Biomedical subjects
Publications and source records attributed to E D Vaughan.
120 cases of orofacial cancer underwent ablative surgery to cure their disease. The resultant defects were reconstructed using free radial fascio-cutaneous forearm flaps with microvascular anastomosis. The cases were consecutive and both ablation and reconstruction were performed by the same operator.
Total lower abdominal wall resection was required to remove a recurrent exophytic bladder carcinoma in a 36-year-old woman. The resulting 25 x 30-cm fascial defect was repaired with Marlex mesh. Bilateral rectus femoris myocutaneous flaps were rotated to close the 25 x 18-cm area of skin deficiency. These provided the advantages of robust cover of the lower abdominal wall in a single-stage procedure and primary closure of the donor sites.
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It is the alterations in renal function associated with age that necessitate physicians treating geriatric patients to have an understanding of the fragile senescent kidney. This article examines the physiologic impact of the aging kidney on homeostasis and includes a discussion of altered pharmacodynamics occurring with impaired renal function. We also discuss the limitations of various quantitative methods of measuring renal function and present several "bedside techniques" for the assessment of renal function.
Of 133 patients with advanced urothelial tract cancer given methotrexate (MTX), vinblastine (VBL), Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (DDP) (M-VAC regimen), significant tumor regression occurred in 72% +/- 8% of 121 with transitional cell carcinoma (TCC) evaluable for response. Complete remission (CR) was achieved in 36% +/- 9% of patients, of whom 11% required the addition of surgical resection of residual disease. Although 68% of CR patients have relapsed, CR median survival will exceed 38 months compared with 11 months for partial (36%) and minor (6%) responders, and 8 months for nonresponders: 2-year and 3-year survivals were 68% and 55%, respectively, versus 0% to 7% for the remaining patients. Sixteen percent of responders developed brain lesions, half of whom had no systemic relapse at the time of progression. Three patients with non-TCC histologies did not respond. In 32 patients who had pathologic restaging, the clinical (T) understaging (T less than pathologic [P] restaging) error was 35%. Although all metastatic sites showed evidence of tumor regression, CR was noted more frequently in lung, in intraabdominal lymph nodes and masses, and in bone (24% to 35%); the rate for hepatic lesions was 15%. There were 52% of 21 N3-4M0 patients who achieved CR versus 33% of 100 with N0-+M+ lesions. Toxicity was significant with 4 (3%) drug-related deaths, 25% incidence of nadir sepsis, 58% greater than or equal to 3+ myelosuppression, and 49% with mucositis. Responsiveness of metastasis in various sites, patterns of relapse, and the usefulness of the new CR response criteria are reported, as is the current status of cisplatin and methotrexate combination regimens.
Murine monoclonal antibody (mAb) F31 detects a heat-stable antigen (URO-8) found in the acidic lipid fraction of renal cancer cell extracts. Serological analysis of mAb F31 reactivity was assayed on 176 human cell lines. mAb F31 reacted with 38 of 45 renal cancers, a subpopulation of cells in primary cultures of normal renal epithelia, and two of 13 colon, two of 15 lung, and four of five ovarian cancers. No other epithelial, hematopoietic, or neuroectodermal cell lines tested were reactive. Immunofluorescence and immunoperoxidase analyses of fresh frozen tissue sections revealed mAb F31 reactivity in kidney, gastrointestinal tract, biliary canaliculi, bronchial epithelium, and skin. Within the kidney, mAb F31 immunoreactivity was confined to the straight portion of the proximal tubule. A panel composed of previously characterized mAbs as well as mAb F31 defines the antigenic phenotype of proximal convoluted tubular cells as URO-2+/URO-3+/URO-4+/URO-10+/URO-8-/URO-5-; proximal straight tubular cells as URO-2+/URO-3+/URO-4+/URO-10-/URO-8+/URO-5-; and cells of the descending thin limb of Henle as URO-2-/URO-3+ or -/URO-4+/URO-10-/URO-8-/URO-5+. While adult proximal tubular cells demonstrated reciprocal expression of URO-8 and URO-10, fetal kidney proximal tubule progenitor cells coexpressed both antigens (URO-10+/URO-8+). Fifty renal cancer specimens were typed with these antibodies. Fourteen cases were URO-10+/URO-8-, ten cases were URO-10-/URO-8+, and 25 cases expressed both antigens (URO-10+/URO-8+). These phenotypes are consistent with derivation of these particular subsets from the proximal convoluted tubule, the pars recta, or a proximal tubule progenitor cell, respectively. Only one specimen failed to express either URO-8 or URO-10.
Although solutions containing disodium ethylenediaminetetraacetic acid (EDTA) will dissolve calcium oxalate stones in vitro, the safety of such solutions as urinary tract irrigants is questionable. These studies were designed to assess the degree of urothelial damage produced by the mildest EDTA formulation which has been reported to be effective. Rabbit bladders were irrigated antegrade via a ureterotomy for 20 hours and then removed for histological examination. A 0.03 M solution of disodium EDTA at pH 7.5 produced considerably more urothelial injury than did an otherwise identical solution of calcium EDTA (p = 0.006). The bladders from the latter group were undistinguishable from those irrigated with saline. As prior saturation of EDTA with calcium completely eliminated the tissue injury, these studies indicate that the same calcium chelating property which makes this chemical effective also makes it toxic. There was enough tissue damage from the relatively mild formulation used to suggest no EDTA solution yet formulated is safe for clinical use.
The role of alpha 2 adrenergic receptors in the prostate in vivo is unknown. A model was developed to measure canine prostatic urethral pressure in vivo, and to assess the ability of various alpha adrenergic blocking agents to affect prostatic pressure. In this model, an esophogeal pressure catheter is inserted into the prostatic urethra to record prostatic urethral pressure. We investigated the effects of alpha adrenergic agonists and antagonists on prostatic pressure using this model. Dose-response curves were generated for epinephrine, and were then repeated in the presence of either prazosin (alpha 1 antagonist), yohimbine (alpha 2 antagonist) or SK&F-86466 (alpha 2 antagonist). Prazosin was the most potent of the three drugs in competitively blocking epinephrine-induced contraction of the prostate, with an inhibition constant of 0.24 micrograms./kg. calculated from the double reciprocal plot. Clonidine, an alpha 2 adrenergic agonist, caused contraction of the prostate, which was also blocked by prazosin. Furthermore, the specific alpha 2 agonist BHT-920 was totally inactive in our system. These results demonstrate that the increase in urethral pressure caused by alpha-adrenergic agonists can be blocked by alpha adrenergic antagonists. However, the specific alpha 1 antagonist, prazosin, is more potent than alpha 2 antagonists, and is also effective against an alpha 2 agonist, clonidine. This suggests that blockade of alpha 1 receptors may be a more useful strategy for causing relaxation of the prostate than blockade of alpha 2 receptors.
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We quantitated c-myc oncoprotein in 44 squamous cell carcinomas of the head and neck using an enzyme-linked immunosorbence assay. The clinicopathological parameters of these patients were followed up for between 3 and 60 months and analysed for any correlations with observed levels of c-myc protein using the Kruskal-Wallis one-way analysis of variance method. Although no statistical correlation was found between different clinicopathological parameters (patient age, sex, TNM staging, number of lymph nodes invaded, extracapsular rupture of the tumour, its histopathological differentiation, or its site), the survival periods of patients with tumours possessing elevated levels of c-myc protein were found to be statistically shorter than those with lower levels of c-myc expression, (P less than 0.02). This indicates that c-myc expression may be an effective prognostic indicator in head and neck cancer.
Unilateral ureteral obstruction (UUO) results in increased renal resistance as well as in exaggerated prostaglandin (PG) release from the obstructed hydronephrotic kidney (HNK). We have reported previously that platelet-activating factor (PAF) dose-dependently stimulates the release of PGs from both the HNK and unobstructed contralateral kidney (CLK), with CLK release being 10% that of the HNK. In the present report, we studied the interaction of PAF with its receptor by examining the effects of PAF-receptor antagonists on the release of PGs from the isolated perfused rabbit HNK and CLK stimulated by PAF; angiotensin II (AII), and bradykinin (BK) were also used as agonists. In the HNK, kadsurenone (3 microM) inhibited PAF-stimulated PGE2 and thromboxane B2 (TxB2) release by 28.2 and 62.5% respectively. CV-3988 (20 microM) and triazolam (5 microM) also preferentially diminished PAF-stimulated TxB2 release. In addition, all three drugs significantly diminished BK- and AII-stimulated TxB2 release, while CV-3988 was the only antagonist to affect peptide-stimulated PGE2 release. While effective against agonist-stimulated PG synthesis, these drugs had no direct effect on arachidonic acid metabolism to PGs. Furthermore, in the CLK, CV-3988 had no effect on BK- or AII-stimulated PGE2 release, whereas it totally inhibited PAF-stimulated release of PGE2. These results show that PAF-receptor antagonists in the HNK preferentially inhibit TxB2 release whether stimulated by PAF, AII or BK; in the CLK only PAF-stimulated PG release is affected. This biochemical difference may be of physiological significance and explain some of the functional differences between the HNK and CLK. Therefore, PAF may be an important mediator of some of the biochemical and functional changes associated with UUO.
A study was done comparing the charges and outcomes for extracorporeal shock-wave lithotripsy (ESWL) with those for percutaneous nephrostolithotomy (PCN), which was the treatment of choice at our hospital for stones of the upper urinary tract when ESWL was introduced. Using a retrospective cohort design, patients were matched for age, sex, physical status index (American Society of Anesthesiologists), stone size, and urinary tract obstruction. Twenty-nine pairs of PCN and ESWL patients with complete data were matched. The groups were not significantly different in the matching parameters. Seventy-two per cent of patients in each group (21/29) were stone-free after the initial hospitalization. PCN patients required more auxiliary procedures per patient than did the ESWL patients; in addition, 5 (17%) of the PCN patients had perforation of the renal pelvis and 5 (17%) required transfusions. On discharge, 48 per cent (14/29) of the PCN patients had nephrostomies compared with none of the ESWL patients. The ESWL group had a shorter mean length of stay (2.9 vs 8.7 days, p less than 0.0005) and lower charges in all categories. Total charges were significantly less for ESWL ($9,290 vs $11,796 for PCN, p less than 0.005) as were physicians' fees ($3,391 vs $5,607, p less than 0.0005), room and board charges ($825 vs $2,164, p less than 0.0005), and operating room fees ($313 vs $1,452, p less than 0.0005). We conclude that ESWL is a cost-effective means for treating stones of the kidney and upper urinary tract.
Haemangiopericytomas are rare tumours derived from the pericyte. Two cases originating in the head and neck are described and the methods of treatment outlined.
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To define the prevalence of prostatic bacterial infection or colonization, tissue from 209 patients undergoing prostatectomy (204 transurethral and 5 suprapubic) was submitted for quantitative bacterial tissue cultures. Tissue from 44 patients (21 per cent) yielded positive, single organism bacterial growth. In an attempt to identify preoperatively this patient subgroup, multiple preoperative and intraoperative variables were examined. Although the presence of a preoperative indwelling catheter was associated with positive prostate cultures, only 34 per cent (24 of 70) of the patients with preoperative catheters had positive prostate cultures. Of the 44 patients with positive prostate cultures 36 (82 per cent) had sterile urine cultures documented preoperatively, all urine specimens having been obtained in the absence of antibiotics. The data support a significant prevalence (21 per cent or more) of prostatic infection in patients undergoing prostatic surgery for obstructive symptoms and an apparent paucity of reliable indicators by which to identify preoperatively this patient population.
Five educators concerned with changes occurring in the financing of medical education and care reviewed the present status of residency programs and their financing. Future support depends on political decisions as well as demonstrable needs. The effects of anticipated reductions in funding for residents and their programs may be countered by the development of alternative sources and the restructuring of present programs for more efficient operation. The need for leadership is clear.
Of 92 patients who received methotrexate, vinblastine, doxorubicin and cisplatin complete and partial remissions were observed in 69 +/- 10 per cent of 83 adequately treated measurable and evaluable patients with advanced stages (N+M0 and N0M+) transitional cell urothelial cancer. Complete remission was achieved in 37 +/- 10 per cent of the patients clinically, pathologically and after surgical resection of residual disease. With 17 of 31 complete responders (55 per cent) surviving for 26+ to 49+ months, the estimated probability of survival at 2 and 3 years was 71 and 55 per cent, respectively. Partial remission occurred in 31 +/- 10 per cent of the patients, while 8 per cent had a minor response and 23 per cent had progression with median survivals of 11, 11 and 7 months, respectively. Whereas all metastatic sites responded, including the bone and liver, complete tumor regression was observed more frequently with nodal, pulmonary and local-regional lesions. Brain metastases occurred within 6 to 42 months in 18 per cent of the responders, half of whom never had systemic relapse. Of the remaining 9 patients 2 with nontransitional cell histological tumors did not respond, 5 (5 per cent) were inadequately treated and 2 were excluded from response data because of inevaluable disease parameters but they were free of disease at 16+ and 31+ months. Toxicity was significant, with 20 per cent of the patients experiencing nadir sepsis, 4 per cent a drug-related death, 31 per cent +1 renal toxicity and 41 per cent +1 mucositis. The applications and advantages of the newly proposed international response criteria for bladder cancer are discussed in reference to 25 patients who underwent surgical re-staging, indicating that the disease was understaged clinically in 24 per cent (T less than P), as well as in reference to attainment of true (pathological) complete remission and to other urothelial tract trials. While this therapy seems to have limited antitumor activity against nontransitional cell histological cancer, stage Tis disease and later development of de novo lesions, the regimen is efficacious in selected patients with advanced urothelial tract transitional cell carcinoma.
Extracorporeal shock wave lithotripsy has become a major treatment modality for symptomatic upper tract renal stone disease. Although proved to be effective in disintegrating stones the short-term and long-term effects on renal function are not yet known. We evaluated several basic physiological parameters, namely creatinine clearance, fractional sodium excretion, protein excretion and urine osmolality before and after extracorporeal shock wave lithotripsy in 26 consecutive patients in an attempt to quantitate changes in renal function. In addition, a 3 to 6-month followup study of patients showing excessive protein excretion with extracorporeal shock wave lithotripsy also is reported. Our data suggest that with extracorporeal shock wave lithotripsy transient nephrotic range proteinuria occurs immediately after treatment, returning to normal values within 3 to 6 months after treatment without a change in the glomerular filtration rate. The glomerular filtration rate increases after successful extracorporeal shock wave lithotripsy in patients with kidneys obstructed by the treated stone before the start of the procedure, and the kidney appears to maintain its ability to dilute urine and to conserve sodium after treatment.