Long-term outcomes following single-portal endoscopic carpal tunnel release.

BACKGROUND: There is limited published information about long-term outcomes and recurrence rates following single-portal endoscopic carpal tunnel release. METHODS: We reviewed symptom and function outcomes from a prospectively collected database of patients who underwent single-portal endoscopic carpal tunnel release at a minimum of 8 years follow-up. Out of 207 patients in the original database, we were able to confirm correct current contact information for 106 patients. Of these, 91 patients with 115 single-portal endoscopic carpal tunnel releases agreed to participate. All of these patients were eligible for this long-term follow-up study based on documented preoperative and 6-month postoperative Levine-Katz questionnaire scores. Patients then completed a current update of the Levine-Katz questionnaires to assess function and symptom outcomes at latest follow-up. RESULTS: The average 6-month postoperative scores were significantly lower compared with the average preoperative scores and were maintained at long-term follow-up. There were no significant differences in average change in scores at long-term follow-up compared to 6-months postoperative. CONCLUSIONS: Single-portal endoscopic carpal tunnel release is an effective surgical treatment for carpal tunnel syndrome. Low recurrence rates and maintenance of low symptom and function scores can be expected at 8 to 10 years following this technique.

A 6-year outcome of patients who cancelled carpal tunnel surgery.

The long-term outcomes of patients with carpal tunnel syndrome who were scheduled for release but did not proceed to surgery were compared to patients who underwent surgery, matched on preoperative symptom scores. Both groups completed the Levine-Katz questionnaire 6 years after enrolment to our multicentre carpal tunnel syndrome outcomes database. Symptom and function scores improved for the surgical (n = 24) and non-surgical (n = 36) groups (p < 0.001). Improvement in symptom scores was greater in surgical patients compared to non-surgical patients (n = 24 matched pairs; p = 0.007) but improvement in function scores between groups was not significantly different (p = 0.13). For surgical patients, function and symptom scores improved by 6 months and were unchanged at 6 years. Patients planning surgical release can expect symptomatic and functional benefits within 6 months. Overall improvement was experienced by both groups, with a superior outcome achieved with surgery. The symptoms of carpal tunnel syndrome may improve without surgery, but further studies are needed to understand the natural history of the disorder.

Study to assess differences in outcome following open carpal tunnel decompressions performed by surgeons of differing grade.

INTRODUCTION: Carpal tunnel decompression is the most commonly performed surgical procedure within a hand unit. Although very effective, the complications following the procedure can be significant. In an attempt to identify the causes of such complications, we assessed whether seniority of the surgeon impacts on outcome for open carpal tunnel decompression. PATIENTS AND METHODS: Data were jointly and prospectively gathered from two units from either side of the Atlantic - the Pulvertaft Hand Center, UK and the Curtis Hand Center, USA. The aim of the study was to assess outcome following carpal tunnel decompression. Completed data were gathered following open carpal tunnel decompression on 352 hands. Surgeons of a consultant grade had performed 123 of these procedures whilst surgical trainees had performed 229 of the procedures. Assessment was by Levine Katz questionnaire results, Semmes-Weinstein testing, grip strength and pinch grip strength testing performed both pre-operatively and 6 months' postoperatively. Complications following the procedure were also recorded. RESULTS: Mean results were found to be better in those patients where the surgeon was of a consultant grade. However, this was only found to be of statistical significance on Semmes-Weinstein testing. Complications following the procedure were also noted to be higher in the group of patients operated on by trainee grades. CONCLUSIONS: Our results show the carpal tunnel decompression performed by a surgeon of consultant grade offers slightly better results in objective neurological testing when compared with those performed by a more junior grade.

A prospective assessment of carpal tunnel surgery with respect to age.

Six hundred and thirty five carpal tunnel decompressions in 490 patients were studied prospectively in two hand surgery centres to assess the effect of increasing age on the outcome after surgery. The outcome was assessed using the Levine-Katz carpal tunnel questionnaire, Tinel's sign, Phalen's test, Semmes-Weinstein monofilaments and pinch and grip strengths. Assessments were made pre-operatively, at 2 weeks and 6 months postoperatively. Information was also sought concerning co-morbid conditions. Cases were divided into four groups (less than 40 years of age, 40 to 60, 61 to 80, and over 80 years of age). Patients improved significantly in all age groups after carpal tunnel surgery. Despite a relatively high number of co-morbidities, older patients had an acceptable complication rate and their improvement was comparable to all other age groups.

Digital anaesthesia: comparison of the efficacy and pain associated with three digital nerve block techniques.

There are three commonly used methods of digital block anaesthesia: viz. subcutaneous, metacarpal and transthecal. A randomized, single-blinded study on 50 healthy volunteers was performed to determine time to onset, pain level and preference. Volunteers each received all three blocks, serving as their own controls. Time to onset was significantly longer (P<0.001) for the metacarpal block than for the subcutaneous or transthecal blocks. There was no significant difference in average pain level between the methods, as measured on a scale from 1 to 10. Volunteers chose the subcutaneous block (43%) as their first choice over the metacarpal block (33%) or the transthecal block (25%). The transthecal block had prolonged discomfort lasting 24 to 72 hours after injection in 20 subjects (40%). These findings suggest that subcutaneous block is effective and preferred by healthy volunteers for digital anaesthesia.

Serum and urine markers of bone metabolism during the year after hip fracture.

OBJECTIVE: As part of a larger study to describe indices of recovery during the year after hip fracture, the current prospective study investigated longitudinal changes in serum and urine markers of bone metabolism for the year after hip fracture and related them to bone mineral density (BMD). DESIGN: A representative subset of participants provided serum and urine samples and had bone density measured at 3, 10, 60, 180, and 365 days postfracture. SETTING: Two Baltimore hospitals. PARTICIPANTS: The subjects were 205 community-dwelling, white women age 65 and older with fresh proximal femur fractures. MEASUREMENTS: Samples were assayed for specific bone-related proteins and bone turnover markers, including serum osteocalcin (OC), procollagen type 1 carboxy-terminal extension peptide (PICP), bone-specific alkaline phosphatase (BAP), and urinary deoxypyridinoline (DPD) cross-links. Selected hormonal regulators of bone metabolism, including parathyroid hormone (PTH), calcitonin (CT), 1,25-dihydroxy vitamin D(3) (1,25 (OH)(2)D), and estrone (E(1)) were measured from serum samples. Repeated measures analyses were used to evaluate postfracture changes in each of the markers. RESULTS: BAP, OC, and PICP were most active during the early postfracture period (3-60 days). BAP and OC remained elevated at 365 days compared with 3 days. DPD rose 48% from 3 days to 60 days, but this difference was not statistically significant. PTH and 1,25 (OH)(2)D increased steadily and significantly from 3 to 365 days. E(1) was highest at baseline and decreased at each time point, whereas CT showed no significant changes. When subjects were stratified into high-, medium-, and low-BMD groups based on their measurement at 3 days, both osteoclastic and osteoblastic markers in the low-BMD group displayed exaggerated and different patterns over time compared with the other groups. CONCLUSION: Currently, the standard treatment of care for hip fractures still results in high morbidity and mortality and failure to regain prefracture quality of life. Gaining an understanding of bone cell activity in these patients after hip fracture, derived by measuring markers longitudinally during recovery, provides a baseline by which to measure the effectiveness of new interventions to improve recovery from hip fracture.

Semen pH in patients with normal versus abnormal sperm characteristics.

OBJECTIVE: The World Health Organization laboratory manual, last revised in 1992, states that the normal pH of semen ranges from 7.2 to 8.0. Our experience has been that values in our patient population are consistently higher than this range. To confirm this we reviewed >1100 semen records. STUDY DESIGN: All patient records from January 1994 to December 1998 that had semen pH measurements and sperm concentration and motility measurements recorded were included in this study. We also determined the semen pH in a subgroup of patients who underwent sperm preparations for intrauterine inseminations that resulted in documented pregnancies. Histograms were used to describe the populations and the Mann-Whitney test was used for group comparisons. RESULTS: For all patients (N = 1199) mean (+/-SD) semen pH was 8.2 +/- 0.3. The range was 7.3 to 9.5, with pH <8.0 in 32% of the samples. The semen pH among the patients with normal sperm concentration and motility values (n = 602) was not different from that among those with abnormal parameters (n = 597). Mean semen pH value was 8.2 for both groups. In a small group of patients (n = 19) whose sperm preparations had been documented to result in a clinical pregnancy after intrauterine insemination the semen pH was 8.3 +/- 0.3, with a range of 7.9 to 8.7. CONCLUSION: Our study questions the reference range defined by the World Health Organization for semen pH of 7.2 to 8.0. The mean values that we observed in our population, including those of samples from patients with normal sperm parameters, consistently lay outside that range.

In vitro effects of sildenafil and phentolamine, drugs used for erectile dysfunction, on human sperm motility.

OBJECTIVE: The aim of this study was to determine the effects of sildenafil and phentolamine on sperm motility in vitro. STUDY DESIGN: Semen or washed sperm was mixed with various doses of sildenafil or phentolamine and analyzed for motility during a 30-minute period. The pH was measured for each of the samples tested. Statistical analyses were performed with analysis of variance. RESULTS: A 200-microg/mL dose of sildenafil had no effect on sperm motility. However, the highest dose (2000 microg/mL) significantly reduced motility by about 50%. The pH was reduced in this high-dose sample. The lowest dose of phentolamine (20 microg/mL) had no effect, whereas a dose of 200 microg/mL resulted in a significant reduction in sperm motility. The highest dose (2000 microg/mL) stopped virtually all sperm from moving. CONCLUSION: This study demonstrated a direct dose-related effect of phentolamine on reducing sperm motility. Only the highest dose of sildenafil had an effect, which may have been caused by a decline in pH.

The effect of raloxifene on the uterine weight response in immature mice exposed to 17beta-estradiol, 1,1,1-trichloro-2, 2-bis(p-chlorophenyl)ethane, and methoxychlor.

OBJECTIVE: The purpose of this study was to determine the effects of raloxifene on the uterine responses to both estradiol and the environmental estrogens 1,1,1-trichloro-2, 2-bis(p-chlorophenyl)ethane and methoxychlor in immature mice. STUDY DESIGN: Immature female mice received the following compounds alone or in combination: sesame oil (control), 17beta-estradiol 1 mg/kg body weight, tamoxifen 1 mg/kg body weight, raloxifene 5 mg/kg body weight, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane 10 mg/kg body weight, and methoxychlor 10 mg/kg body weight. The animals were treated subcutaneously once a day for 5 consecutive days with the compound or compounds of interest in 0.1 mL sesame oil. Approximately 24 hours after the final treatment the animals were killed and the uteri were excised, stripped of remaining fat and mesentery, and weighed. Groups were analyzed with analysis of variance. RESULTS: Estradiol increased the mean (+/-SE) weight from 20 +/- 6.4 mg (as measured in the control group) to 77 +/- 6.2 mg. Tamoxifen increased uterine weight to 60 +/- 6.2 mg; however, raloxifene had no effect on uterine weight. Both 1,1,1-trichloro-2, 2-bis(p-chlorophenyl)ethane and methoxychlor increased uterine weight significantly, to 82 +/- 2.4 mg and 35 +/- 6.0 mg respectively. When raloxifene was coadministered with 17beta-estradiol it did not block the increase in uterine weight; however, when raloxifene was coadministered with 1,1,1-trichloro-2, 2-bis(p-chlorophenyl)ethane or methoxychlor, it completely blocked the uterine weight gain induced by either xenoestrogen. CONCLUSION: Raloxifene blocked the xenoestrogens 1,1,1-trichloro-2, 2-bis(p-chlorophenyl)ethane and methoxychlor but did not block 17beta-estradiol in the mouse model described. These results suggest that the xenoestrogens exert their estrogenic activities through a different site on the estrogen receptor or through a different mechanism than 17beta-estradiol.

Risk of breast cancer and organochlorine exposure.

A prospective investigation of breast cancer and organochlorine (OC) exposures was undertaken in the New York University Women's Health Study. Cases (n = 148) and individually matched controls (n = 295) were identified among women whose blood had been obtained 6 months or more prior to breast cancer diagnosis. In addition, among 84 cases and 196 controls, two or more consecutive annual blood samples were available to estimate half-lives of 1,1-dichloro-2,2-bis(p-chlorophenyl) ethene (DDE) and polychlorinated biphenyls (PCBs). Cases and controls had similar levels of DDE (geometric mean, 6.95 versus 7.27 ng/ml; lipid-adjusted geometric mean, 977 versus 1100 ng/g) and PCBs (5.04 versus 4.97 ng/ml; lipid-adjusted geometric mean, 683 versus 663 ng/g). These differences remained nonsignificant when estrogen receptor status of tumors was considered. DDE and PCB half-lives did not differ in case versus control patients. In control patients, DDE and PCB half-lives were strongly correlated (r(s) = 0.71), and the half-life of DDE (but not that of PCB) was inversely correlated with body mass index (BMI), yet the blood serum levels of PCB (but not those of DDE) were correlated with BMI. We conclude that there is no evidence for an association of breast cancer risk with DDE or PCB levels in blood (based on samples collected during the period 1987-1992) nor with their elimination half-lives. However, changes in DDE and PCBs over time are influenced by metabolism, BMI, and current OC exposures, and each may affect interpretation of OC levels in risk assessment models.

The rate at which human sperm are immobilized and killed by mild acidity.

OBJECTIVE: To determine the rate at which mild acidity immobilizes and kills human sperm and to evaluate an acidic microbicide, BufferGel, for sperm immobilization. DESIGN: Controlled in vitro study. SETTING: An academic research university and hospital andrology lab. PATIENT(S): Eight volunteer male sperm donors. INTERVENTION(S): Semen samples were treated with hydrochloric acid (HCl) or BufferGel. MAIN OUTCOME MEASURE(S): Sperm motility was measured by using a computerized automated semen analyzer and video microscopy. Sperm membrane permeability and intracellular pH were measured by using fluorescent techniques. RESULT(S): In semen acidified with HCl to pH 4.0, sperm were rapidly immobilized (within 1 min) and were irreversibly immobilized (killed) within 10 minutes. The speed of immobilization and of killing were both linearly proportional to hydrogen ion activity over a pH range of 7.5-4.0. Across the same range, the intracellular pH of human sperm equilibrated to within 0.5 pH units of extracellular pH within 1-2 minutes. BufferGel immobilized sperm significantly faster than HCl from pH 4.0-6.0. CONCLUSION(S): Exposure to mild acidity rapidly acidifies the intracellular pH of human sperm and is rapidly spermicidal. BufferGel accelerates acid immobilization of sperm.

Serum concentrations of steroids, parathyroid hormone, and calcitonin in postmenopausal women during the year following hip fracture: effect of location of fracture and age.

BACKGROUND: Hip fracture in the aged is a major health problem, especially considering the increasing proportion of the elderly in the population. This study examines changes in circulating levels of hormones, which are purported to affect bone metabolism, in response to hip fracture in postmenopausal women. METHODS: Patients consisted of women ages 65 and older who had surgery within 2 days of fracture. Serum samples were obtained at 3, 10, 60, 180, and 360 days postfracture. Healthy women without hip fractures from the same age range served as a control group (n = 17). Hormones were determined by radioimmunoassay. Subjects with fractures in the neck region of the femur (n = 78) were compared to subjects with fractures in the trochanteric region (n = 88). RESULTS: Estrone concentration (47.6 +/- 5.7 pg/mL; mean +/- SEM) at 3 days postfracture was elevated (p < .001) compared to control levels of 20.7 +/- 4.6 pg/mL. By 2 months, levels had declined to control levels. Androstenedione and the adrenal hormones, DHEAS and cortisol, displayed similar responses. Parathyroid hormone (PTH) levels were not significantly different from the control concentration at 3 days following fracture, but increased (p < .001) during the year following fracture. Calcitonin concentrations were much higher (p < .001) 3 days postfracture (42.1 +/- 3.7 pg/mL) compared to controls without fracture (9.8 +/- 3 pg/mL). Except for testosterone, no differences could be attributed to fracture location. Only PTH, with concentrations higher in the older age groups (p < .001), showed an age-related response. CONCLUSIONS: Following hip fracture, there are some dramatic responses in hormones that purportedly are mechanistically important in bone metabolism. These changes include transient increases in steroid hormones, chronic elevations in calcitonin, and rising levels of PTH during the year after fracture.

Recombinant growth hormone's effects on the strength and thickness of radiation-injured ileal anastomoses: a rat model.

BACKGROUND: Small bowel resections following radiotherapy for gynecologic cancers have resulted in significant rates of morbidity and mortality. The objective of this study was to evaluate the effect of rGH on the breaking strength and thickness of radiation-injured ileal anastomoses in an animal model. MATERIALS AND METHODS: Sprague-Dawley rats were treated with 1800 cGy of pelvic irradiation in a single fractionation. Seventeen weeks following pelvic teletherapy an ileo-ileostomy was performed. The rats were randomized to receive 2.0 mg/kg/day of rGH for 7 days or placebo. On the seventh postoperative day a segment of ileum surrounding the anastomosis was resected. The segments were tested for breaking strength or were histologically measured for anastomotic thickness. RESULTS: The ileal anastomotic breaking strength in the rGH group was 181 +/- 8.4 g (mean +/- standard error). The breaking strength of ileal anastomoses in the placebo group was 133 +/- 6.9 g (P < 0.05). The rGH group demonstrated a greater anastomotic thickness (1.65 +/- 0.116 mm) than the placebo group (1.17 +/- 0.113 mm, P < 0.05). Of placebo rats 14.7% developed anastomotic leaks compared to 0% of rGH-treated animals (P < 0.05). CONCLUSIONS: RGH increased the ileal anastomotic breaking strength by 36% in radiated rats. The anastomotic leak rate was reduced from 14.7% in the placebo group to 0% in the rGH group. These findings correlated with a 41% increase in the thickness of the anastomotic connective tissue in the rGH group. Clinical investigation in selected patients is warranted.

Serum autoantibodies recognizing 5-hydroxymethyl-2'-deoxyuridine, an oxidized DNA base, as biomarkers of cancer risk in women.

Human sera contain anti-5-hydroxymethyl-2'-deoxyuridine (HMdU; an oxidized thymidine) autoantibodies (aAbs), which are significantly higher in chronic inflammatory diseases. The intent of this study was to establish whether anti-HMdU aAbs can serve as predictors of breast and colorectal cancer risk. Sera of 169 women were analyzed by ELISA. Women healthy at blood donation but who were diagnosed 0.5-6 years later with breast or colorectal cancer exhibited significantly increased anti-HMdU aAbs over the age-matched controls (P = 0.028 and P < 0.001, respectively). Subjects diagnosed with rectal cancer had the highest levels of anti-HMdU aAbs (44.80 +/- 11.50; n = 6) in comparison to colon (29.03 +/- 2.49; n = 33) and breast (35.86 +/- 8.55; n = 9) cancers. Individuals with benign breast disease also had elevated anti-HMdU aAb (35.12 +/- 8.77; n = 10), with a borderline statistical significance (P = 0.095), whereas those with benign gastrointestinal tract diseases had those titers (30.95 +/- 3.64; n = 8) significantly increased (P < 0.02). Anti-HMdU aAb levels in subjects with a family history of any cancer (23.57 +/- 2.86; n = 55) did not significantly differ from those of the controls (19.41 +/- 2.90; n = 48), but women with a family history of breast cancer (two primary relatives or one with a bilateral disease) showed increased levels (34.48 +/- 8.16; n = 8; P = 0.024). Ps for linear trend of age-adjusted odds ratios were 0.049 for breast and < 0.001 for colorectal cancers. Anti-HMdU aAb titers showed a remarkable stability over a period of 6 years, with a low (14%) intraindividual variance. Thus, elevated anti-HMdU aAb titers may be an early signal of cancer risk, because they were significantly increased in otherwise healthy women who had a family history of breast cancer; in those who had benign breast disease or benign gastrointestinal tract diseases; and, most importantly, in those who at 0.5-6 years after the initial blood donation developed breast or colorectal cancer.

The effect of recombinant growth hormone on the strength of ileal anastomoses in a rat model.

OBJECTIVE: In gynecologic surgery, the ileum is the primary site of bowel injury. Recombinant growth hormone (rGH) has been shown to improve the strength of colonic anastomoses in experimental models. The purpose of this study is to evaluate the effect of rGH on small bowel anastomoses, specifically in the ileum. METHODS: Twenty large female rats underwent segmental ileal resections and end-to-end ileoileostomies. The rats were randomized to be treated for 7 postoperative days with either rGH (2.0 mg/kg/day) or placebo starting on the day of surgery. On the seventh postoperative day, a segment of ileum surrounding the anastomosis was resected. The anastomoses were tested for breaking strength on a tensiometer and for tissue concentrations of hydroxyproline. RESULTS: The ileal anastomotic breaking strength in the rGH group was 163.5 +/- 6.0 g (mean +/- standard error). In the placebo group, the breaking strength of ileal anastomoses was 125.0 +/- 3.0 g (P < .001). No significant difference was demonstrated with respect to the hydroxyproline concentration between the rGH group (15.2 +/- 2.0 micrograms/mg) and the placebo group (14.6 +/- 1.0 micrograms/mg). CONCLUSION: In an animal model, a 31% increase in ileal anastomotic breaking strength was induced by rGH administration. With further research this may translate into decreases in the surgical complications that occur in ileal anastomoses. Furthermore, these serve as preliminary data to a study that evaluates the effect of rGH on ileal anastomoses in radiation-injured bowel.

Poly(ADP-ribose) polymerase in human breast cancer: a case-control analysis.

The importance of a genetic polymorphism (A/B allele) of poly(ADP-ribose) polymerase (PARP) pseudogene on chromosome 13q34-qter, and PARP enzyme activities in the development of human breast cancer were evaluated in a cancer case-control study. A total of 309 Caucasian women (> or = 50 years old) were evaluated for the PARP genotype, 70 of whom had histologically confirmed breast cancer, 128 women with benign breast diseases as study controls, and 111 reference controls. Age was significantly associated with case-control status (p < 0.0001), but family history of breast cancer, age at menarche, age at first live birth and parity were not. The frequency of the PARP B allele was similar in breast cancer cases (0.14), study controls (0.13), and reference controls (0.15). In a subset of 14 breast cancer cases and 32 study controls, the mean PARP enzyme activities (induced by H2O2 or oligonucleotide) were observed to be lower in cancer cases; an age-adjusted odds ratio of 3.40 (95% confidence interval = 0.70-19.54) for the below-median oligonucleotide-induced PARP was suggestive of an association. In subjects with the AB or BB genotype, the mean H2O2-induced PARP enzyme activity was significantly higher (p = 0.02, adjusted for case-control status and age) compared with that in subjects with the AA genotype. These findings indicate that: (a) the genetic polymorphism of the PARP pseudogene on chromosome 13 is not associated with the development of breast cancer in our study population; (b) oligonucleotide-induced PARP activity may be useful for identifying postmenopausal women at increased risk for breast cancer; and (c) there is a possible functional link between the genotype of the PARP pseudogene and enzyme activation.

Comparison of standard and loupe colposcopy (part I).

BACKGROUND: Our objective was to determine whether colposcopy can be performed with surgical-type loupes. METHODS: Sixty-one patients with abnormal Papanicolaou (Pap) smear test reports were examined with 6× loupes supplied by Designs For Vision, Inc. (Ronkonkoma, NY) and with a standard Zeiss Colposcope (Model OM-1). Comparisons between the two instruments were made for colposcopic impression and final histological analysis. Statistical analysis was performed by using the Kappa test. RESULTS: Comparison of the two methods of examination demonstrated excellent agreement (κ = .86) with Pap smear and biopsy results. CONCLUSIONS: We decided that surgical loupes are adequate for colposcopic examination.

Comparison of Standard and Loupe Colposcopy (Part II): Initial Experience with a New 6×-10× Surgical Loupe.

BACKGROUND: Our objective was to describe our experience in using a newly designed surgical loupe as a substitute device for colposcopy. METHODS: Eighty-two patients were examined with a prototype surgical loupe. The instrument has a self-contained halogen light source, allows for 6× and 10× magnification, and has a green filter. Colposcopic impression within one degree of the histological diagnosis was considered in agreement. The colposcopic impression using the new instrument was compared to biopsy diagnoses. RESULTS: Colposcopic impressions with this new instrument agreed with final histological diagnoses in 93% of cases. The instrument was easy to use. CONCLUSION: The 6× to 10× surgical loupe is comfortable to use. Correlation with final pathological evaluation is comparable to standard colposcopic instruments. A trial of this instrument against a standard colposcope is ongoing.

Radiotherapy as a cisplatin-sensitizer in a resistant ovarian carcinoma cell line.

BACKGROUND: Stage III ovarian carcinoma has shown resistance to adjuvant chemotherapy following surgical cytoreduction. With recurrence of ovarian carcinoma, cell lines may develop resistance to previously used chemotherapy. This contributes to the fact that survival rates for patients with ovarian carcinoma have not been dramatically improved in decades. The objective of this study is to evaluate radiotherapy as a cisplatin-sensitizer in a cisplatin-resistant ovarian carcinoma cell line. METHODS: In vitro OVCAR-3 human ovarian carcinoma cells were irradiated with external beam radiation (XRT) at doses of 500, 1,500, and 4,500 centigray (cGy) in a single fractionation. Twelve hours after XRT, cells were treated with a dose of cisplatin for 2 hours (0, 1, 3, 9, and 90 micrograms/mL). Cell attachment was determined by cell counts using a hemocytometer under phase-contrast microscopy. Analysis of variance followed by the Student Newman Keuls Test were used for statistical analysis. RESULTS: Dose-response curves demonstrate the results of this study as follows: (1) XRT has a significant direct effect on cell attachment of OVCAR-3 cells in a dose-response relationship. (2) cisplatin has no effect on cell attachment in the absence of XRT. (3) When cells are exposed to XRT, cisplatin demonstrates a dose-response effect on cell attachment with a dose of XRT as low as 500 Gy. CONCLUSIONS: This in vitro study suggests that XRT sensitizes cisplatin-resistant OVCAR-3 to cisplatin. This occurred with doses of radiation low enough to suggest a potential clinical role in treating resistant ovarian carcinoma.

Effects of dietary supplementation of alpha-tocopherol on plasma glutathione and DNA repair activities.

In a randomized double-blind trial of alpha-tocopherol (vitamin E), we investigated the effects of alpha-tocopherol supplementation on lipid- and water-soluble antioxidants in plasma and DNA repair activities in peripheral mononuclear leukocytes. Baseline levels of antioxidants and DNA repair activities were assessed twice before alpha-tocopherol intervention: on day 1 (visit 1) and day 3 (visit 2). During the second visit, participants were randomized to receive one of three dosages of alpha-tocopherol, 15, 60, or 200 mg/day for 4 weeks. The same biochemical measurements as at baseline were repeated twice after intervention: on day 17 (visit 3) and day 31 (visit 4). A total of 31 healthy volunteers were eligible for the study, completed all four visits and were included in the final data analysis. At baseline, no appreciable differences of dietary intake of vitamin E and plasma alpha-tocopherol were observed among the three dosage groups. In general, supplementation of alpha-tocopherol for 2-4 weeks resulted in a dose-dependent increase of plasma level of alpha-tocopherol (compared to baseline); significant increases of plasma alpha-tocopherol at visits 3 and 4 were observed in the two higher dosage groups, 60 and 200 mg, but not in the lowest dosage group, 15 mg. At visit 4 (but not visit 3), plasma glutathione levels were significantly elevated (compared to baseline) in the two higher dosage groups, 60 and 200 mg, but not in the lowest dosage group, 15 mg. In addition, there was an increase in the lipid protection ratio by supplementation of alpha-tocopherol for 2-4 weeks in the two higher dosage groups, 60 and 200 mg, but not in the lowest dosage group, 15 mg. In general, there were no consistent effects of alpha-tocopherol on DNA repair activities in peripheral mononuclear leukocytes after being adjusted for baseline DNA repair activities. Results from this study demonstrate the interrelationship between alpha-tocopherol and other antioxidants in plasma; total plasma antioxidants can be modulated by short-term dietary supplementation of alpha-tocopherol.