be taken to develop a normal hip and so prevent the crippling arthritis of later life. Although it is not certain that dysplasia develops in every person having a shallow acetabulum, this structural abnormality is known to be a strongly predisposing factor and therefore should be corrected.     

DYSPLASIA OF THE HIP: A FACTOR IN THE DEVELOPMENT OF STATIC OSTEOARTHROPATHY

Dysplasia of the hip is associated with a shallow acetabulum. It may be present and unrecognized until middle age when arthritic changes develop as a result of repeated microtraumata. By that time the process is irreversible.It can be recognized in infancy by roentgenographic study of the hips, and corrective measures can be taken to develop a normal hip and so prevent the crippling arthritis of later life. Although it is not certain that dysplasia develops in every person having a shallow acetabulum, this structural abnormality is known to be a strongly predisposing factor and therefore should be corrected.     

Legal Implications of Sterilization

Sexual sterilization is legal when it is an integral part of a procedure for the preservation of the life or health of a patient. Done for other reasons it may not be illegal, but this has not been tested in Canadian courts. It is, broadly speaking, a surgical procedure; it is commonly, but not always, successful; complications, while rare, do occur; the results tend to be irreversible. The same end, the prevention of pregnancy, may be attained by other methods which are safer, less liable to complications, less permanent and so should be used unless contraindicated. Patients'' statements that they do not like contraceptives should not be accepted as a reason for sterilization. Sexual sterilization should be reserved for those occasions when it is necessary for the preservation of the health or life of the individual who is to be sterilized.     

Free energy and time economy for the mutual selection of monomers in biosynthesis, primarily protein synthesis

The starting point of this work is the fact that the correction of errors in biosynthesis must be paid for by an increased dissipation (free energy loss) or a time delay. Further, a low accuracy is wasteful in this respect as the cell then produces a number of non-functioning products with a significant "production cost". One can then look for the situations of best "economy" for the selection processes. This is particularly obvious in reciprocal selections, where in some cases a substrate A shall be selected but discriminated against a competitor B, and in other cases, the opposite is true, B shall be selected with A as a competitor. It can be expected only in certain symmetric situations that these reciprocal selections are made in an equal way. Because one substrate shall be selected more often or it may be more relevant for the product, it may occur in higher concentrations and/or be selected more accurately (at a higher cost). The opposite selection may then be less accurate. The work studies various aspects of this.     

荧光标记的染色体原位杂交及其在人类基因组研究中的应用

FISH技术是80年代开始发展起来的一种新的定位技术.在人类基因组研究中得到了广泛的应用.通过中期染色体的FISH可以进行SCP,Cosmid和YAC的染色体定位,嵌合克隆的鉴别;通过间期核的FISH可以在50kb的分辨率下进行基因作图;最新的研究进展已可以进行伸展的染色质丝(chromatin fibre)的FISH,直接测量基因的长度,从而达到高精度基因作图的目的.总之,随着FISH技术本身的发展,它将在人类基因组研究中发挥更大的作用.     

Permeability,phase-boundary potential and conductance in a cholinergic channel without constant field.

A potassium-selective, chemically excitable channel, whose characteristics cannot be accurately described by constant-field theory, is studied by a new approach based on diffusion theory but with no need for the classical assumptions of constant field, homogeneous membrane, and equal phase-boundary potentials at both interfaces. Permeability is defined, free of these constraints, and the Goldman coefficient is demonstrated to be a special case useful only when the constraints apply. Permeability can be evaluated directly from current-voltage data, and it is found not to be a parameter in this channel, but rather a function of both the voltage and the concentration of the permeant ion. However, it becomes concentration-independent when the membrane voltage is equal to the sum of the phase-boundary potentials. That sum can therefore be determined from these data, and it is -65 mV in this channel. The permeability at that potential is a channel parameter, and equal to 8.66 X 10(-6) cm/s for this channel. A constant field is shown not to exist in this channel and the Goldman coefficient not to be a parameter but a function of potential and concentration. Although errors introduced into this coefficient by nonconstant field and unequal surface potentials partially cancel each other, the coefficient is nevertheless not a correct measure of permeability.     

Valoración funcional en la demencia grave

Severe dementia is currently one of the main causes of dependence and is defined as cognitive impairment that interferes with the performance of basic activities of daily living. However, in clinical practice severe dementia is difficult to define.Assessment of the ability to perform activities of daily living is a key factor in patients with severe dementia, since functional impairment is a defining feature. Assessment allows an accurate prognosis to be made and a care plan to be established, as well as the effectiveness of the intervention to be evaluated, when necessary.Functional assessment in dementia is complex, since functional status is the expression of multiple interactions, especially in geriatric patients. Functional status is measured by functional scales. In severe dementia, these scales must evaluate basic activities of daily living in the different types of dementia with high sensitivity to changes and strong discriminatory capacity. They should also be culturally adapted and validated in the community and institutional settings. Consensus should be established on the use of these instruments to allow them to be standardized and their results to be compared.     

Optimized Transection: A Prelude to Oriented Sectioning

A technique is described which permits blocks of tissue to be flat-embedded in euhedral plastic castings and then to be transected along a plane so that sections may be cut which are optimally oriented to the internal ultrastructure of the block. In the transection procedure a hollow plastic cylinder is placed on the specimen trimming block. The cylinder's top prescribes a plane to which the tissue block is accurately oriented and clamped at a predetermined level. Two hand files and a burnisher are worked across the cylinder's top to 1) remove extraneous material above the plane of transection, 2) expose the tissue for sectioning and 3) smooth the block face. The clear plastic at the periphery of the exposed tissue is then easily trimmed away with a razor blade. The result is a block face with a flat, reflective surface which may be quickly aligned to the knife on the ultramicrotome. The effort needed to transect, align and face the block is minimal and 1-micron or semithin sections produced will be precisely parallel to, and at, the plane of transection. Dust produced by the transection procedure is easily eliminated from the work area by use of a small disposable vacuum cleaner. The technique of producing optimally oriented light microscope sections, using the transector, is enhanced by application of solvents to the block face which cause it to develop a temporary low relief, exactly matching the structural detail of sections cut from the block face. Areas of interest can be accurately located and isolated on the block face, using only a hand-held razor blade, so that oriented ultrathin sections of important regions can be routinely cut and examined in the electron microscope.     

Workshop on algal polysaccharides

Summary This workshop was an impromptu event, but the fact that a number of interesting problems were identified by the participants from the floor may indicate that it is worth repeating. If it is to be repeated, however, it is important that notice be given, and that the scope of the workshop be defined in advance, so that participants can be better informed and bring supporting data. The best approach would be to identify a convenor and define the scope of the workshop prior to the first circular for the next Seaweed Symposium; invitations could then be issued by the convenor for specific topics and data, and a very brief program could be issued with the third circular. Such a procedure may very well allow the identification of new areas for research.     

SEEDLING BLIGHT OF SUGAR-CANE-A NEW DISEASE CAUSED BY HELMINTHOSPORIUM SACCHARI BUTLER

The fungus Helminthosporium sacchari Butler, known to be the cause of eye spot, a common air-borne disease of sugar-cane leaves, is now shown to be the cause of an undescribed seed-borne disease of sugar-cane seedlings. It is therefore suggested that the disease should be renamed eye spot and seedling blight of sugarcane.
The symptoms of seedling blight are described, and the pathogenicity of the fungus to sugar-cane seedlings is confirmed. Incidence of seedling blight is shown to be markedly affected by the growing conditions, and disease-escape is common. The two most important factors predisposing seedlings to attack appear to be (i) the relative humidity of the atmosphere, and (ii) the occurrence of a check to the continuous growth of the seedlings.
With the discovery of the existence of seedling blight, eye spot assumes a particular significance in plant-breeding plots, because it may be responsible for the loss of sugar-cane seedlings, any one of which is potentially a desirable new variety.     

Single-salt behavior of a symmetrical 4-site channel with barriers at its middle and ends

The theory of a symmetrical 3-barrier, 4-site, single-filing ionic channel is developed. The model goes beyond earlier models by including additional sites, as well as barriers which need not be symmetrical in the applied field, and contains the earlier models as special cases. It is itself a special case of the most general 4-site model, which has 5 barriers. By considering the barriers at the mouth and middle of the channel to be sufficiently larger than the barriers separating the sites in each channel half, these barriers can be neglected; thus this case reduces to a 3-barrier model where the sites in each channel half can then be assumed to be in equilibrium with each other. The alternative 3-barrier, 4-site case, where the barrier between the sites is considered to be larger than that at the mouth of the channel, is considered elsewhere. Pure cation permeation is considered and only single-salt properties of the system are analyzed, namely occupancy, conductance, flux ratio exponent and current-voltage relation. The concentration dependences of these properties are computed and interrelated and, where possible, also given in analytical form. The mathematical relations are obtained for a channel which is symmetrical around its middle, which is the appropriate assumption for the gramicidin channel. However, the barriers themselves are allowed to be asymmetric with respect to the potential dependence, which has been found to be essential for gramicidin. Mathematically, a straight-forward matrix formulation is used; but a general theoretical method is presented for reducing a complex model (with more than 2 sites) to a simpler cases when equilibrium exists across one or several barriers, as is often the cases. This method is a prototype which makes analytical solutions of complex barrier models possible in many cases.     

Demonstration of the facts and research of the causes in environmental epidemiology: methodological aspects

There are usually three major steps in the study of the possible impact of environmental factors on health: 1) to demonstrate that there is an association between exposure to the factor and the disease under study; 2) to demonstrate that this association is causal; 3) to evaluate the health benefit that could be obtained by removing the source of exposure. Statistical methods are commonly assumed to provide an objective way of achieving these three steps. This paper reviews some of the conditions that have to be met to allow proper interpretations and to avoid some of the controversies that are often found in health-environment studies. First, it should be remembered that the so-called P value which is used to qualify 'statistically significant' associations between risk factors and diseases does not give any indication of the probability that this association is actual, while far too often it is believed that it does. The probability that an association between an environmental factor and a disease is real could, however, be estimated by using Bayesian methods. These methods require that the a priori probabilities be stated, which is difficult to do in practice. Some directions to overcome this difficulty are presented. Second, the analysis of causality cannot be carried out on statistical grounds alone and the so-called 'causality criteria' are of limited practical interest. Definition of what is a cause, and upon which conditions a candidate factor of a disease can be considered as a cause, deserves much research effort, and careful consideration of the huge literature (mostly outside of the epidemiological field, for example in logic) which is devoted to this subject. Finally, the measurement of the role of a factor in a disease is very often assessed through the use of 'attributable fraction' or 'attributable mortality'. This should be done only when it is demonstrated that the considered factor is causal. Moreover, the interpretation of attributable fractions to a specific factor may be difficult in the (general) case where there are multiple causal factors implied in the development of the disease. Demographic measures of 'potential years (or days, etc.) of life lost' should in general be used, rather than 'numbers of deaths' to quantify the possible impact of environmental factors. Also, as the personal factors are generally extremely important in the determinism of the causes of death associated to environmental factors, and as they cannot be controlled through ecological studies, epidemiological designs where these cofactors can be evaluated individually on cases and controls should be preferred.     

Is affordable and cost-effective assisted reproductive technology in low-income countries possible? What should we know to answer the question?

¹ Correspondence address. E-mail: j.d.f.habbema{at}erasmusmc.nl Decision making on infertility treatment in low-income countries(LIC) assumes answers to quite a few questions: how should theinfertility problem be defined? How often does infertility occur?What is the burden-of-disease of infertility? What is the incomein LIC, and what can be spend on health care? How cheap shouldIVF be in order to be accessible to a considerable part of thepopulation? With what alternative health interventions shouldinfertility treatment be compared? How cost-effective shouldIVF be in order to compete with those other interventions? Thesequestions will be discussed. The emphasis is on the situationin Sub-Saharan Africa (SSA). It is concluded that a place forART in a health care package is not straightforward. Many ofthe questions are not or only partially answered. Moreover,cheap and effective ART has yet to be developed and tested.From the limited evidence available for each of the questions,it could be calculated that an IVF cycle should cost between50 and 75 dollar in order to be a candidate for the inclusionin a health package in SSA. This estimate can easily changeconsiderably when in the future the calculations will be basedon thorough research. Thus, a targeted research programme foranswering the open questions, especially on quality-of-lifeimplications of infertility in different societies, is the preferredoption for facilitating the future evaluation of ART in LIC.     

The role of bioregenerative life-support systems in a manned future in space

Thus far in the manned space program, human life support has depended on storage of air, water, food, and energy. There are no refrigerators on Shuttle, and fresh foods are limited to what can be stowed in lockers for the first 3 days of a mission, when spoilage becomes a factor. Oxygen is stored, CO2 is scrubbed, and water is stored and treated. As we approach the Space Station era, life support will be a combination of storage and resupply. Duty cycles will be 90 days, and physico-chemical (P/C) systems will be important for recycling oxygen and water. Nutritionists seek a capability for refrigerated storage of fresh food on Station. However, most food still will be thermostabilized, rehydratables that can be stored at room temperature. Present Shuttle food is not much more sophisticated than repackaged camp food, and tends to be high in salt content. Hopefully, menus will be healthier on Station, where dietary countermeasures against biomedical responses to chronic microgravity might be implemented, and certainly need to be studied.     

Asthma in children--problems in diagnosis

Bronchial asthma in children may be difficult to diagnose. Education of the parents regarding allergic conditions, specifically bronchial asthma, is exceedingly important in order to assure satisfactory treatment and clinical results. Chest symptoms of unexplained origin in early life should immediately arouse suspicion of allergic disease. Other causes of asthmatic symptoms must be borne in mind and excluded before a positive diagnosis of bronchial asthma is established. Of the many factors to be considered in investigating a child with asthma, a comprehensive history is most essential. The climate to which the patient is exposed and the psychic influences must be taken into account. Physical examination, x-ray films and laboratory procedures should be carefully executed. Skin testing, especially with food allergens, should not be relied upon to give all the information in allergic disease. Some form of diet trial, such as elimination diets, should be used if sensitivity to food is suspected.     

Process design for enzymatic adipyl-7-ADCA hydrolysis

Adipyl-7-ADCA is a new source for 7-aminodeacetoxycephalosporanic acid (7-ADCA), one of the substrates for antibiotics synthesis. In this paper, a novel process for enzymatic 7-ADCA production is presented. The process consists of a reactor, a crystallization step, a membrane separation step, and various recycle loops. The reactor can either be operated batch-wise or continuously; with both types of processing high yields can be obtained. For batch reactors chemical degradation of 7-ADCA can be neglected. For continuous reactors, chemical stability of 7-ADCA is a factor to be taken into account. However, it was shown that the reaction conditions and reactor configuration could be chosen in such a way that also for continuous operation chemical degradation is not important. Downstream processing consisted of crystallization of 7-ADCA at low pH, followed by a nanofiltration step with which, at low pH, adipic acid could be separated from adipyl-7-ADCA and 7-ADCA. The separation mechanism of the nanofilter is based on size exclusion combined with charge effects. Application of this filtration step opens possibilities for recycling components to various stages of the process. Adipic acid can be recycled to the fermentation stage of the process while both adipyl-7-ADCA and 7-ADCA can be returned to the hydrolysis reactor. In this way, losses of substrates and product can be minimized.     

Shave excision of superficial solar skin lesions

Shave excision is a useful technique for the treatment of superficial solar lesions. The most common of these is the solar keratosis, which can be a red or gray scaling lesion. This can at times be difficult to differentiate from the superficial basal cell carcinoma or squamous cell carcinoma or their more infiltrating types. Shave excision gives the advantage of a histopathologic report. Lesions found to be infiltrating or in danger of recurrence can then be further excised. The cosmetic appearance of the healed shave excision site is generally quite good, although it can be paler than the surrounding skin. If this is likely to be a problem, the shave graft can be applied, as with deeper shave excisions. A thin shave graft also can be used to repigment pale scarred areas. A series of 1313 shave excised lesions is analyzed.