Biomedical subjects

J L Flowers

Publications and source records attributed to J L Flowers.

At least 19 recordsLinked to original sources

PubMed2003

Warm ischemia time does not correlate with recipient graft function in laparoscopic donor nephrectomy.

BACKGROUND: Laparoscopic donor nephrectomy (LDN) has been shown to be a safe and effective option for renal procurement. Studies comparing open nephrectomy and hand-assisted laparoscopy have emphasized decreased warm ischemia time when compared with "pure" laparoscopic retrieval. However, no data exist that define exactly what constitutes a prolonged warm ischemia time in terms of recipient graft function. The aim of this study was to use a large, single-institution experience with LDN to determine if warm ischemia time correlates with recipient graft function as measured by serum creatinine levels. METHODS: A total of 640 LDNs were performed from March 1996 to August 2001. Warm ischemia times were prospectively collected and were defined as the time from renal artery occlusion to immersion in iced saline. Serial recipient creatinine levels were measured at 1 week and 1, 3, 6, and 12 months (when possible) from the transplant. Data were analyzed using Pearson correlation analysis at a confidence interval of 95%. RESULTS: Mean warm ischemia time was 151 s with a standard error of 3.4 s and ranged from 35 to 720 s. Recipient creatinine mean at 1 week was 1.94 mg/dl with a standard error of 0.06 mg/dl and ranged from 0.5 to 10.5 mg/dl. Recipient creatinine mean at 1 month was 1.68 mg/dl with a standard error of 0.06 mg/dl and ranged from 0.6 to 8.5 mg/dl. Recipient creatinine mean at 3 months was 1.60 mg/dl with a standard error of 0.04 mg/dl and ranged from 0.6 to 8.8 mg/dl. Recipient creatinine mean at 6 months was 1.63 mg/dl with a standard error of 0.06 mg/dl and ranged from 0.7 to 13.5 mg/dl. Recipient creatinine mean at 12 months was 1.70 mg/dl with a standard error of 0.07 mg/dl and ranged from 0.5 to 14.5 mg/dl. No correlation was found between warm ischemia time and recipient creatinine levels at 1 week (p = 0.4737), 1 month (p = 0.9180), 3 months (p = 0.6227), 6 months (p = 0.8349), or 12 months (p = 0.2835). CONCLUSIONS: Warm ischemia time does not correlate with recipient graft function in LDN within the range of times studied. Shorter warm ischemia time associated with open donor nephrectomy and hand-assisted LDN does not necessarily offer a measurable advantage in recipient graft function. During extraction of the kidney, expediency to minimize warm ischemia time should not supersede controlled and safe maneuvers in renal vessel division and extraction of the kidney.

Creatinine↗

PubMed2002

Small bowel obstruction after laparoscopic donor nephrectomy.

BACKGROUND: Laparoscopic live donor nephrectomy has become the procedure of choice for kidney procurement at many centers worldwide. A decrease in postoperative pain and length of stay, a faster return to work, and no difference in morbidity and mortality compared to open nephrectomy have all been reported. However, few data exist regarding the complication of postoperative internal hernia and small bowel obstruction, which is unique to a laparoscopic/transperitoneal approach. METHODS: We present three case reports of patients who developed small bowel obstruction from an internal hernia and mesenteric defect after laparoscopic donor nephrectomy. RESULTS: A total of 635 patients underwent laparoscopic donor nephrectomy between March 1996 and August 2001 at our institution. Small bowel obstruction developed in three patients (0.47%) within 1 week postoperatively. Each case involved an internal hernia through a left colon mesenteric defect at the site of nephrectomy. Reoperation was necessary in each case and was associated with a prolonged hospital stay (mean, 22.3 days; range, 6-37). Two patients were managed with laparotomy; one patient underwent a laparoscopically assisted exploration. One patient required an additional open exploration for intraabdominal sepsis and cholecystectomy. CONCLUSIONS: Small bowel obstruction from internal hernia following laparoscopic donor nephrectomy is a rare event, but it can lead to significant morbidity in an otherwise healthy patient. These patients may be at higher risk for bowel obstruction given the soft tissue defect remaining after nephrectomy. Vigilance is required when mobilizing the colon to ensure that mesenteric defects are recognized and repaired.

Adult↗

PubMed2001

Impact of upper endoscopic survey during percutaneous endoscopic gastrostomy tube placement.

BACKGROUND: No consensus exists concerning the utility of a full diagnostic upper endoscopy during percutaneous endoscopic gastrostomy (PEG) tube placement. We evaluate the effect of a complete survey on identifying and treating unsuspected gastrointestinal pathology. METHODS: During a 10-year period (1990-2000), 1,706 patients underwent attempted PEG tube placement by five different surgical endoscopists at one institution. A complete survey of the esophagus, stomach, and proximal duodenum was attempted in all cases. Endoscopic findings and recommendations were recorded in a computerized log and patient charts. Pathology results were obtained from a computerized pathology database and patient charts. RESULTS: Placement of a PEG tube was successful in 97%, and a full survey was possible in 99% of the cases. Pathologic findings were found in 38% of the surveyed patients (esophagus, 7%; stomach, 24%; duodenum, 7%). One group with gastrointestinal polyps or gastric ulcers (5.7%) was identified as possible candidates for endoscopic intervention. In 30% of this group (1.8% of the total) a biopsy was performed, or bleeding was treated endoscopically. In a second group pathology was identified in the duodenum (6.4%) that would not have been recognized without a full survey. These duodenal findings resulted in a recommendation for treatment change in 38% of this group (2.4% of the total). CONCLUSIONS: Upper endoscopic survey before PEG tube placement showed a significant amount of unsuspected gastrointestinal pathology. Findings requiring biopsy, immediate treatment, or a change in medical treatment occurred in 4.2% of the cases, and these findings did not prevent PEG tube placement in any patient.

Adolescent↗

PubMed2001

Laparoscopic right donor nephrectomy: technique and comparison with left nephrectomy.

BACKGROUND: Laparoscopic donor nephrectomy (LDN) preferentially involves the left kidney to optimize vessel length, but occasionally, right nephrectomy is preferred. Right LDN differs markedly in anatomic relations and the need for a fourth port. This retrospective study compares donor outcomes and graft function of right and left LDN and describes the technique. METHODS: Consecutive patients undergoing right LDN from March 26, 1996 to December 31, 2000 were compared with those undergoing left LDN. Age, height, weight, body mass index, creatinine, creatinine clearance, operative time, warm ischemia time, analgesic requirements, serial postoperative creatinine, time to diet resumption, and hospital stay were compared. A second cohort matched for age, gender, race, and temporal left LDN also were compared with the group undergoing right LDN. RESULTS: No significant differences were found for any of the parameters measured. CONCLUSION: This study demonstrates that despite substantial differences in the procedures, donor outcome and graft survival are similar for right and left LDN.

Adult↗

PubMed2001

Nitric oxide enhancement of fludarabine cytotoxicity for B-CLL lymphocytes.

Fludarabine is active but not curative in the treatment of chronic lymphocytic leukemia (B-CLL). Nitric oxide (NO) supplied from exogenous, NO-donating pro-drugs can also induce apoptosis and death of acute leukemia cells. This study investigated combinations of fludarabine with NO-donating pro-drugs for their cytotoxicity against freshly isolated B-CLL lymphocytes following a 72 h exposure in vitro. The median IC(50)for fludarabine was 2.2 microM (n = 85). The nitric oxide donors DETA-NO, PAPA-NO, and MAHMA-NO were also cytotoxic, and their effects were inversely related to rates of NO release. Neither DETA-NO depleted of NO nor DETA itself was effective, indicating that NO was required for cytotoxicity. Drug interactions were evaluated by a modified combination index method. Synergy was observed in combinations of fludarabine or nelarabine (506U78) with DETA-NO in 52% and 88% of samples, respectively. Interestingly, the combination of fludarabine and DETA-NO was more cytotoxic in B-CLL cells less sensitive to fludarabine. DETA-NO did not enhance the activity of other DNA anti-metabolites, topoisomerase I and II inhibitors, or alkylating agents. Finally, the anti-leukemic activity of fludarabine alone or in combination with DETA-NO was found to correlate with inhibition of cellular RNA synthesis. These results indicate that NO donors could enhance fludarabine therapy for B-CLL.

Adult↗

PubMed2001

Are concerns over right laparoscopic donor nephrectomy unwarranted?

OBJECTIVE: To examine the ability of several large, experienced transplantation centers to perform right-sided laparoscopic donor nephrectomy safely with equivalent long-term renal allograft function. SUMMARY BACKGROUND DATA: Early reports noted a higher incidence of renal vein thrombosis and eventual graft loss. However, exclusion of right-sided donors would deprive a significant proportion of donors a laparoscopically harvested graft. METHODS: A retrospective review was performed among 97 patients from seven centers performing right-sided laparoscopic donor nephrectomy. Surgical and postoperative demographic factors were evaluated. Complications were identified and long-term renal allograft function was compared with historical left-sided laparoscopic donor nephrectomy cohorts. RESULTS: Right laparoscopic donor nephrectomy was performed for varying reasons, including multiple left renal arteries or veins, smaller right kidney, or cystic right renal mass. Mean surgical time was 235.0 +/- 66.7 minutes, with a mean blood loss of 139 +/- 165.8 mL. Conversion was required in three patients secondary to bleeding or anatomical anomalies. Mean warm ischemic time was limited at 238 +/- 112 seconds. Return to diet was achieved on average after 7.5 +/- 2.3 hours, with mean discharge at 54.6 +/- 22.8 hours. Two grafts were lost during the early experience of these centers to renal vein thrombosis. Both surgical and postoperative complications were limited, with few long-term adverse effects. Mean serum creatinine levels were higher than open and left laparoscopic donor nephrectomy on postoperative day 1, but at all remaining intervals the right laparoscopic donors had equivalent creatinine values. CONCLUSIONS: These results confirm that right laparoscopic donor nephrectomy provides similar patient benefits, including early return to diet and discharge. Long-term creatinine values were no higher than in traditional open donor or left laparoscopic donor cohorts. These results establish that early concerns about high thrombosis rates are not supported by a multiinstitutional review of laparoscopic right donor nephrectomies.

Adolescent↗

PubMed2001

Dual role of glutathione in modulating camptothecin activity: depletion potentiates activity, but conjugation enhances the stability of the topoisomerase I-DNA cleavage complex.

Depletion of glutathione (GSH) in MCF-7 and MDA-MB-231 cell lines by pretreatment with the GSH synthesis inhibitor buthionine sulfoximine potentiated the activity of 10,11-methylenedioxy-20(S)-camptothecin, SN-38 [7-ethyl-10-hydroxy-20(S)-camptothecin], topotecan, and 7-chloromethyl-10,11-methylenedioxy-20(S)-camptothecin (CMMDC). The greatest potentiation was observed with the alkylating camptothecin CMMDC. Buthionine sulfoximine pretreatment also increased the number of camptothecin-induced DNA-protein crosslinks, indicating that GSH affects the mechanism of action of camptothecin. We also report that GSH interacts with CMMDC to form a stable conjugate, 7-(glutathionylmethyl)-10,11-methylenedioxy-20(S)-camptothecin (GSMMDC), which is formed spontaneously in buffered solutions and in MCF-7 cells treated with CMMDC. GSMMDC was synthesized and found to be nearly as active as 10,11-methylenedioxy-20(S)-camptothecin in a topoisomerase (topo) I-mediated DNA nicking assay. The resulting topo I cleavage complexes were remarkably stable. In cell culture, GSMMDC displayed potent growth-inhibitory activity against U937 and P388 leukemia cell lines. GSMMDC was not active against a topo I-deficient P388 cell line, indicating that topo I is its cellular target. Peptide-truncated analogues of GSMMDC were prepared and evaluated. All three derivatives [7-(gamma-glutamylcysteinylmethyl)-10,11-methylenedioxy-20(S)-camptothecin, 7-(cysteinylglycylmethyl)-10,11-methylenedioxy-20(S)-camptothecin, and 7-(cysteinylmethyl)-10,11-methylenedioxy-20(S)-camptothecin] displayed topo I and cell growth-inhibitory activity. These results suggest that 7-peptidyl derivatives represent a new class of camptothecin analogues.

Antineoplastic Agents, Phytogenic↗

PubMed2000

Laparoscopic nephrectomy in the markedly obese living renal donor.

OBJECTIVES: To determine whether laparoscopic living donor nephrectomy is safe and efficacious in markedly obese renal donors. METHODS: From 1996 to 1999, 431 laparoscopic living donor nephrectomies were performed. The markedly obese group consisted of 41 patients with a body mass index (BMI) greater than 35. Forty-one controls with a BMI less than 30 were matched to the obese donors by sex, age, race, and date of surgery. RESULTS: The markedly obese and control groups were closely matched in sex, race, age, serum creatinine level, creatinine clearance, HLA match to recipient, side of donated kidney, and experience level of the surgeons. The obese patients had a BMI range of 35.2 to 53.9 (mean 39.3), and the control patients had a BMI range of 18.4 to 29.0 (mean 24.3). Donor operations in the markedly obese were significantly longer by an average of 40 minutes. The greater intraoperative blood loss and longer extraction incision length seen in the markedly obese did not reach statistical significance. More and larger laparoscopic ports were used in the markedly obese. Obese donors were more likely to require conversion from laparoscopic nephrectomy to open nephrectomy than ideal-sized donors. The postoperative recovery of the gastrointestinal tract, hospitalization time, analgesic requirements, and total complications were equal in the two groups, although the obese donors' complications tended to be cardiopulmonary problems. The recipient graft function was equivalent between the two groups. CONCLUSIONS: Laparoscopic living donor nephrectomy is more difficult to perform in the markedly obese but is associated with an equivalent donor morbidity and recipient renal outcome.

Blood Loss, Surgical↗

PubMed2000

Camptothecin analogues with enhanced antitumor activity at acidic pH.

BACKGROUND: Camptothecin (CPT) is a specific inhibitor of the nuclear enzyme topoisomerase I, which is involved in cellular DNA replication and transcription. Topoisomerase I is therefore an attractive target for anticancer drug development, and two analogues of CPT, topotecan (TPT) and irinotecan (CPT-11), have demonstrated significant antitumor activity in the clinic. This activity is limited, however, by lability of the CPT E ring lactone, which forms the inactive hydroxy acid at physiological pH. The reaction is reversible at acidic pH, which provides a rationale for selectivity, because many solid tumors create an acidic extracellular environment while maintaining a normal intracellular pH. PURPOSE: To exploit the tumor-selective pH gradient to improve the efficacy of CPT-based chemotherapy. METHODS: CPT analogues were evaluated by growth inhibition assay in three human breast cancer cell lines that had been adapted to in vitro culture at acidic pH versus the respective cells cultured at physiological pH. The MCF-7, MDA-MB-231, and MCF-7/hc cell lines represent the hormone-dependent and hormone-independent stages of the disease, and a MCF-7 variant that is resistant to the alkylating agent 4-hydroperoxycyclophosphamide (4-HC), respectively. Antiproliferative activity of SN-38 (the active metabolite of CPT-11), and TPT was compared to that of CPT and two CPT analogues, 10,11-methylenedioxy-CPT (MDC), and the alkylating derivative, 7-chloromethyl-10,11-MDC (CMMDC). RESULTS: In general, MDC was the most potent and TPT or CPT the least potent analogue, regardless of pH. However, if the comparison was based on magnitude of potentiation by pH, a different rank order emerged. CPT was modulated 4-fold; MDC, SN-38, and TPT were each modulated 5- to 6-fold, while the activity of CMMDC was increased 10- to 11-fold by acidic pH in MCF-7 lines, and 65-fold in MDA-MB-231 cells. Thus MDC was the superior CPT analogue based on potency, but CMMDC was the best candidate for pH modulation. Drug specificity was also observed. While the alkylating agent, 4-HC, was 2- to 3-fold more active at acidic pH, modulation was not observed for 5-fluorouracil, doxorubicin, or paclitaxel. Preliminary mechanism studies indicated that pH modulation of CPT analogues was directly correlated to intracellular levels of glutathione. In addition, protein-associated DNA strand breaks were more rapidly induced at acidic pH. CONCLUSION: These results suggest that CPT-based drug development and resulting chemotherapy could benefit from evaluation of differential activity at acidic versus physiological pH. Analogues have been identified that could have improved therapeutic indices based on the pH gradient that selectively exists in human tumors.

Antineoplastic Agents, Phytogenic↗

PubMed2000

Evidence for a role of chloroethylaziridine in the cytotoxicity of cyclophosphamide.

UNLABELLED: A number of investigators have observed that the use of 4-hydroperoxycyclophosphamide (4-HC) in multiwell plate cytotoxicity assays can be associated with toxicity to cells in wells that contain no drug. Previous reports have implicated diffusion of 4-HC decomposition products, and acrolein in particular, as the active species. PURPOSE: The purpose of this study was to elucidate the species responsible for the airborne cytotoxicity of 4-HC, and to devise ways to minimize such effects in chemosensitivity assays. METHODS: To this end, analogues of 4-HC were synthesized to identify the contributions of individual cyclophosphamide metabolites to cytotoxicity. The analogues were then tested for activity against three human breast tumor cell lines (including a line resistant to 4-HC), and one non-small-cell lung carcinoma line. Cytotoxicity was evaluated by assays that quantitate cellular metabolism and nucleic acid content. RESULTS: Didechloro-4-hydroperoxycyclophosphamide, a compound that generates acrolein and a nontoxic analogue of phosphoramide mustard, gave no cross-well toxicity. In contrast, a significant neighboring well effect was observed with phenylketophosphamide, a compound that generates phosphoramide mustard but not acrolein. Addition of authentic chloroethylaziridine reproduced the airborne toxicity patterns generated by 4-HC and phenylketophosphamide. Increasing the buffering capacity of the growth medium and sealing the microtiter plates prevented airborne cytotoxicity. CONCLUSION: Since it is unlikely that phosphoramide mustard is volatile, these findings implicate chloroethylaziridine rather than acrolein as the volatile metabolite of 4-HC that is responsible for airborne cytotoxicity. The fact that chloroethylaziridine is generated in amounts sufficient to volatilize, diffuse across wells and cause cytotoxicity indicates that it is an important component in the overall cytotoxicity of 4-HC in vitro. Furthermore, these findings suggest that chloroethylaziridine may also contribute to the toxicity of cyclophosphamide in vivo.

Acrolein↗

PubMed2000

Simultaneous cadaver pancreas living-donor kidney transplantation: a new approach for the type 1 diabetic uremic patient.

OBJECTIVE: To review the authors' experience with a new approach for type I diabetic uremic patients: simultaneous cadaver-donor pancreas and living-donor kidney transplant (SPLK). SUMMARY BACKGROUND DATA: Simultaneous cadaver kidney and pancreas transplantation (SPK) and living-donor kidney transplantation alone followed by a solitary cadaver-donor pancreas transplant (PAK) have been the transplant options for type I diabetic uremic patients. SPK pancreas graft survival has historically exceeded that of solitary pancreas transplantation. Recent improvement in solitary pancreas transplant survival rates has narrowed the advantage seen with SPK. PAK, however, requires sequential transplant operations. In contrast to PAK and SPK, SPLK is a single operation that offers the potential benefits of living kidney donation: shorter waiting time, expansion of the organ donor pool, and improved short-term and long-term renal graft function. METHODS: Between May 1998 and September 1999, the authors performed 30 SPLK procedures, coordinating the cadaver pancreas transplant with simultaneous transplantation of a laparoscopically removed living-donor kidney. Of the 30 SPLKs, 28 (93%) were portally and enterically drained. During the same period, the authors also performed 19 primary SPK and 17 primary PAK transplants. RESULTS: One-year pancreas, kidney, and patient survival rates were 88%, 95%, and 95% for SPLK recipients. One-year pancreas graft survival rates in SPK and PAK recipients were 84% and 71%. Of 30 SPLK transplants, 29 (97%) had immediate renal graft function, whereas 79% of SPK kidneys had immediate function. Reoperative rates, early readmission to the hospital, and initial length of stay were similar between SPLK and SPK recipients. SPLK recipients had a shorter wait time for transplantation. CONCLUSIONS: Early pancreas, kidney, and patient survival rates after SPLK are similar to those for SPK. Waiting time was significantly shortened. SPLK recipients had lower rates of delayed renal graft function than SPK recipients. Combining cadaver pancreas transplantation with living-donor kidney transplantation does not harm renal graft outcome. Given the advantages of living-donor kidney transplant, SPLK should be considered for all uremic type I diabetic patients with living donors.

Adult↗

PubMed2000

Laparoscopic live donor nephrectomy: the University of Maryland 3-year experience.

PURPOSE: We determined whether laparoscopic living donor nephrectomy decreases the morbidity of renal donation for the donor, while providing a renal allograft of a quality comparable to that of open donor nephrectomy. MATERIALS AND METHODS: In a 3-year period laparoscopic donor nephrectomy was performed via the transperitoneal approach. We evaluated donor and recipient medical records for preoperative donor characteristics, intraoperative parameters and complications, and postoperative recovery and complications. RESULTS: Of the 320 laparoscopic donor nephrectomies performed the left kidney was removed in 97.5%. Intraoperative complications, which developed in 10.4% of cases, tended to occur early in the experience and required conversion to open nephrectomy in 5. Average operative time was 31/2 hours and warm ischemia time was 21/2 minutes. As the series progressed, blood loss as well as laparoscopic port size and number decreased but extraction site size remained constant at 7 cm. Urinary retention, prolonged ileus, thigh numbness and incisional hernia were the most common postoperative complications. Postoperative analgesic requirements were low and average hospitalization was 66 hours. CONCLUSIONS: Laparoscopic donor nephrectomy appears to be safe and decreases morbidity in the renal donor. Allograft function is comparable to that in open nephrectomy series. The availability of laparoscopic harvesting may be increasing the living donor volunteer pool.

Adult↗

PubMed1999

Laparoscopic versus open donor nephrectomy: comparing ureteral complications in the recipients and improving the laparoscopic technique.

BACKGROUND: Laparoscopic live donor nephrectomy (LDN) is a recently developed procedure, the performance of which needs to be studied. Given the reported advantages in the donors, this study looks at graft outcome and ureteral complications in recipients of kidneys procured by open donor nephrectomy (ODN) versus LDN. METHODS: The LDN recipients consisted of 193 patients since 3/27/96. A total of 168 ODN recipients from 1991 to 1998 served as controls. Immunosuppression protocols were similar for both groups. RESULTS: Two-year graft survival for LDN and ODN was 98% and 96%, respectively. Two-year patient survival for LDN and ODN was 98% and 97%, respectively. The incidence of delayed graft function and mean serum creatinine at 3 and 12 months was similar in both groups. However, the number of ureteral complications that required operative repair was significantly higher for LDN recipients compared to ODN recipients, 7.7% (n=15) vs. 0.6% (n=1) respectively (P=0.03). Ureteral stenting was required in an additional 3.1% (n=6) of LDN and 2.4% (n=4) of ODN (P=NS). There was, however, a learning curve with time. For the first 130 LDN patients, a total of 20 ureteral complications were recorded, whereas only one occurred in the more recent 63 patients (P=0.03). CONCLUSIONS: The higher ureteral complication rate in LDN recipients has improved over time as technical causes have been identified. We have noted significant improvement in ureteral viability by using the endogastrointestinal anastomosis instrument on the ureter and peri-ureteral tissue. LDN is therefore an excellent alternative to ODN. Identification of hazards unique to this technique is critical before its broader application.

Adult↗

PubMed1999

Pre-clinical evaluation of SN-38 and novel camptothecin analogs against human chronic B-cell lymphocytic leukemia lymphocytes.

The topoisomerase I inhibitor camptothecin and its analogs have potent activity against a wide range of solid tumors and several hematologic malignancies. Previous studies with these compounds using the MTT metabolic inhibition assay have shown significant cytotoxicity against lymphocytes from patients with chronic B-cell lymphocytic leukemia (B-CLL). Yet the water soluble analogue, topotecan, which was inhibitory at > 1 microM in vitro, had no clinical activity in vivo. In the present study, we evaluated the in vitro cytotoxicities of SN-38, the active form of irinotecan, and two newer water soluble camptothecin derivatives 10,11-methylenedioxy-20(S)-camptothecin glycinate (MDCG) and 7-chloromethyl-10,11-methylenedioxy-20(S)-camptothecin glycinate (CMMDCG). These two glycinate esters are prodrugs for 10,11-methylenedioxy-20(S)-camptothecin (MDC) and 7-chloromethyl-10,11-methylenedioxy-20(S)-camptothecin (CMMDC), respectively. Effects on cellular metabolism, induction of apoptosis, and overall cell survival were used to evaluate chemosensitivity. We report that the relative cytotoxic potency for these compounds is MDC > or = CMMDC > or = SN-38 >> TPT > CPT-11, where MDC, CMMDC, and SN-38 were over an order of magnitude more cytotoxic than TPT and CPT-11. We also investigated potential mechanisms underlying the unexpected cytotoxicity of these camptothecin derivatives in B-CLL cells that are known to be arrested in G0/G1 of the cell cycle, and found that this class of compounds inhibited [3H]uridine incorporation. We therefore postulate that the inhibition of RNA rather than DNA synthesis may be responsible for the observed cytotoxicity in non-cycling B-CLL cells.

Antineoplastic Agents, Phytogenic↗

PubMed1999

Transesophageal echocardiographic detection of gas embolism and cardiac valvular dysfunction during laparoscopic nephrectomy.

UNLABELLED: We used transesophageal echocardiography (TEE) to monitor venous gas embolism, cardiac performance, and the hemodynamic effects of positioning and pneumoperitoneum in 16 healthy kidney donors undergoing laparoscopic nephrectomy. A four-chamber view was used continuously, except at predetermined intervals, when a complete TEE examination for cardiac function was performed. Other clinical variables recorded include systolic, diastolic, and mean arterial blood pressure; heart rate (HR), pulse oximetric saturations; and end-tidal CO2. Baseline valvular incompetence was seen in 13 of the 16 patients when supine and asleep. After positioning for surgery and induction of pneumoperitoneum, TEE revealed valvular incompetence with regurgitation more pronounced from baseline in 15 of the 16 patients. In one patient, during renal vein dissection, gas entered the right atrium from the inferior vena cava, worsening tricuspid regurgitation. Hemodynamic variables and ejection fraction were tested by using repeated-measures analysis of variance for significance (P < 0.05). Pneumoperitoneum increased (P < 0.05) systolic blood pressure (from 102.8 +/- 3.89 to 120.8 +/- 3.88 mm Hg) and HR (from 68.9 +/- 3.19 to 75.6 +/- 2.62). Ejection fraction was unchanged. The high incidence of valvular incompetence indicates that further studies are needed to assess these effects during laparoscopic nephrectomy with cardiac disease. IMPLICATIONS: Laparoscopic surgery has gained popularity as a procedure for the removal of donated kidneys. Although the insufflation of gas necessary for this relatively simple approach poses a low risk of venous air embolism, it may increase the risk of changes in valvular competency.

Adult↗

PubMed1999

Living donor nephrectomy.

The need for more organs for kidney transplantation is increasing. Cadaver sources for these organs are stable, therefore living donation must increase if the need is to be met. Less perfect kidneys are now being transplanted. The pool of potential donors is being expanded. The process of kidney donation is being made easier in an effort to increase the number of donors. The donor work-up is being streamlined. Laparoscopic donor nephrectomy has been introduced, and appears to be promising as a technique of lessening donor pain and suffering, while maintaining excellent graft results.

Animals↗

PubMed1998

Laparoscopic living donor nephrectomy and multiple renal arteries.

BACKGROUND: Laparoscopic donor nephrectomy (LDN) is a new technique. While the short-term recipient renal function is equivalent to that of the traditional open nephrectomy (ODN), long-term function and potential exclusion criteria, such as the presence of multiple renal arteries, are as yet unknown. METHODS: Retrospective review of 124 consecutive LDN performed from March 1996 to September 1997 with 117 ODN as historical controls. RESULTS: The 1-year actuarial graft and patient survival for LDN kidneys were 94% and 95%, respectively. These were not statistically different from that of the ODN controls. The presence of multiple renal arteries did not alter graft and patient survival or prevalence of immunologic events. The number of recipient ureteral complications in the LDN group was 11.2% compared with 3.4% in ODN (P < 0.01). Following correction for a learning curve with accompanying technical modifications, the prevalence of recipient ureteral complications has decreased to 7% in the last 94 patients (P = nonsignificant versus ODN). CONCLUSIONS: LDN represents a viable alternative to ODN for living renal transplants. Advantages for the donor are matched by equivalent functional results for the recipients.

Adult↗

PubMed1998

Effects of split torso positioning and laparoscopic surgery for donor nephrectomy on respiratory mechanics.

STUDY OBJECTIVE: To test whether split torso positioning, abdominal insufflation, and other procedures performed during laparoscopic nephrectomy would affect mechanical impedances to inflation [i.e., elastance (E) and resistance (R) of the total respiratory system (Ers, and Rrs), lungs (EL and RL), and chest wall (Ecw and Rcw)] differently from previously studied laparoscopic procedures. DESIGN: Unblinded study, each patient serving as own control. SETTING: University hospital. PATIENTS: 12 ASA physical status I and II patients scheduled for laparoscopic donor nephrectomy, all without cardiopulmonary disease. INTERVENTIONS: Patients were anesthetized and paralyzed, tracheally intubated and mechanically ventilated at 10, 20, and 30 breaths/minute and at tidal volumes of 250, 500, and 800 ml. Measurements were made in the following positions: supine, split torso, abdominal insufflation (Pab = 15 mmHg), and supine after deflation. MEASUREMENTS AND MAIN RESULTS: Airway flow and pressure and esophageal pressure were measured. Discrete Fourier transformation was used to calculate E and R. These were analyzed with repeated measures, linear multiple regression with accepted level of significance at p < 0.05. Ers, Ecw, and Rcw increased (p < 0.05) while EL decreased (p < 0.05) when patients changed from supine to split torso. During Pab = 15 mmHg, Ers, Ecw, and Rcw increased further and Rrs and RL increased (p < 0.05). Following abdominal deflation, Ecw and Ers remained elevated (p < 0.05). The changes in Ecw caused by laparoscopy and surgery were greater than we have previously measured in other laparoscopic procedures, while the changes in EL were less. CONCLUSIONS: Laparoscopic nephrectomy affects lung and chest wall mechanical properties differently from other laparoscopic procedures. This finding could be due to the split torso positioning, and the effects of abdominal swelling on the chest wall caused by administration of more perioperative fluids with laparoscopic nephrectomy.

Adult↗