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Biomedical subjects

W G Jones

Publications and source records attributed to W G Jones.

At least 55 records · Page 3Linked to original sources
PubMed1991

Diabetes impairs the late inflammatory response to wound healing.

Diabetes mellitus is recognized as a risk factor for compromised wound healing. This study examines leukocyte infiltration and the appearance of tumor necrosis factor-alpha (TNF) and IL-6 in wound chambers implanted in normal and streptozotocin-induced diabetic mice. Perforated silicone wound chambers containing a strip of polyvinyl alcohol sponge were implanted along the flanks of normal and diabetic mice. Wound fluid aspirated from the chambers 1, 3, and 7 days following implantation was analyzed for the total number of leukocytes and TNF and IL-6 levels. While the number of leukocytes in the wound fluid was similar on Days 1 and 3 following implantation, there were significantly fewer inflammatory cells in wound fluid from diabetic animals (13.8 X 10(6)/ml) than in wound fluid from normal animals (28.5 Z 10(6)/ml) on Day 7 following implantation. TNF levels in the cell-free exudate fluid were similar between the two groups on all days examined. IL-6 levels were similar on Days 1 and 3 following implantation between the two groups, but there was significantly more IL-6 in wound fluid from normal animals (10,998 U/ml) than in wound fluid from diabetic animals (2096 U/ml) on Day 7 following implantation. Histologic evaluation of chambers 8 days following implantation revealed decreased neovascularization and less organization of granulation tissue. These data suggest that delayed healing in diabetes is associated with altered leukocyte infiltration and wound fluid IL-6 levels during the late inflammatory phase of wound healing.

Animals↗
PubMed1991

Long-term follow-up of non-seminomatous testicular cancer patients with mature teratoma or carcinoma at postchemotherapy surgery. EORTC Genitourinary Tract Cancer Cooperative Group (EORTC GU Group)

From 1979 to 1983 the EORTC GU Group treated 239 patients with disseminated non-seminomatous testicular cancer with combination chemotherapy comprising cisplatin, vinblastine and bleomycin in a prospectively controlled trial. The protocol required complete resection of residual masses after induction chemotherapy, provided that serum tumour markers were normal. 102 patients were operated on. 27 patients had mature teratoma (teratoma differentiated) in the resected specimens and 23 had viable cancer. Follow-up data were available for 26 and 22 of these patients, respectively. 23 of 26 patients (88%) with mature teratoma are alive and disease free after a follow-up of 53-110 months (median 92 months). 3 patients developed progressive disease; 1 died. A peculiar case of growing mature teratoma on the forearm is described. 13 of 22 patients (59%) with residual carcinoma are alive and disease free after a follow-up of 74-112 months (median 95 months). The prognosis of patients with carcinoma is shown to be correlated with the completeness of surgery, which in turn is correlated with the initial tumour mass before chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

BOP/VIP--a new platinum-intensive chemotherapy regimen for poor prognosis germ cell tumours.

Ninety-one patients with poor prognosis non-seminomatous germ cell tumours (NSGCT) were treated with an initial intensive chemotherapy schedule. Suitable patients fulfilled one or more of the following criteria: lymph node metastases greater than 10 cm diameter; liver, brain or bone metastases; serum HCG level greater than 50,000 IU/L; and extragonadal primary tumours. Treatment consisted of 3 cycles of bleomycin, vincristine and cisplatin (BOP) administered at 10 day intervals, followed by 3 cycles of etoposide, ifosfamide and cisplatin (VIP) at 21 day intervals. A total of 64 patients (70%) achieved a complete remission. This comprised 46 patients who received BOP/VIP only, and 18 patients who received additional chemotherapy after BOP/VIP. Of these 64 patients, 51 underwent complete surgical resection of residual masses, including 11 in whom there was evidence of teratoma with cellular atypia or non-germ cell cancer in the resected tissue. A further 9 patients had persisting unresected radiological masses in the presence of marker complete remission. The overall response rate was 80%. Currently 57 patients (63%) remain alive and free from disease progression. The median follow-up period is 90 weeks (range 24-206 weeks), with a 2 yr actuarial progression-free survival of 66% (95% c.i. 55-77%). Major toxicity was myelosuppression, occurring during the VIP arm of therapy, with a median nadir WBC of 1.1 x 10(9)/L and median platelet count of 51 x 10(9)/L. Other toxicity included peripheral neuropathy (WHO Grade 2 and 3 in 22%). We conclude that treatment results with the BOP/VIP schedule in this poor prognosis patient group are at least comparable with other schedules, and toxicity is manageable.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Differential pathophysiology of bacterial translocation after thermal injury and sepsis.

Bacterial translocation (BT) occurs transiently after thermal injury and may result from an ischemic intestinal insult. To evaluate continued intestinal ischemia in the ongoing BT associated with sepsis after injury, rats were randomized to (1) 30% burn injury with Pseudomonas wound infection (BI), (2) BI + fluid resuscitation (BI + Fluid), (3) BI after allopurinol pretreatment to inhibit xanthine oxidase (BI + Allo), or (4) BI after azapropazone pretreatment to inhibit neutrophil degranulation (BI + Aza). On postburn days (PBD) 1, 4, and 7, animals were studied for evidence of BT and intestinal lipid peroxidation. BI + Fluid, BI + Allo, and BI + Aza significantly (p less than 0.05) reduced rates of BT and ileal lipid peroxidation acutely after thermal injury (PBD 1) compared to BI. All four groups had equally high rates of BT associated with the onset of sepsis (PBDs 4 and 7), without evidence of further intestinal lipid peroxidation. These data indicate that the chronic gut barrier failure associated with sepsis after injury occurs independently of continued intestinal ischemia.

Animals↗
PubMed1991

Splanchnic vasoconstriction and bacterial translocation after thermal injury.

Gut barrier failure and bacterial translocation (BT) after thermal injury may result from splanchnic vasoconstriction and intestinal ischemia. The role of the renin-angiotensin system in intestinal blood flow and BT after thermal injury was studied by pretreatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril in Wistar rats before sham or 30% scald burn. Adequacy of ACE inhibition was documented by the absence of a hypertensive response to angiotensin I, and intestinal blood flow was determined using 51Cr-labeled microspheres. Small bowel blood flow was decreased by 46% at 4-h postburn (P less than 0.05) in untreated burned animals despite maintenance of normal cardiac index but returned to baseline levels by 24 h after injury. Enalapril pretreatment resulted in maintenance of small bowel blood flow after thermal injury and was associated with a significantly reduced incidence of BT (20% vs. 75% in untreated burned animals, P less than 0.01). These findings further implicate intestinal ischemia in the etiology of gut barrier dysfunction after thermal injury, mediated in part by activation of the renin-angiotensin system.

Animals↗
PubMed1990

[Penile cancer].

We review the literature on penis cancer. The disease is rare and most of the cumulative experience is reported in retrospective series. Multi-institutional international collaboration will be needed for prospective studies of certain facets of this disease which are at present controversial. Suggested areas of research are how to treat early invasive tumours, the diagnosis and treatment of inguinal metastases, the improvement of radiotherapy techniques, the development of effective chemotherapy and effective combinations of therapies. This will potentially lead to a more sparing of organs. It is also necessary to study palliation, and aspects of quality of life. The incidence may be further reduced by educating the public about the condition and about genital hygiene, including the necessity for the early treatment of phimosis.

Carcinoma↗
PubMed1990

Cytokine production in a model of wound healing: the appearance of MIP-1, MIP-2, cachectin/TNF and IL-1.

Macrophages are essential for normal wound repair and many of their effects on healing wounds are likely to be mediated by the secretion of cytokines. This study examines the appearance of messenger RNA (mRNA) for cachectin/tumor necrosis factor (TNF), IL 1, and macrophage inflammatory proteins 1 and 2 (MIP-1 and MIP-2), as well as the mature peptides, in a model of wound healing using wound chambers. RNA for all four cytokines can be detected in wound inflammatory cells by polymerase chain reaction amplification throughout the first 7 days. Cachectin/TNF and IL 1 protein levels peaked on the first day after wound chamber implantation, and MIP-1 and MIP-2 were detected only on day 3. The data suggest that these cytokines participate in the early inflammatory response to wounding.

Animals↗
PubMed1990

Investigation, treatment and prognosis of bronchial carcinoma in the Yorkshire Region of England 1976-1983.

We studied all cases presenting during life with carcinoma of the bronchus and registered at the Yorkshire Regional Cancer Registry 1976-1983. During this period fibreoptic bronchoscopy became more widely available in the region, and multiple drug chemotherapy became first line treatment for small cell carcinoma. Although there was little change in the overall incidence of lung cancer during the study period, the proportion of females increased by 4.8% and the mean age at presentation rose by 2.3 years. The histological confirmation rate rose by 29% from 45% to 58%. The proportion of patients with small cell carcinoma treated by chemotherapy increased from 17% to 39%. With this exception therapeutic intervention rates were unaltered. The prognosis of patients with small cell carcinoma treated by chemotherapy improved, particularly so for those less than 60 years. There was a consistent trend for an overall improvement in survival in other groups, and this was significant for those aged 70 and over where it appeared to be related to more appropriate management of squamous cell carcinoma. We conclude from this regional study that increased diagnostic activity in District General Hospitals has allowed an improvement in prognosis both for patients with small cell carcinoma treated by chemotherapy, and in patients over 70 with non-small cell cancer. These trends can be expected to continue over the next few years.

Aged↗
PubMed1990

Bacterial translocation and intestinal atrophy after thermal injury and burn wound sepsis.

Bacterial translocation (BT) occurs after thermal injury in rodents in association with intestinal barrier loss. Infection complicating thermal injury may also affect the intestine producing bowel atrophy. To study these relationships, Wistar rats received either 30% scald followed by wound inoculation with Pseudomonas; 30% scald with pair feeding to infected animals; or sham injury as controls. On days 1, 4, and 7 after injury animals were killed with examination of the bowel and culture of the mesenteric lymph nodes (MLN), livers, spleens, and blood. All burned animals demonstrated BT to the MLN on day 1 after injury, but only burn-infected animals had continued BT on days 4 and 7, with progression of BT to the abdominal organs and blood. Burn injury and infection also resulted in significant atrophy of small bowel mucosa temporally associated with continued BT. Thus injury complicated by infection results in prolonged and enhanced bacterial translocation, perhaps due to failure to maintain the mucosal barrier.

Animals↗
PubMed1990

Antibiotic prophylaxis diminishes bacterial translocation but not mortality in experimental burn wound sepsis.

Pseudomonas (PSA) burn wound sepsis results in prolonged bacterial translocation (BT) of enteric organisms such as E. coli to the mesenteric lymph nodes (MLN) and organs in rats. Intestinal decontamination with oral antibiotics may improve mortality after burn injury, perhaps due to decreased BT. To determine the effect of oral antibiotic prophylaxis effective against E. coli but not PSA on BT and subsequent mortality in a model of PSA burn wound sepsis, rats were given a 30% scald burn and wound inoculation with 10(8) PSA followed by randomization to either ampicillin (50 mg/kg/d) or saline gavage. Cultures of MLN, organs, blood, and cecal contents were obtained on days 1, 4, and 7 after injury, with additional animals observed for 14-day mortality. Although oral antibiotic prophylaxis resulted in increased cecal colony counts, the incidence of BT was unchanged. The number of organisms present in both the MLN and organs, however, was significantly reduced with prophylaxis, indicating cecal overgrowth by non-translocating bacteria. Reduction of the number of translocating organisms did not result in improved mean survival time after injury, suggesting that mortality from PSA burn wound sepsis occurs independently of bacterial translocation.

Ampicillin↗
PubMed1990

Pathophysiologic glucocorticoid elevations promote bacterial translocation after thermal injury.

Thermal injury results in transient elevations of plasma glucocorticoids and promotes translocation of bacteria from the gut to the mesenteric lymph nodes (MLN) in rats. Translocated organisms are quickly cleared following uncomplicated thermal injury. However, subsequent burn wound infection, in temporal association with sustained pathophysiologic elevations of plasma corticosterone, results in the continued presence of enteric bacteria in the MLN. To study the role of sustained pathophysiologic steroid elevations in the mediation of this prolonged bacterial translocation, Wistar rats were randomly placed in groups receiving one of the following: (i) a 30% total body surface area scald injury with placement of a subcutaneous corticosterone pellet, (ii) a 30% total body surface area scald and a sham pellet implantation, (iii) a sham burn and a corticosterone pellet implantation, or (iv) a sham burn and a sham pellet implantation. The animals were sacrificed on days 1 and 4 after injury, and cultures of the MLN, as well as the liver and spleen, were taken. Implantation of corticosterone pellets resulted in sustained elevations of plasma corticosterone compared with controls not receiving corticosterone pellets, similar to results seen in association with injury and infection. These pathophysiologic elevations were associated with the prolonged presence of organisms in the MLN (90% of burned rats with implanted corticosterone pellets versus 25% of rats with uncomplicated burns on postburn day 4; P less than 0.01), but only in the presence of burn injury. Pathophysiologic glucocorticoid elevations did not lead to progression of translocation to the viscera or blood. Thus, the pathophysiologic glucocorticoid response contributes to the translocation of enteric bacteria and their prolonged presence in the MLN after systemic injury.

Animals↗
PubMed1990

Additive effects of thermal injury and infection on the small bowel.

Thermal injury is associated with functional alterations of multiple organ systems, including the gastrointestinal tract. To study the effects of ongoing infection after thermal injury on bowel mass, composition, and blood flow, male Wistar rats were randomized to receive either 30% scald burn, 30% scald burn with Pseudomonas aeruginosa wound inoculation, sham burn, or sham burn with pair feeding to burned and infected animals. On days 3 and 7 after injury, intestinal blood flow was measured with 51Cr-labeled microspheres, and intestinal mass and composition were analyzed. Burned and infected animals demonstrated a chronic loss of small bowel mass not seen in burned animals without infection by day 7 after injury. Compositional alterations of the small bowels of burned and infected animals included protein wasting similar to but occurring earlier than that seen with anorexia alone and significantly decreased deoxyribonucleic acid and ribonucleic acid content, whereas tissue water content remained unchanged. These chronic intestinal alterations in the burned and infected group could not be explained by ongoing ischemia because intestinal blood flow in these animals was not significantly altered at either time point, implying mediation by other pathophysiologic mechanisms.

Animals↗
PubMed1989

Changes in tibial venous blood flow in the evolving compartment syndrome.

A sustained increase in muscle compartment pressures can cause tissue necrosis. When compartment pressures exceed recumbent tibial vein pressures, blood flow in tibial veins may be impaired. These changes can be detected by Doppler venous flow evaluation. In 26 patients at risk for compartment syndrome, serial examinations, Doppler venous flow, and measurements of compartment pressures were performed. All patients with abnormal Doppler venous flow results had or developed neuromuscular deficits. Patients with normal Doppler venous flow either initially or after fasciotomy did not develop the compartment syndrome. This syndrome can be evaluated and followed up sequentially by measuring Doppler venous flow in tibial veins.

Adolescent↗