Independent living and the physical environment: aspects that matter to residents

Field interviews were conducted with seven clients with disabilities for the purpose of developing design guidelines for apartments suitable for independent living. Analysis of these data generated six factors that were highly valued and felt to contribute to the success of these individuals' venture into community living. Control appears to be the central construct and to subsume the other concepts: safety/security, accessibility/mobility, function, flexibility and privacy. These findings are presented and discussed here as a working model of environmental control. These ideas are suggested as hypotheses which would need to be tested and refined further before being used as a model to guide clinical interventions.     

Skin-infiltrating lymphocytes in normal and disordered skin: activation signals and functional roles in psoriasis and mycosis fungoides-type cutaneous T cell lymphoma.

T lymphocytes recruited into the skin can experience several different outcomes. On the one hand, they may be recruited by adhesion molecules and chemoattractants to enter the perivascular space, but never undergo activation. Other T cells undergo activation and further differentiation under the influence of the cutaneous milieu. These activated lymphocytes then coordinate specific and non-specific immune responses characteristic of inflamed tissue. We have explored two models for studying the activation and function of skin infiltrating T lymphocytes (SIL's). In the first model, we have identified a family of Langerhans cell-related professional dendritic antigen presenting cells that exist in the epidermis and dermis of normal skin, atopic skin, and mycosis fungoides skin. These have APC abilities to activate freshly recruited resting blood T cells that are distinct from another family of macrophage-related cells abnormally present in sunburned or psoriatic skin. In the second model, we examined the function of cells that have already been recruited into the skin of patients with psoriasis and mycosis fungoides. Lesional psoriasis and mycosis fungoides T cells exhibited a variety of T cell receptor gene rearrangements, conclusively demonstrating that heterogeneous populations of T lymphocytes exist in inflamed human skin. From psoriasis, clones were identified that were particularly effective at inducing normal keratinocytes to assume "psoriatic" phenotypic features and functions. Thus, lesional psoriatic SIL's could induce HLA-DR, ICAM, and CDw60 on normal keratinocytes. In addition, psoriatic SIL's induced increased keratinocyte proliferation and cytokine profile changes characteristic of psoriatic epidermis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pathophysiology and treatment of gallstones

Spurred on by the discovery of "lithogenic bile" as a precursor, there has been much attention focused on the pathophysiology and treatment of gallstones. The article reviews the progress to date regarding the epidemiology, pathophysiology, diagnosis, therapy, and recurrence/prevention of gallstones.     

Rudimentary meningocele: a variant of "primary cutaneous meningioma"

We studied 5 primary cutaneous meningiomas. All were congenital. Four were nodules or plaques on the scalp, and one was a lumbar polyp. Two were alopecic. A skull defect was present deep to one lesion, and the lumbar polyp was attached to dura. The tumors were concentrated in the subcutis, where strands of meningocytes were embedded in dense collageous tissue. Meningocytes wrapped around collagenous fibers, producing "collagen bodies". These formed the nidus for calcification that included psammoma bodies. Meningocytes also dissected between collagenous fibers, creating anastomosing spaces that mimicked a vascular tumor. Meningothelial-lined clefts, several milimeters in length, were present in 4 cases. Two lesions extended through dermal defects into the superficial dermis, where adnexa were reduced or absent. The meningocytes contained vimentin and epithelial membrane antigen. They lacked cytokeratin, S100 protein, and endothelial markers. The meningothelial lesions described herein lack the nodular and sheet-like growth patterns that typify meningiomas of the central nervous system and most primary ectopic meningiomas, including some that develop within the skin. They appear closely related to meningoceles and should be viewed as developmental abnormalities rather than neoplasms. The term "rudimentary meningocele" seems appropriate for these lesions.     

Assessing psychodynamic conflicts: I. Reliability of the idiographic conflict formulation method

Recent years have seen increasing interest in devising methods of studying psychodynamic phenomena. These efforts have had confront difficulties, first, in specifying the data, the observation language, and rules of inference for psychodynamic propositions, and second, in determining the reliability and validity of the measures used. Given how "fuzzy" traditional psychodynamic concepts are, it is no wonder that psychodynamic clinicians from Freud onward have achieved more success in generating new hypotheses than in testing their validity. As Reichenbach (1938) has observed, science requires that discovery be followed by systematic validation of all new propositions, regardless of their degree of popular acceptance. At the core of efforts to study psychodynamics have been methods to study ego functioning (Bellak and Goldsmith 1984), defense mechanisms (Perry and Copper 1988), and psychodynamic conflicts. This paper reports on the reliability of the Idiographic Conflict Formulation (ICF), a guided method for formulating an individual's psychodynamic conflicts.     

Who manages the managers? The 1989 Harvey Cushing oration

New medical knowledge is emerging at a tremendous rate. Diseases such as Alzheimer's disease. Parkinson's disease, cancer, and others (diseases once considered beyond the scope of medicine) are receiving a great deal of attention. Yet it is a paradox that, at a time when we are learning more about the biology of the human being, it is more difficult to creatively develop the new knowledge into diagnostic tests, surgical interventions, and preventive strategies. The pace of biomedical innovation is being slowed by an increase in the intervention of nonmedical "managers of care." The driving force behind managed care is concern over cost. The managers of medical care have sought to control costs by controlling the doctor's decision making. This is the focus of managed care. The physicians of today, therefore, face a remarkable challenge. They must respond to the needs of patients while being held accountable to an increasing number of overseers in the public and private sectors. These managers of care justify their activities on the notion that the patient will be better off and the cost less if the doctor-patient encounter is regulated by protocols, statistical comparison, utilization review, and fee schedules. While doctor's decisions are being managed by others, who is managing the managers? The answer should be the medical community, principally doctors. Unfortunately, the answer at the moment is the payors--governmental reimbursement agencies, intermediaries, employers, hospitals, or new corporations designed to manage medical costs. The challenge to the physician is to retain the responsibility for those things for which he or she is held accountable. The challenge should not be ignored.     

Serum and testicular testosterone and androgen binding protein profiles following subchronic treatment with carbendazim

While the general toxicity of the benzimidazole pesticides for mammals is low, one of these compounds, carbendazim (MBC), causes degeneration of testicular tissue and decreases spermatogenic activity at doses well below the LD50 value. A study conducted by S. D. Carter, R. A. Hess, and J. W. Laskey (1987, Biol. Reprod. 37, 709-717) showed that treatment with 400 mg/kg/day MBC resulted in severe seminiferous tubular atrophy and infertility. Since spermatogenesis is an androgen-dependent process, we characterized the effects of MBC (0-400 mg/kg/day) on the endocrine function of the rat testes. Following subchronic (85 day) exposure, serum hormones (TSH, LH, FSH, and Prl) were measured as were androgen binding protein (ABP) and testosterone in testicular fluids (interstitial fluid and seminiferous tubule fluid). In addition, the functional capacity of the Leydig cell to secrete testosterone was assessed in vitro following an hCG challenge. Subchronic treatment with MBC at doses of 50-100 mg/kg/day had no effect on pituitary or testicular hormone concentrations: 200 mg/kg/day elevated the testosterone concentration in the seminiferous tubule fluid and the ABP concentration in both the interstitial fluid and the seminiferous tubule fluid without affecting serum testosterone or ABP concentrations. The 400 mg/kg/day dose resulted in increased concentration of both testosterone and ABP in the interstitial fluid and seminiferous tubule fluid and elevated serum ABP, with no change in serum testosterone. This endocrine profile is consistent with the testicular atrophy and "Sertoli cell-only" syndrome seen in these animals as reported by Gray et al. (1987, Toxicologist 7, 717). We conclude that seminiferous tubule fluid testosterone may be a result of two factors: (1) increased interstitial fluid testosterone concentrations and (2) decreased testosterone outflow from the testis to the general circulation. Also, increased ABP in the interstitial fluid may reflect a change in the relative secretion of ABP into the interstitial fluid and the seminiferous tubules.     

An association between variants in the IGF2 gene and Beckwith-Wiedemann syndrome: interaction between genotype and epigenotype

Beckwith-Wiedemann syndrome (BWS) is a fetal overgrowth disorder involving the deregulation of a number of genes, including IGF2 and CDKN1C, in the imprinted gene cluster on chromosome 11p15.5. In sporadic BWS cases the majority of patients have epimutations in this region. Loss of imprinting of the IGF2 gene is frequently observed in BWS, as is reduced CDKN1C expression related to loss of maternal allele-specific methylation (LOM) of the differentially methylated region KvDMR1. The causes of epimutations are unknown, although recently an association with assisted reproductive technologies has been described. To date the only genetic mutations described in BWS are in the CDKN1C gene. In order to screen for other genetic predispositions to BWS, the conserved sequences between human and mouse differentially methylated regions (DMRs) of the IGF2 gene were analyzed for variants. Four single nucleotide polymorphisms (SNPs) were found in DMR0 (T123C, G358A, T382G and A402G) which occurred in three out of 16 possible haplotypes: TGTA, CATG and CAGA. DNA samples from a cohort of sporadic BWS patients and healthy controls were genotyped for the DMR0 SNPs. There was a significant increase in the frequency of the CAGA haplotype and a significant decrease in the frequency of the CATG haplotype in the patient cohort compared to controls. These associations were still significant in a BWS subgroup with KvDMR1 LOM, suggesting that the G allele at T382G SNP (CAGA haplotype) is associated with LOM at KvDMR1. This indicates either a genetic predisposition to LOM or interactions between genotype and epigenotype that impinge on the disease phenotype.     

The biology and tumour-related properties of monocyte tissue factor

Tissue factor (TF, coagulation factor III, CD142) is not only the main physiological initiator of normal blood coagulation, but is also important in the natural history of solid malignancies in that it potentiates metastasis and angiogenesis and mediates outside-in signalling. TF is expressed constitutively by many tissues which are not in contact with blood and by other cells upon injury or activation; the latter include endothelial cells, tissue macrophages, and peripheral blood monocytes. It can exist encrypted and unavailable functionally in the plasma membrane and the appearance of functional TF may be due to synthesis and/or de-encryption. Inflammatory cells often express TF and act to induce its production or de-encryption by other cells locally and, apparently, at remote sites. Inappropriate expression of TF by endothelial cells, macrophages or monocytes is thought to be an important trigger of coagulation in various pathological conditions. Several studies have shown that measurements of monocyte TF (mTF) may provide clinically significant information, particularly in patients with malignant and inflammatory diseases.     

Purification of cold agglutinins from patients with chronic cold haemagglutinin disease. Evidence of their homogeneity from starch gel electrophoresis of isolated light chains

A method is described for the large scale purification of serologically active high-titre cold agglutinins from the sera of patients with chronic cold haemagglutinin disease. Eighteen purified cold agglutinins have been reduced and alkylated and separated into heavy and light chain pools by Sephadex G-100 filtration. The isolated light chains were examined by alkaline urea starch gel electrophoresis and found to be far more homogeneous than normal light chains and comparable in some cases to Bence Jones light chains. However, light chains from different cold agglutinins with the anti-I specificity gave different banding patterns; this might be caused by the fact that they are directed against different parts of the I antigen.