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Biomedical subjects

C N Robertson

Publications and source records attributed to C N Robertson.

51 records · Page 3Linked to original sources

The detection of renal carcinoma extension into the renal vein and inferior vena cava: a prospective comparison of venacavography and magnetic resonance imaging.

Accurate preoperative evaluation of the inferior vena cava and renal vein in patients with renal cell carcinoma is mandatory to plan a successful surgical approach. The presence of venous extension may alter transfusion and anesthetic requirements, as well as require the addition of a vascular surgeon to the operative team. Venacavography traditionally has been considered the most reliable method to identify tumor thrombus, although magnetic resonance imaging has been proposed as a possible noninvasive alternative. We compared prospectively the accuracy of these 2 methods in 44 consecutive patients with renal cell carcinoma who subsequently underwent nephrectomy. Of the 44 patients 11 (25%) had tumor extension into the inferior vena cava and 17 (39%) had involvement of the renal vein at operation. Venacavography and magnetic resonance imaging correctly identified 9 of the 11 patients (82%) with inferior vena caval thrombus. When the results of both tests were combined, all 11 cases of vena caval extension were identified. Venacavography was slightly more sensitive (71%) in identifying the presence of renal vein thrombus than magnetic resonance imaging (65%) but these differences were not statistically significant. Magnetic resonance imaging better localized the thrombus within the renal vein. We conclude that venacavography and magnetic resonance imaging offer equal diagnostic accuracy in the identification of venous extension of renal cell carcinoma. The combination of both tests results in higher diagnostic yield than either test alone. Neither test by itself is reliable in the presence of a large, bulky adenopathic lesion that compresses the inferior vena cava.

Adult↗

The inhibition of human adrenal steroidogenic enzyme activities by suramin.

Suramin has recently been used to treat patients with acquired immune deficiency syndrome because of the action of this drug on reverse transcriptase. Patients so treated developed the symptoms and hormonal profiles of adrenal insufficiency. To evaluate the mechanism of action of suramin on adrenalcortical function, adrenal mitochondrial and microsomal preparations from five subjects were assayed for steroidogenic enzyme activity in the presence and absence of suramin. Specifically, 3 beta-hydroxysteroid dehydrogenase/isomerase, 17 alpha-hydroxylase, 21-hydroxylase, 11 beta-hydroxylase, and 17,20-desmolase activities were measured in the presence of 0-5000 mumol/L suramin concentrations. In all assays, enzyme activities decreased in a dose-dependent fashion as suramin concentrations increased. The drug doses (calculated) that caused 50% inhibition of enzyme activity were: 21-hydroxylase activity, 50 mumol/L; 17 alpha-hydroxylase activity, 25 mumol/L; 17,20-desmolase activity, 50 mumol/L; 11 beta-hydroxylase, 2 mumol/L, and 3 beta-hydroxysteroid dehydrogenase/isomerase, 1200 mumol/L. These results suggest that suramin has a concentration-dependent inhibitory effect on the key P-450-regulated enzymatic steps in adrenal glucocorticoid steroidogenesis, which may explain the development of adrenal insufficiency in acquired immune deficiency syndrome patients treated with suramin.

Acquired Immunodeficiency Syndrome↗

Late hematogenous infection of penile prostheses.

Late deep wound infection caused by hematogenous bacterial spread from a remote focus is a rare but disastrous complication of prosthetic devices. Six patients with probable late hematogenous infection are described. The initial implantation was free of contamination and infection, and a long functional interval ensued. A febrile process associated with a painful, swollen penis followed a probable remote infection source that was not covered with prophylactic antibiotics. All prostheses required removal. Prophylactic antibiotics may prevent these late hematogenous infections.

Adult↗

Fournier gangrene: diagnosis with scrotal US.

Skin thickening and subcutaneous air were detected at ultrasound (US) of the scrotum in a patient with normal-appearing testicles and signs and symptoms suggestive of an acute inflammatory process, such as epidydimitis or orchitis. The patient was found to have Fournier gangrene. In more advanced cases, US can demonstrate that this skin thickening and subcutaneous air extends posteriorly to include the perineum and buttocks. Because of the high mortality of this mixed anaerobic and aerobic infection, it is important to recognize Fournier gangrene early so that the correct surgical and medical treatment can be promptly instituted. To the authors' knowledge, this is the first description of the US characteristics of Fournier gangrene.

Fasciitis↗

Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: a pilot study.

Clinical investigations using the adoptive transfer of lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) to treat patients with advanced cancer have yielded encouraging results. We have thus sought ways to enhance the effectiveness of adoptive immunotherapy while minimizing its toxic side effects. Murine experiments have identified tumor-infiltrating lymphocytes (TIL) as killer cells more effective than LAK cells and less dependent on adjunctive systemically administered IL-2 to mediate antitumor effects. Accordingly, we performed a pilot protocol to investigate the feasibility and practicality of administering IL-2-expanded TIL to humans with metastatic cancers. Twelve patients, including six with melanoma, four with renal cell carcinoma, one with breast carcinoma, and one with colon carcinoma, were treated with varying doses and combinations of TIL (8.0 X 10(9) to 2.3 X 10(11) cells per patient), IL-2 (10,000 to 100,000 U/kg three times daily to dose-limiting toxicity), and cyclophosphamide (CPM) (up to 50 mg/kg). Two partial responses (PR) to therapy were observed: pulmonary and mediastinal masses regressed in a patient with melanoma, and a lymph node mass regressed in a patient with renal cell carcinoma. One additional patient with breast cancer experienced a partial regression of disease in lymph nodal and cutaneous sites with complete elimination of malignant cells from a pleural effusion, although cutaneous disease recurred at 4 weeks. The toxicities of therapy were similar to those ascribed to IL-2; no toxic effects were directly attributable to TIL infusions. In five of six melanoma patients, TIL demonstrated lytic activity specific for the autologous tumor target in short-term chromium-release assays, distinct from the nonspecific lytic activity characteristic of LAK cells. This study represents an initial attempt to identify and use lymphocyte subsets with enhanced tumoricidal capacity in the adoptive immunotherapy of human malignancies.

Adult↗

A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone.

We studied the effects of adoptive immunotherapy with lymphokine-activated killer (LAK) cells plus interleukin-2 or therapy with high-dose interleukin-2 alone in 157 patients with metastatic cancer for whom standard therapy had proved ineffective or no standard effective treatment was available. One hundred eight patients were treated with 127 courses of LAK cells plus interleukin-2, and 49 patients were treated with 53 courses of high-dose interleukin-2 alone. Of 106 evaluable patients receiving LAK cells plus interleukin-2, 8 had complete responses, 15 had partial responses, and 10 had minor responses. The median duration of response was 10 months among those with complete responses and 6 months among those with partial responses; the patient with the longest complete response was still in remission 22 months after treatment. Of 46 evaluable patients treated with high-dose interleukin-2 alone, 1 had a complete response (remission greater than 4 months), 5 had partial responses (2, greater than 3, greater than 5, 7, and greater than 11 months), and 1 had a minor response. Seven of the total of nine complete responses still remain in remission. Hypotension, weight gain, oliguria, and elevation of bilirubin and creatinine levels were common, but these side effects resolved promptly after interleukin-2 administration was stopped. There have been four treatment-related deaths among these 157 patients. This immunotherapeutic approach can result in marked tumor regression in some patients for whom no other effective therapy is available at present. Determining its ultimate role in cancer therapy awaits further attempts to increase the therapeutic efficacy of treatment and decrease its toxicity and complexity.

Adolescent↗

Use of the rectus abdominis muscle flap in urological reconstructive procedures.

The rectus abdominis muscle flap has been used successfully in 4 reconstructive procedures complicated by tissue loss or urinary fistula. This simple procedure is advocated as an alternative to the use of omentum when prior abdominal surgery precludes omental mobilization. No adverse functional nor cosmetic result to the abdominal wall resulted.

Abdominal Muscles↗

Bladder substitution in children.

In spite of all the difficulties, cystoplasty, particularly with the ileocecal segment, has proved rewarding. Undiversion is easily accomplished in this way. Most patients are outwardly well and happy. Reflux usually does no harm in the near term, especially if infection can be prevented, and bladder pressures are not elevated. However, we believe that we are close to being able to prevent reflux in a reliable manner. If this is the case, the ileocecal segment or hemi-Kock pouch may clearly become the optimal choice for bladder substitution in patients with reflux or ureteral obstruction, as well as those with short ureters or very small bladders, or as a standard method of undiversion. We have also employed the intussuscepted ileum as the antireflux mechanism in patients undergoing bladder substitution using a patch of small bowel as in the hemi-Kock. This technique allows one to leave the cecum and ileocecal valve in situ, reducing the risk of chronic postoperative diarrhea. In addition, small bowel is proving to be more compliant on the average than large bowel segments when used in bladder reconstruction. Whether the ileocecal segment or the hemi-Kock cystoplasty has a permanent place in undiversion and in the treatment of chronic or pharmacoresistant noncompliant bladder, neuropathic or otherwise, the techniques learned are making total replacement of the bladder with bowel segments a more attractive and feasible undertaking. The pool of patients susceptible to such maneuvers is a large one.

Cecum↗

The vascularized skin island urethroplasty: its role and results in urethral stricture management.

We report 11 vascularized island skin flap urethroplasties. Results appear to be excellent when the procedure is used for strictures of the pendulous urethra. Use of vascularized skin flap urethroplasties for the repair of bulbar and membranous strictures has been complicated by pseudodiverticula and stone formation, and in this portion of the urethra the technique probably should be reserved for cases in which local factors mitigate against alternative 1-stage procedures.

Adult↗

Lethal complications of standard self-retaining ureteral stents in patients with ileal conduit urinary diversion.

While standard commercially available pigtail ureteral stents are used commonly in the obstructed patient, particularly when metastatic disease has been identified, our recent experience suggests caution in the use of such stents for patients with ileal conduits. Rapid obstruction of these stents occurs with unacceptable frequency, which has resulted in urosepsis and death, and they do not appear to be cost-effective even for palliation. Although these standard pigtail stents have physical properties that allow easy placement by angiographic wire guidance, they are not to be recommended. Safe internal ureteral diversion in patients with an ileal conduit awaits further evolution in stent technology.

Aged↗

Isolation and characterization of a novel human bladder cancer cell line: BK10.

Molecular studies of bladder carcinomas have aided in determining causative genetic events and the prognosis of cancers endowed with certain abnormalities. In vitro bladder cancer characterization of key cytogenetic alterations is useful for study of molecular changes that may promote oncogenic events. In our laboratory, a novel human bladder cancer cell line, BK10, has been established in vitro and passaged for more than 20 mo. This new bladder cancer cell line (BK10) was derived from bladder tissue containing grade III-IV/IV transitional cell carcinoma. Bladder cancer tissue was obtained at the time of radical cystoprostatectomy extirpation. Cell cultures derived from this surgical sample exhibited an epithelial morphology and expressed epithelial cytokeratins. Immunostains of BK10 were negative for prostate specific antigen (PSA), fibronectin, smooth muscle actin alpha, and desmin. Karyotypic analysis revealed an aneuploid chromosomal content <4n> with many numerical and structural abnormalities previously linked to bladder oncogenesis. Translocations occurred in chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, 15, 16, 17, 19, 20, 21, 22, X and Y. G-banding analysis revealed rearrangements involving chromosomes 9q and 17p, and the location of the ab11 oncogene and the p53 gene, respectively. The availability of this bladder cancer cell line will provide a useful tool for the further study of bladder carcinoma oncogenesis and gene therapy.

Aged↗

Endoscopic brush cytology of the upper urinary tract. Evaluation of its efficacy and potential limitations in diagnosis.

OBJECTIVE: To evaluate the efficacy of endoscopic brush cytology in diagnosing transitional cell carcinoma of the upper urinary tract. STUDY DESIGN: Sixty-three endoscopic brush cytology specimens from 48 patients were compared with corresponding cytologic specimens obtained by irrigation and catheterization as well as histologic specimens. RESULTS: Twenty patients (25 brushes) had histologically documented transitional cell carcinoma (TCC) or carcinoma in situ (CIS) of either the ureter or renal pelvis. Among these, 8 (32%) of the brush samples were reported as positive for TCC, 10 (40%) atypical or suspicious, and 7 (28%) negative. The seven negative cases were ultimately shown to be low grade (I-II/IV) TCC. Combining atypical and positive diagnoses, the calculated sensitivity for diagnosis of TCC by this technique was 72%. The irrigations or catheterized urines from these same patients yielded lower sensitivity, 48%, and detected only higher grade lesions. Ten patients were proven histologically to have nonneoplastic disease (hydroureter, obstruction, inflammation). Sixteen of the 17 brush specimens from these patients were negative, resulting in a specificity of 94%. In the remaining 18 patients (21 brushes) there were 17 negatives and 4 atypicals. Concomitant cytology supported the brush diagnosis in all but one sample. CONCLUSION: Brush cytology is a specific and more sensitive sampling method than irrigation or catheterized urine in detecting TCC of the upper urinary tract. Brush cytology does not appear to be successful in diagnosing dysplasia or CIS. As with urinary cytology in general, the technique is less effective in diagnosing low grade (I and II) lesions.

Carcinoma in Situ↗

Heat shock protein 70 (HSP70) does not prevent the inhibition of cell growth in DU-145 cells treated with TGF-beta1.

BACKGROUND: Mitogen-activated protein kinase (MAPK) is one of the transforming growth factor-beta (TGF-beta signaling pathways while heat shock protein 70 (HSP70) prevents apoptosis by affecting MAPK signaling downstream. However, the interrelationship between TGF-beta and HSP70 signaling is still unknown. MATERIALS AND METHODS: DU-145 prostate cancer cells were treated with 40 pM and 200 pM TGF-beta1. After 3, 6, 9, 12 and 24 hours, cell proliferation assay and cell cycle analysis were performed. The activities of HSP70 and MAPKs (c-Jun N-terminal kinase 1 (JNK1), extracellular signal-regulated kinase 1 (ERK1), ERK2 and p38) were analyzed by Western blot at each time-point. RESULTS: TGF-beta1 inhibited the cell growth in a dose-dependent manner at 3 hours. Late G1 accumulation in the cell cycle was observed in a dose-dependent manner after 24 hours. HSP70 and JNK1 increased only at 3 hours and decreased for up to 24 hours thereafter. ERK1, ERK2 and p38 decreased from 3 to 24 hours after TGF-beta1 treatment. CONCLUSION: These data suggest that HSP70 does not prevent the inhibition of cell growth in DU-145 cells treated with TGF-beta1.

Blotting, Western↗

Serum androgens: associations with prostate cancer risk and hair patterning.

Cancer of the prostate is the leading cancer among American men, yet few risk factors have been established. Hair growth and development are influenced by androgens, and it has long been suspected that prostate cancer also is responsive to these hormones. A blinded, case-control study was undertaken to determine if hair patterning is associated with risk of prostate cancer, as well as specific hormonal profiles. The study accrued 315 male subjects who were stratified with regard to age, race, and case-control status (159 prostate cancer cases/156 controls). Hair-patterning classification and serum levels of total and free testosterone (T), sex hormone binding globulin, and dihydrotestosterone (DHT) were performed. Data indicate that hair patterning did not differ between prostate cancer cases and controls; however, significant hormonal differences were detected between the two groups. Free T was greater among cases than in controls (16.4 +/- 6.1 vs. 14.9 +/- 4.8 pg/ml, P = 0.02). Conversely, DHT-related ratios were greater among controls (P = 0.03 for DHT/T and P = 0.01 for DHT/free T). Several strong associations also were found between hormone levels and hair patterning. Men with vertex and frontal baldness had higher levels of free T (16.5 +/- 5.5 and 16.2 +/- 8.0 pg/ml, respectively) when compared to men with either little or no hair loss (14.8 +/- 4.7 pg/ml) (P = 0.01). Data suggest that increased levels of free T may be a risk factor for prostatic carcinoma. In addition, although no differences in hair patterning were detected between cases and controls within this older population, further research (i.e., prospective trials or case-control studies among younger men) may be necessary to determine if hair patterning serves as a viable biomarker for this disease, especially given the strong association between free T levels and baldness.

Aged↗