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Biomedical subjects

W G Jones

Publications and source records attributed to W G Jones.

At least 37 records · Page 2Linked to original sources

Staged approach to combined repair of pectus excavatum and lesions of the heart.

The combined repair of severe pectus excavatum and cardiac lesions remains technically difficult. We report our experience with a patient undergoing such a combined repair of pectus and implantation of an aortic valved conduit in the setting of the Marfan syndrome. The procedure was staged such that the dissection and bony mobilization was done at the first procedure before heparin administration in combination with a sternal split and subsequent aortic repair. The second stage of sternal repositioning and cartilage resection was completed several days later with excellent cardiopulmonary and cosmetic results. The technique and a review of the literature are included.

Adult↗

The clamshell incision: an improved approach to bilateral pulmonary and mediastinal tumor.

Median sternotomy has been the accepted approach for dealing with mediastinal tumors or bilateral pulmonary disease, but exposure to the lower lobes and to mediastinal tumors extensively involving a hemithorax is often limited. Based on the reported experience from double-lung transplantation, we explored the use of clamshell incisions for these difficult problems. From March 1991 to December 1993, we prospectively studied the utility of clamshell incisions in 90 patients for the following indications: bilateral pulmonary metastases (62 patients), primary lung carcinoma with mediastinal involvement (13 patients), primary tumors of the mediastinum (14 patients), and mesothelioma (1 patient). Bilateral anterior thoracotomies with a transverse sternotomy (clamshell incision) were employed in 71 patients and a unilateral anterior thoracotomy with partial or complete median sternotomy (hemiclamshell incision) was used in 19 patients. For closure, we used pericostal sutures and sternal wires, usually augmented by sternal K-wire stents or Steinmann pins to prevent sternal override. Exposure to all areas of the mediastinum, pericardium, pleura, and lung was excellent. Specifically, the clamshell incision afforded markedly better access to lower lobe disease and hemithoracic extension of mediastinal disease than that possible with median sternotomy. There were no deaths or significant morbidity, and all patients tolerated the incisions well without mechanical respiratory difficulties. There was one wound infection. There was no late sternal override and the cosmetic results were found to be excellent during a follow-up of 2 to 33 months. We conclude that clamshell incisions constitute an improved surgical approach for the management of bilateral pulmonary or combined pulmonary and mediastinal disease.

Bone Nails↗

Gynaecomastia caused by a primary mediastinal seminoma.

The case of a young man aged 26 is reported. He presented with a short history of painful gynaecomastia, and no other associated symptoms. Radiological investigations showed a mass in the anterior mediastinum. Endocrine investigations showed high circulating oestradiol and high hCG-beta levels. There was no evidence of primary testicular tumour or metastases. Surgical removal of the mediastinal mass led to normalization of oestradiol and hCG-beta levels and regression of gynaecomastia. Histology showed the tumour to be a primary mediastinal seminoma staining positively for hCG-beta. Further treatment consisted of chemotherapy with etoposide and cis-platinum. The patient has remained well with no evidence of disease recurrence. The tumour markers remain normal.

Adult↗

Characterization of air contaminants formed by the interaction of lava and sea water.

We made environmental measurements to characterize contaminants generated when basaltic lava from Hawaii's Kilauea volcano enters sea water. This interaction of lava with sea water produces large clouds of mist (LAZE). Island winds occasionally directed the LAZE toward the adjacent village of Kalapana and the Hawaii Volcanos National Park, creating health concerns. Environmental samples were taken to measure airborne concentrations of respirable dust, crystalline silica and other mineral compounds, fibers, trace metals, inorganic acids, and organic and inorganic gases. The LAZE contained quantifiable concentrations of hydrochloric acid (HCl) and hydrofluoric acid (HF); HCl was predominant. HCl and HF concentrations were highest in dense plumes of LAZE near the sea. The HCl concentration at this sampling location averaged 7.1 ppm; this exceeds the current occupational exposure ceiling of 5 ppm. HF was detected in nearly half the samples, but all concentrations were <1 ppm Sulfur dioxide was detected in one of four short-term indicator tube samples at approximately 1.5 ppm. Airborne particulates were composed largely of chloride salts (predominantly sodium chloride). Crystalline silica concentrations were below detectable limits, less than approximately 0.03 mg/m3 of air. Settled dust samples showed a predominance of glass flakes and glass fibers. Airborne fibers were detected at quantifiable levels in 1 of 11 samples. These fibers were composed largely of hydrated calcium sulfate. These findings suggest that individuals should avoid concentrated plumes of LAZE near its origin to prevent over exposure to inorganic acids, specifically HCl.

Air Pollutants↗

Organic dust exposures from compost handling: case presentation and respiratory exposure assessment.

Inhalation of dust from contaminated organic materials may result in acute respiratory tract illness. Possible mechanisms include toxic and cellular reactions to microbial and other organic products or immunologic responses after prior sensitization to an antigen. A case is presented of a 52 year old male who developed fever, myalgia, and marked dyspnea 12 hr after shoveling composted wood chips and leaves. Inspiratory crackles, hypoxemia, and bilateral patchy pulmonary infiltrates were seen. Precipitating antibody tests for the usual antigens were inconclusive. He improved over 3 days. In order to assess the environmental conditions the patient had experienced, we returned to the site to reproduce and measure respiratory exposures during hand loading of the compost. Visible clouds of fine particulate were easily generated during handling activities. Microscopic examination of these dusts indicated a predominance of spores. Endotoxin concentrations from inspirable and respirable dust samples ranged from 636 to 16,300 endotoxin units/m3. Levels of contaminants found were consistent with those associated with respiratory illness in other agricultural settings. Two respiratory disorders, hypersensitivity pneumonitis (HP) and organic dust toxic syndrome (ODTS), may occur after exposure to organic dusts containing fungal spores and endotoxins. Despite extensive clinical and environmental investigations, we were unable to differentiate these two disorders, and suggest they may represent parts of a spectrum of responses to complex organic dusts, rather than completely distinct clinical entities.

Agriculture↗

Organic dust exposure from compost handling: response of an animal model.

The objective of this investigation was to elucidate the pulmonary responses of an animal model to dust generated from leaf/wood compost which had caused a severe case of acute respiratory illness in an individual. Guinea pigs were exposed for 4 hr to 30 mg/m3 of aerosolized leaf/wood compost dust. Inhalation resulted in significant cellular activation and changes in pulmonary mechanics. Maximal elevation in breathing rate (increases 36%) was observed 12-18 hr postexposure. Similarly, maximal granulocyte infiltration (increases 1,600%) and activation of alveolar macrophages (increases 65%) occurred 18 hr postexposure. In contrast, maximal airway obstruction (increases 120%) occurred immediately after exposure and returned toward normal (increases 53%) by 18 hr postexposure. In several respects, the airway obstruction and pulmonary inflammation described in the animal model were comparable to the human response to compost dust. Therefore, this animal model may be useful in predicting the potential respiratory hazard associated with exposure to various organic dusts.

Agriculture↗

Testicular seminoma metastasizing to palatine tonsil.

Patients presenting with Stage I seminoma of the testis have an excellent prognosis after treatment by orchidectomy and prophylactic radiotherapy to the paraaortic and pelvic lymph nodes. Only 2% subsequently recur but relapse in these cases has been reported in unusual sites such as the prostate and mesentery. We report a case of Stage I seminoma relapsing in another rare site for secondary malignant deposits, the palatine tonsil. This case further illustrates the favourable prognosis for this tumour even in cases of distant recurrence.

Adult↗

A phase II study of epirubicin in advanced transitional cell bladder cancer. The Yorkshire Urological Cancer Research Group.

A multicentre Phase II study of epirubicin has been performed in patients with measurable or evaluable recurrent or metastatic transitional cell bladder cancer. Epirubicin was given intravenously every 3 weeks at a dose of 100 mg/m2. An objective response rate of 28% was observed (one complete and nine partial remissions) in an evaluable group of 36 patients, (confidence interval 15%-45%). Subjective improvements in the condition of patients were seen in responding and 'no change' patients. An interesting observation was the good response seen in patients with recurrent bladder disease who had previously received radial radiotherapy. Toxicity was considered to be acceptable and manageable, the most frequent being alopecia, and nausea and vomiting. Haematological toxicity was slight. One patient developed skin pigmentation, a not previously recognized complication of epirubicin treatment. Three cases of possible cardiotoxicity were seen in the 43 patients evaluable for toxicity. Epirubicin in thus an active agent in transitional cell carcinoma of the bladder, with a role as a single agent for palliation. It may also be useful in combination regimens for more aggressive treatment.

Carcinoma, Transitional Cell↗

Changes in target volume during radiotherapy treatment of invasive bladder carcinoma.

Ninety patients with stage T3 Nx Mo carcinoma of the urinary bladder were treated with radical megavoltage external beam radiotherapy. Planning for treatment was undertaken on a treatment planning system utilizing CT scan slices to define the target volume and patient outline. All patients underwent a second CT scan half way through their course of treatment to assess any change in target volume and the continued adequacy of the original treatment plan. Seventy-two patients (80%) had no spatial shift in target volume, but, of the 18 patients with such a shift, treatment plans were changed in seven. The majority of patients had no delay in continuing their treatment after replanning, but one patient had a gap of 5 days before restarting treatment. An analysis of the factors possibly associated with a change in target volume showed that a primary tumour at the bladder base, rather than elsewhere in the bladder, was the single most important criterion for predicting target volume changes. There was no correlation between the size of the initial tumour, or the size of the prostate gland in male patients, and the occurrence of a shift in volume outside the initial target volume. Some method of regularly assessing the continued relevance of the target volume may be needed in this group of patients to improve the precision of treatment and also improve results.

Aged↗

Early detection of relapse after treatment for metastatic germ cell tumour of the testis: an exercise in medical audit.

The relapse patterns of 29 patients who recurred following treatment for metastatic germ cell tumours of the testis (seminoma n = 7, non-seminomatous germ cell tumour n = 22) have been analysed and the relative effectiveness of clinical follow-up and routine investigations in detecting relapse at an early stage have been examined. The analysis shows that routine estimation of the serum tumour markers human chorionic gonadotrophin and alpha-foetoprotein (HCG and AFP) is the single most important follow-up procedure. This is so, even in patients who were previously marker negative; it was the first indicator of relapse in 55% of the patients. Regular clinical examination and chest radiograph in asymptomatic patients was of little value. Chest radiograph gave the first evidence of relapse in only 2 cases (7%). The optimum frequency for follow-up computed tomographic scanning of the chest and abdomen remains debatable. In this series, it was the first abnormal investigation in 7 patients (24%) and proved to be particularly important in patients who had residual radiological abnormalities at the end of initial therapy. Cost analysis shows that intensive follow-up produces a total expenditure on investigations of approximately 4,500 pounds per relapse detected. Regular computed tomographic scanning is especially demanding on resources and costs approximately 12,880 pounds per relapse detected if the recommended protocol is followed.

Adult↗

Prognostic factors in metastatic non-seminomatous germ cell tumours: an interim analysis of the EORTC GU-Group experience.

Univariate and multivariate analyses were performed in 632 patients treated with cisplatin combination chemotherapy for metastatic non-seminomatous testicular germ cell tumours. Multivariately, the most important poor prognosis factors for the prediction of survival were: HCG > or = 10,000 IU/l, lung metastases > or = 10, abdominal metastases with a horizontal diameter of > or = 5 cm and the presence of supraclavicular metastases. If patients had 2 or more of these factors the death rates increased from 30% for patients with 2 factors to 65% for patients with 3 or 4 factors. The patients studied here are not a random sample of the metastatic testicular cancer patients in general, as the population studied comprised a large proportion of low volume metastatic disease patients. Therefore, the final analysis will include patients from all the recently completed trials.

Analysis of Variance↗

Macrophage inflammatory protein 1 modulates macrophage function.

Macrophage inflammatory protein 1 (MIP 1), initially purified from the conditioned medium of endotoxin-stimulated macrophages, is a low m.w. heparin-binding protein doublet comprising two peptides, MIP 1 alpha and MIP 1 beta. Although native doublet MIP 1 has previously been shown to exert pyrogenic, mitogenic, and proinflammatory effects on other cell types, its actions on its cell of origin, the macrophage, have not been well catalogued. Our study reports several aspects of macrophage function that are modulated by MIP 1. MIP 1 was not directly cytotoxic for WEHI tumor cells, but MIP 1-treated macrophage exhibited enhanced antibody-independent macrophage cytotoxicity for tumor targets. MIP 1 treatment stimulated proliferation of mature tissue macrophages, and this effect was enhanced upon costimulations with either CSF-1 or granulocyte-macrophage-CSF. Thioglycollate-elicited peritoneal exudate macrophages incubated with native doublet MIP 1-secreted bioactive TNF and IL-6, as well as immunoreactive IL-1 alpha, and these effects were enhanced significantly when the cells were costimulated with IFN-gamma. Purified preparations of the recombinantly derived MIP 1 alpha peptide alone stimulated the secretion of TNF, IL-1 alpha, and IL-6 by peritoneal macrophages, but MIP 1 beta did not. In fact, as little as eightfold excess MIP 1 beta blocked TNF-induction by MIP 1 alpha to a significant degree. By contrast to these apparent "macrophage activating" properties of MIP 1, the cytokine failed to trigger the macrophage oxidative burst, or to up-regulate the expression of Ia on the macrophage surface. Taken together, these data reveal that MIP 1 peptides act as autocrine modulators of their cells of origin, and raise the possibility that MIP 1 peptides may play a role in modulating macrophage responses to inflammatory stimuli in vivo.

Animals↗

Esophageal perforation: a continuing challenge.

Perforation of the esophagus remains a diagnostic and therapeutic challenge. Currently, the most common cause of perforation is instrumentation of the esophagus, and the incidence of esophageal perforations has increased as the use of endoscopic procedures has become more frequent. Diagnosis depends on a high degree of suspicion and recognition of clinical features, and is confirmed by contrast esophagography or endoscopy. Outcome after esophageal perforation is dependent on the cause and location of the injury, the presence of underlying esophageal disease, and the interval between injury and initiation of treatment. Reinforced primary repair of the perforation is the most frequently employed and preferable approach to the surgical management of esophageal perforations. Nonoperative management consisting of antibiotics and parenteral nutrition is particularly successful for limited esophageal injuries meeting proper selection criteria.

Esophageal Perforation↗

Effect of cyclosporine on adrenocortical response to injury and infection.

The effects of cyclosporine administration on the adrenocortical response to the severe stress of burn wound sepsis were studied in Wistar rats. Animals were treated with cyclosporine (10 mg/kg/day) or saline by gavage for 10 days, then subjected to 30% scald burns with wound inoculation with Pseudomonas. Animals were sacrificed on Postburn Days (PBDs) 1, 4, and 7 for determination of serum corticosterone and ACTH levels and adrenal weights and histology. Adrenal glands from animals sacrificed on PBD 7 were also analyzed for DNA, RNA, and protein content. Cyclosporine treatment without injury had no significant effect on body weight gain, adrenal mass, or baseline ACTH or corticosterone levels. During sepsis, cyclosporine-treated animals demonstrated a significantly diminished adrenocortical response compared to those given only saline. Serum corticosterone levels in the cyclosporine group were 45, 53, and 62% lower on PBDs 1, 4, and 7, respectively, than in saline-treated controls (P < 0.01 on each day). ACTH levels were 43 and 36% lower in cyclosporine-treated animals on PBDs 4 and 7, respectively, compared to the saline-treated group (P < 0.05 on each day). Adrenal hyperplasia occurred in both groups by PBD 7, but increases in adrenal mass and in histologic changes associated with hyperplasia (lipid depletion, vascular dilation) were less pronounced in cyclosporine-treated animals compared to those receiving saline, while adrenal composition remained similar between the two groups. Thus, cyclosporine administration is associated with an attenuated adrenocortical response to the stress of sepsis due to diminished circulating levels of ACTH.

Adrenal Cortex↗

Effect of sepsis on intracellular sodium activity, sodium concentration, and water content in thermal injured rat.

The effects of sepsis on intracellular Na+ activity, Na+ concentration, and H2O partition in skeletal muscle were investigated in a burn rat model. Studies were performed on either postburn day 3 or day 7 during evolving burn wound sepsis. Data are compared among 3 groups of rats: burned and infected (BI), burned not infected (B), and sham burn (C). After 3 days postburn both Na+ activity and concentration decreased in the BI group as compared with B and C groups. By postburn day 7, the BI group developed septic shock and had increased intracellular Na+ activity and concentration. The resting membrane potentials of skeletal muscle cells depolarized. The finding of an increased cell membrane relative permeability of Na+ to K+ could account for the increase in Na+ influx into cells. In addition, intracellular and total muscle H2O contents decreased and extracellular H2O increased. Hypernatremia, hyperchloremia, and hyperosmolality were also observed in the BI group. However, the fact that there was no significant difference between B and C groups indicates that the late derangements were due to septic shock rather than simple burn injury. Thus, the deleterious effects of the evolving burn wound sepsis on Na+ homeostasis might be due to the detrimental effect of increased intracellular Na+ activity on mitochondrial respiratory control with subsequent impairment of cellular functions.

Animals↗

Pathophysiologic glucocorticoid levels and survival of translocating bacteria.

Burn wound sepsis in rats results in sustained corticosterone elevations and the prolonged presence of translocated bacteria in the mesenteric lymph nodes (MLNs). To determine if survival of bacteria in the MLNs may be influenced by pathophysiologic corticosterone levels, MLNs were quantitatively analyzed from rats randomized to the following groups: burn wound sepsis (BI); BI with adrenocortical response attenuated by cyclosporine (cyclosporine/BI); or cyclosporine/BI with corticosterone replacement (cyclosporine/BI + P). Although rates of bacterial translocation were similar, corticosterone levels were significantly different among the three groups and correlated with the number of lymphocytes and the number of enteric bacteria present per gram of MLN. Thus, pathophysiologic elevations of corticosterone levels during sepsis may exert an effect that allows survival of translocated bacteria in the MLNs of rats, perhaps due to glucocorticoid-associated alterations in regional immunity.

Administration, Cutaneous↗

Bacterial overgrowth and intestinal atrophy in the etiology of gut barrier failure in the rat.

Bacterial translocation occurs in animal models of shock, trauma, sepsis, and parenteral or elemental enteral alimentation. Bowel atrophy and cecal bacterial overgrowth have both been implicated in the pathophysiology of bacterial translocation in many of these models. To further define the etiology of bacterial translocation resulting from dietary manipulations, rats were fed a elemental/defined-formula diet (DFD) for 2 weeks ad libitum and then randomized to either intestinal decontamination with a nonabsorbable antibiotic (neomycin) or no antibiotic treatment. Neomycin treatment significantly (p less than 0.01) reduced the incidence of bacterial translocation after DFD, in association with a significant reduction in the number of cecal gram-negative bacteria. Neither loss of bowel mass after DFD nor bowel composition was affected by oral neomycin. Bacterial translocation after DFD would thus appear to be the result of cecal bacterial overgrowth rather than a loss of a physical intestinal barrier due to atrophy.

Animals↗