Successful cannulation of the subclavian vein.
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Catheterization, Central Venous↗
Biomedical subjects
J M Thomas
Publications and source records attributed to J M Thomas.
Malignant epithelial parotid tumours.
Formal parotidectomy was performed in 120 patients by one surgeon over 7 years. Eighteen patients were referred with malignant salivary tumours (eight recurrent). Low-grade tumours (LGT) were treated by surgery alone; untreated high-grade tumours (HGT) were treated by pre- or post-operative radiotherapy according to clinical findings. The aim of surgery was to obtain tumour clearance, to preserve the facial nerve where possible, and to perform radical neck dissection for HGT when peroperative jugulodigastric lymph node biopsy confirmed metastasis. Five patients (all HGT) with complete facial palsy due to tumour underwent radical parotidectomy; of the remainder, only one suffered further deterioration of facial nerve function after surgery. After 5 years median follow-up from presentation, four patients with HGT have died from metastases; one has developed local recurrence. No patient with LGT has died or developed local recurrence. The survival difference between patients with HGT and LGT is statistically significant (P less than 0.05). A logical management policy for malignant parotid tumours requires knowledge of tumour grade.
Adult↗
Specific unresponsiveness to skin allografts in burns.
We have examined the potential to provide long-term or even permanent wound coverage in a mouse model of a 30% total body surface area burn using skin allografts. Treatment of the recipient mouse with rabbit anti-mouse thymocyte serum (ATS) followed by donor bone marrow infusion induces a state of specific unresponsiveness to the skin allograft without the need for chronic immunosuppression. Specifically, a B6AF1 mouse receives a burn on Day -2 relative to grafting, ATS on Day -1, and Day +2, a skin allograft from a C3H/He mouse on Day 0, and infusion of C3H/He donor bone marrow on Day +6. We studied three groups of burned mice: Group I, allograft control (n = 5); Group II, allograft plus ATS (n = 12); and Group III, allograft plus ATS and bone marrow infusion (n = 15). Mean graft survival was compared using a one-way analysis of variance and a Student-Newman-Keuls post hoc test. There was no statistical difference in animal mortality among any of the three groups, and there was no evidence of infectious morbidity. Mean skin allograft survival was as follows: Group I, 9 days; Group II, 29 days; and Group III, 66 days (P less than 0.05 vs Group I and II). Nine animals in Group III had intact hair bearing grafts at 90 days when the study was terminated. This study suggests the potential use of induced specific unresponsiveness to skin allografts for wound coverage in thermal injury without use of chronic immunosuppression. In our animal study this was accomplished without increased mortality or apparent infectious morbidity.
Animals↗
Development of a statewide trauma registry.
In October 1986, the Pennsylvania Trauma Systems Foundation (PTSF) developed a statewide registry. Development concentrated on four major issues: 1) data elements; 2) patient selection; 3) confidential mandatory involvement for trauma centers; and 4) reporting/analysis. The overall compliance of the trauma centers was 81.5%. Documentation of prehospital run times and admission trauma scores were 21% and 70%, respectively. PTSF patients 55 years or older (27.9%) had twice the mortality as younger patients. Falls accounted for 76% of injuries to elderly patients. Finally, 42.6% of survivors had moderate to severe disabilities. Defining the "major trauma patient" is extremely difficult. A registry must have uniform quality data without undue costs. To obtain such data, maintenance of an active registry must be viewed as important as medical care, if organized trauma systems are to remain cost effective.
Abbreviated Injury Scale↗
Promotion of incompatible allograft acceptance in rhesus monkeys given posttransplant antithymocyte globulin and donor bone marrow. II. Effects of adjuvant immunosuppressive drugs.
Previous studies from this laboratory demonstrated prolonged acceptance of MHC-mismatched kidney allografts in rhesus monkeys treated with posttransplant rabbit antithymocyte globulin (RATG)* and donor-specific bone marrow (DBM). Here we have investigated the effect of adjunctive immunosuppressive drugs on induction of allogeneic unresponsiveness in this primate model. Parameters examined included median kidney allograft survival time (MST), development of specific antidonor T lymphocyte-mediated cytotoxicity (LMC) and antidonor antibody-dependent cellular cytotoxicity (ADCC). Posttransplant infusion of DBM in RATG-treated kidney allograft recipients resulted in 70 days MST and a dramatic reduction in the incidence of antidonor LMC. However, development of antidonor ADCC was similar to that of RATG controls, suggesting an immune deviation or split tolerance in these animals. Adjunctive azathioprine did not have a beneficial effect in recipients given RATG & DBM, resulting in decreased MST and increased antidonor LMC responses. In contrast, adjunctive cyclosporine (CsA) and low-dose prednisone (P) exerted an additive immunosuppressive effect resulting in a 50% increase in MST and no detectable antidonor LMC. However, CsA & P appeared to enhance the humoral alloimmune response, increasing the incidence of recipients with antidonor ADCC. Long-term graft survival in this group was limited by chronic rejection and especially by CsA-associated toxicity. These studies point out deterrents and also directions for optimizing adjunctive immunosuppression in primates treated with posttransplant RATG & DBM. The results with CsA are relatively encouraging. However, the prevalence of alloantibody and of chronic rejection in these animals suggests that more homogeneous success with tolerance induction in this model may require adjunctive immunosuppressive strategies that reduce humoral immunity.
Adjuvants, Immunologic↗
Vertical and horizontal variations in the physiological diversity of the aerobic chemoheterotrophic bacterial microflora in deep southeast coastal plain subsurface sediments.
Aerobic chemoheterotrophic bacteria were isolated from surface soils and coastal plain subsurface (including deep aquifer) sediments (depths to 265 m) at a study site near Aiken, S.C., by plating on concentrated and dilute media. Morphologically distinct colonies were purified, and their responses to 21 selected physiological tests were determined. These isolates were quite diverse; 626 physiologically distinct types (i.e., types with a unique pattern of responses to the 21 tests) were detected among the 1,112 isolates obtained. Physiologically distinct types were isolated on concentrated and dilute media (only 11% overlap between the groups); isolates from surface soils and subsurface sediments were also quite different (only 3% overlap). The surface soil isolates more readily utilized all but 1 of 12 carbon sources offered, and a significantly larger proportion of them hydrolyzed esculin and gelatin. Only 4% of the subsurface isolates fermented glucose, even though 82% of them could use it aerobically. l-Malate and d-gluconate were utilized by at least 75% of the subsurface isolates, and seven other carbon sources were used by at least 40% of them. Subsurface isolates from different geological formations (depths) and, to a lesser extent, from the same geological formation at different boreholes differed distinctly in their group responses to certain physiological tests. Moreover, sediments from different depths and boreholes contained physiologically distinct types of bacteria. Thus, considerable bacterial diversity was observed in coastal plain subsurface sediments, even within defined geological formations.
Journal Article↗
Cellular tolerance to adenosine receptor-mediated inhibition of lipolysis: altered adenosine 3',5'-monophosphate metabolism and protein kinase activation.
Prolonged exposure of many types of cells to drugs or hormones that inhibit the activity of the enzyme adenylate cyclase, such as narcotics and alpha 2-adrenergic agonists, leads to enhanced accumulation of cAMP upon removal of the inhibitory drug. We have found previously that chronic infusion of the adenosine A1 receptor agonist phenylisopropyladenosine (PIA), an inhibitor of adenylate cyclase, into rats leads to enhanced isoproterenol-stimulated cAMP accumulation in adipocytes isolated from these animals. The enhanced cAMP accumulation was associated with an impaired ability of PIA to inhibit lipolysis in these cells. In the present study we have investigated the mechanism of the enhanced cAMP accumulation in adipocytes from PIA-infused rats and the relationship of these changes to the impaired antilipolytic action of the drug. The enhanced isoproterenol-stimulated cAMP accumulation in adipocytes prepared from PIA-infused rats was due to both an increased rate of cAMP synthesis and a decreased rate of cAMP metabolism at high concentrations of cAMP without a change in phosphodiesterase activity. There was heterologous desensitization of the ability of PIA, prostaglandin E1, and nicotinic acid to inhibit cAMP accumulation in the adipocytes from PIA-infused rats; there was an increase in the EC50 of each of these agonists, although maximal inhibition of cAMP accumulation was similar. The relationship between the activation of cAMP-dependent kinase and extent of lipolysis was similar in the two groups of cells. We demonstrated that the explanation for the impaired ability of PIA to decrease the rate of isoproterenol (10(-7) M)-stimulated lipolysis in the cells from the PIA-infused rats was due to the markedly increased concentrations of cAMP in these cells, which led to sufficient activation of the kinase to maintain a high rate of lipolysis even in the presence of PIA. In addition, we found that the changes induced by the PIA infusion were largely reversible over a 2-day period after discontinuing the PIA infusion. These results demonstrate that adipocytes from PIA-infused rats provide an interesting model to investigate the mechanisms of tolerance to inhibitory drugs.
3',5'-Cyclic-AMP Phosphodiesterases↗
Chronic somatostatin treatment induces enhanced forskolin-stimulated cAMP accumulation in wild-type S49 mouse lymphoma cells but not in protein kinase-deficient mutants.
Many different types of cells exhibit a supersensitivity of adenylate cyclase after chronic treatment with inhibitory drugs; this phenomenon is manifested by enhanced cAMP accumulation upon removal of the inhibitory drug. Acute treatment of wild-type S49 cells with the somatostatin analog SMS 201-995 (SMS) results in inhibition of cAMP accumulation. We have found that chronic SMS treatment of S49 cells results in enhanced isoproterenol- and forskolin-stimulated cAMP accumulation after removal of the SMS. The forskolin-stimulated cAMP synthetic rate was about 57% higher in SMS-pretreated cells (14.22 +/- 1.02 pmol of cAMP/10(6) cells/min) than in untreated control cells (9.08 +/- 0.84 pmol of cAMP/10(6) cells/min). The time course of forskolin-stimulated intracellular cAMP accumulation is complex, with desensitization of cAMP synthesis and marked egress of cAMP from the cells. We have modeled the forskolin-stimulated cAMP time course to a simple function incorporating the initial synthetic rate and rate constants for desensitization and elimination (degradation plus egress). The mathematical modeling suggests that the difference in forskolin-stimulated cAMP time courses between control and SMS-pretreated cells can be explained on the basis of a difference in initial synthetic rates. We tested the hypothesis that the SMS-induced change in forskolin-stimulated cAMP accumulation is triggered by the decrement in the concentration of intracellular cAMP caused by SMS. We studied two independently isolated mutants of S49 cells that are devoid of cAMP-dependent protein kinase activity (kin-). Although SMS acutely inhibits cAMP accumulation in both kin- mutants, neither mutant exhibited an enhanced forskolin-stimulated cAMP synthetic rate after chronic SMS treatment. These results suggest that cAMP-dependent protein kinase is important in the induction of adenylate cyclase supersensitivity in wild-type S49 cells. The mechanistic signal for induction of supersensitivity may be the decreased cAMP accumulation that occurs in response to stimulation of inhibitory receptors, although other hypothetical mechanisms may be invoked.
Adenylyl Cyclase Inhibitors↗
Biotechnology for in situ restoration of ground water contaminated by the petroleum industry.
As a result of increasing incidents of ground water contamination, several methods to restore polluted aquifers have been developed. These include 1) physical containment, 2) hydrodynamic controls, 3) withdrawal and treatment, 4) in situ physical and chemical treatment, and 5) in situ biological treatment. The fifth technology, in situ biological treatment (in situ biorestoration), is an innovative technique which involves the use of the indigenous subsurface microflora to degrade ground water pollutants. The most important factor in successful application of the process is the presence of metabolically appropriate microorganisms in a perfusable aquifer. As a result of the high levels of carbonaceous material contaminating the subsurface as petroleum waste, nutrients such as oxygen, phosphorus, and nitrogen are often limiting. Stimulation of the microflora is therefore achieved by perfusing the aquifer with the limiting nutrients; the nutrients must be transported to the zone of contamination to be effective. Aquifers with high clay contents and low permeabilities are not good candidates for in situ biorestoration systems nor other treatment strategies which involve plume management using well systems. In conclusion, in situ biorestoration is an innovative technique that can be used to remediate contaminated aquifers which are permeable and contain a metabolically active microflora; in contrast to other remedial methods, the contamination can be completely destroyed rather than transferred to another part of the environment.
Bacteria↗
Two-color fluorescence activated flow cytometric analysis of T cells in fine needle aspirates for diagnosis of rejection.
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Biopsy, Needle↗
Better surgeons get better results.
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Colorectal Neoplasms↗
Predicting insulin-dependent diabetes.
719 first-degree relatives of diabetic children were followed up to assess the value of HLA haplotype sharing and of islet-cell antibodies (ICA) for prediction of insulin-dependent diabetes (IDDM). Within a maximum of 8 years' follow-up (3384 patient-years of observation) 16 unaffected relatives (5 parents and 11 siblings) became insulin dependent. The cumulative risk of becoming insulin dependent by age 25 was 16% for siblings sharing two HLA haplotypes with the proband, 9% for those sharing one haplotype, and zero for those sharing none. 13 of 24 (54%) subjects positive for complement-fixing ICA on three or more occasions became insulin dependent, as against 1 of 30 (3%) with noncomplement-fixing ICA alone and 2 of 665 (0.3%) ICA-negative subjects; by life-table analysis the risks after 8 years of known ICA status are 76%, 3%, and 0.6%, respectively. In terms of total time at risk ICA-positive family members had a relative risk of 75.2 compared with ICA-negative individuals. With positivity for complement-fixing ICA the relative risk was 188.5.
Actuarial Analysis↗
Omental viability and incisional herniation after omental transposition for the repair of chest wall defects.
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Aged↗
Screening for breast cancer: some clinical aspects.
There is little doubt that screening by palpation and mammography will reduce the mortality from breast cancer. Most of the studies have been designed to test survival difference and, following diagnosis, patients were treated by a variety of surgeons and methods. We present clinical and pathological data on 32 asymptomatic patients who were screened and found to have breast cancer. Investigation and treatment was performed by one surgeon according to a defined protocol. We confirm that mammography is a more sensitive diagnostic tool than palpation and describe how a review of the patient with the suspicious mammogram will increase the incidence of palpable tumours. We stress the importance of fine-needle aspiration cytology as a diagnostic and localization method. The low incidence of axillary node metastasis in patients with invasive carcinoma is described. More importantly, no patient in this series required treatment by mastectomy. In our experience patients with breast cancer detected by screening are eminently suitable for treatment by breast conservation.
Adult↗
The pattern of basal and stimulated insulin responses to intravenous glucose in first degree relatives of type 1 (insulin-dependent) diabetic children and unrelated adults aged 5 to 50 years.
The pattern of insulin secretion was studied in 107 normal individuals aged 5 to 50 years. Intravenous glucose tolerance tests were performed on 64 islet-cell antibody negative siblings of diabetic children and on 43 normal adults. Puberty was staged using Tanner's criteria and subjects were grouped as follows: I - stage 1 (n = 22), II - stages 2 and 3 (n = 18), III - stages 4 and 5 (n = 20), IV - adults greater than 17 years (n = 47). Basal and stimulated (incremental 0-10 and 10-60 min areas) insulin responses rose throughout puberty (Groups I-III), declined following puberty until the third decade (Groups III and IV) and then appeared constant thereafter. Insulin levels in the 17.6-22.5 year group were lower than in the 12.6-15 year group (p less than 0.01). Fasting insulin to glucose ratios and incremental 0-60 min insulin to glucose area ratios produced a similar age-related pattern indicating that changes in insulin levels were independent of glucose concentrations. Gender did not affect these changes and multiple regression analysis showed that HLA haplotype sharing did not influence insulin responses in siblings of diabetic patients. Age and pubertal status must be carefully considered when interpreting intravenous glucose tolerance tests from patients suspected of having early abnormalities of carbohydrate metabolism.
Adolescent↗
Between and within subject variation of the first phase insulin response to intravenous glucose.
Eight normal subjects underwent two intravenous glucose tolerance tests to determine the between and within subject variation of the first phase insulin response. Variability was represented by the coefficient of variation. The between subject variation for the incremental 0-10 min insulin area was 58%, and the within subject variation was 22% (median value), range 3-55%. The variation of the first phase response expressed in four different ways was compared. The total and incremental (above fasting levels) 0-10 min areas provided less variable results (variation 52 and 58%) than the 1 + 3 min insulin levels (variation 72%) or mean of the incremental 3-5 min insulin levels (variation 66%). The ratio of the incremental 0-10 min insulin to glucose areas was as variable (variation 53%) as the insulin responses alone. The variability of insulin responses to intravenous glucose severely limits their value as early predictors of B-cell failure.
Adult↗
Natural killer cells in rhesus monkeys: properties of effector cells which lyse Raji targets.
Spontaneously occurring natural killer cell activity of rhesus monkey peripheral blood mononuclear cells was assayed against five human cell lines, three of which were Epstein-Barr virus (EBV) positive, including the human B cell line Raji. The lytic activity to Raji cells was high, significantly higher than to any other cell line tested. Raji cells are normally insensitive to spontaneous lysis by human NK cells, and the contrasting vigor of the rhesus monkey cytolytic activity to Raji prompted us to investigate the properties of this effector cell. We found the effector cell-mediating lysis of Raji to be nonadherent and phagocytic with lytic activity slightly enhanced in the E-rosette-forming cell (ERFC+) fraction and decreased in the ERFC- fraction. Further isolation of FcIgG receptor-positive and FcIgG receptor-negative subsets by rosetting resulted in significant enrichment of NK activity to Raji in the positive fraction and a loss of activity in the negative fraction. Depletion studies with various monoclonal antibodies (mAb's) confirmed that nearly all lytic activity was contained in the CD16+ (Leu 11b+) population, while subsets of effector cells expressed CD2 (9.6) and CD8 (OKT8). Depletion of CD4 (OKT4)-, HLADR (OKIa)-, or LFA1 (MAC-1)-positive populations failed to reduce NK activity. We compared the phenotypic properties of alloimmune effector cells exhibiting specificity for allogeneic donor targets with those exhibiting lysis of Raji targets. Results indicated that allospecific cytotoxic T lymphocytes expressed a CD16-, CD2+ phenotype, a pattern distinct from that of the effector cell population recognizing Raji targets. The presence of CD2 mAb's in the culture had no effect on NK lytic activity. In contrast, mAbs CD8 and Leu 11b were inhibitory. This would suggest a functional role for CD8 and FcIgG molecules in the lysis of Raji cells by rhesus effectors. In summary, these studies describe a distinct population of effector cells in the blood of rhesus monkeys which exhibit spontaneous lytic activity to Raji cells and exhibit the properties of NK cells.
Animals↗
Clostridium difficile infection in patients with haematological malignant disease. Risk factors, faecal toxins and pathogenic strains.
Two hundred and forty-eight patients from shared oncology and general medical wards were prospectively studied over a 6-month period for carriage of Clostridium difficile during an outbreak of clinical disease with an epidemic strain of the organism. Risk factors for infection were assessed. Acute leukaemia and/or its treatment were identified as significantly increasing the risk of infection. The relationship between the type of C. difficile isolated (as defined by a typing system based on the incorporation of [35S]methionine into bacterial proteins followed by gel electrophoresis), the presence of faecal toxins A and B and clinical symptoms were analysed. Carriage of the epidemic strain, type X, had a significant association with symptoms amongst oncology patients, with two thirds of these patients having detectable faecal toxin A and one third detectable faecal toxin B. During an outbreak of C. difficile-associated disease, typing the organism and assaying for both faecal toxins in symptomatic patients may be of benefit in determining which patients require specific, urgent treatment.
Adolescent↗