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Biomedical subjects

P S Malone

Publications and source records attributed to P S Malone.

At least 19 recordsLinked to original sources
PubMed2005

The effect of short-chain fatty acids butyrate, propionate, and acetate on urothelial cell kinetics in vitro: potential therapy in augmentation cystoplasty.

The intestinal element of enterocystoplasty is affected by chronic inflammatory changes, which lead to excess mucus production, urinary tract infections, and stone formation. There is also an increased risk of malignancy. These inflammatory changes may be due to diversion colitis, which affects colonic segments excluded from the faecal stream and likewise may respond to intraluminal short-chain fatty acid (SCFA) therapy. The SCFAs have interesting antiproliferative, differentiating, and pro-apoptotic effects, which are protective against colorectal cancer and may influence the risk of malignancy in enterocystoplasty. Before intravesical therapy can be considered, the effect on normal urothelium must be investigated. Primary urothelial cells cultured from biopsy specimens and transformed urothelial (RT112 and MGH-U1) and intestinal cell lines (HT29 and CaCo-2) were incubated with SCFAs. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure the residual viable biomass to assess cell proliferation. Proliferation of primary and transformed urothelial cells in culture was inhibited by all SCFAs in a similar time- and dose-dependent manner. The concentration of SCFA required to inhibit growth of primary cells by 50% (IC50) was 20 mM of butyrate, 120 mM of propionate, and 240 mM of acetate after incubation for 1 h. After 72 h the IC50 was 2 mM of butyrate, 4 mM of propionate, and 20 mM of acetate. Transformed urothelial and colon cancer cell lines demonstrated similar growth inhibition. Butyrate was the most potent inhibitor of cell proliferation, followed by propionate and then acetate. Growth inhibition is not an immediate cytotoxic effect, and urothelial cells show a degree of adaptation to butyrate and growth recovery after incubation with butyrate. In conclusion, butyrate- and propionate-induced growth inhibition is potentially clinically significant and may have therapeutically beneficial implications in vivo.

Acetates↗
PubMed2001

Synchronous bladder reconstruction and antegrade continence enema.

PURPOSE: We assess the long-term outcome of synchronous bladder reconstruction and antegrade continence enema in a large series of patients. MATERIALS AND METHODS: We retrospectively reviewed records of the last 50 consecutive patients treated at 1 unit in Southampton and 1 in Denver. RESULTS: A total of 46 patients were available for analysis, including 24 from Southampton and 22 from Denver. Median patient age at operation was 12 years (range 4 to 30), median followup was 44 months (range 7 to 100), and 80% of patients had neuropathy and anorectal malformation. A variety of bladder reconstructive procedures were performed and 58% of patients underwent a simultaneous Mitrofanoff procedure. Fecal and urinary continence was achieved in 76% of patients but the rate of revision surgery was high. The most common complication was stomal stenosis (17%). Secondary procedures consisted of refashioning urethral length, closure of the bladder neck, bladder augmentation and conduit revision. CONCLUSIONS: It is now possible to produce double continence in some patients with synchronous combined surgery, a goal that was not achievable without colostomy before the development of the antegrade continence enema in 1990. However, the surgery is demanding with high revision rates and we emphasize that it should only be performed in patients who are highly motivated and have reasonable dexterity and intelligence. This careful patient selection is confirmed by the fact that surgery was performed on 2 to 3 patients a year at each unit. This surgery should only be performed at facilities which can provide long-term patient followup.

Adolescent↗
PubMed2001

Diversion colitis in children with colovaginoplasty.

OBJECTIVE: To highlight the occurrence of diversion colitis and its effects in colovaginoplasty. Patients and methods The records of 18 children who had undergone colovaginoplasty were reviewed retrospectively. Nine patients had androgen-insensitivity syndrome and three each had congenital adrenal hyperplasia, vaginal agenesis and Mayer-Rokitansky syndrome. Through an abdominoperineal approach a segment of sigmoid colon was isolated on its vascular pedicle and brought to the perineum in the plane between the urethra and rectum, as a blind pouch or as an interposition between the proximal vagina and the perineum. The mean (range) follow-up was 5 (1.5-8) years. RESULTS: There were no major complications during the early follow-up. Three patients developed severe vaginal discharge with bleeding 2-7 years after colovaginoplasty; examination showed erythema, oedema, ulceration and bleeding. Histology confirmed the classic features of diversion colitis in all three patients. One child responded to vaginal irrigation with a solution of short-chain fatty acids, and the other two were treated with steroid enemas and mesalazine after a poor response to short-chain fatty acids. One of these patients has required surgical reduction of an excessively long neovagina. Conclusion Symptomatic diversion colitis can occur after colovaginoplasty. The severity of the symptoms raises concerns about the use of colovaginoplasty in children and alternative techniques of vaginal replacement should be considered in the first instance.

Anastomosis, Surgical↗
PubMed2000

Congenital megaprepuce: an emerging condition--how to recognize and treat it.

OBJECTIVE: To highlight the clinical presentation, pathological anatomy and surgical management of an emerging condition, the congenital megaprepuce (CM). PATIENTS AND METHODS: All patients with CM treated at Southampton between 1994 and 1998 were reviewed retrospectively; 20 patients underwent surgery (mean age at operation 16 months, range 6-43). Surgical correction developed over this period and variations on a basic technique are now used, depending on the precise pathological anatomy. These techniques are described and illustrated. Cosmetic and functional success, and parental satisfaction, were assessed by a review of the case-notes. RESULTS: After a follow-up of >/= 6 months, the cosmetic and functional outcome was very successful, with the parents of 19 of the 20 patients satisfied. Five patients underwent re-operation, all requiring excision of redundant penile skin. CONCLUSIONS: CM is a striking condition which cannot be easily missed or hidden; we propose that it is a newly emerging and distinct condition which should not be confused with a buried, concealed, webbed, trapped or micropenis. Early surgical correction is recommended and circumcision should be avoided.

Attitude to Health↗
PubMed1999

Antenatal minimal hydronephrosis: is its follow-up an unnecessary cause of concern?

The aim of this study was to determine if follow-up of antenatally diagnosed minimal hydronephrosis (anteroposterior renal pelvis diameter <10 mm) is justified or if it is an unnecessary cause of concern for the parents involved. A case-control study, with subjects and controls selected from the Wessex Antenatally Detected Anomalies Register was performed. Information regarding antenatal and postnatal follow-up, renal tract morbidity and degree of concern was obtained from a parental questionnaire. 70 of the 115 subjects contacted (60.9 per cent) and 52 of the 81 controls (64.2 per cent) returned the questionnaire. 65 of the 70 subjects (92.9 per cent) were rescanned postnatally when 28 cases (43.1 per cent) had resolved. Coexisting ureteric and/or calyceal dilatation was evident postnatally in 12 cases and this group was significantly more likely to have underlying pathology than the group with isolated renal pelvis dilatation. Subjects were significantly more likely than controls to have a UTI. The degree of concern was significantly greater in the subject group and subject parents thought about the result significantly more often than controls. From our results we concluded that the follow-up of minimal hydronephrosis can be modified. There is no need for repeated antenatal scanning, a change that could reduce the level of parental anxiety. Postnatal follow-up is required in all patients to exclude an underlying uropathy but again this can be modified, with the majority of patients requiring only an ultrasound scan. This reduced intensity of investigation accompanied with careful explanation to the parents should help to minimize their concerns.

Anxiety↗
PubMed1999

The MACE procedure: experience in the United Kingdom.

BACKGROUND/PURPOSE: The Malone Antegrade Continence enema (MACE) procedure has become commonplace in the treatment of patients with faecal incontinence and constipation. To ascertain its place in paediatric practice, the authors surveyed members of the British Association of Paediatric Surgeons (BAPS) to see if they have performed a MACE and continue to do so. The authors also assessed their indications, success rate, and complications. METHODS: Members were asked to give the diagnosis of the patients submitted for surgery before September 1996, the procedure used to constructthe MACE, the rate of failure, and complications encountered. RESULTS: A total of 300 MACE were reported, and the mean follow-up was 2.4 years. The diagnosis of 273 patients was known: spina bifida, 108; anorectal anomaly, 90; Hirschsprung's disease, 22; constipation, 23; other, 30. The most popular procedure was appendix disconnection and reimplantation. The overall success rate for all diagnoses was 79%. The main complication was stomal stenosis, 30%. CONCLUSIONS: These figures confirm that MACE is a useful operation. Improved patient selection, improvement in techniques, and increasing knowledge regarding continued management should lead to improving results across the country.

Adolescent↗
PubMed1999

The incidence of hypospadias in two English cities: a case-control comparison of possible causal factors.

OBJECTIVES: To determine the incidence and severity of hypospadias amongst children born in Southampton and Portsmouth during 1992-94, and to identify possible causal factors by comparing patients with a control group. PATIENTS AND METHODS: All patients with hypospadias born in Southampton and Portsmouth during 1992-94 were identified. The Southampton cases were matched with controls; the case notes of each affected child were reviewed. The incidence determined by this study was compared with data provided by the Central Statistics Office. RESULTS: There was no apparent increase in the incidence of hypospadias in Southampton and Portsmouth during 1982-94. However, there was a clear local variation in incidence, with a significantly lower incidence in Portsmouth than in Southampton and the rest of England and Wales. The severity of hypospadias was also more marked in Southampton than in Portsmouth. The only recognisable aetiological factor was a positive family history, supporting the concept of a polygenic mode of inheritance. All the environmental factors investigated were unrelated, but there was a suggestion of clustering in a single water-quality zone. CONCLUSIONS: This study identified no increase in the incidence of hypospadias but it did detect local variations in both the incidence and severity of the condition, and these need to be considered when planning surgical services.

Case-Control Studies↗
PubMed1999

The Pippi Salle urethral lengthening procedure; experience and outcome from three United Kingdom centres.

OBJECTIVE: To assess the outcome of the Pippi Salle (Kropp onlay) urethral lengthening procedure in the treatment of neuropathic urinary incontinence. PATIENTS AND METHODS: Twenty-eight patients (12 males and 16 females, mean age at surgery 12.6 years, range 7-32) were identified who underwent the procedure between 1993 and 1997 in the United Kingdom. Outcomes were assessed by a review of the case notes. RESULTS: Of the 28 patients, 18 (64%) were rendered continent by day, and 17 (61%) by day and night. Twelve of the 16 females were completely dry, and a further girl was dry by day, giving overall daytime continence in 13 patients; five males were rendered continent (P=0.03, chi-square test). Four patients required revision surgery; in five patients (two females and three males) the method was abandoned and they underwent an alternative procedure, and a further four are being reassessed. CONCLUSION: The Pippi Salle procedure should be considered as a first-line treatment option for neuropathic incontinence in females. Its place in the management of incontinent males is less convincing.

Adolescent↗
PubMed1999

Tubularization of the incised urethral plate (Snodgrass procedure) for primary hypospadias surgery.

OBJECTIVE: To evaluate the Snodgrass procedure for patients with hypospadias who have not undergone previous surgery and whose urethral plate is too narrow for tubularization alone. PATIENTS AND METHODS: Thirty-two boys (mean age 18 months) underwent primary hypospadiac surgery performed by one surgeon (P.S.M.). Twenty-five boys had a distal hypospadias (coronal, subcoronal) and seven had a more proximal defect (penile shaft, penoscrotal). The operation involved incision of the urethral plate, which was then tubularized (Snodgrass procedure). The neourethra was then covered with a de-epithelialized pedicled dartos flap from the inner prepuce before glans and skin closure. RESULTS: With a mean follow-up of 10 months (range 2-14) there were two complications; one child with a coronal hypospadias developed a fistula whist one with a penile shaft defect had complete breakdown of the neourethra. The cosmetic appearance in the other 30 patients is that of a normal slit-like terminal meatus. CONCLUSION: Tubularization of the incised urethral plate is a safe advance in the surgery of hypospadias. We recommend it for both distal and proximal defects, in patients where the urethral plate is insufficient for tubularization alone.

Child↗
PubMed1998

The antegrade continence enema procedure why, when and how?

Following the description of the antegrade continence enema (ACE) 7 years ago, it has become widely performed and accepted as the most successful treatment for intractable faecal incontinence. Modifications of the operative technique and enema regimen have been described, but the basic principle remains. This paper traces the evolution of the ACE and describes criteria for patient selection, operative technique and enema regimens.

Appendix↗
PubMed1998

Effects of short-chain fatty acids on primary urothelial cells in culture: implications for intravesical use in enterocystoplasties.

The presence of inflammatory changes and mucopus production in an enterocystoplasty may be similar to the condition of diversion colitis and starvation diarrhea caused by a lack of luminal short-chain fatty acids (SCFAs). We postulate a therapeutic role for intravesical SCFA. Because this treatment will also contact the urothelium, we have assessed the effect on cellular proliferation by utilizing primary urothelial cells in culture. Primary urothelial cells were grown from biopsy samples of normal urothelium obtained intraoperatively. A cocktail of SCFA used in the treatment of diversion colitis was incubated with these cells for time intervals ranging from 30 minutes to 72 hours at drug concentrations ranging from 0.04 to 20 mmol/L butyrate equivalent (BE). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure the residual viable biomass to assess growth inhibition. These experiments were repeated on cells grown on matrigel substrate. The human urothelial cancer line RT112 was likewise exposed to SCFAs to assess selectivity between primary and transformed cells. Primary urothelial cells in culture undergo growth inhibition when exposed to SCFAs. The concentration of SCFAs required to reduce the general biomass by 50% or more (IC> or =50) was 20 mmol/L BE when exposure was for 2 hours or less. When drug exposure was prolonged for 72 hours, the IC> or =50 was 2.5 mmol/L BE. Cells grown on matrigel had their growth similarly inhibited. The IC > or = 50 for the RT112 cell line was 2.5 mmol/L BE after 72 hours of drug incubation. Primary urothelial cells in culture undergo a time- and dose-dependent growth inhibition when exposed to SCFAs. This inhibition is particularly apparent at the higher doses similar to those in use in clinical practice. Cells grown on a matrigel substrate suffer growth attenuation similar to that affecting cells grown on polystyrene plates. In vivo assessment in a rodent intravesical model is advisable before considering instillations in patients.

Cell Division↗
PubMed1998

How to achieve a successful Malone antegrade continence enema.

BACKGROUND/PURPOSE: The Malone antegrade continence enema (MACE) has proved invaluable in the management of children with faecal incontinence. The authors have reviewed their experience in depth to try and ascertain why some MACEs fail. METHODS: The records of 31 children who had a MACE procedure between 1990 and 1995 were reviewed. Their preoperative bowel management, the operative procedure, the postoperative washout regime, and the outcome were assessed. Success was graded either as full, described as totally clean or minor rectal leakage on the night of the washout; partial, described as clean but significant stomal or rectal leakage, occasional major leaks, still wearing protection, and perceived improvement by the parents or child; or failure, described as regular soiling or constipation, no perceived improvement, and the procedure abandoned. There were 18 boys and 13 girls in the series. The mean age at survey was 8.4 years. RESULTS: Overall success rate was 19 of 31 (61%) with a mean follow-up of 3.25 years. The diagnosis and success rates were: anorectal anomaly 11 (success, 8 of 11, 73%), neuropathic bowel 11 (8 of 11, 73%), chronic constipation 8 (3 of 8, 38%).

Appendix↗
PubMed1998

Transversely tubularized ileal segments for the Mitrofanoff or Malone antegrade colonic enema procedures: the Monti principle.

OBJECTIVE: To assess the use of a transverse tubularized segment(s) of ileum in the Mitrofanoff or Malone antegrade colonic enema (MACE) procedures. PATIENTS AND METHODS: Eleven patients in three centres underwent the formation of a continent conduit to bowel (MACE, eight patients) and/or bladder (Mitrofanoff, four) using either a single segment of transverse tubularized ileum (10 patients) or two segments of ileum anastomosed and tubularized into a single conduit (two). RESULTS: Within a follow-up of 8 weeks to 6 months, all conduits were continent and catheterized easily. One stomal stenosis required a revision procedure. CONCLUSION: This method for forming a continent catheterizing conduit, based on the Mitrofanoff principle, appears to be effective and is recommended in cases where the appendix cannot be used or where a second conduit is required.

Adolescent↗
PubMed1996

Antenatal diagnosis of renal tract anomalies: has it increased the sum of human happiness?

When used as a screening procedure, ultrasound examination of the fetal urinary tract seldom leads to beneficial interventions. There is also a cost in terms of parental anxiety and unnecessary investigation and treatment. A formal screening programme would therefore be unjustified. However, screening of women for obstetric purposes will continue to reveal fetal abnormalities, and a strategy for dealing with these is needed. Antenatal treatments remain experimental; for most of the common conditions postnatal treatment has no urgency; and, in cases of minor abnormality detected by ultrasound, the best course may be to do nothing.

Female↗