Biomedical subjects
Publications and source records attributed to A C Miller.
A case of cutaneous Mycobacterium chelonae infection with sporotrichoid spread and extensive antibiotic resistance is presented. Control of this problem was only achieved after extensive debridement and grafting of the involved limb. The importance of surgery in management is discussed and the literature is reviewed.
1. Polysomes were isolated from the brain of infant rabbits at 22 days of age. The animals received s.c. injections 3 times weekly of aluminium (Al) maltolate (3 mg Al/kg body wt) or Al lactate (16 mg Al/kg body wt) from 5 days of age. 2. The polysomes were used to direct the incorporation of [14C]leucine into peptides in a brain protein synthesizing system and exhibited a decreased activity when obtained from aluminum exposed infants. 3. The mRNA obtained from the polysomes was used to direct the incorporation of [35S]methionine into peptides in an mRNA dependent rabbit reticulocyte lysate. The translatability of the mRNA derived from aluminum exposed infant brains was significantly lower than that of preparations from control infant rabbits. 4. Al bound to maltolate, a ligand soluble in lipids as well as water, was considerably more detrimental to brain protein synthesis than Al bound to lactate.
A prospective randomized double-blind study evaluated the efficacy of i.v. immune globulin in preventing infectious complications in severely burned patients. Fifty patients were randomized to receive either i.v. immune globulin or placebo. Each group of patients was treated with twice weekly infusions for either 5 weeks or until the patients' wounds were covered. Patients treated with the immune globulin had an immediate correction of their depressed serum IgG levels, however there was no change in the infection or mortality rates. No adverse effects were noted with the immune globulin treatments. One potential weakness of this study was the greater burn surface area and a higher incidence of inhalation injury in adult patients treated with i.v. immune globulin compared to controls.
A laboratory experiment was performed to evaluate the effects of intermittent suspended solids exposure on the unionid clams Quadrula pustolosa, Fusconaia cerina and Pleurobema beadleanum. Intermittent impacts of this type are important effects of commercial navigation traffic in freshwater. Clams were cyclically exposed to turbulence alone or accompanied by 600-750 mg litre(-1) of suspended inorganic solids for 9 days. Clams exposed to suspended solids every 3 h reduced their metabolic rate but did not shift from the mainly protein based catabolism of controls. Feeding impairment was apparently compensated for by a reduction in metabolic demand. Conversely, clams exposed every 0.5 h to suspended solids shifted to virtually complete reliance on non-protein body stores as indicated by O:N values averaging 197.
Clinical observations by Navy psychiatrists and psychologists who concurrently conducted therapy groups at three separate military treatment facilities between 1981 and 1984 were recorded. The reasons they returned to active duty or remained in the service, how and why they were referred to therapy, issues that arose in group therapy, and factors that were believed to have influenced the successful outcome are summarized and discussed.
We report five cases, all male, of diverse clinical findings of scattered erythematous, violaceous, or centrally blue plaques. Eight biopsies from the five patients showed nodular or diffuse dermal and subcutaneous infiltration, predominantly of eosinophils and histiocytes, with "flame figures" composed of granules of eosinophils that surround collagen bundles, whose staining quality is thereby altered. Two patients were children, the younger only 18 months old. Three patients initially presented clinical evidence of insect bites, and in one of these the biopsy showed cutaneous pseudolymphoma underlying dermal changes of eosinophilic cellulitis. Eosinophilic infiltration with flame figures is a distinctive reaction to various stimuli. It may be seen in a wide variety of clinical conditions and is not confined solely to patients with Wells' syndrome, which may be an acceptable term for clinically typical cases. Eosinophilic infiltration with flame figures is preferred descriptively to identify the microscopic changes in Wells' syndrome and in other cases like that of our patient with pseudolymphoma, in which the cutaneous reaction may be secondary to some other disease.
The influence of cellular glutathione (GSH) levels on the response to photodynamic treatment (PDT) in vitro was determined in cells which either were depleted of GSH by buthionine sulfoximine (BSO) or were genetically GSH deficient. The effects of GSH depletion on cellular radiosensitivity were studied in parallel for the purpose of comparison. BSO treatments which reduced GSH levels in four cell lines (CHO, V79, EMT6, RIF) to approximately 80% of controls, 30% of controls, or undetectable levels uniformly decreased cell survival. This decrease was directly related to GSH depletion levels and was expressed mainly in a reduction of the width of the survival curve shoulder (Dq). GSH level-dependent aerobic radiosensitization following BSO treatment was likewise found in all four cell lines. In contrast to PDT, however, cell survival changes were expressed in the dose slopes (Do's) of the survival curves. Cell survival of GSH-deficient human fibroblasts (GM 3877) was decreased following PDT and gamma irradiation when compared to their normal counterparts (GM 5659). In both modalities the difference was mainly due to a reduction in the Dq's, while the Do's were only slightly affected. The augmented response to PDT was not caused by interference by BSO or GSH with either cellular porphyrin uptake or singlet oxygen production during the photodynamic process. Possible mechanisms of GSH effects on PDT were discussed.
The effects of various scavengers of reactive oxygen and/or radical species on cell survival in vitro of EMT6 and CHO cells following photodynamic therapy (PDT) or gamma irradiation were compared. None of the agents used exhibited major direct cytotoxicity. Likewise, none interfered with cellular porphyrin uptake, and none except tryptophan altered singlet oxygen production during porphyrin illumination. The radioprotector cysteamine (MEA) was equally effective in reducing cell damage in both modalities. In part, this protection seems to have been induced by oxygen consumption in the system due to MEA autoxidation under formation of H2O2. The addition of catalase, which prevents H2O2 buildup, reduced the effect of MEA to the same extent in both treatments. Whether the remaining protection was due to MEA's radical-reducing action or some remaining oxygen limitation is unclear. The protective action of MEA was not mediated by a doubling of cellular glutathione levels, since addition of buthionine sulfoximine, which prevented glutathione increase, did not diminish the observed MEA protection. The hydroxyl radical scavenger mannitol also afforded protection in both kinds of treatment, but it was approximately twice as effective in gamma irradiation as in PDT. This is consistent with the predominant role of OH radicals in ionizing radiation damage and their presumed minor involvement in PDT damage. Superoxide dismutase, a scavenger of O2, acted as a radiation protector but was not significantly effective in PDT. Catalase, which scavenges H2O2, was ineffective in both modalities. Tryptophan, an efficient singlet oxygen scavenger, reduced cell death through PDT by several orders of magnitude while being totally ineffective in gamma irradiation. These data reaffirm the predominant role of 1O2 in the photodynamic cell killing but also indicate some involvement of free radical species.
The response of murine EMT6 and RIF tumors to DL-buthionine-S, R-sulfoximine (BSO), a glutathione (GSH) depletor, given either as a single dose, continuous oral administration, or in multiple doses, was determined with the use of a tumor-growth-delay assay. BSO consistently caused significant tumor growth delay in EMT6 tumors, which reached 5-7 days (two doubling times) after a single BSO dose (40 mumol/kg or 4 mmol/kg), 3 days (one doubling time) with continuous oral administration (20 mM), and 9 days (three doubling times) with daily BSO administrations (4 mmol/kg) starting at the time of tumor inoculation. Growth inhibition persisted after discontinuation of BSO treatment. Some complete tumor regressions were observed. Only slight tumor growth delay (one doubling time) was observed in RIF tumors at all treatment modes. No direct correlation was observed between tumor GSH content and the effects on tumor growth. In vitro BSO pretreatment (2 mM, 24 hr) of EMT6 tumor cells prior to tumor inoculation, which reduced cellular GSH levels to 34% of controls, did not influence subsequent tumor growth. Pretreatment of mice with BSO (4 mmol/kg, 1 daily sc injection for 7 days) prior to tumor inoculation led to a reduction of tumor takes by 25% when compared to 100% tumor takes in untreated mice. These data imply a BSO-induced change in the host response to tumor development.
Treatment of neurotropic malignant melanoma of the nasal ala combining microscopically controlled surgery and examination of formalin-fixed paraffin-embedded tissue cut in the horizontal plane followed by S100 immunohistochemical staining is described. The spindle-shaped cells were strongly S100 positive and detection of the melanoma cells, which were embedded in a dense collagenous stroma and infiltrating into the neurovascular spaces, was greatly accentuated by the S100 immunohistochemical stain. The coordinated skills of the dermatologic surgeon, dermatopathologist, and plastic surgeon contributed toward the best treatment for neurotropic melanoma in this patient.
We performed immunoperoxidase stains on skin biopsies taken from nine patients with recurrent peripheral herpes simplex lesions at 12 h to 6 d after onset of signs of symptoms to phenotype the inflammatory infiltrate, to detect cells producing interferons alpha and gamma, and to locate herpes simplex virus antigen-containing cells. Viral glycoprotein antigen was located in the nuclei and cytoplasm of necrotic epidermal cells, often within vesicles, in biopsies taken between the first and third day. Histologically, biopsies of all stages showed intradermal focal perivascular and diffuse mononuclear inflammatory infiltrates. The cells constituting the infiltrates were predominantly T lymphocytes with lesser numbers of histiocytes; Leu 7+ (most natural killer/killer) cells and B cells were rare in the biopsy specimens. Leu 3a+ ("helper") T lymphocytes predominated in both subepidermal and perivascular regions of early lesions (12-24 h). Tissue helper/suppressor ratios ranged from 6.3 to 3.4 compared with 1.9-1.0 in blood. In later lesions (after 2 d), monocytes/macrophages were more prominent in tissue sections and the helper/suppressor ratios (2.3-2.5) more nearly approximated those of blood (1.6-2.7). The negative correlation of tissue ratios with time was significant (P less than or equal to 0.02). A large proportion of the infiltrated T lymphocytes expressed DR antigens. There was also diffuse strong DR expression on epidermal cells in five cases (all of two or more days). In six biopsies, scattered macrophages and small cells, presumably lymphocytes, demonstrated cytoplasmic or membrane staining for a substance which copurifies with interferon gamma. We identified such stained cells within vessels, suggesting that these cells circulate. Gamma interferon might have an important role within the herpetic lesions, possibly inducing macrophage activation and cytotoxic T lymphocytes and increasing DR expression on monocyte and epidermal cells.
An 80-year-old man who had had plaque-type psoriasis for 40 years experienced a rapid onset of generalized pustular psoriasis three days after initiation of propranolol hydrochloride therapy. Trial therapy with propranolol on two occasions resulted in similar episodes. The skin lesions and systemic symptoms resolved after the discontinuation of propranolol therapy and administration of methotrexate sodium. This case study documents propranolol--a beta-blocker--as another causal factor for pustular psoriasis.
Anthralin is effective in the management of psoriasis. Because of frequent skin irritation, staining of skin and clothing, and patients' difficulty in using stiff paste and ointment preparations in traditional regimens, newer treatment protocols are being evaluated. We report a four-week study of twenty patients using an anthralin cream for thirty-minute short-contact therapy. Both 0.5 percent and 1.0 percent anthralin concentrations were evaluated. We found that short contact therapy with the anthralin cream preparations was effective. In four weeks it resulted in the clearing of treated areas in more than one-third of the patients, and significant improvement in an additional 35 percent. Little difference in efficacy was noted between the 0.5 percent and 1.0 percent concentrations. Most patients found the treatment regimen cosmetically acceptable and experienced minimal problems with staining and skin irritation.
The features of the chest radiographs of 49 adults with legionnaires' disease were compared with those of 91 adults with pneumococcal pneumonia (31 of whom had bacteraemia or antigenaemia), 46 with mycoplasma pneumonia, and 10 with psittacosis pneumonia. No distinctive pattern was seen for any group. Homogeneous shadowing was more frequent in legionnaires' disease (40/49 cases) (p less than 0.005), bacteraemic pneumococcal pneumonia (25/31) (p less than 0.01) and non-bacteraemic pneumococcal pneumonia (42/60) (p less than 0.05) than in mycoplasma pneumonia (23/46). Multilobe disease at presentation was commoner in bacteraemic pneumococcal pneumonia (20/31) than in non-bacteraemic pneumococcal pneumonia (15/60) (p less than 0.001) or legionnaires' disease (19/49) (p less than 0.025). In bacteraemic pneumococcal pneumonia multilobe disease at presentation was associated with increased mortality. Pleural effusions and some degree of lung collapse were seen in all groups, although effusions were commoner in bacteraemic pneumococcal pneumonia. Cavitation was unusual. Lymphadenopathy occurred only in mycoplasma pneumonia (10/46). Radiographic deterioration was particularly a feature of legionnaires' disease (30/46) and bacteraemic pneumococcal pneumonia (14/27), and these groups also showed slow radiographic resolution in survivors. Radiographic resolution was fastest with mycoplasma pneumonia; psittacosis and non-bacteraemic pneumococcal pneumonia cleared at an intermediate rate. Residual intrapulmonary streaky opacities remained in over a quarter of survivors from legionnaires' disease (12/42) and bacteraemic pneumococcal pneumonia (5/19).
This paper describes the theory and structure of a day unit designed to intervene in the systems of families who present with severe or multiple problems to agencies attempting to help them, but who are difficult to engage in a therapeutic pact and unresponsive to attempts at outpatient therapy. An analysis of these families is offered in terms of the relations between internal and external boundaries and difficulties in making transitions in the daily contexts of life. The principles of the unit are described in terms of the creation of an artificial extended family, the intensification of sequence and patterns of interaction, and the making and traversing of boundaries. Particular attention is paid to the function of agency interventions in family patterns and to redefining the relationship between family and agencies.
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Tumour cell mass (TCM) in patients with multiple myeloma has been measured by synthetic rate studies of bone-marrow tumor cells in culture. From the measurements of Salmon and co-workers, a simple clinical staging system in which TCM is calculated by a programmable pocket calculator has been developed. We have compared the measurement and calculation of TCM in patients with IgG and IgA multiple myeloma by these methods in our own laboratory. There was correlation between synthetic rate and serum IgG paraprotein concentration but not the serum IgA paraprotein concentration. In patients with IgG myeloma there was correlation between measured and calculated TCM as well as measured TCM and serum IgG paraprotein concentration, urine Bence-Jones protein excretion, and serum albumin concentration. Measured TCM also inversely correlated with haemoglobin concentration. In patients with IgA myeloma, however, there was no correlation between measured TCM and calculated TCM or any other individual clinical laboratory parameter. A number of problems have contributed to the overall failure of this method to measure and calculate TCM including methodological differences, definition of myeloma cells, proteolysis of newly synthesized paraprotein in culture, changes in synthetic rates with time and assessment of the degree of bone lesions by skeletal roentgenograms. We cannot recommend these methods as they stand to measure and calculate TCM in patients with multiple myeloma.
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