Delivery Models and Health Economics of Supportive Care Services in England: A Multicentre Analysis.

AIMS: Improvements in cancer treatment have led to more people living with and beyond cancer. These patients have symptom and support needs unmet by current services. The development of enhanced supportive care (ESC) services may meet the longitudinal care needs of these patients, including at the end of life. This study aimed to determine the impact and health economic benefits of ESC for patients living with treatable but not curable cancer. MATERIALS AND METHODS: A prospective observational evaluation was undertaken over 12 months across eight cancer centres in England. ESC service design and costs were recorded. Data relating to patients' symptom burden were collected using the Integrated Palliative Care Outcome Scale (IPOS). For patients in the last year of life, secondary care use was compared against an NHS England published benchmark. RESULTS: In total, 4594 patients were seen by ESC services, of whom 1061 died during follow-up. Mean IPOS scores improved across all tumour groups. In total, £1,676,044 was spent delivering ESC across the eight centres. Reductions in secondary care usage for the 1061 patients who died saved a total of £8,490,581. CONCLUSIONS: People living with cancer suffer with complex and unmet needs. ESC services appear to be effective at supporting these vulnerable people and significantly reduce the costs of their care.

Accelerated post traumatic osteoarthritis in a dual injury murine model.

OBJECTIVE: Joint injury involving destabilisation of the joint and damage to the articular cartilage (e.g., sports-related injury) can result in accelerated post-traumatic osteoarthritis (PTOA). Destabilised medial meniscotibial ligament (DMM) surgery is one of the most commonly used murine models and whilst it recapitulates Osteoarthritis (OA) pathology, it does not necessarily result in multi-tissue injury, as occurs in PTOA. We hypothesised that simultaneous cartilage damage and joint destabilisation would accelerate the onset of OA pathology. METHODS: OA was induced in C57BL/6 mice via (a) DMM, (b) microblade scratches of articular cartilage (CS) or (c) combined DMM and cartilage scratch (DCS). Mice were culled 7, 14 and 28 days post-surgery. Microcomputed tomography (µCT) and histology were used to monitor bone changes and inflammation. Dynamic weight bearing, an indirect measure of pain, was assessed on day 14. RESULTS: Osteophytogenesis analysis via µCT revealed that osteophytes were present in all groups at days 7 and 14 post-surgery. However, in DCS, osteophytes were visually larger and more numerous when compared with DMM and cartilage scratch (CS). Histological assessment of cartilage at day 14 and 28, revealed significantly greater damage in DCS compared with DMM and CS. Furthermore, a significant increase in synovitis was observed in DCS. Finally, at day 14 osteophyte numbers correlated with changes in dynamic weight bearing. CONCLUSION: Joint destabilisation when combined with simultaneous cartilage injury accelerates joint deterioration, as seen in PTOA. Thus, DCS provides a novel and robust model for investigating multiple pathological hallmarks, including osteophytogenesis, cartilage damage, synovitis and OA-related pain.

Surveillance for upper respiratory tract disease and Mycoplasma in free-ranging gopher tortoises (Gopherus polyphemus) in Georgia, USA.

Abstract Upper respiratory tract disease (URTD) in the gopher tortoise (Gopherus polyphemus) is highly contagious and has been implicated in the reduction of populations throughout the range. With the exception of a few limited studies, the prevalence of URTD in Georgia, USA tortoise populations is poorly known. We found that exposure to Mycoplasma agassizii and Mycoplasma testudineum, associated with URTD, varied geographically among 11 Georgia tortoise populations. The prevalence of antibodies to M. agassizii in individual populations was either very low (0-3%, n=7 populations) or very high (96-100%, n=4 populations), whereas there was variation in the prevalence of antibodies to M. testudineum among populations (20-61%, n=10) with only one site being negative. Five sites had tortoises with antibodies to both pathogens, and these were the only sites where we observed tortoises with clinical signs consistent with URTD. We did not find tortoises with clinical signs of URTD at sites with tortoises with antibodies only to M. testudineum, which provides evidence that this organism may be of limited pathogenicity for gopher tortoises. Collectively, these data indicate that both M. agassizii and M. testudineum are present in Georgia populations of gopher tortoises and that clinical disease is apparent in populations where both pathogens are present. Additional research is needed to better understand the role of these two pathogens, and other potential pathogens, in the overall health of tortoise populations, especially if future conservation efforts involve translocation of tortoises.

The essential role of the Deinococcus radiodurans ssb gene in cell survival and radiation tolerance.

Recent evidence has implicated single-stranded DNA-binding protein (SSB) expression level as an important factor in microbial radiation resistance. The genome of the extremely radiation resistant bacterium Deinococcus radiodurans contains genes for two SSB homologs: the homodimeric, canonical Ssb, encoded by the gene ssb, and a novel pentameric protein encoded by the gene ddrB. ddrB is highly induced upon exposure to radiation, and deletions result in decreased radiation-resistance, suggesting an integral role of the protein in the extreme resistance exhibited by this organism. Although expression of ssb is also induced after irradiation, Ssb is thought to be involved primarily in replication. In this study, we demonstrate that Ssb in D. radiodurans is essential for cell survival. The lethality of an ssb deletion cannot be complemented by providing ddrB in trans. In addition, the radiation-sensitive phenotype conferred by a ddrB deletion is not alleviated by providing ssb in trans. By altering expression of the ssb gene, we also show that lower levels of transcription are required for optimal growth than are necessary for high radiation resistance. When expression is reduced to that of E. coli, ionizing radiation resistance is similarly reduced. UV resistance is also decreased under low ssb transcript levels where growth is unimpaired. These results indicate that the expression of ssb is a key component of both normal cellular metabolism as well as pathways responsible for the high radiation tolerance of D. radiodurans.

The development and evaluation of a questionnaire to assess the impact of vulval intraepithelial neoplasia: a questionnaire study.

OBJECTIVE: To develop and evaluate a questionnaire to assess the burden of vulval intraepithelial neoplasia (VIN) in women. DESIGN: A questionnaire development study. SETTING: Vulval Disorders Clinic serving a regional population. SAMPLE: Fifty-eight women with a histological diagnosis of VIN registered with the Vulval Disorders Clinic. METHODS: A 37-item questionnaire was developed through a comprehensive literature review, consultation with specialist clinicians and pretesting to assess the burden experienced by women. The questionnaire was assessed for validity and reliability against existing questionnaires used in related disease areas. MAIN OUTCOME MEASURES: Spearman correlations were calculated between items in the VIN questionnaire with the scores of the Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS), Sabbatsberg Sexual Self-Rating Scale (SSRS) and the Process Outcome Specific Measure (POSM) to assess the new questionnaire's validity. Internal consistency was measured using Cronbach's alpha. Test-retest reliability was calculated using quadratic weighted kappa. RESULTS: The VIN questionnaire had a high degree of internal consistency (Cronbach's alpha, 0.89). Test-retest reliability was assessed, with most questions showing a quadratic weighted kappa value of 0.5 or above. Most questions showed a stronger correlation with the corrected total VIN score than with HADS anxiety and depression subscales and the SSRS, indicating discriminant validity. Most questions correlated significantly with the DLQI and POSM scores, indicating convergent validity. CONCLUSIONS: Initial assessment of the VIN questionnaire demonstrated that it is a valid and reliable measure of the burden of disease for women. The questionnaire could be used to compare new and existing treatments for VIN or to assess or monitor the impact of care.

PAR(2) expression in peripheral blood monocytes of patients with rheumatoid arthritis.

OBJECTIVES: Proteinase-activated receptor 2 (PAR(2)) is a G protein-coupled receptor activated by serine proteinases with proinflammatory activity. A study was undertaken to investigate the presence and functional significance of PAR(2) expression on rheumatoid arthritis (RA)-derived leucocyte subsets. METHODS: Venous blood was obtained from patients with RA and osteoarthritis (OA) as well as healthy control subjects. Surface expression of PAR(2) on peripheral blood mononuclear cells (PBMCs) was analysed by flow cytometry and interleukin 6 (IL-6) generation by ELISA. RESULTS: Patients with RA had elevated but variable surface expression of PAR(2) on CD14+ monocytes compared with control subjects (median (1st to 3rd quartiles) 1.76% (0.86-4.10%) vs 0.06% (0.03-0.81%), p<0.0001). CD3+ T cells showed a similar pattern with significantly higher PAR(2) expression in patients with RA compared with controls (3.05% (0.36-11.82%) vs 0.08% (0.02-0.28%), p<0.0001). For both subsets, PAR(2) expression was significantly higher (p<0.00001) in patients with high levels of disease activity: PAR(2) expression for both CD14+ and CD3+ cells correlated to C reactive protein and erythrocyte sedimentation rate. Furthermore, in a cohort of patients with newly diagnosed RA, elevated PAR(2) expression in both CD14+ and CD3+ cells was significantly reduced 3 months after methotrexate or sulfasalazine treatment and this reduction correlated significantly with the reduction in the 28-joint Disease Activity Scale score (p<0.05). PAR(2) expression on cells from patients with OA was low, similar to levels seen in control subjects. Generation of IL-6 by monocytes in response to a selective PAR(2) agonist was significantly greater in patients with RA than in patients with OA and control subjects (p<0.05). CONCLUSIONS: These findings are consistent with a pathogenic role for PAR(2) in RA.

Salmonella from gopher tortoises (Gopherus polyphemus) in south Georgia.

From 2002 to 2006, gopher tortoises (Gopherus polyphemus) were collected at Moody Air Force Base, Lowndes/Lanier counties, Georgia, USA, and opportunistically surveyed for the presence of Salmonella species. Four of 155 (2.6%) cloacal swabs collected from 80 tortoises were positive for the presence of Salmonella enterica, and the following serovars were identified: Give, Hartford, Javiana, and Luciana. Female tortoises (5%) were infected at a rate similar to male tortoises (5%). All isolates were obtained from adult tortoises (n = 73); subadults (n = 7) were all negative. Each isolated serovar is a potential human pathogen, suggesting appropriate precautions should be emphasized when handling these animals.

Angiotensin II type 1 receptor as a novel therapeutic target in rheumatoid arthritis: in vivo analyses in rodent models of arthritis and ex vivo analyses in human inflammatory synovitis.

OBJECTIVE: Angiotensin II (Ang II) is known to have proinflammatory actions, and Ang II type 1 (AT(1)) receptors are up-regulated in the rheumatoid synovium, suggesting that this receptor could be a therapeutic target. The purpose of this study was to investigate the antiinflammatory potential of the selective AT(1) receptor antagonist losartan, which is currently used for the treatment of cardiovascular disease. METHODS: Dose-ranging studies of losartan (1-50 mg/kg) were initially conducted in a rat model of acute (carrageenan/kaolin) arthritis, with subsequent evaluation in a rat model of adjuvant-induced arthritis (Freund's complete adjuvant). Losartan (10(-10) to 10(-6)M) was further tested ex vivo in human inflammatory synovitis, using collagenase-digested synovium. RESULTS: Western blot and immunohistochemical analyses both revealed a substantial increase in AT(1) receptor protein content in synovium from acutely and chronically inflamed rat knee joints. Similarly, synovial Ang I/II protein content was elevated during inflammation. Losartan inhibited acute joint inflammation in a dose-dependent manner, with 15 mg/kg being the optimal dose (and used in subsequent studies). Both prophylactic and therapeutic administration of 15 mg/kg of losartan substantially reduced knee joint swelling in rats with adjuvant monarthritis (> or =50%; P < 0.0001). Losartan also suppressed tumor necrosis factor alpha generation from inflamed human synovium in a dose-dependent manner (P < 0.05). CONCLUSION: Targeting the angiotensin pathway, particularly AT(1) receptors, could have significant therapeutic potential. Randomized placebo-controlled trials are now warranted to establish the extent to which angiotensin receptor blockers may provide antiinflammatory benefits.

Protective effect of sensory denervation in inflammatory arthritis (evidence of regulatory neuroimmune pathways in the arthritic joint).

OBJECTIVE: To investigate the direct effect of joint innervation on immune mediated joint inflammation in a patient with psoriatic arthritis (PsA). CASE REPORT: The patient developed arthritis mutilans in all digits of both hands with the exception of the left 4th finger, which had prior sensory denervation following traumatic nerve dissection. Plain radiography, ultrasonography and nerve conduction studies of the hands confirmed the absence of articular disease and sensory innervation in the left 4th digit. METHODS: This relationship between joint innervation and joint inflammation was investigated experimentally by prior surgical sensory denervation of the medial aspect of the knee in six Wistar rats in which carrageenan induced arthritis was subsequently induced. Prior sensory denervation--with preservation of muscle function--prevented the development of inflammatory arthritis in the denervated knee. DISCUSSION: Observations in human and animal inflammatory arthritis suggest that regulatory neuroimmune pathways in the joint are an important mechanism that modulates the clinical expression of inflammatory arthritis.

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

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

Devastating complications after brachytherapy in the treatment of prostate adenocarcinoma.

OBJECTIVE: To report a retrospective chart review of patients who developed recto-urethral fistula (RUF) or several bladder neck contracture (BNC) recurrences after brachytherapy for treating localized prostate cancer. PATIENTS AND METHODS: In the past 3 years 18 patients with devastating complications after prostate brachytherapy were referred to our centre (RUF in 11, BNC in seven; mean age 63 years, range 60-81). All patients with RUF initially underwent diverting colostomy (six cystoprostatectomy with closure of the fistula, omental interposition and urinary diversion; one prostatectomy, bladder neck closure, fistula closure with omentum flap and continent vesicostomy). Three patients had the fistula closed with gracilis muscle flap using the York-Mason approach (one had a bladder neck closure and suprapubic tube; one elected to have no treatment). All patients with BNC had received three or more procedures to resect or incise their contracture. Four had diversion with a catheterizable segment, two used an indwelling Foley catheter and one uses intermittent catheterization. RESULTS: All six patients who had cystoprostatectomy with urinary diversion have had no recurrence of their RUF. All three treated with the York-Mason procedure healed well. One developed recurrent prostate adenocarcinoma and two a secondary neoplasia in the prostate or rectum (leiomyosarcoma and neuroendocrine, respectively). The enterocystoplasty patient developed sepsis after colostomy reversal and subsequently died. In those patients with BNC, the four who underwent urinary diversion fared well; two tolerate the indwelling catheter poorly, and the seventh uses intermittent catheterization with occasional difficulty. CONCLUSIONS: Brachytherapy with or without external irradiation can be associated with severe complications. RUF managed with aggressive anterior pelvic exenteration and urinary diversion can be associated with excellent results. The York-Mason procedure in patients with an adequate urinary continence mechanism and bladder dynamics may provide good functional results. The presence of a secondary malignancy in patients deserves further investigation. Many recurrences of a BNC tend be refractory to transurethral resection/incision; indwelling catheters are then poorly tolerated and patients may require a major reconstructive procedure.

Combined inhibition of nitrergic and prostanoid pathways in J774 macrophages.

OBJECTIVES: Nitric oxide and prostaglandins are both implicated in the pathogenesis of inflammatory conditions such as rheumatoid arthritis (RA). The hypothesis that simultaneous inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) was more effective than inhibition of either enzyme alone was tested. METHODS: J774 macrophages were pre-incubated with L-NAME and/or indomethacin, prior to activation with LPS (10 micrograms/ml). RESULTS: LPS significantly increased NO2-; PGE2 and TNF-alpha levels by 24 h. Quantitative real-time PCR demonstrated a dose-dependent reduction in the expression of COX-2 in the presence of increasing doses of L-NAME. NO2- and PGE2 production were inhibited in a dose-dependent manner by either indomethacin or L-NAME. Combined administration of L-NAME and indomethacin produced a significantly greater inhibition of NO2- and PGE2 than either inhibitor alone. CONCLUSION: The data supports the therapeutic potential of combined inhibition of the prostanoid and nitrergic systems as an anti-inflammatory treatment strategy and supports the progression of this work into models of arthritis.

Multi-institutional experience with the gastrointestinal composite reservoir.

PURPOSE: We evaluated multi-institutional experience with the gastrointestinal composite reservoir in patients with metabolic acidosis, the short bowel syndrome, severe pelvic radiation and/or renal insufficiency. MATERIALS AND METHODS: At 4 institutions 33 patients underwent construction of a gastrointestinal composite reservoir, including 19 with the short bowel syndrome, 13 with metabolic acidosis and 7 who also had renal insufficiency. A total of 16 patients underwent conversion of a previous diversion and the remaining 17 received new urinary diversion. Charts were reviewed for the metabolic impact of the gastrointestinal reservoir as well as any long-term sequelae. RESULTS: At a mean followup of 54 months there was a significant (p < or =0.05) improvement in mean preoperative and postoperative serum chloride (106 versus 102 mEq./l.), serum bicarbonate (23.3 versus 25 mEq./l.) and serum pH (7.36 versus 7.4). Mean serum creatinine did not significantly differ during followup in patients with normal renal function or renal insufficiency. Complications were not different than those of standard intestinal or gastric reservoirs. CONCLUSIONS: The gastrointestinal reservoir has provided an excellent metabolic balance in a large series of compromised patients with few side effects. We believe that the gastrointestinal composite reservoir represents the urinary diversion of choice when standard intestinal urinary reservoirs cannot be created in the setting of metabolic acidosis, the short bowel syndrome and severe pelvic radiation. However, the value of the gastrointestinal composite in the setting of renal insufficiency remains undetermined.

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

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

The cytosolic termini of the beta- and gamma-ENaC subunits are involved in the functional interactions between cystic fibrosis transmembrane conductance regulator and epithelial sodium channel.

Epithelial sodium channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR) are co-localized in the apical membrane of many epithelia. These channels are essential for electrolyte and water secretion and/or reabsorption. In cystic fibrosis airway epithelia, a hyperactivated epithelial Na(+) conductance operates in parallel with defective Cl(-) secretion. Several groups have shown that CFTR down-regulates ENaC activity, but the mechanisms and the regulation of CFTR by ENaC are unknown. To test the hypothesis that ENaC and CFTR regulate each other, and to identify the region(s) of ENaC involved in the interaction between CFTR and ENaC, rENaC and its mutants were co-expressed with CFTR in Xenopus oocytes. Whole cell macroscopic sodium currents revealed that wild type (wt) alphabetagamma-rENaC-induced Na(+) current was inhibited by co-expression of CFTR, and further inhibited when CFTR was activated with a cAMP-raising mixture (CKT). Conversely, alphabetagamma-rENaC stimulated CFTR-mediated Cl(-) currents up to approximately 6-fold. Deletion mutations in the intracellular tails of the three rENaC subunits suggested that the carboxyl terminus of the beta subunit was required both for the down-regulation of ENaC by activated CFTR and the up-regulation of CFTR by ENaC. However, both the carboxyl terminus of the beta subunit and the amino terminus of the gamma subunit were essential for the down-regulation of rENaC by unstimulated CFTR. Interestingly, down-regulation of rENaC by activated CFTR was Cl(-)-dependent, while stimulation of CFTR by rENaC was not dependent on either cytoplasmic Na(+) or a depolarized membrane potential. In summary, there appear to be at least two different sites in ENaC involved in the intermolecular interaction between CFTR and ENaC.

Postradiation therapy adenosquamous cell carcinoma of the prostate.

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

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

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

Injury of the rectum during vaginal surgery.

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

Evaluation of flap valve as an alternative continence mechanism in the Florida pouch.

OBJECTIVES: To evaluate urodynamic findings in a successful flap valve (FV) continence mechanism in association with a continent colonic urinary reservoir (Florida pouch) and to compare the urodynamic findings of the FV mechanism with the doubly plicated (PI) standard anti-incontinence segment in the same reservoir. METHODS: Thirteen patients who successfully received the Florida pouch between 1988 and 1996 agreed to undergo urodynamic evaluation as part of a pilot study. Eight patients had a PI continence mechanism and a mean time from surgery of 51 months; 5 had a FV continence mechanism and a mean time from surgery of 14 months. Enterocystometry was performed with a trans-stomal Bard triple channel 7F catheter. Volume and pressure at first desire to empty (VFDE, PFDE), as well as maximal enterocystometric capacity and pressure (VMEC, PMEC), were recorded. Maximal outlet pressure (MOP) was recorded using the catheter withdrawal technique. RESULTS: PI and FV groups demonstrated the following mean values respectively: VFDE, 692.7 and 403 mL; PFDE, 19.5 and 19.2 cm H2O; VMEC, 876.5 and 515 mL; PMEC, 25.9 and 24.6 cm H2O; MOP, 57.5 and 51.2 cm H2O (reservoir empty) and 50.5 and 52.6 cm H2O (reservoir full); and functional length of outlet, 24.3 and 24.6 cm. MOP measurement demonstrated greater variability in the PI than in the FV group. CONCLUSIONS: Urodynamic comparison of these mechanisms reveals that MOP measurement was closer to the mean among FV than PI patients. In addition, the mean VFDE (692.7 mL for PI versus 403 mL for FV, P < 0.05) and the mean VMEC (876.5 mL for PI versus 515 mL for FV, P < 0.05) were significantly less in the FV group. Lower VMEC and less variability in MOP indicate that continence may be more dependent on MOP in the FV mechanism. A longer follow-up time and a larger number of patients will be of assistance in clarifying these findings.

Nurses' perceptions of head and neck oncology patients after surgery: severity of facial disfigurement and patient gender.

The purpose of this study was to determine nurses' perceptions of facial disfigurement in patients following surgery for head and neck cancer; to compare differences based on nurses' experience in head and neck oncology; and to explore differences in perceptions based on patient gender.