The use of hydrogen peroxide to enhance the efficacy of doxorubicin hydrochloride in a murine bladder tumor cell line.

PURPOSE: We determined whether the cytotoxicity of doxorubicin hydrochloride would be enhanced by adding hydrogen peroxide as a source of oxygen free radicals. MATERIALS AND METHODS: Mouse bladder tumor cells (MBT-2) were grown in RPMI 1640 medium and treated with various concentrations of doxorubicin hydrochloride for 2 hours. Protein content was assayed as a measure of cell growth. A similar set of experiments was done with cells exposed to hydrogen peroxide only and combined doxorubicin and hydrogen peroxide. Protein content was again assayed as a measure of cell growth. Cells were also assayed for glutathione peroxidase and malonyl dialdehyde, a product of lipid peroxidation, to determine the mechanism of cell damage. Furthermore, MBT-2 cells were incubated with 100 M. alpha-tocopherol, a free radical scavenger, before exposure to hydrogen peroxide to determine whether the effects of hydrogen peroxide could be reversed. RESULTS: We observed a dose dependent inhibition of MBT-2 cell growth after exposure to doxorubicin hydrochloride. Exposure to doxorubicin and hydrogen peroxide resulted in greater cell growth inhibition than exposure to either agent alone. The effects of hydrogen peroxide on cell proliferation were reversed by pre-incubation with alpha-tocopherol. CONCLUSIONS: As a source of oxygen free radicals, hydrogen peroxide enhances the antiproliferative effect of doxorubicin hydrochloride on a mouse bladder tumor cell line. Thus, hydrogen peroxide may be a relatively inexpensive, nontoxic method of augmenting the cytotoxicity of doxorubicin hydrochloride. Further studies are warranted to determine whether these observations may have clinical application.

Histopathological features of flexural melanocytic nevi: a study of 40 cases.

Melanocytic nevi in certain locations such as the genital and acral sites may have atypical histologic features simulating melanoma. We studied the microscopic findings of 40 melanocytic nevi of flexural sites (axilla, umbilicus, inguinal creases, pubis, scrotum and perianal area) to verify if flexural nevi show distinctive features similar to melanocytic nevi of the genital skin. The patients were young (mean age 20 years), the lesions were mostly removed for cosmetic reasons and we are not aware of any deaths or complications related to the removed nevi. We found that 22 (55.5%) out of 40 flexural nevi had "a nested and dyshesive pattern" similar to the melanocytic nevi of genital skin. This pattern was characterized by the confluence of enlarged nests with variation in size, shape and position at the dermo-epidermal junction and by the diminished cohesion of melanocytes. Dermatopathologists should pay attention to the "nested and dyshesive pattern" of flexural nevi that may mimick histologic changes of melanoma.

Congenital melanocytic nevi with placental infiltration by melanocytes: a benign condition that mimics metastatic melanoma.

BACKGROUND: Placental metastases from cutaneous malignant melanoma from both the mother and the fetus have been reported. The finding of benign-appearing melanocytes in the placenta in association with congenital melanocytic nevi (CMN) is more exceptional, with only 6 reports in the literature. Clinically, the finding of melanocytes in the placenta in this setting can be alarming and might erroneously lead to the diagnosis of metastatic melanoma. OBSERVATIONS: Herein, we describe 3 additional patients with CMN with placental infiltration by melanocytes with a benign phenotype. In the results of immunoperoxidase stains, the melanocytic cells were positive for S-100 protein and HMB-45 in the 2 lesions available for study. Staining of placental vessels with Ulex europaeus agglutinin I (Vector Laboratories, Burlingame, Calif) failed to show intravascular melanocytes in the 1 lesion available for study. We report for the first time DNA diploidy in 2 lesions available for study, which were analyzed by DNA image cytometry. We describe the first patient with a relatively small, nongiant CMN. CONCLUSIONS: We support the notion of the aberrant migration of melanocytes from the neural crest during fetal development as the most likely explanation of this phenomenon and note the similarity to the association of CMN and leptomeningeal melanocytosis. However, the precise histogenesis of this process remains uncertain. Most importantly, our data provide further evidence for the benign nature of this condition. Awareness of this entity is of vital importance in avoiding overdiagnosis of melanoma in this clinical setting.

Comparison of vasovasostomy techniques in rats utilizing conventional microsurgical suture, carbon dioxide laser, and fibrin tissue adhesives.

An evaluation of vas reanastomoses in rats comparing suture only, carbon dioxide (CO2) laser-assisted, and fibrin-based tissue adhesive was performed in our laboratory. A cohort of 60 known fertile male Sprague Dawley rats initially underwent lower midline abdominal exploration and transection of their vas deferens bilaterally, followed by immediate microsurgical vasovasostomy by one of the three experimental methods. All groups initially had the severed vasa ends coapted by two or three transmural (mucosa through serosa) sutures of 10-0 nylon under an operating microscope. The conventionally sutured group had an additional four to six nylon 10-0 sutures placed externally in the serosa only to complete the anastomosis. The CO2 laser-assisted group underwent laser welding with denaturation of the serosa to seal the anastomosis. A fibrin-based tissue adhesive, produced by combining human cryoprecipitate and thrombin, was placed topically over the coapted vas ends to seal the anastomosis in the third group. Postoperative evaluation revealed similarities among the three surgical groups with the fibrin-based tissue adhesive group resulting in the highest patency rate (89%) and pregnancy rate (85%) as well as the lowest granulation rate (18%) and shortest operative time (27 minutes). The laser-assisted group resulted in the lowest pregnancy rate (68%), while the sewn anastomosis group had the lowest patency rate (76%). Both laser-assisted and conventionally sewn vasectomy reversals required significantly longer operative time (39 and 46 minutes, respectively) compared with the fibrin-based tissue adhesive-assisted procedures (p < 0.01). This study provides evidence that alternative microsurgical techniques may be utilized to perform uncomplicated, expeditious, and successful vasectomy reversals.

Benign prostatic hyperplasia in a transgenic mouse: a new hormonally sensitive investigatory model.

Recent advances in molecular biology have enabled incorporation of proto-oncogenes into the mouse germline. In this study we use a transgenic mouse line that overexpresses the fibroblastic growth factor (FGF) family member, int-2, under the control of mouse mammary tumor virus (MMTV) regulatory elements. One of the tissues targeted by MMTV is the mouse prostate. Expression of the MMTV-int-2 transgene in male transgenic mouse carriers results in a dramatic enlargement of the prostate gland which on histologic examination closely resembles the epithelial/glandular BPH observed in human and canine models. Pre- and postpubertal transgenic (NR) and wild-type (WT) FVB/N male mice were evaluated for the effects of hormonal manipulation by orchiectomy and orchiectomy followed by androgen replacement. Orchiectomy results in a significant decrease in size of the prostate in both NR and WT mice (p < 0.05), regardless of sexual maturity. Exogenous hormonal replacement with testosterone or dihydrotestosterone following orchiectomy results in significant regrowth of the prostate in both NR and WT mice. Flutamide, a potent nonsteroidal anti-androgen, resulted in a 55% reduction in size of the NR prostate (p < 0.002) and a similar 44% reduction in size of the WT prostate. Similarly, treatment of both NR and WT mice with leuprolide, a GnRH agonist, resulted in a significant decrease in prostate size (p < 0.05). Treatment of both NR and WT mice with finasteride (MK-906), a 5-alpha reductase inhibitor, failed to produce any significant regression in prostatic tissue. Based upon these data, we conclude that this transgenic mouse model, expressing int-2, produces an epithelial BPH histologically similar to other animal models. This transgenic model is hormonally sensitive and appears to represent a unique model for the investigation of BPH and growth factor induced epithelial cell hyperplasia.

Efficacy of endoscopic hydrocele ablation.

We describe a new endoscopic technique that was used for the treatment of symptomatic scrotal hydroceles in 10 men. Through a small skin incision, the parietal surface of the tunica vaginalis was ablated endoscopically using either electrocautery or the KTP:YAG laser. This approach permitted visual inspection of the scrotal contents with minimal manipulation and was performed using monitored local anesthesia with bilateral spermatic cord blocks. With a mean follow-up interval of 6.1 months, no hydrocele recurrences, wound infections, or hematomas have been detected. The mean operative time was comparable (53 minutes) to that in a historical control group consisting of 15 men who had undergone open hydrocelectomy at our institution (46 minutes). Postoperative scrotal discomfort was minimal, with 6 of the 10 patients requiring no analgesics. Patients were able to resume their preoperative lifestyles an average of 2 days after surgery. In contrast, 11 of the 15 men in the control group was still complaining of scrotal pain, requiring oral analgesics, at their 2-week follow-up visit. Thus, endoscopic hydrocele ablation appears to be an effective and well-tolerated alternative to treat hydroceles with minimal postoperative discomfort.

Endoscopic hydrocele ablation.

A new technique for the treatment of hydroceles by percutaneous drainage and endoscopic ablation under direct vision is described. The possible benefits and drawbacks of this treatment modality for symptomatic hydroceles are discussed.

Expressed emotion in staff working with the long-term adult mentally ill.

Staff-patient relationships in long-term settings were examined in 35 staff and 61 patients. Measures were also taken of the staff's general health, their coping style in relation to work events, and job satisfaction. A range of ratings of EE was evident in staff descriptions of patients under their care. Strain and criticism in the relationship were not associated with identified stressors in the workplace, or the general health of the carer. When patients were grouped according to high-EE and low-EE interviews, there were no significant differences in their symptoms. Criticism was associated with other patient characteristics, including aggressive and attention-seeking behaviour, underactivity, and limited social interaction. The findings have implications for staff training and for the maintenance of optimal staff-patient relationships in services supporting severely disabled patients.

Microsurgical nerve graft repair of the ablated cavernosal nerves in the rat.

Erectile dysfunction is a significant complication of radical pelvic surgery in men. Using the rat as an experimental model, we investigated the feasibility of repairing surgically ablated cavernosal nerves. Known fertile male Sprague-Dawley rats were randomly divided into three surgical groups of 30 animals (60 study nerves) per group consisting of nerve ablation, immediate nerve reconstruction, and control groups. The nerve ablation group had 5-mm sections of the cavernosal nerve excised bilaterally. The nerve graft group had 5-mm sections of the cavernosal nerve excised bilaterally, followed by immediate microsurgical reconstruction with an autologous interposition nerve graft utilizing the ipsilateral genitofemoral nerve bilaterally. The anastomoses were performed with 10-O nylon sutures at 16 to 25x magnification. The control group underwent sham operations with the cavernosal nerves being exposed only. Erectile function was evaluated at 1, 2, 4, and 6 months postoperatively. Return of erectile function was defined as tumescence of the corporal bodies with application of direct electrical stimulation (3 V of 5 msec pulses at 20 Hertz) to the proximal cavernosal nerves. The 4- and 6-month electrical stimulation studies resulted in tumescence from 65 and 75% of the grafted nerves, which represented a significant difference compared to the ablated group 11 and 5%, respectively (P less than 0.001 at 4 and 6 months). Behavioral copulatory studies, performed prior to electrical stimulation testing, corresponded closely with the results of electrically induced tumescence. We conclude that in this experimental model immediate nerve graft repair appears to be a successful method of salvaging erectile function when the cavernosal nerves have been divided.

Entubulization repair of severed cavernous nerves in the rat resulting in return of erectile function.

Erectile dysfunction is a significant complication of radical pelvic surgery in men. Using the rat as an experimental model, we investigated the feasibility of repairing surgically ablated cavernous nerves utilizing silastic tube nerve growth conduits filled with nerve growth enhancing media. Known fertile male Sprague-Dawley rats were randomly divided into four surgical groups consisting of nerve ablation, immediate nerve reconstruction utilizing the entubulization technique (two groups) and control. The nerve ablation group had five mm. sections of the cavernosal nerve excised bilaterally. The entubulization nerve graft group had five mm. sections of the cavernous nerve excised bilaterally, followed by immediate microsurgical reconstruction with a silastic nerve tube conduit filled with either Matrigel and heparin (MA) or Matrigel and heparin plus acidic fibroblast growth factor (MA/aFGF), interposed between the severed cavernous nerve stumps bilaterally. The control group underwent sham operations with the cavernous nerves being exposed only. Erectile function was evaluated at one, two, and four months postoperatively. Return of erectile function was defined as tumescence of the corporal bodies with application of direct electrical stimulation (four volts of five millisecond pulses at 20 Hertz) to the proximal cavernous nerves. The two and four month electrical stimulation studies resulted in tumescence from 50% and 58% of the entubulization nerve reconstructed nerves with MA/aFGF versus 29% and 30% for the MA only group and only 5% and 11% for the ablated group, respectively. We conclude that in this experimental model immediate nerve graft repair utilizing entubulization techniques with the addition of nerve growth enhancing media appears to be a successful method of salvaging erectile function when the cavernous nerves have been divided.

The current cavernosometric criteria for corporovenous dysfunction are too strict.

In an attempt to define the hemodynamic and radiographic parameters of normal erectile function 6 patients 20 to 41 years old (mean age 30.3 years) with erectile dysfunction that spontaneously resolved after a comprehensive evaluation were reviewed. The results included normal hormonal assays, normal penile biothesiometry and normal penile brachial index. The sleep tumescence and rigidity tracings were abnormal according to the criteria that sleep erections occur every 90 minutes, are associated with penile rigidity of greater than 550 gm. plus an increase in penile circumference of greater than 1.5 cm. and last longer than 15 minutes. High resolution ultrasonography, pulse wave Doppler ultrasound, dynamic pharmacocavernosometry and dynamic cavernosography were performed. After testing the patients were informed that no organic abnormalities had been detected. No medical or surgical treatment was given. The hemodynamic values are presented as suggested normal parameters: maintenance rate (mean 11 +/- 3 cc per minute), initial decompression rate (mean 59 +/- 17 mm. Hg/30 seconds) and radiographic findings (visualization of the cavernous, external pudendal and deep dorsal veins during pharmacocavernosography, performed at intracorporeal pressures of 100 mm. Hg). All 6 patients had maintenance rates of greater than 5 cc per minute. Of these 6 patients 5 had initial decompression rates of greater than 48 mm. Hg/30 seconds and 4 had 5-minute, post-infusion steady state values of less than 50 mm. Hg, criteria that have been used to define corporovenous dysfunction.

Expressed Emotion in community care staff. A comparison of patient outcome in a nine month follow-up of two hostels.

Expressed Emotion was measured in the staff of two similar hostels for the long term mentally ill in an Inner London Borough (Hostel A and Hostel B). Patients in the two hostels showed similar levels of disturbance as measured by the PSE and symptom and behaviour profile scores. Staff from Hostel B displayed higher levels of EE, and were more critical, and these attitudes generalised easily into hostility and rejection. Those from Hostel A showed lower EE with warmth and positive attitudes towards clients. At 9 month follow up, Hostel A and B had similar levels of relapse requiring hospital admission. However Hostel B had a 64% discharge rate compared with 12.5% for Hostel A. These results are discussed with reference to the literature.

EMS under siege: a tale of four cities.

This article depicts the escalating violence throughout the United States and the increased danger of working on the front lines of medicine. Find out what four U.S. cities are presently doing to combat such dangers.

Symptoms and social adjustment in Jewish depressives.

In 25 Jewish and 26 non-Jewish depressives resident in Hackney, the PSE revealed that 'hypochondriasis' and 'tension' were more common in the Jewish group, and special features of depression, containing symptoms connected with guilt, was less common. These differences could not be explained by variation in severity of illness as both groups had similar scores on the HRSD. The 'social maladjustment' scores were similar, very probably reflecting an elderly, deprived, inner-city population.

Glucocorticoid induced stress susceptibility in swine: adrenocortical pathology.

The studies reported here were undertaken to better characterize the role of the adrenal cortex in the increased susceptibility to stress observed in porcine stress syndrome. Since adrenal hypofunction was suggested during early studies as a factor in events leading to porcine stress syndrome it was decided to produce such a state by the exogenous administration of the glucocorticoids prednisolone and fluoroprednisolone.A total of 34 pigs (weighing 90 to 100 kg) received a series of graded doses (given intramuscularly) of one or the other of the foregoing compounds and were necropsied 48, 72, and 120 hours after the last treatment. The major adrenocortical changes produced by these treatments were atrophy, an accentuation of degenerative changes which could be observed in milder form in many of the 30 control pigs examined, a marked increase in stainable lipid 120 hours after the last fluoroprednisolone treatment and, ultrastructurally, an increase in lysosome-like bodies and cellular debris ("myelin bodies").Adrenocortical atrophy is not a feature of porcine stress syndrome nor were the localized depositions of stainable lipid within the zona reticularis, described in porcine stress syndrome, found in the glucocorticoid treated pigs. Consequently, the findings reported here bear a somewhat limited resemblance to those observed in pigs affected by porcine stress syndrome and cast some doubt on whether adrenal hypofunction plays a role in the pathogenesis of the latter condition.