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Biomedical subjects

D L McCullough

Publications and source records attributed to D L McCullough.

At least 55 records · Page 3Linked to original sources

Effect of acoustic shock waves on clonogenic growth and drug sensitivity of human tumor cells in vitro.

Focused acoustic shock waves were studied for their effects on human tumor cell viability, clonogenicity, and sensitivity to chemotherapeutic agents. The elastic shock waves used in this investigation were generated with the Dornier HM3-Lithotripter by underwater spark discharge with fixed electrical parameters employing a voltage of 18 kV and a capacitance of 80 nanoFarads. These waves are characterized by a fast varying compression phase, strong asymmetrical pressure and tension phases, and a maximum amplitude of roughly 10(8) Pascal (kg.m-1 s-2). Doses as high as 2000 focused shocks showed little effect on the viability of two different cell lines. There was, however, a dose dependent inhibition of tumor cell proliferation as determined by the growth of clones in soft agarose. Each of the two cell lines showed a unique degree of colony inhibition by shock waves. It was demonstrated that shock wave effects resulted from elastic shock wave interaction with the cells and were not caused by the emission of ultraviolet light coincident with shock wave generation. Shocks were applied at a rate of 100 minute-1 in a 200 l. water bath, thereby removing the possibility for temperature changes during treatments. After treatment with shock waves it was found that tumor cells became more sensitive to growth inhibition by chemotherapeutic agents. Cisplatin, doxorubicin, and 4-hydroperoxycyclophosphamide were each more effective in blocking cell growth after the target cells had been treated with acoustic shocks. Enhanced efficacies ranged from three to 10-fold potentiation of colony inhibition. These results indicate that weak shock waves, which can be focused to a defined target region, may have utility as a cancer treatment modality either alone or in combination with cytotoxic agents.

Acoustic Stimulation↗

A multicenter, double-blind, trimethoprim-sulfamethoxazole controlled study of enoxacin in the treatment of patients with complicated urinary tract infections.

In a double-blind, randomized, controlled trial, 249 patients with complicated urinary tract infections received either 400 mg. enoxacin or 160 mg. trimethoprim plus 800 mg. sulfamethoxazole orally every 12 hours for 14 days. The clinical outcome at the end of treatment revealed that all 89 evaluable patients (100 per cent) in the enoxacin group and 88 of 90 (98 per cent) in the trimethoprim-sulfamethoxazole group had satisfactory clinical responses (cure or improvement). Bacteriological effectiveness was measured cumulatively based on responses during and at the end of treatment, and 7 days later at followup. Satisfactory bacteriological responses (eradication or superinfection at all evaluations throughout the study) were achieved in significantly more (p equals 0.03) patients treated with enoxacin (93 per cent) than in those treated with trimethoprim-sulfamethoxazole (83 per cent). Both study medications were well tolerated. These results indicate that oral enoxacin was more effective clinically and bacteriologically (the latter statistically so) than trimethoprim-sulfamethoxazole when given as empiric therapy in the treatment of complicated urinary tract infections.

Adult↗

Effects of shock waves on the rat ovary.

The studies reported in this paper were undertaken to investigate the effect of shock waves on ovarian function. In an initial study, five female Wistar rats underwent general anesthesia. One ovary was then exposed to 1500 shock waves at 20 kV using the Dornier XL-1 experimental lithotripter. One week following this treatment, the animals were sacrificed and both ovaries were step sectioned. We counted all follicles that contained both an oocyte and antrum. These follicles in turn were classified further as being healthy or atretic. No statistical difference in these counts was observed between shocked and unshocked ovaries taken from the same animal. In the definitive study, thirty-one adult female Wistar rats underwent unilateral oophorectomy. These rats were then divided into treated, sham-treated and control groups. The eleven treated animals were given general anesthesia and received 1500 shocks at 15 kV directed at their remaining ovary using the Dornier XL-1 lithotripter. The ten sham treated animals received identical anesthesia and duration of waterbath immersion as the treated group. In contrast, however, sham treated animals were positioned outside the path of the focused shock wave. The control group received no treatment. Normal estrus cycle was maintained in all groups following shock wave exposure. Two weeks after this exposure, all three groups of animals were allowed to mate. All animals in each of the three groups became pregnant. There was no statistical difference in litter size or fetal weights at three weeks gestation. No gross teratogenic effects were observed. The rat ovary appears to be structurally and functionally resistant to the shock wave energy levels used in this experiment.

Animals↗

Effects of shock waves on the structure and growth of the immature rat epiphysis.

The left proximal tibia of eighteen five week old male Sprague-Dawley rats was exposed to 1500 shock waves at 20 kV in a Dornier XL-1 experimental lithotripter. Six of these rats, and six age-matched controls, were sacrificed two, four and ten weeks later. Eight of 18 (44%) of treated animals had lesions of focal growth plate dysplasia attributable to treatment. In the absence of extensive lesions, no significant difference was identified in the growth plate thickness of shocked versus unshocked limbs. In the group sacrificed at ten weeks, two of six (33%) treated animals had extensive dysplastic lesions which were associated with marked shortening of the shocked limb. In the absence of extensive lesions, there was no significant shortening of shocked limbs. Shock wave exposure of the rat epiphysis can affect subsequent bone growth.

Animals↗

Neoadjuvant treatment of stages T2 to T4 bladder cancer with cis-platinum, cyclophosphamide and doxorubicin.

In an ongoing phase II study 17 patients with potentially operable transitional cell carcinoma of the bladder (stages T2 to T4, Nx, Mo) have been treated with intravenous cis-platinum (50 mg.per m.2), cyclophosphamide (400 mg.per m.2) and doxorubicin (40 mg.per m.2). They were to receive 3 treatments at 3-week intervals before cystectomy and 2 treatments at 3-week intervals commencing 5 weeks after cystectomy. Of 17 patients 14 (82 per cent) completed all 3 preoperative treatments but only 7 (41 per cent) continued on to complete the entire 5 treatments. In most cases incomplete therapy was due to patient refusal. Toxicity was low as measured by World Health Organization standards. Of the 17 patients 9 (53 per cent) exhibited objective tumor response (pathological downstaging or greater than 50 per cent reduction of tumor volume determined by either computerized tomography scan and/or endoscopic examination. When the determination was made by endoscopy the changes were dramatic and not borderline.) No patient demonstrated a pathological complete response. All 9 of the responders (100 per cent) remain clinically free of disease at a median follow-up of 19 months (range 4 to 30 months). The 8 nonresponders have done poorly with 5 dead of disease, 1 alive with pelvic recurrence and 2 free of disease at 4 and 12 months. These tumor response rates compare favorably with other cis-platinum-based combination regimens. The response to the chemotherapy appears to be an important prognostic indicator. Phase III trials must be conducted to determine whether this neoadjuvant chemotherapy regimen has a significant effect on long-term patient survival.

Aged↗

Testicular germ cell tumors in HLA-genotype non-twin brothers.

The diagnosis of metastatic testicular carcinoma in a thirty-three-year-old man and his nineteen-year-old brother is reported. Histologically, the tumor of the older brother consisted predominantly of embryonal carcinoma with minor components of seminoma and adult teratoma; the tumor of the younger brother consisted entirely of embryonal carcinoma. Since previous reports suggest the possibility that the HLA genotype may be a factor in the etiology of testicular cancer, we typed the parents and four children of this family. The two affected brothers shared a paternal HLA-A3, Cw-,B7,DR2 haplotype that had not been transmitted to the two other living siblings. Analysis of the distribution of HLA haplotypes of the affected non-twin brothers of this family and those of three other non-twin pairs of brothers that have been reported showed that the affected pairs in each family shared one HLA haplotype. The differences between the expected and the observed distribution of HLA haplotypes in the four sibling pairs is not statistically significant, perhaps because of the small number of patients typed. Two of the four pairs shared a common haplotype. Additional family studies are required to establish a genetic origin of testicular tumors and to determine whether or not a "testicular carcinoma disease" gene is linked to the HLA complex. A large number of multicase families will be required for linkage analysis.

Adult↗

End stage renal disease associated with acquired cystic disease and neoplasia.

Acquired renal cystic disease is a recently recognized disease entity that primarily afflicts patients on chronic hemodialysis. The incidence of acquired renal cystic disease in patients with end stage renal disease ranges from 30 to 95 per cent. The major complications of acquired renal cystic disease appear to be neoplasia and hemorrhage. Neoplasia has been demonstrated in up to 45 per cent of all end stage kidneys with acquired cystic disease. Our surgical experience with 7 cases of end stage renal disease is reported. Acquired renal cystic disease was noted in 4 of the 7 cases (57 per cent) and renal neoplasia was evident in all 7. Worldwide experience to date in combined pathology and radiology series of patients undergoing hemodialysis demonstrates that acquired cystic disease, "tumor" (usually adenoma or oncocytoma) and renal carcinoma occur at respective rates of 47.1, 4.8 and 1.5 per cent. Since the pathologist will detect more tumors and cysts than the radiologist, these figures probably are an underestimate of the true incidence. Long-term surveillance of patients harboring end stage kidneys is recommended beginning with a baseline ultrasound.

Adenoma↗

Radiologic contribution to the management of patients undergoing extracorporeal shock wave lithotripsy.

Since its first clinical application in 1980, the use of extracorporeal shock wave lithotripsy (ESWL) has dramatically changed the treatment of urinary tract stone disease. More than 80% of patients with urolithiasis will undergo ESWL as a first line therapy. Detection of stones, appropriateness of ESWL treatment, successful stone therapy, termination of the ESWL procedure, and evaluation of treatment complications are all dependent on radiologic input. The application of adjuvant interventional radiologic percutaneous techniques will extend the use of ESWL to an additional 15% of patients and reduce the need for surgical intervention. Additionally, percutaneous techniques can be used to improve success rates in problematic cases and to treat complications related to the ESWL procedure. This article discusses the pre- and postprocedural radiologic evaluation of patients undergoing ESWL. Adjuvant interventional radiologic techniques useful in the management of these patients are also discussed.

Humans↗

Primary renal lymphoma. Does it exist?

Although secondary renal involvement from systemic lymphoma is common, primary lymphoma of the kidney is not well recognized. One case is reported and 27 cases purported to be primary tumors are reviewed. From these cases three conclusions have been drawn: it is reasonable to assume that renal lymphoma can be a primary lesion; almost all patients with primary renal lymphoma will develop extrarenal lymphomatous disease shortly after diagnosis of their renal tumor; and survival for more than 1 year after diagnosis is rare.

Angiography↗

Radiation exposure to patients during extracorporeal shock wave lithotripsy.

Extracorporeal shock wave lithotripsy is rapidly becoming an accepted treatment of renal calculi. Since fluoroscopy is involved to image the stones it is important to know how much radiation the patient receives during this proCedure. Surface radiation exposure to the patient was measured in more than 300 fluoroscopic and radiographic procedures using thermoluminescent dosimeters. Initial results showed an average skin exposure of 10.1 rad per procedure for each x-ray unit, comparing favorably with exposure rates for percutaneous nephrostolithotomy and other routine radiological procedures. Factors influencing exposure levels include stone characteristics (location, size and opacity), physician experience and number of shocks required. Suggestions are given that may result in a 50 per cent reduction of radiation exposure.

Humans↗

Extracorporeal shock wave lithotripsy in childhood.

Extracorporeal shock wave lithotripsy is the treatment of choice for the majority of upper urinary calculi in adults. Technical limitations, including patient size and concerns over post-treatment stone fragment passage, have made the application of extracorporeal shock wave lithotripsy in children less clearly defined. We report the successful application of the Dornier lithotriptor in the management of 18 children (22 kidneys) with upper urinary calculi.

Adolescent↗

Magnetic resonance imaging of the renal mass.

To compare the effectiveness of magnetic resonance imaging with that of excretory urography, retrograde pyelography, ultrasound, computerized tomography, angiography and venography 34 patients with renal masses, including 25 renal cell carcinomas, were examined on a 0.15 Tesla Picker 1100 magnetic resonance imager with multiple pulse sequences. Pathological proof was available for all cases except renal cysts, for which ultrasound or computerized tomographic findings were accepted. Differentiation of solid from cystic lesions was seen with magnetic resonance imaging, ultrasound and computerized tomography but not excretory urography. Tumor invasion of the renal vein and inferior vena cava was visualized in 7 patients by magnetic resonance imaging, ultrasound, computerized tomography and venography but not by excretory urography. Magnetic resonance T1 contrast scans best characterized renal masses, with good resolution of metastatic lymphadenopathy and renal cysts. Scans showing T2 contrast were best for identification of pseudocapsules in renal carcinoma, venous invasion by tumors and papillary adenocarcinoma. Advantages of magnetic resonance imaging include differentiation of solid masses from benign cystic lesions, and identification of major blood vessels and vascular invasion without administration of contrast medium. Disadvantages of magnetic resonance imaging are long imaging times and motion artifacts. Advances by the manufacturer in solving these problems will strengthen the role of magnetic resonance imaging in renal evaluation.

Angiography↗

Postoperative anatrophic nephrolithotomy bleeding.

We reviewed 530 patients treated with anatrophic nephrolithotomy during a 14.5-year period. Significant postoperative renal bleeding occurred in 34 cases (6.4 per cent). The average postoperative blood transfusion requirement in this group was 5,279 cc. Bleeding patients were significantly older and they had worse renal function compared to the nonbleeding group. If bleeding did not begin immediately it usually started 5 to 8 days postoperatively. Bleeding dyscrasias were identified in 6 patients and correction allowed nonoperative management in 4. Epsilon aminocaproic acid was helpful only in the treatment of patients with slow, lower volume bleeding. Eight patients required 9 open renal explorations to control bleeding. Two arteriovenous fistulas and 1 false aneurysm were identified. An attempt at angiographic embolization of an arteriovenous fistula was unsuccessful. Only 1 patient required a nephrectomy (1 of 34 or 2.9 per cent) and there was no mortality. A treatment plan for this complication is described.

Adult↗

Pediatric anatrophic nephrolithotomy.

A 15-year experience with pediatric anatrophic nephrolithotomy was reviewed. There were 11 procedures performed in 10 patients. Average patient age was 9.43 plus or minus 1.54 years (standard error of the mean). Preoperative urine cultures were positive in 6 of 11 cases. Metabolic or structural defects were identified in all patients. Postoperative morbidity was minimal. Adequate followup was available in 9 patients, for an average length of 4.6 plus or minus 0.96 years. Stones recurred in 7 of 9 patients (78 per cent) but in 2 the new calculi were small and asymptomatic. Anatrophic nephrolithotomy can be performed safely in children but a high incidence of structural and metabolic abnormalities predisposes these patients to recurrent stones.

Adolescent↗

Use of the flexible fiberoptic nephroscope in the preoperative evaluation and delayed repair of traumatic urethral strictures.

A flexible, fiberoptic nephroscope was used in the preoperative evaluation and subsequent repair of obliterative, post-traumatic urethral strictures in 2 men. Antegrade passage of the flexible nephroscope through a previously established suprapubic cystostomy tract afforded direct visualization of the bladder neck and uninvolved urethra proximal to the strictures. Thereby, precise definition of involvement of the membranous urethra and striated external sphincter was established. This facilitated selection between transperineal and transpubic operative approaches as well as intraoperative localization of the proximal margins of the strictures.

Adult↗