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.     

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.     

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.     

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.     

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.     

Note on a mechanism of the distribution of wealth

A population of individuals is considered to be characterized by a distribution of wealth which is the result of gain and loss from the outside as well as a result of exchange. The population is assumed to be uniform except for the variation in a parameter determining the manner of partition during exchange. The parameter is assumed to be normally distributed over the population. The resulting distribution of wealth is calculated for some special cases and it is found to be very asymmetric.     

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.     

A review about nothing: Are apolar cavities in proteins really empty?

Cavities within proteins that are strictly apolar typically appear to be empty. It has been suggested, however, that water molecules may be present within such cavities but are too disordered to be seen in conventional crystallographic analyses. In contrast, it is argued here that solvent mobility will be limited by the size of the cavity and for this reason high‐occupancy solvent in cavities of typical volume should be readily detectable using X‐ray crystallography. Recent experimental studies of cavity hydration are reviewed. Such studies are consistent with theoretical predictions that it is energetically unfavorable to have a single water molecule in an apolar cavity. As apolar cavities become larger, a point is reached where it is favorable to have the cavity occupied by a cluster of mutually H‐bonded water molecules. The exact size of such a cavity in a protein is yet to be verified.     

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.     

A neurobiophysical interpretation of certain aspects of the problem of risks

A situation is considered in which an individual is given an opportunity to risk a certain amount of money or goods in order to gain a larger amount, providing the result of some uncertain event proves favorable. A neural mechanism is introduced in which the probability of success can be ordered according to its value. The response to a situation thus becomes dependent upon the probability. An expression is then derived for the amount that would be risked in terms of the probability and of the amount that would be gained in the event of a successful outcome. Similar expressions are obtained for the case of insurance against loss. Results of questionnaires indicate that individuals can be classified according to their pattern of behavior in the situation considered. The various types can be most easily recognized when a plot is made of the relative amount risked against the probability of success. In a general way, these types can be understood in terms of the equations derived.     

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.     

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 impossibility of estimating a negative binomial clustering parameter from presence-absence data: a comment on He and Gaston

An important problem is to infer the abundance of a species in an area from its presence or absence in the cells of a uniform grid. If the abundance is assumed to be distributed over cells according to a negative binomial model, a value of the clustering parameter k is needed to infer the abundance. It is shown that, despite a proposal in the literature, k cannot be estimated from presence-absence data but must be given from outside information.     

CEREBRAL ANGIOGRAPHY—Its Use in Acute Head Injuries and Undiagnosed Coma

One of the major factors in treating a patient with acute alteration of consciousness is to determine if progressive intracranial hemorrhage is present. Similar problems are encountered in cases of cerebrovascular disease where increasingly effective medical and surgical methods of treatment are available. Progressive cerebral thrombosis can be arrested by anticoagulants, intracranial hemorrhage can be controlled and atheromatous occlusion of a major artery can be corrected. Intracranial mass lesions can be detected when the history is not available or is misleading.Cerebral angiography is a relatively safe diagnostic test that is certainly preferable to delayed or haphazard treatment when an exact diagnosis is uncertain in an unconscious patient.     

Assessment of the potential germ cell mutagenicity of industrial and plant protection chemicals as part of an integrated study of genotoxicity in vitro and in vivo

An approach is described that enables the germ cell mutagenicity of chemicals to be assessed as part of an integrated assessment of genotoxic potential. It is recommended, first, that the genotoxicity of a chemical be defined by appropriate studies in vitro. This should involve use of the Salmonella mutation assay and an assay for the induction of chromosomal aberrations, but supplementary assays may be indicated in specific instances. If negative results are obtained from these 2 tests there is no need for the conduct of additional tests. Agents considered to be genotoxic in vitro should then be assessed for genotoxicity to rodents. This will usually involve the conduct of a bone marrow cytogenetic assay, and in the case of negative results, a genotoxicity test in an independent tissue. Agents found to be non-genotoxic in vivo are regarded as having no potential for germ cell mutagenicity. Agents found to be genotoxic in vivo may either be assumed to have potential as germ cell mutagens, or their status in this respect may be defined by appropriate germ cell mutagenicity studies. The basis of the approach, which is supported by the available experimental data, is that germ cell mutagens will be evident as somatic cell genotoxins in vivo, and that these will be detected as genotoxins in vitro given appropriate experimentation. The conduct of appropriate and adequate studies is suggested to be of more value than the conduct of a rigid set of prescribed tests.     

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.     

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.