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Biomedical subjects

J Lockhart

Publications and source records attributed to J Lockhart.

At least 19 recordsLinked to original sources
PubMed2004

A multi-institutional study of orthotopic neobladders: functional results in men and women.

OBJECTIVES: To analyse the incidence of diurnal incontinence (DI) and nocturnal incontinence (NI), the need for intermittent catheterization (IC),and the rate of ureteric obstruction (UO) among a group of men and women with ileal and colonic orthotopic neobladders in four countries. PATIENTS AND METHODS: In all, 138 patients (113 men and 25 women) had an orthotopic neobladder constructed after radical cystectomy for carcinoma. The mean(range) age was 61.3 (28-76) years and the follow-up 41 (6-144) months. All patients underwent surgery by experienced surgeons associated with the Confederation of American Urology. A retrospective evaluation was designed to review the functional results and the incidence of UO. The technique of orthotopic neobladder construction was at each surgeon's discretion. Various detubularized bowel segments were used, including ileum, colon or sigmoid. Patients were followed by chart reviews and personal interviews at 1, 3 and 6 months after surgery and then every 6 months, and were evaluated by a physical examination, urine analysis, cytology and renal ultrasonography. RESULTS: An ileal or colonic neobladder was constructed in 74 and 64 patients, respectively. Five (7%), 23 (31%), 10 (14%) and 14(9.6%) with an ileal neobladder developed DI, NI, IC and UO, respectively; the respective values for patients with a colonic neobladder were eight (12%), 19 (30%), seven (11%)and 15 (12%). Statistical analysis by Fisher's exact test showed no significant differences between the ileal and colonic neobladder groups or with gender. CONCLUSIONS: Using this specific protocol for evaluating many men and women with ileal and colonic orthotopic neobladders showed no significant differences in the incidence of DI, NI, IC or UO. Neobladders constructed from detubularized bowel, irrespective of bowel segment(s) used, can provide satisfactory diurnal results. A moderate incidence of NI and UO continue to be a problem.

Adult↗
PubMed2001

pH alterations "reset" Ca2+ sensitivity of brain Na+ channel 2, a degenerin/epithelial Na+ ion channel, in planar lipid bilayers.

Members of the degenerin/epithelial Na(+) channel superfamily of ion channels subserve many functions, ranging from whole body sodium handling to mechanoelectrical transduction. We studied brain Na(+) channel 2 (BNaC-2) in planar lipid bilayers to examine its single channel properties and regulation by Ca(2+). Upon incorporation of vesicles made from membranes of oocytes expressing either wild-type (WT) BNaC-2 or BNaC-2 with a gain-of-function (GF) point mutation (G433F), functional channels with different properties were obtained. WT BNaC-2 resided in a closed state with short openings, whereas GF BNaC-2 was constitutively activated; a decrease in the pH in the trans compartment of the bilayer activated WT BNaC-2 and decreased its permeability for Na(+) over K(+). Moreover, these maneuvers made the WT channel more resistant to amiloride. In contrast, GF BNaC-2 did not respond to a decrease in pH, and its amiloride sensitivity and selectivity for Na(+) over K(+) were unaffected by this pH change. Buffering the bathing solutions with EGTA to reduce the free [Ca(2+)] to <10 nm increased WT single channel open probability 10-fold, but not that of GF BNaC-2. Ca(2+) blocked both WT and GF BNaC-2 in a dose- and voltage-dependent fashion; single channel conductances were unchanged. A drop in pH reduced the ability of Ca(2+) to inhibit these channels. These results show that BNaC-2 is an amiloride-sensitive sodium channel and suggest that pH activation of these channels could be, in part, a consequence of H(+) "interference" with channel regulation by Ca(2+).

Acid Sensing Ion Channels↗
PubMed2001

Regions in the carboxy terminus of alpha-bENaC involved in gating and functional effects of actin.

Gating differences occur between the alpha-subunits of the bovine and rat clones of an amiloride-sensitive epithelial Na+ channel (ENaC). Deletion of the carboxy terminus of bovine alpha-ENaC (alpha-bENaC) at R567 converted the gating properties to that of rat alpha-ENaC (alpha-rENaC). The equivalent truncation in alpha-rENaC was without effect on the gating of the rat homologue. The addition of actin to ENaC channels composed of either alpha-rENaC or alpha-bENaC alone produced a twofold reduction in conductance and an increase in open probability. Neither alpha-rENaC (R613X) nor alpha-bENaC (R567X) was responsive to actin. Using a chimera consisting of alpha-rENaC1-615 and alpha-bENaC570-650, we examined several different carboxy-terminal truncation mutants plus and minus actin. When incorporated into planar bilayers, the gating pattern of this construct was identical to wild-type (wt) alpha-bENaC. Premature stop mutations proximal to E685X produced channels with gating patterns like alpha-rENaC. Actin had no effect on the E631X truncation, whereas more distal truncations all interacted with actin, as did wt alpha-bENaC. Key findings were confirmed using channels expressed in Xenopus oocytes and studied by cell-attached patch-clamp recording. Our results suggest that the site of actin regulation at the carboxy terminus of the chimera is located between residues 631 and 644.

Actins↗
PubMed2000

Postradiation therapy adenosquamous cell carcinoma of the prostate.

The objective of this study was to present two cases of adenosquamous cell carcinoma of the prostate following radiation therapy. Two patients with history of prostate cancer treated with radiation therapy presented with rectal bleeding and a large ulcerated rectal mass. The rectal biopsy revealed on both cases squamous cell carcinoma. The initial diagnosis was invasive squamous cell carcinoma from anal origin. Both patients underwent pelvic exenteration with continent urinary diversion. After extensive histological sampling and immuno-histochemisty, they were correctly diagnosed of adenosquamous cell carcinoma of the prostate with invasion of the rectum. The patients died 6 and 16 months after surgery with widespread metastases. A review of the literature is presented. Adenosquamous cell carcinoma of the prostate is an unusual histological variant of prostate cancer. To our knowledge, only three cases of adenosquamous cell carcinoma of the prostate following radiation therapy have been reported. The unusual clinical and histopathological features of the two cases reported here led to an initial mistaken diagnosis. Adenosquamous cell carcinoma of the prostate should be considered in the differential diagnosis when a patient with prostate cancer develops a rectal mass or rectal bleeding following radiation therapy and the rectal biopsy reveals squamous cell carcinoma. Prostate Cancer and Prostatic Diseases (2000) 3, 53-56

Journal Article↗
PubMed2000

Accurate repair of the prolapsed vagina by use of measured lateral flaps.

OBJECTIVE: We report our experience with a technique for planning the final vaginal caliber and location of the vaginal apex in patients with severe vaginal prolapse. STUDY DESIGN: During the 2-year period ending April 1998, the technique was used in all 27 patients who were undergoing vaginal repair of prolapse performed by Mitchel S. Hoffman, MD, and who desired to retain the vagina but required at least partial excision. The major steps included determination of sites for lateral apical support, definition of the desired introital caliber, marking of the measured lateral vaginal flaps, excision of the intervening epithelium (and uterus if present, n = 14), high peritoneal closure, closure of the anterior vaginal wall, placement of apical supporting sutures, and completion of closure with tying of supporting sutures. Small flaps were designed for the 8 patients who did not anticipate further sexual intercourse. RESULTS: The only intraoperative complication was hemorrhage >1000 mL in 3 patients. Immediate anatomic results were considered excellent for 26 patients. The only early postoperative complication was hemorrhage in a patient being treated with an anticoagulant; she responded to conservative management. Follow-up was available for 24 patients (21-42 months of follow-up; mean, 29 months). All patients had complete relief of prolapse symptoms. Anatomic results remained excellent for 21 of the 24 patients; in the remaining 3 patients asymptomatic grade 2 cystoceles developed at 6 to 12 months. Three patients had new urinary symptoms that persisted. Nine patients resumed sexual intercourse, with no difficulties noted. CONCLUSION: Defining the vaginal apex and designing lateral vaginal flaps facilitate the precise creation of an anatomically and functionally appropriate vagina, with reasonable morbidity, good symptomatic relief, and mild alteration of surrounding organ function.

Aged↗
PubMed1999

Injury of the rectum during vaginal surgery.

OBJECTIVE: We sought to report our experience with injury of the rectum during vaginal surgery. STUDY DESIGN: A retrospective chart review of a vaginal surgery database was performed. RESULTS: Nine injuries were identified. Four patients with posthysterectomy vault prolapse incurred a rectal laceration just above the perineum during an attempt to develop the rectovaginal space. Another rectal laceration occurred just above the perineum during an attempt to develop the rectovaginal space during vaginectomy-hysterectomy for gender dysphoria. Three other injuries occurred between the vaginal cuff and peritoneum while posterior culdotomy for vaginal hysterectomy was attempted. The remaining injury was in a Schuchardt incision. All 9 injuries were recognized, repaired, and healed without complication. CONCLUSIONS: Laceration of the rectum is an uncommon complication of vaginal surgery. Prompt recognition and repair result in uncomplicated primary healing.

Female↗
PubMed1999

A feasibility study of gene gun mediated immunotherapy for renal cell carcinoma.

PURPOSE: Gene modified autologous tumor cell vaccines have demonstrated a protective and therapeutic effect in murine tumor model systems. The majority of trials to date have used viral methods of gene transfer for vaccine construction. An alternative approach to transfer genes into tumor cells is to use the gene gun, which is a physical method of gene transfection that produces high levels of gene expression without viral agents. We establish the feasibility of generating cytokine secreting autologous renal tumor cell vaccines for use in gene therapy for metastatic renal cell carcinoma. MATERIALS AND METHODS: We obtained 1 cm3 tumor tissue from 12 patients undergoing resection of primary or metastatic renal cell carcinoma. The tumor was disaggregated and placed in culture. The phenotype of the primary renal cell lines was established by microscopy and immunohistochemistry. The 1x10(7) lethally irradiated tumor cells were transfected with plasmid deoxyribonucleic acid containing the human (h) granulocyte-macrophage colony-stimulating factor (GM-CSF) gene under control of a cytomegalovirus promoter using the gene gun. The hGM-CSF production was assayed by enzyme-linked immunosorbent assay in the cell culture media 24 hours after transfection. RESULTS: Of 12 tumor samples 8 grew rapidly to produce a mean of 1.8x10(8) cells after 4 to 5 passages in culture, which was sufficient to produce between 24 and 32 vaccines. Immunocytochemistry confirmed that all cultures were almost exclusively renal tumor cells. Gene gun mediated transfection of lethally irradiated tumor cells resulted in high levels of hGM-CSF production (mean 330 ng./10(6) cells per 24 hours). CONCLUSIONS: We have demonstrated the feasibility of producing cytokine secreting tumor cell vaccines from primary and metastatic human renal tumors, and plan to use this approach in phase I clinical trials of gene therapy for metastatic renal cell carcinoma.

Biolistics↗
PubMed1997

The failed anti-incontinence mechanism: a flap valve or cecal wrap for surgical reconstruction.

PURPOSE: On a long-term basis patients with continent urinary diversions may have an acceptable number of complications, such as urinary incontinence. We report on a new surgical technique for treatment of the incompetent anti-incontinence segment. MATERIALS AND METHODS: Seven patients presented with a large capacity, low pressure reservoir and an incompetent anti-incontinence mechanism. The original anti-incontinence mechanism consisted of an intussuscepted reimplanted appendix (Mitrofanoff) in 2 patients, tapered ileum and reinforced ileocecal valve in 3, and tapered and reimplanted ileal segment in 2. Surgical reconstruction involved 2 stages: stage 1 - lengthening and tubularizing the cecum with the anti-incontinence segment and stage 2 - creation of the flap valve mechanism. Stage 2 required intraoperative modification when abundant peri-reservoir fibrosis, a thin-walled reservoir (cecal wrap) or an excessive thickened mesentery was encountered. RESULTS: After a mean followup of 7 months 6 of 7 patients performed catheterization every 4 hours and were continent. Several patients required a concomitant procedure with the incontinence revision. CONCLUSIONS: We describe a 2-stage technique for correction of a variety of untoward anatomical conditions related to a failed anti-incontinence segment with continent urinary reservoirs. Concomitant repair of other coexisting structural abnormalities related to the continent reservoir may also be necessary.

Adult↗
PubMed1997

The Hickman peel-away sheath: alternative for pediatric percutaneous nephrolithotomy.

Percutaneous nephrolithotomy presents a therapeutic challenge in children because of the disproportion between the sizes of the instruments and the kidneys. A technique for pediatric nephrolithotomy used on a 2-year-old female child is presented. The patient was born prematurely and developed kidney stones as a complication of furosemide therapy. She failed medical management with hydrochlorothiazide, and the stone did not disintegrate following extracorporeal shockwave lithotripsy (ESWL). A Chiba needle was used to access the renal collecting system percutaneously. Using a guidewire, sequential dilatation was performed to 16F. A 15F Hickman catheter introduction kit was then used, and the sheath was partially peeled away. A 10F pediatric cystoscope and grasper were inserted through the sheath to remove the stones. A 12F catheter was then placed through the sheath; the sheath was peeled away, and the catheter was left indwelling for 48 hours. No complications ensued. A postoperative nephrostogram showed free drainage and absence of residual stones. Utilization of the Hickman peel-away sheath constitutes an excellent alternative nephrolithotomy technique for children with stones unresponsive to more conservative treatment.

Catheters, Indwelling↗
PubMed1997

Laparoscopic nephrectomy using the harmonic scalpel.

Laparoscopic nephrectomy is gaining popularity. Improved instrumentation is making surgery easier with fewer complications. Our first three laparoscopic nephrectomies using the Harmonic Scalpel were performed on two women and one man. The surgical indications were nonfunctioning kidneys (two left, one right) with hypertension in one patient and stone disease in two. The three patients had a mean age of 46.3 years. The average hospital stay was 4 days, the average operative time 3.7 hours, and the average blood loss 160 mL. No complications occurred. Patients resumed oral intake within 8 hours postoperatively. We found the Harmonic Scalpel easy and safe to use. It saved time, was cost effective, and was capable of easily controlling small-vessel bleeding. In conclusion, the Harmonic Scalpel could be used effectively for both dissection and bleeding control without suction or other instrumentation.

Equipment Design↗
PubMed1997

Evaluation and management of parastomal hernia in association with continent urinary diversion.

PURPOSE: We discuss the incidence and diagnosis of parastomal hernias in association with continent urinary reservoirs. We also present a surgical technique appropriate for correction of this complication. MATERIALS AND METHODS: We evaluated 21 patients with parastomal hernia after construction of a continent urinary reservoir. The hernia developed secondary to diversion with an ileocecal segment in 19 patients and a Kock procedure in 2. Subsequent to development of the parastomal hernia 13 patients (61.9%) had simultaneous urinary incontinence, 2 (9.5%) had difficulty catheterizing the reservoir and 4 (19.047%) had associated pain over the stomal area. Evaluation was primarily by physical examination. However, 2 patients (9.5%) required abdominal computerized tomography to confirm the diagnosis of parastomal hernia. Surgical repair was recommended for all patients, and 19 underwent repair with or without revision of the anti-incontinence segment. Reconstruction included transabdominal takedown of the anti-incontinence segment from the abdominal wall with parastomal hernia closure through a midline incision, external reinforcement of the hernia opening with Marlex mesh when the diameter exceeded 6 cm., revision of the anti-incontinence mechanism when simultaneous urinary incontinence existed preoperatively and repositioning of the stoma site through a new selected area in the abdominal wall. RESULTS: The success rate (mean followup 23.4 months) with this surgical approach was 89.5%. Incontinence due to failure of the anti-incontinence mechanism was successfully corrected in 13 patients (100%). CONCLUSIONS: Long-term followup of continent urinary reservoirs is often associated with development of parastomal hernia. This complication can be associated with urinary incontinence, peristomal pain and difficult catheterization. Evaluation is primarily by physical examination but selected clinical situations require abdominal computerized tomography to confirm the diagnosis. The surgical technique following the steps described has been associated with minimal morbidity and has provided excellent surgical results (89.5% success rate).

Adult↗
PubMed1996

Ancillary techniques in the followup of transitional cell carcinoma: a comparison of cytology, histology and deoxyribonucleic acid image analysis cytometry in 91 patients.

PURPOSE: Voided urine and bladder washing cytology are used frequently in the evaluation of transitional cell carcinoma of the bladder. As part of an ongoing investigation we report on the role of deoxyribonucleic acid (DNA) image analysis cytometry as an adjunct to cytology in the followup of patients with transitional cell carcinoma. MATERIALS AND METHODS: Urine cytology and image analysis cytometry were performed independently on aliquots of voided urine, catheterized urine or bladder washings from 91 patients with previous or active transitional cell carcinoma of the bladder, and the results were compared to those of concurrent biopsy and clinical followup. RESULTS: Of 75 recurrent transitional cell carcinomas 42 were detected by cytology, while 63 and 64 were identified by image analysis cytometry and biopsy, respectively, for a sensitivity of 57, 84 and 85%, respectively. Combined cytology and image analysis cytometry detected 67 recurrences, for an overall sensitivity of 89%. Of 11 cases undetected by concurrent biopsy 9 had abnormal DNA histograms with transitional cell carcinoma at followup and 2 were DNA diploid but with grade 1 transitional cell carcinoma at followup. Of 12 cases undetected by image analysis cytometry 8 were grade 1 and 4 were grade 2 transitional cell carcinoma. CONCLUSIONS: Urine cytology and image analysis cytometry detect most recurrent tumors. Their combined use is indicated in the followup of patients with bladder transitional cell carcinoma.

Adult↗
PubMed1996

Bladder Replacement and Urinary Diversion After Radical Cystectomy.

BACKGROUND: The optimal mode of urinary tract reconstruction following cystectomy continues to challenge the urologic surgeon. Disadvantages with bowel conduits have prompted the search for better techniques to improve patient outcomes. METHODS: The development of urinary tract reconstruction is reviewed, and results from several forms of continent urinary diversion and bladder replacement construction are presented. The authors report on their experience in creating continent reservoirs or neobladders in over 400 patients. RESULTS: Several surgical approaches are now available for continent urinary diversion. Metabolic and nutritional abnormalities, stone formation, infection, and cancer formation are potential complications. CONCLUSIONS: Advances in surgical techniques, an understanding of the physiology of isolated bowel segments, and improvements in pre- and post-operative care have altered the field of urinary reconstruction after cystectomy for bladder cancer. Most patients can expect minimal morbidity and mortality.

Journal Article↗
PubMed1993

Direct (nontunneled) ureterocolonic reimplantation in association with continent reservoirs.

A total of 190 patients underwent continent urinary diversion using the Florida pouch. Direct mucosa-to-mucosa ureterocolonic reimplantation was used in 165 patients (326 ureters). Of the first 30 ureters in patients who underwent antireflux tunneled reimplantation obstruction occurred in 4 (13.3%). Obstruction developed directly in 16 of the ureters reimplanted (4.9%), and 3 of the 6 plicated and reimplanted megaureters (50%). Among the obstructed units 3 (13%) were treated unexpectedly by autonephrectomy, while the other 20 units (87%) were treated with percutaneous balloon dilation and internal stenting for 6 to 8 weeks. In the latter group 12 units (60%) recovered function, 3 (15%) had pyelonephritis requiring nephrectomy and 5 (25%) stabilized following a new reimplantation. Reflux was demonstrated in 23 units (7%). All units with reflux are being followed conservatively and renal deterioration has not been demonstrated. The incidence of ureteral obstruction with direct reimplantation is lower compared to a tunneled technique. This reimplantation procedure is technically simpler than others and is safe in adults when performed in association with a large volume, continent colonic reservoir.

Colon↗
PubMed1993

Role of DNA image cytometry in the follow-up of patients with urinary tract transitional cell carcinoma.

Detection of recurrent urinary tract transitional cell carcinoma (TCC) is a frequent diagnostic challenge in exfoliative cytology because of the difficulty in distinguishing reactive changes from low grade tumors. This study evaluated the role of DNA analysis by image cytometry (ICM) as a diagnostic aid to cytology. Eighty-seven urine samples from patients with a known history of transitional cell carcinoma were examined by both cytology and ICM, and the results were compared with concurrent surgical biopsy specimens and patients' follow-up data. Twenty-seven patients were also examined by cystoscopy, and the results were compared to those of DNA analysis, cytology and biopsy. Urine samples were cytocentrifuged and stained with Papanicolaou stain for general cytology and Feulgen stain for ICM. DNA ploidy and the proliferating cell fraction (SG2M) were measured using the CAS 200 image analyzer. Among the 87 specimens included in the study, 59 were from patients considered to have recurrent disease when urine was obtained. Of the 59 recurrences, 33 were detected by cytology, 50 by ICM and 50 by biopsy, resulting in 55%, 85% and 85% sensitivity, respectively. When combined, cytology and ICM detected 53 recurrences and achieved 90% sensitivity. Nine cases originally undetected by biopsy had abnormal DNA histograms and were found to have TCC on follow-up examination. All cases undetected by ICM were low grade lesions with DNA diploidy and low proliferation. Among the 27 patients examined by cystoscopy, 14 had recurrent disease; 5, 13 and 6 of those cases were detected by cystoscopy, DNA analysis and cytology, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Transitional Cell↗
PubMed1992

Conversion from external appliance wearing or internal urinary diversion to a continent urinary reservoir (Florida pouch I and II): surgical technique, indications and complications.

A total of 20 patients with diversion requiring an external appliance or internal urinary diversion underwent conversion to a continent urinary reservoir (Florida pouch I or II). All patients subsequently reported an improvement in the quality of life and expressed satisfaction with the new urinary diversion procedure. Of the patients 15 (75%) previously had an ileal conduit, while 1 (5%) had undergone ureterosigmoidostomy, 1 (5%) had cutaneous ureterostomy, 1 (5%) had a suprapubic tube, 1 (5%) had a sigmoid conduit and 1 (5%) had a cecal conduit. After the original diversion 3 patients (15%) had recurrent urinary infections, 3 had complications related to the stoma and external appliance (stenosis and skin dermatitis) and 5 (25%) had ureteral obstruction in 7 ureters. A total of 17 patients with conduits (85%) underwent conversion via different surgical technical aspects depending on the status of the intestinal segment from the conduit and the function of the ureteral reimplantation: in 14 the conduit was discarded or was used only to patch the newly created Florida I colonic pouch, while in 6 the conduit was preserved and 9 ureterointestinal reimplantations were left undisturbed (Florida pouch II). Among 7 ureters preoperatively obstructed (original diversion), reimplanting them into the pouch failed to prevent further renal damage in 5 (71%). Three renal units required nephrectomy, 2 kidneys deteriorated and 2 recovered renal function after percutaneous balloon dilation and stenting. Among 31 preoperatively nonobstructed renoureteral units (original diversion), 22 were reimplanted into the colonic reservoir. One of these units (4.2%) became obstructed postoperatively and 3 (13.5%) presently have reflux. The 10 reimplantations left undisturbed in the detubularized conduit drain satisfactorily without postoperative obstruction and in 6 reflux has not been demonstrated. Renal function (serum creatinine) is preserved in all patients but 15 (75%) have hyperchloremia of mild degree. Two patients (10%) have acidosis and 1 (5%) of these had low red blood cell folic acid. Conversion of an external or internal diversion to a continent colonic urinary reservoir (Florida pouch I or II) can be successful and improve the quality of life of the patient. The functioning renal units that were preoperatively obstructed were associated with a high failure rate (71%) after reimplantation. Metabolic alterations will require long-term followup, and are particularly worrisome in children and young adults.

Adolescent↗
PubMed1990

Doppler color flow in echocardiography: analytical and in-vitro investigations of the quantitative relationship between orifice flow and color jet dimensions.

The goal of this investigation was to explore the relationship between orifice flow rate and the dimensions of the resulting color jet. Equations were derived which describe flow rate as a function of the color jet dimensions, instrument characteristics, and a coefficient which represents the unknown velocity profile across the jet. Experiments in which fluid was injected at a variety of flow rates via an assortment of orifice sizes into a compliant, axisymmetric chamber were performed for comparison with the analytical results. During each injection, orifice flow rate and color jet dimensions were recorded. The experimental results were closely predicted (r = 0.97) by an equation which expresses flow rate as a function of the ratio of the color jet area and color jet length, and with a coefficient which approximates that of a parabolic velocity profile.

Blood Flow Velocity↗