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A discussion of a rational technique of evaluation, diagnosis, and surgical therapy of temporomandibular joint disorders is presented. A retrospective analysis of operations for temporomandibular joint that occurred in a 30-month period is presented in light of this approach.
This article has attempted to summarize the increasing number of pharmacologic and physiologic variables that are being recognized as important determinants in the response to vasodilator therapy in patients with severe chronic heart failure. It is apparent that a careful consideration of many factors is necessary before proper selection of a specific drug can be made for a specific patient, since not all patients with refractory heart failure demonstrate beneficial hemodynamic and clinical responses to all agents. Each patient presents us with a unique set of physiologic variables; each drug has its own advantages and limitations. Identification of those subgroups of patients most likely to benefit from a specific agent or combination of agents is a major goal for future research. Although a number of hemodynamic variables can be made to improve acutely with a wide variety of vasodilator drugs, well tolerated sustained meaningful clinical benefits are probably observed in relatively few patients. Rational and successful vasodilator therapy is possible only through a highly individualized approach.
Most public health programs are created through a political process and the health administrator's resource allocation decision is influenced not only by the relative performance of the subunits but also by political considerations. This paper presents a goal programming model for rationing available grants to competing health care subunits on the basis of performance subject to resource and political constraints. Performance is defined in terms of output adjusted for non-compliance on the identified quality of care and administrative efficiency criteria. The quality and efficiency criteria are those specified by the Federal agency as amended by local funding authorities and subunit administrators through a Delphi process. The model has the advantage of flexibility and can be easily adapted to suit prevailing financial and political conditions. In particular, it can be used as a viable analytical tool in health care and other public service agencies where political considerations are important in resource allocation decisions.
Extractions of Cu, Zn, Cd and Pb from soils by dilute salt solutions have been rationalized by a simple chemical equilibrium relation which includes the total load of metals, soil pH, soil cation exchange capacity (CEC), and extractant ionic strength. Correlations between metal uptakes by ryegrass and lettuce with calculated concentrations of Cu, Zn, or Cd in a fictitious soil solution at zero ionic strength are comparable to those obtained with the weakest salt solutions, 0.1 mol.l-1 NaNO3 and 0.05 mol.l-1 CaCl2. The other salt solutions correlate slightly less well. Uptake of Pb is not represented well.
The structure of a psychiatric service in an urban general hospital is complex. Varied intrainstitutional and extrainstitutional relationships create stress, which can lead to rational and irrational reactions, often in combination. Psychologic mechanisms that exist in individuals also occur as shared defense mechanisms in an institutional setting, serving to reduce anxiety and stress but often at the expense of accurate reality perception. Good communication can play a vital role in reducing reality distortions but is itself often blocked or impaired by the same defense mechanisms that led to the distortions. An awareness of how these mechanisms operate in an institutional setting can aid the psychiatric administrator in correcting distortions and maintaining good channels of communication.
A systematic evaluation of 15 rhinovirus capsid-binding agents against all 100 serotyped human rhinoviruses revealed the existence of two virus groups, based upon differential susceptibility to antiviral compounds. Elongated and short-chained compounds preferentially inhibited groups A and B. The positions of the rhinoviruses within a map derived from a multivariate analysis allow for the selection of a panel of 17 rhinoviruses, for which the median antiviral inhibitory value against them will accurately predict the median value against 100 serotypes. This rationalizes the search for broad-spectrum capsid-binding antirhinovirus drugs, or combinations of drugs with complementary spectra that may be necessary to effectively inhibit both type A and type B viruses.
The human immunodeficiency virus (HIV-1), associated with the AIDS (acquired immunodeficiency syndrome) epidemic, encodes an aspartyl protease that is essential for polyprotein processing in the virus (Navia et al., 1989). It has been demonstrated that inactivation of the protease either catalytically or by an inhibitor prevents infectious virion formation (Kohl et al., 1988; Darke et al., 1989). The acquired knowledge of key molecular interactions occurring between inhibitors and aspartyl proteases, as well as the structural similarities between HIV-1 protease and human renin was used to rationally select candidates for HIV-1 screening from the pool of analogs designed as renin inhibitors. A minimal number of chosen compounds were tested in an HIV-1 protease assay system. Two structurally novel peptides emerged as potent enzymatic protease inhibitors. This study highlights the selection process and characterizes the antiviral properties of the two novel analogs.
Two major strategies for generating novel biological catalysts exist. One relies on our knowledge of biopolymer structure and function to aid in the 'rational design' of new enzymes. The other, often called 'irrational design', aims to generate new catalysts, in the absence of detailed physicochemical knowledge, by using selection methods to search a library of molecules for functional variants. Both strategies have been applied, with considerable success, to the remodeling of existing ribozymes and the development of ribozymes with novel catalytic function. The two strategies are by no means mutually exclusive, and are best applied in a complementary fashion to obtain ribozymes with the desired catalytic properties.
The influence of the initial concentration of beta-propiolactone, the composition of the solution, temperature, and pH on the bacteriophage MS2 infectivity inactivation kinetics has been studied. Rate constants have been determined for the infectivity inactivation and for the change in the concentration (the consumption) of the reactant under inactivation conditions. These constants have been shown to permit a sufficiently precise description of the phage MS2 survival curves under the action of beta-propiolactone. These data have been used to put forward a kinetic approach for the rational determination of conditions for inactivation of the viral infectivity to a required extent with agents whose concentration decreases during inactivation as a result of hydrolysis and reactions involving the medium components.
The safe administration of i.v. fluids is one of the most significant advances in the care of critically ill patients this century. However, despite advances in the monitoring of cardiovascular variables, the questions of what? when? and how much? remain areas of enormous controversy. Ironically as the choice of i.v. fluids becomes greater and the monitoring more sophisticated the controversy grows. This article will concentrate on the diagnosis of hypovolaemia, the consequences of hypovolaemia and the rational use of i.v. fluids, particularly colloids, to treat it.
The application of the Kepner-Tregoe (C. H. Kepner and B. B. Tregoe, 1981, The New Rational Manager, Princeton Res. Press, Princeton, N. J.) problem solving technique to the evaluation and interpretation of toxicological information is described. Data from a chronic study provide an illustrative example. In this study an excess in the number of urinary bladder neoplasms was observed in male rats exposed to diets containing the test chemical. No similar effect was seen in treated female rats. Both male and female mice exposed to treatment also exhibited no effect. Whether treatment was the cause of the observed increase should be based on all the scientific and technical information that is relevant to this decision. The Kepner-Tregoe method of problem analysis captures this information in a framework that makes it easily understood. This is especially desirable if the judgments that are a vital part of regulatory decision making are to be adequately communicated.
Irrational, wasteful, and even dangerous medicine use is a serious problem in developing countries. It is important to work to solve it through the provision of safe, efficacious and affordable drugs, through strengthening the drug regulatory systems and through the education of health care providers. However, it is important as well that the population learns to use medicines wisely. Educating children in developing countries about appropriate use of medicines is a strategy that has the potential to improve medicine use throughout the communities where the children live and for future generations. Currently, very few children's health education curricula include anything on appropriate medicine use, and what exists has not been based on what children know, or on their behavior or expectations relative to medicines in the context of their cultures. Support is sought for the inclusion of rational medicine use in comprehensive school health curricula and researchers are encouraged to develop and evaluate culturally sensitive, age appropriate, and acceptable medicine use education programs.
The thermodynamics of protein unfolding can be rationalized if the temperature dependence of the partial molar volumes and heat capacities of their constituent groups are known reliably. Despite many experimental and theoretical studies there are still several inconsistencies in the published thermodynamic data. We have investigated some of these inconsistencies by applying high sensitivity scanning densimetry and microcalorimetry to aqueous solutions of tripeptides of the structure Gly-X-Gly, where X is one of the amino acids Met, Asn, Gly and Ile. For these side-chains either no direct data have been determined or serious discrepancies exist between the values published by different laboratories. Partial molar heat capacities and volumes have been determined for the peptides in pure water, in water adjusted to pH = 4 and in 0.5 M sodium acetate buffer at pH = 4. The results obtained are critically compared with those in the literature.
Although rarely recognized, the piriformis syndrome appears to be a common cause of buttock and leg pain as a result of injury to the piriformis muscle. Four cases representing a broad spectrum of presentations are described here. The major findings include buttock tenderness extending from the sacrum to the greater trochanter and piriformis tenderness on rectal or pelvic examination. Symptoms are aggravated by prolonged hip flexion, adduction, and internal rotation, in the absence of low back or hip findings. Minor findings may include leg length discrepancy, weak hip abductors, and pain on resisted hip abduction in the sitting position. Myofascial involvement of related muscles and lumbar facet syndromes may occur concurrently. The diagnosis is primarily clinical as no investigations have proved definitive. The role of MRI of the piriformis muscle is assessed and other investigative tools are discussed. A rational management schema is demonstrated: (1) underlying biomechanical factors and associated conditions should be corrected; (2) the patient is instructed in a home program of prolonged piriformis muscle stretching which may be augmented in physical therapy by preceding ultrasound or Fluori-Methane (dichlorodifluoromethane and trichloromonofluoromethane spray); (3) a trial of up to three steroid injections is attempted; and (4) if all these measures fail, consideration should be given to surgical sciatic nerve exploration and piriformis release.
Parts of rural, southern Illinois, like many rural areas throughout the world, are medically underserved. An innovative, rational solution to the physician shortage in those parts of rural, southern Illinois, which may be applied to other medically underserved areas, rural or urban, is proposed in this manuscript. To attract physicians to or near medically underserved, rural areas in southern Illinois it is proposed that Primary Care and Referral Centers be set up in southern Illinois. This could be done by adding well trained general practitioners, family physicians, or general internists to the staff of each emergency center of the Total Emergency Medical Service System for (southern) Illinois that is located in or near an otherwise medically underserved, rural area of southern Illinois. These additional physicians would diagnose and treat within their capabilities all non-emergency cases coming to the primary care centers and refer non-emergency cases needing referrals. Referrals would be either for secondary or tertiary health care. The Primary Care and Referral Centers should be self-supporting from pre-paid patient fees. For almost ten years a health center like a Primary Care and Referral Center has been operating at SIU/Edwardsville.
We suggest that polymyalgia rheumatica with giant cell arteritis (PR-GCA) is an arachidonic acid metabolites mediated disease which can be diagnosed more accurately and monitored more precisely for therapeutic benefits by the serial determinations of the major urinary prostaglandin F, serum urinary lysozymes, serum acid phosphatase, and serum angiotensin converting enzyme rather than by the erythrocyte sedimentation rate, and, when necessary by temporal artery biopsy. The pathogenetic role proposed for prostaglandins (PG) and, even more precisely perhaps, the leukotrienes in this disease is consistent with the several published clinical observations that non-steroidal anti-inflammatory drug treatment produces in some cases a therapeutic paradox of symptomatic relief with concurrent, if clinically silent, progression of the arteritis, even to blindness. Furthermore, the impressive response of PR-GCA to low maintenance dose steroid therapy, a clinical conundrum for decades, is rationally explained on the basis of depressed or obstructed PG metabolism early on in the metabolic cascade. These views warrant clinical evaluation, confirmation or correction in whole or in part, and may increase our understanding of PR-GCA.
In attempts to develop a rational anticancer strategy the same homologous tissue in 3 conditions were used side by side as targets: normal epidermis of the mouse back. Tween 60R-provoked benign epidermal hyperplasia, and carcinogen-provoked malignant condition. In contrast to the highest tolerated doses of the cytostatics conventionally used, the dose was stepwise decreased towards the subthreshold level. Then the smallest dose that caused the slightest detectable injury to the malignant cells was employed. The results show that the dose of the cytostatics (colchicine, and vinblastine sulfate) can be reduced to 1/12 if the drug is linked to dimethyl-sulfoxide (DMSO), a compound with unique hydrating and oxido-reducing properties. The cytostatic-DMSO complex acts selectively, sparing the viability of the normal and hyperplastic cells, but at the same time increasing the vulnerability of the malignant cells. The specific target for cytostatic-DMSO complex is the 3-dimensional cytoskeleton (the differentiation organelle) which is deranged in malignant cells. The measure causes a morbid swelling (20-fold, or more) of the cytoplasm which leads to collapse of the cytoskeleton, so that the marginal quantities of the cytostatics can exert their effects in the highly re-hydrated water matrix of the malignant cells. It is, moreover, probable that the doses of the cytostatic in DMSO could be further reduced to 1/100, or even to 1/1,000. The polarization microscopic technique reveals events down to the (sub)-molecular level. The cytological material comprises 930,000 karyokinetic assemblies and 14,522,600 corresponding nucleated non-dividing cells in various cutaneous conditions of 1,860 mice. The conclusions were drawn only when the differences between corresponding parameter pairs were statistically highly significant (P less than 0.001).
The present study proposes a novel type of synthetic chimaeric polypeptides potentially useful in the therapy of various diseases. The prototype peptide termed 'synthetic inducible biological response amplifier' (SIBRA) would comprise a ligand-binding site, a DNA-binding region, a trans-activating domain as well as strings of residues ensuring bioavailability and targeting to specific compartments such as the cell nucleus. These domains would be selected from cellular proteins, artificially tailored to a SIBRA and further modified towards a molecule with both in vivo and intracellular activity. Since proposed to resemble a host molecule with autoregulatory properties, a SIBRA would be activated upon exposure to a defined environmental stimulus and amplify host responses appropriate for this stimulus. Proteins would accumulate that share functional domains with the administered SIBRA and have a positive autoregulatory capacity. The latter may involve the interaction of the induced protein with the promoter of its gene resulting in a direct positive autoregulatory loop or require the induction of intermediary proteins that eventually upregulate the production of SIBRA-like host proteins. Since the ligand-binding site of a SIBRA is rationally designed to target a pathogenic protein, SIBRAs could be regarded as the product of an artificial acceleration and refinement of strategies intrinsic to the immune system.