Ultrasound Appearance of the Endometrium Post-Radiofrequency Ablation.

OBJECTIVE: To describe the ultrasonographic appearance of the post-ablative endometrium to improve knowledge of its sonographic findings. METHODS: This was an Institutional Review Board approved prospective study of patients who underwent second-generation endometrial ablation from 2016 to 2019 at a single health system. Patients had postoperative transvaginal ultrasounds at 2, 6, and 12 months. Ultrasound reports were analyzed for endometrial thickness, description of the endometrium and myometrium, presence of uterine fibroids, and uterine size. Statistical tests for repeated measures were utilized. RESULTS: There were 68 patients with the average age of 42 (SD 6) years and a BMI of 33 (SD 8). Preoperatively the average endometrial thickness was 10 mm, uterine length was 9.7 cm, and 38.2% had leiomyoma. The average endometrial thickness decreased at each ultrasound: 8.4 mm (SD 3.4), 7.2 mm (SD 3.0), and 5.8 mm (SD 2.5) at 2, 6, and 12 months, respectively. When comparing endometrial thickness postoperatively there was a significant difference at 2 and 12 months (P = .041), and 6 and 12 months (P = .031). There was no change during the postoperative period in the presence of leiomyoma, hyperechoic endometrium, hypoechoic endometrium, heterogeneous endometrium, and cystic endometrium on the ultrasounds. CONCLUSION: After ablation with a second-generation device, the endometrial thickness on ultrasound decreases with time following surgery. Additional studies correlating these findings to clinical outcomes would be useful.

Milnacipran Ameliorates Executive Function Impairments following Frontal Lobe Traumatic Brain Injury in Male Rats: A Multimodal Behavioral Assessment.

Traumatic brain injuries (TBIs) affect more than 10 million patients annually worldwide, causing long-term cognitive and psychosocial impairments. Frontal lobe TBIs commonly impair executive function, but laboratory models typically focus primarily on spatial learning and declarative memory. We implemented a multi-modal approach for clinically relevant cognitive-behavioral assessments of frontal lobe function in rats with TBI and assessed treatment benefits of the serotonin-norepinephrine reuptake inhibitor, milnacipran (MLN). Two attentional set-shifting tasks (AST) evaluated cognitive flexibility via the rats' ability to locate food-based rewards by learning, unlearning, and relearning sequential rule sets with shifting salient cues. Adult male rats reached stable pre-injury operant AST (oAST) performance in 3-4 weeks, then were isoflurane-anesthetized, subjected to a unilateral frontal lobe controlled cortical impact (2.4 mm depth, 4 m/sec velocity) or Sham injury, and randomized to treatment conditions. Milnacipran (30 mg/kg/day) or vehicle (VEH; 10% ethanol in saline) was administered intraperitoneally via implanted osmotic minipumps (continuous infusions post-surgery, 60 µL/h). Rats had a 10-day recovery post-TBI/Sham before performing light/location-based oAST for 10 days and, subsequently, odor/media-based digging AST (dAST) on the last test day (26-27 days post-injury) before sacrifice. Both AST tests revealed significant deficits in TBI+VEH rats, seen as elevated total trials and errors (p < 0.05), which generally normalized in MLN-treated rats (p < 0.05). This first simultaneous dual AST assessment demonstrates oAST and dAST are sufficiently sensitive and robust to detect subtle attentional and cognitive flexibility executive impairments after frontal lobe TBI in rats. Chronic MLN administration shows promise for attenuation of post-TBI executive function deficits, thus meriting further investigation.

Comparison of Contrast-Enhanced Ultrasound Versus Magnetic Resonance Imaging in the Detection and Characterization of Uterine Leiomyomas.

OBJECTIVES: Uterine fibroids are common findings in women with pelvic pain and abnormal uterine bleeding. The reference standard test in the pretreatment evaluation of fibroids is contrast-enhanced magnetic resonance (MR) imaging. This study compared the number, size, location, and enhancement of uterine fibroids identified by contrast-enhanced ultrasound (CEUS) and MR. The aim of this study was to demonstrate that CEUS performs similarly to MR and could be used as an alternative imaging modality. METHODS: In this prospective observational study, 26 women underwent transabdominal CEUS and MR examinations. Blinded to the original clinical MR interpretations, 2 readers reviewed the MR and CEUS studies for each patient. The number, size, location, and enhancement of each fibroid per patient were reported by MR and CEUS. A Pearson correlation coefficient was calculated for the number of fibroids identified by each modality. RESULTS: In total, 126 fibroids were imaged: 115 (91.3%) were observed on both examinations; 9 (7.1%) were observed by MR only; and 2 (1.6%) were observed by CEUS only. A high correlation was found between the modalities for the number of fibroids identified per patient (r = 0.97; P < .001). There was also no significant difference between the modalities for each patient in the fibroid number, size, location, or enhancement. CONCLUSIONS: These findings suggest that transabdominal CEUS may represent an alternative to MR in pretreatment evaluation of uterine fibroids and could serve as a test of choice in patients with a contraindication to MR.

Preoperative Gabapentin for Minimally Invasive Hysterectomy: A Randomized Controlled Trial.

STUDY OBJECTIVE: To evaluate whether a single dose of gabapentin given preoperatively reduces narcotic use 24 hours after minimally invasive hysterectomy (MIH). DESIGN: Randomized controlled trial. SETTING: Single academic-affiliated community hospital. PATIENTS: Women undergoing MIH for benign indications between June 2016 and June 2017. INTERVENTIONS: Subjects were randomized to receive a preoperative regimen of acetaminophen, celecoxib, and gabapentin versus acetaminophen and celecoxib alone. MEASUREMENTS AND MAIN RESULTS: The primary outcome assessed was the total amount of narcotics used at 24 hours after surgery. Secondary outcomes included adverse effects from gabapentin use, total narcotics used, and pain scores at 2 weeks after surgery. A total of 129 women were randomized and eligible for analysis in the gabapentin study arm (n = 68) or the control arm (n = 61). Demographic characteristics and surgical details were similar between groups. Narcotics used at 24 hours after surgery totaling 168 versus 161 oral morphine milligram equivalents in the gabapentin and control groups, respectively, did not significantly differ between groups (p = .60). Total narcotics used and pain scores at 2 weeks after surgery and the rates of adverse effects from gabapentin were also similar between study arms. CONCLUSION: Single-dose, preoperative gabapentin for women undergoing benign MIH does not reduce total opioid use 24 hours after surgery.

Incidence and predictors of failed second-generation endometrial ablation.

BACKGROUND: The need for any treatment following an endometrial ablation is frequently cited as "failed therapy," with the two most common secondary interventions being repeat ablation and hysterectomy. Since second-generation devices have become standard of care, no large cohort study has assessed treatment outcomes with regard to only these newer devices. We sought to determine the incidence and predictors of failed second-generation endometrial ablation, defined as the need for surgical re-intervention.We performed a retrospective cohort study at a single academic-affiliated community hospital. Subjects included women undergoing second-generation endometrial ablation for benign indications between October 2003 and March 2016. Second-generation devices utilized during the study period included the radiofrequency ablation device (RFA), hydrothermal ablation device (HTA), and the uterine balloon ablation system (UBA). RESULTS: Five thousand nine hundred thirty-six women underwent endometrial ablation at a single institution (3757 RFA (63.3%), 1848 HTA (31.1%), and 331 UBA (5.6%)). The primary outcome assessed was surgical re-intervention, defined as hysterectomy or repeat endometrial ablation. Of the total 927 (15.6%) women who required re-intervention, 822 (13.9%) underwent hysterectomy and 105 (1.8%) underwent repeat endometrial ablation. Women who underwent re-intervention were younger (41.6 versus 42.9 years, p < .001), were more often African-American (21.8% versus 16.2%, p < .001), and were more likely to have had a primary radiofrequency ablation procedure (hazard ratio 1.37; 95%CI 1.01 to 1.86). Older age was associated with decreased risk for treatment failure with women older than 45 years of age having the lowest risk for failure (p < .001). Age between 35 and 40 years conferred the highest risk of treatment failure (HR 1.59, 95% CI 1.32-1.92). Indications for re-intervention following ablation included menorrhagia (81.8%), abnormal uterine bleeding (27.8%), polyps/fibroids (18.7%), and pain (9.5%). CONCLUSION: Surgical re-intervention was required in 15.6% of women who underwent second-generation endometrial ablation. Age, ethnicity, and radiofrequency ablation were significant risk factors for failed endometrial ablation, and menorrhagia was the leading indication for re-intervention.

Does Time Affect Patient Satisfaction and Health-Related Quality of Life After Reduction Mammoplasty?

OBJECTIVE: A total of 62,611 patients with breast hypertrophy underwent breast reduction surgery in 2013 in the United States to improve their symptoms and health-related quality of life. While multiple studies utilizing various outcome instruments demonstrate the efficacy of reductive surgery, it is presently unknown how the postoperative course affects patient satisfaction and health-related quality of life as measured by the BREAST-Q. Our objective was to determine the temporal relationship of patient satisfaction and health-related quality of life after reduction mammoplasty. METHODS: Patients prospectively completed the BREAST-Q reduction mammoplasty module at 3 time points during their treatment: preoperatively, at less than 3 months postoperatively, and at more than 3 months (<12 months) postoperatively. A single surgeon (N.P.P.) performed all of the breast reduction procedures. RESULTS: Each time point contained 20 questionnaires. Mean preoperative BREAST-Q scores were significantly lower than scores at the less than 3-month postoperative time point for the scales Satisfaction With Breasts, Psychosocial Well-being, Sexual Well-being, and Physical Well-being (P < .001). There was no significant difference in BREAST-Q scores between the postoperative time points in these measures. CONCLUSION: Breast reduction surgery offers a vast improvement in patients' satisfaction and health-related quality of life that is maintained throughout the postoperative period. These findings can assist surgeons in managing patient expectations after reduction mammoplasty and help improve the probability of obtaining prior authorization for insurance coverage.

Traditional Versus Simulation Resident Surgical Laparoscopic Salpingectomy Training: A Randomized Controlled Trial.

STUDY OBJECTIVES: To evaluate the effectiveness of the porcine training model for obstetrics-gynecology (OB/GYN) residents in laparoscopic salpingectomy. DESIGN: Randomized, controlled single-blinded trial. CLASSIFICATION: Canadian Task Force Classification I. SETTING: A large community-based teaching hospital. PARTICIPANTS: All postgraduate year 1 through year 4 OB/GYN residents were enrolled (n = 22). INTERVENTION: All participants underwent a preintervention objective skills assessment test (OSAT), in which the participant performed live human laparoscopic salpingectomy. Residents were randomly assigned (using a computer-generated randomization table, in blocks of 2, stratified by ranked baseline OSAT scores) to the intervention or control group. The intervention group consisted of 1 educational session with presession assigned reading, a 40-min didactic lecture, viewing of a procedural video, and simulation and practice of laparoscopic salpingectomy on a porcine cadaver. The control group received traditional training per routine residency rotations. MEASUREMENTS AND MAIN RESULTS: Laparoscopic salpingectomy was performed on live patients by study participants pre- and postintervention. These procedures were video recorded, and then scored by a single blinded evaluator of the OSATs. Nine pre- and postintervention OSAT indicators, reflecting provider knowledge and skill, were the primary outcome measures. Secondary outcomes were the changes in 10 subjective measures of comfort, assessed by a pre- and postintervention survey. The outcomes were assessed using 5-point Likert scales (for OSATs 1 = lowest score; for the subjective survey 1 = highest score). The control group OSAT scores did not change (pre: 26.6 ± 10.8, post: 26.2 ± 10.1; p = .65). There were significant improvements in 2-handed surgery (pre: 2.8 ± 1.6, post: 3.5 ± 1.3; p = .004) and use of energy (pre: 2.9 ± 1.3, post: 3.6 ± 1.0; p = .01) in the intervention group, contributing to an overall score change (pre: 26.7 ± 10.6, post: 29.9 ± 9.8; p ≤ .001). The control group had no change in comfort levels. The intervention group experienced both increases (anatomy, steps of surgery, 2-handed surgery, and use of energy) and decreases (reading and learning in operating room) in reported comfort levels. CONCLUSION: This study demonstrates that simulation can improve surgical technique OSATs. However, of 45 possible points, both groups' average scores were <70% of the optimum. Thus, the improvement, although statistically significant, was relatively small and indicates that further supplementation in training is needed to substantially increase the residents' surgical skills.

A novel three serum phospholipid panel differentiates normal individuals from those with prostate cancer.

BACKGROUND: The results of prostate specific antigen (PSA) and digital rectal examination (DRE) screenings lead to both under and over treatment of prostate cancer (PCa). As such, there is an urgent need for the identification and evaluation of new markers for early diagnosis and disease prognosis. Studies have shown a link between PCa, lipids and lipid metabolism. Therefore, the aim of this study was to examine the concentrations and distribution of serum lipids in patients with PCa as compared with serum from controls. METHOD: Using Electrospray ionization mass spectrometry (ESI-MS/MS) lipid profiling, we analyzed serum phospholipids from age-matched subjects who were either newly diagnosed with PCa or healthy (normal). RESULTS: We found that cholester (CE), dihydrosphingomyelin (DSM), phosphatidylcholine (PC), egg phosphatidylcholine (ePC) and egg phosphatidylethanolamine (ePE) are the 5 major lipid groups that varied between normal and cancer serums. ePC 38:5, PC 40:3, and PC 42:4 represent the lipids species most prevalent in PCa as compared with normal serum. Further analysis revealed that serum ePC 38:5 ≥0.015 nmoles, PC 40.3 ≤0.001 nmoles and PC 42:4 ≤0.0001 nmoles correlated with the absence of PCa at 94% prediction. Conversely, serum ePC 38:5 ≤0.015 nmoles, PC 40:3 ≥0.001 nmoles, and PC 42:4 ≥0.0001 nmoles correlated with the presence of PCa. CONCLUSION: In summary, we have demonstrated that ePC 38:5, PC 40:3, and PC 42:4 may serve as early predictive serum markers for the presence of PCa.

Outcomes of delayed abdominal-based autologous reconstruction versus latissimus dorsi flap plus implant reconstruction in previously irradiated patients.

BACKGROUND: Local recurrence after breast conservation therapy is usually managed with salvage mastectomy. Multiple methods of reconstruction are possible, although delayed autologous reconstruction provides the most reliable results. METHODS: We compared complications in delayed abdominal-based [transverse rectus abdominis muscle (TRAM)/deep inferior epigastric perforator (DIEP)] reconstruction with delayed latissimus dorsi plus implant-based reconstruction in previously irradiated breasts. The authors reviewed 133 consecutive cases of delayed breast reconstructions performed in patients who had postmastectomy radiation therapy and reconstruction with abdominal-based methods (single-pedicle TRAM, supercharged pedicle TRAM, muscle-sparing TRAM free flap, DIEP flap, and superficial inferior epigastric artery flap) or a pedicled latissimus dorsi flap plus implant. Complications for donor and recipient sites were recorded including infection, seroma, hematoma, and partial flap loss. RESULTS: Seventy-five patients were reconstructed with abdominal-based flaps (37 muscle-sparing TRAMs, 19 pedicled TRAMs, 12 DIEPs, 6 supercharged pedicled TRAMs, and 1 superficial inferior epigastric artery). Their median age was 50 years and mean follow-up was 22.7 months. Three (4.0%) patients required reoperation during the same hospital visit for vascular compromise that resulted in 2 (2.7%) flap failures. Three (4.0%) patients had partial flap loss that ultimately required debridement and primary closure. Seventeen (22.7%) patients had minor complications including seroma, small hematoma, cellulitis, and abdominal bulge. Fifty-six patients were reconstructed with latissimus dorsi flaps plus implants. Their median age was 47 years and mean follow-up was 32 months. Three (5.4%) patients developed infections resulting in implant loss. Four (7.1%) patients had partial flap loss that required debridement and primary closure. Thirteen (23.2%) patients had minor complications including seroma (12 patients) and hematoma (1 patient) that required drainage. Fisher exact test was used to determine statistical significance of complication and failure rates between the 2 types of reconstruction. In patients who had postmastectomy radiation therapy, those with abdominal-based reconstructions had fewer complications compared with latissimus dorsi flap plus implant reconstructions (28.0% vs 30.4%, P=0.846). Also, fewer reconstructions failed in patients with abdominal-based reconstruction (2.7% vs 5.4%, P=0.650). CONCLUSIONS: Abdominal-based autologous reconstruction had fewer complications and fewer reconstruction failures than latissimus dorsi flap plus implant reconstructions in patients with postmastectomy radiation therapy in our series; however, these rates were not statistically significant.

The use of the multi-island vertical rectus abdominis myocutaneous flap in head and neck reconstruction.

BACKGROUND: Head and neck cancer extirpation frequently creates complex 3-dimensional defects involving both intraoral and external tissues. Reconstruction can be accomplished either with 2 free flaps, a simultaneous free and pedicle flap, or a single double-island folded free flap. Herein, the outcomes and rationale for reconstruction of multilaminar head and neck defects using the multi-island vertical rectus abdominis myocutaneous (MI-VRAM) flap are reported. METHODS: A retrospective review was performed of a prospectively collected database of all head and neck reconstructions completed by a single surgeon between 1992 and 2011. Forty-six patients were identified who underwent reconstruction of composite defects using MI-VRAM flaps. Oncologic defects were classified into 3 categories based on anatomic location, namely, the midface, lower face, and neck. Indications and outcomes were reviewed. RESULTS: Patients' ages ranged from 7 to 84 years with two thirds being male; 45% received preoperative radiation. Average MI-VRAM skin paddle size was 9×25.5 cm. Of the 46 reconstructions, 27 (59%) were performed in the midface, 14 (30%) in the lower face, and 5 (11%) in the neck region. There were no complete flap loses; however, 1 patient lost the external skin island, requiring pectoralis flap coverage. Of these cases, 15% had surgically related complications. Ten patients required secondary contouring procedures to revise bulky flaps. CONCLUSIONS: The MI-VRAM flap is a safe and reliable technique for reconstruction of complex defects throughout the head and neck region. Compared to 2 simultaneous free flaps or a free flap combined with a regional flap, it saves time and eliminates a second donor site. LEVEL OF EVIDENCE: Level IV. Clinical question addressed in this paper is whether a multi-island VRAM flap is a safe technique in head and neck reconstruction.

A new dimension: robotic reconstruction in plastic surgery.

BACKGROUND: Robot-assisted surgery was first approved by the Federal Drug Administration in 1994. The robotic system has the advantages of three-dimensional visualization of the operating field, 7° range of motion, tremor elimination, 360°of freedom at 10-mm distance, and a comfortable, seated operating posture. The purpose of this paper is to present a new surgical tool, the robot, for use in reconstructive surgery. METHODS: A case is presented in which the robotic system was used to elevate a pedicled, myocutaneous latissimus dorsi flap for shoulder reconstruction. RESULTS: The robot was used successfully to harvest a pedicled latissimus dorsi flap. Since this case, we have used the robotic system to harvest one other pedicled latissimus flap for breast reconstruction as well as to perform the microvascular anastomoses in a radial forearm and rectus abdominus free flaps to the lower extremity. CONCLUSION: There is great potential for the use of robot as a surgical tool in the field of plastic surgery. The advantages are numerous, including superior visibility, greater range of motion as a more comfortable position for the operating surgeon. The limitations include the learning curve and the lack of biofeedback.

Treatment of keratoacanthoma: Is intralesional methotrexate an option?

BACKGROUND: Keratoacanthomas (KAs) are a variant of squamous cell carcinomas. Some KAs have shown aggressive behaviour, leading to metastasis and death. Surgical excision is the treatment of choice for most KA patients. Intralesional methotrexate (MTX) may also be a potential treatment option for KAs. OBJECTIVE: To evaluate intralesional MTX as a treatment modality for KA. METHODS: A retrospective chart review of nine patients with KAs treated with intralesional MTX was performed. Each patient had biopsy-proven KA. The lesion was initially debulked, and MTX was injected at the base. Patients were seen weekly in the office, and reinjected with intralesional MTX depending on the response of the lesion. Each patient was evaluated for their response to the intralesional MTX injections, the number of injections required and complications. RESULTS: Patients required approximately two to four intralesional injections (12.5 mg to 25 mg per injection) before KA resolution. Eight of nine (88.9%) patients experienced complete resolution of their tumours. One patient experienced treatment failure, and underwent surgical excision of the KA. The average follow-up period was 2.8 years, and there were no recurrences. CONCLUSION: The results from the present retrospective study show that intralesional MTX injection is an effective treatment option for KAs. The authors propose that intralesional MTX injection with initial debulking of the KA should be used as a first line of treatment when KAs present on the extremities, in cosmetically sensitive areas and in elderly patients with multiple comorbities.

Median cleft of the upper lip: a rare case.

Median cleft lip is a midline vertical cleft through the upper lip. This is a rare anomaly with very few cases described in the literature. Median cleft lip has been thought to be associated with hypertelorism or hypotelorism. It is caused by the failure of fusion of the medial nasal prominences. In this case report, a 4½-year-old girl with a median cleft is presented. The patient has no other anomalies of the nose or alveolus. The patient has normotelorism. A shortened bifid frenulum of the upper lip is present. A technique using an elliptical excision of the cleft with muscle approximation is described.

Keloid treatment: is there a role for acellular human dermis (Alloderm)?

BACKGROUND: Keloid management is faced with high recurrence rates. Keloid fibroblasts lack the normal negative feedback mechanism resulting in an exuberant scar formation. Alloderm doesn't undergo the same proliferative process as keloidal scar dermis. OBJECTIVE: To evaluate Alloderm as a treatment modality for keloids METHODS: A retrospective chart review of six patients with a total of eight large recurrent keloids was performed. Patients were treated with excision of the keloid followed by placement of Alloderm. Each patient was evaluated for recurrence and complications. RESULTS: During follow-up ranging from 1 month to 4(1/2) years there were 0% recurrences. Two out of 8 (25%) had residual induration. one of the two patients with residual induration, required an intralesional injection of kenalog at 6 months post-op. CONCLUSION: Our results from this small study show that with the use of Alloderm after keloid excision, recurrence is low. Further study is warranted.

Wound education: American medical students are inadequately trained in wound care.

Millions of patients are treated annually in the United States with either acute or chronic wounds, costing billions of dollars. This is a retrospective study designed to quantify the directed education that medical students receive in their 4 years of training on 3 wound-related topics: physiology of tissue injury, physiology of wound healing, and clinical wound healing. The mean hours of education in physiology of tissue injury at 50 American medical schools are 0.5 hours and 0.2 hours, respectively, in the first year and second years and none in the third and fourth years. The mean hours of directed education in the physiology of wound healing are 2.1 hours and 1.9 hours in the first and second years. The data in our study show there is scant directed education in relevant wound topics in American medical schools. Considering the immense economic and social impact of wounds in our society, more attention should be paid to the education of our physician trainees on this important topic.

Uncommon leg ulcers in the lower extremity.

OBJECTIVE: To determine the prevalence of uncommon ulcers, unrelated to venous or arterial etiology, in patients presenting to vascular clinics. METHODS: This was a multicenter prospective study of consecutive patients presenting with lower extremity ulceration. The settings were university hospital outpatient centers and venous clinics. A total of 799 limbs in 710 patients with leg ulcers were evaluated. Patients with venous ulcer disease and with evidence of arterial disease with an ankle-brachial index less than 0.7 were excluded from the study. Out of 710 patients, 17 patients with a total of 21 limbs fit the criteria for inclusion. All limbs included in this study underwent physical examination, ankle-brachial index measurements, duplex ultrasonography, and skin biopsies. RESULTS: The mean age of patients with uncommon ulcers was 65.6 years, and the mean duration was 5.5 years. A total of 2.1% of all leg ulcers seen were due to uncommon etiology unrelated to venous or arterial pathology. Most of these ulcers were located in the medial lower calf (n = 19). In six patients with ulcers, the histology did not reveal any specific cause; five had a neoplasia, three had chronic inflammation, two had sickle cell disease, two had vasculitis, one had rheumatoid arthritis, one had pyoderma gangrenosum, and one had ulcer due to hydroxyurea. CONCLUSIONS: The prevalence of leg ulcers unrelated to arterial and venous disease that presented with signs and symptoms of chronic venous disease was 2.1%. Their etiology is variable, most often including vasculitis, neoplasia, metabolic disorders, infection, and other rare causes. Early identification of uncommon ulcers may facilitate timely and appropriate management.

Current management of venous ulceration.

It has been estimated that chronic venous insufficiency affects 10 to 35 percent of the entire U.S. population and that 4 percent of people older than 65 have active venous ulcers. The high prevalence of the disease results in an annual expenditure of more than 1 billion dollars a year to the U.S. health care system. To have a rational approach toward patients with venous ulcers, it is important to understand the pathophysiology and clinical characteristics of the disease process, in order to initiate appropriate treatment and prevent venous ulcer recurrence.

Impaired mitochondrial function protects against free radical-mediated cell death.

Free radical damage can have fatal consequences. Mitochondria carry out essential cellular functions and produce high levels of reactive oxygen species (ROS). Many agents also generate ROS. Using the yeast Saccharomyces cerevisiae as a eukaryotic model, the role of functional mitochondria in surviving free radical damage was investigated. Respiratory-deficient cells lacking mitochondrial DNA (rho(0)) were up to 100-fold more resistant than isogenic rho(+) cells to killing by ROS generated by the bleomycin-phleomycin family of oxidative agents. Up to approximately 90% of the survivors of high oxidative stress lost mitochondrial function and became "petites." The selective advantage of respiratory deficiency was studied in several strains, including DNA repair-deficient rad52/rad52 and blm5/blm5 diploid strains. These mutant strains are hypersensitive to lethal effects of free radicals and accumulate more DNA damage than related wild-type strains. Losses in mitochondrial function were dose-dependent, and mutational alteration of the RAD52 or BLM5 gene did not affect the resistance of surviving cells lacking mitochondrial function. The results indicate that inactivation of mitochondrial function protects cells against lethal effects of oxygen free radicals.