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S K Sundaram

Publications and source records attributed to S K Sundaram.

17 recordsLinked to original sources

A survey of follow-up practice of urologists across Britain and Ireland following nephrectomy for renal cell carcinoma.

AIM: To determine the follow-up protocol for interval assessment of patients following radical nephrectomy for renal cell cancer and to compare them with the recommendations proposed in the literature. METHODS: Consultant urologists across Britain and Ireland completed a postal questionnaire. One follow-up mailing was used to encourage non-responders. The responses were analysed in the light of the recommendations from European Association of Urology and American guidelines. Also information was collected from the respondents on the choice of follow-up investigations for renal cell cancer and the total duration of follow-up. RESULTS: Of the 480 urologists surveyed 292 (60.8%) responded. Most respondents recommended regular follow-up with chest radiography (CR), ultrasound and computed tomography (CT). For T1 disease CR was requested by 28, 62 and 55%; for T2 disease by 30, 66 and 51%; for T3 disease by 39, 63, and 48% at 3, 6 and 12 months, respectively. For T1 disease US was requested by 5, 23 and 30%; for T2 disease 6, 27 and 30%; for T3 disease 8, 25, and 26% at 3, 6 and 12 months, respectively. For T1 disease an abdominal CT was requested by 2, 17 and 21%; for T2 disease 3.7, 19.5 and 26%; for T3 disease 10, 31, and 33% at 3, 6 and 12 months, respectively. Only one respondent followed the guidelines suggested in the literature. Further follow-up after 12 months for 5 and 10 years was suggested by 58.2 and 21.3% for T1, 53 and 24.73% for T2, and 45.5 and 25.5% for T3, respectively. There is appreciable variation in the frequency of use and timing of imaging. CONCLUSIONS: Most respondents perform follow-up after radical nephrectomy in patients with renal cancer, with considerable variability in their practices. In the current increasingly cost-conscious healthcare industry a scientifically justified follow-up should be considered.

Carcinoma, Renal Cell↗

A study of the morbidity, mortality and long-term survival following radical cystectomy and radical radiotherapy in the treatment of invasive bladder cancer in Yorkshire.

OBJECTIVES: To study the morbidity of radical cystectomy and radical radiotherapy in the treatment of patients with invasive carcinoma of the bladder and to report the long-term survival following these treatments. PATIENT AND METHODS: 398 patients with invasive carcinoma of the bladder treated between 1993 and 1996 in the Yorkshire region were studied. Of 398 patients studied, 302 patients received radical radiotherapy and 96 underwent radical cystectomy. A retrospective review of patients' case notes was performed to construct a highly detailed database. Crude estimates of survival differences were derived using Kaplan-Meier methods. Log-rank tests (or, where appropriate, Wilcoxon tests) were used to test for the equality of these survivor functions. These functions were produced as all-cause survival. The proportional hazards regression modelling was used to assess the impact of definitive treatment on survival. A backwards-stepwise approach was used to derive a final predictive model of survival, with likelihood ratio tests to assess the statistical significance of variables to be included in the model. RESULTS: The patients undergoing radiotherapy were significantly older (mean age: 71 years versus 66 years), but no difference was identified in the distribution of American Society of Anaesthesiologists (ASA) grades in the two treatment groups. The stage distribution of cases in the treatment groups was not significantly different. Significant treatment delays were observed in both treatment groups. The median time from being seen in the clinic to transurethral resection of bladder tumour (TURBT) and subsequent radical treatment (cystectomy or radiotherapy) was 4.3 and 9 weeks, respectively. Age was the most significant independent factor accounting for treatment delays (p < 0.001). The 30-day and 3-month treatment-associated mortality for radical cystectomy and radiotherapy was 3.1% and 8.3% and 0.3% and 1.65%. Of the patients who received radiotherapy, 57 (18.8%) were subsequently subjected to a salvage cystectomy. For these 57 patients, 30-day and 3-month mortality after the salvage cystectomy were 8.8% and 15.7%. Gastrointestinal complications were the major source of early morbidity after primary and salvage cystectomy. Bowel leakage occurred in 3% following radical and 8.7% after salvage cystectomy. Bowel complications (leakage and obstruction) were the major cause of death following salvage cystectomy. No specific cause was predominant in those undergoing radical cystectomy with intestinal anastomotic leakage and urinary leakage accounting for one death each. Exacerbation of co-morbid conditions accounted for the remaining causes of mortality. Urinary leakage occurred in 4% following both forms of cystectomy. Recurrent pyelonephritis and intestinal obstruction were responsible for the majority of complications in the follow-up period. Bladder and gastrointestinal complications accounted for the majority of complications following radical radiotherapy. Some degree of irritative bladder and rectal were noted commonly. Severe bladder problems, which rendered the bladder non-functional or required surgical correction, occurred in 6.3% of patients. 2.3% of patients underwent surgery for bowel obstruction related to radiotherapy induced bowel strictures. Following radiotherapy, 43.6% of patients had a recurrence in the bladder at varying intervals post-treatment. Of these, 40% had > or =T2 disease. The 5-year survival following radiotherapy (with or without salvage cystectomy) was 37.4% while 36.5% of patients were alive 5 years after radical cystectomy. There was no statistically significant difference in the overall 5-year survival figures between the two primary treatments. Tumour stage, ASA grade and sex were the only independent predictors of 5-year survival on multivariate analysis. CONCLUSIONS: This retrospective regional study shows that there is no significant difference in the 5-year survival of patients with invasive bladder cancer treated with either radical radiotherapy or radical cystectomy. All forms of radical treatment for bladder cancer are associated with a significant treatment-associated morbidity and mortality. Gastrointestinal complications were responsible for the majority of complications. The treatment-associated mortality at 3 months was two- or three-fold higher than the 30-day mortality; emphasising its importance as an indicator of the true risks of cystectomy. The clinical T stage, the sex and the ASA grade of the patient were the only independent predictors of survival. The data in this series suggests that radical radiotherapy and radical cystectomy should be both considered as valid primary treatment options for the management of invasive bladder cancer.

Adult↗

Inducing and probing non-thermal transitions in semiconductors using femtosecond laser pulses.

Soon after it was discovered that intense laser pulses of nanosecond duration from a ruby laser could anneal the lattice of silicon, it was established that this so-called pulsed laser annealing is a thermal process. Although the radiation energy is transferred to the electrons, the electrons transfer their energy to the lattice on the timescale of the excitation. The electrons and the lattice remain in equilibrium and the laser simply 'heats' the solid to the melting temperature within the duration of the laser pulse. For ultrashort laser pulses in the femtosecond regime, however, thermal processes (which take several picoseconds) and equilibrium thermodynamics cannot account for the experimental data. On excitation with femtosecond laser pulses, the electrons and the lattice are driven far out of equilibrium and disordering of the lattice can occur because the interatomic forces are modified due to the excitation of a large (10% or more) fraction of the valence electrons to the conduction band. This review focuses on the nature of the non-thermal transitions in semiconductors under femtosecond laser excitation.

Electrons↗

Corporal plication for penile curvature caused by Peyronie's disease: the patients' perspective.

OBJECTIVE: To determine the acceptability by patients of corporal plication for Peyronie's disease. PATIENTS AND METHODS: A postal questionnaire was sent to 69 patients who had undergone corporal plication for Peyronie's disease between 1992 and 1999, to ascertain the subjective outcome and acceptance by the patients and their sexual partners of the results of the procedure. Of the 65 patients who were still alive, 44 (68%) returned the questionnaire. RESULTS: The mean (range) follow-up was 4.1 (0.5-7.25) years and the mean age of the patients 54.6 (32-80) years. Of the 44 patients responding, 24 (55%) were sexually active; after surgery, 16 (36%) had significant impairment of erections, seven (16%) continued to have significant penile discomfort and 15 (34%) could feel nodules at the suture site. Twenty-five (57%) patients reported a mild and six (14%) a severe persistent penile deformity; 40 (90%) reported having a shorter penis, of whom 22 (55%) thought it significant. Overall, 14 (32%) reported 'numbness' of the glans penis. Only 23 (52%) of the patients would recommend the surgery, with 25 (57%) reporting a deterioration in their overall quality of life. Of the partners of the evaluable patients, 38 (86%) responded, and a significant deterioration in sexual performance was reported by 19 (35%). CONCLUSIONS: Overall, the long-term results of corporal plication appear to be disappointing. These poor results could be related to a current lack of understanding of the natural history and progression of the disease, to case selection, or to the surgery. We intend to use these results to counsel our patients before such surgery and inform them of the possible outcome in the long term.

Adult↗

Evaluation of the clinical value of urinary NMP22 as a marker in the screening and surveillance of transitional cell carcinoma of the urinary bladder.

PURPOSE: To prospectively evaluate the clinical role of urinary NMP22 as a marker for transitional cell carcinoma of the urinary bladder in screening and surveillance settings. PATIENTS AND METHODS: Single voided specimens were obtained from 211 consecutive patients who presented for flexible cystoscopy. Of these, 96 patients presented with haematuria or irritative symptoms (screening), the remaining 115 were patients with known transitional cell carcinoma on follow-up (surveillance). The urine sample was used for urine microscopy, cytology and for measuring NMP22 levels. RESULTS: Bladder tumours were found in 16 of 96 (16.6%) patients in the screening group and 17 of 115 (15.6%) patients on surveillance. The NMP22 levels were significantly lower in patients with lower stage (Ta vs. T1-3), low grade (G1, G2 vs. G3, CIS) and papillary morphology. The optimum threshold for NMP22 obtained from the ROC curve was 4.75 U/ml, providing a sensitivity, specificity, positive predictive value and negative predictive value of 42.4, 85, 38.5 and 88.6%, respectively. Sensitivity and specificity were better in patients being screened than in those on surveillance. In both groups, urinary NMP22 had similar diagnostic characteristics as urinary cytology. CONCLUSIONS: Urinary NMP22 levels are significantly higher in patients with bladder tumour than in those negative for tumours, and test predictability improves with increasing stage and grade. The overall sensitivity for urinary NMP22 is similar to, but not superior to urine cytology. Our study suggests that the clinical role of urinary NMP22 as a diagnostic marker can be at best supportive only.

Biomarkers, Tumor↗

Is it necessary to perform urine cytology in screening patients with haematuria?

UNLABELLED: All patients with gross haematuria and those older than 50 years with microscopic haematuria need investigations to rule out the presence of a urological malignancy. OBJECTIVE: To study the role of urine cytology in the evaluation of patients with haematuria. METHODS: Two hundred and eighty-five patients were evaluated. All patients underwent evaluation including urine cytology, flexible cystoscopy, ultrasonography and/or IVU. RESULTS: The mean age of the patients was 62.4 years. Sixty-five percent had gross and 35% microscopic haematuria. Fifty-five tumours were discovered (19.2%); of these 48 were transitional cell carcinomas, 3 renal cell carcinomas and 3 carcinomas of the prostate. Thirty-seven urinary cytologies were abnormal. The overall sensitivity of urinary cytology was 42.4% and specificity 94.3%. Of 18 patients with positive cytology, all were found to have transitional cell carcinomas on cystoscopy or imaging. Of 19 patients with suspicious cytologies, only 6 were found to have tumours. The remaining 13 patients had no evidence of tumour on combined upper tract imaging (IVU and ultrasound) or on rigid cystoscopy and bladder biopsy. Whilst all the other investigation modalities contributed to diagnoses (and/or exclusion of tumours), no additional tumours were discovered solely by urinary cytology. A moderate cost saving could be made without compromising diagnostic accuracy. CONCLUSION: Our study suggests that performing routine urine cytology is not relevant in the investigation of patients with haematuria, its role is at best supportive.

Algorithms↗

The use of valrubicin for the chemoresection of superficial bladder cancer -- a marker lesion study.

OBJECTIVES: To assess the effect and tolerance of a 6-week course of intravesical valrubicin on a tumour intentionally left in the bladder (marker lesion) following incomplete transurethral resection of the bladder (TURBT). PATIENTS AND METHODS: In a prospective phase II study, 40 patients with refractory superficial transitional cell carcinoma (TCC), with or without carcinoma in situ, underwent TURBT at which a tumour <1 cm in diameter was deliberately left in the bladder. They were then treated with six instillations of 800 mg valrubicin at weekly intervals. Patients were assessed three months after the initial TURBT by cystoscopy and biopsy. Patients remaining clear of disease underwent repeat cystoscopies at 3-monthly intervals until recurrence or for up 2 years. RESULTS: 21/39 (54%) of patients were found to be clinically clear of disease upon cystoscopic examination at 3 months. 18/39 (46%) of patients were considered histologically clear of bladder disease. The current estimate of the mean time to recurrence is 248 days. CONCLUSIONS: A 6-week course of intravesical valrubicin has proved effective in ablating a marker tumour left in the bladder after incomplete TURBT and in preventing or delaying recurrence of further tumours in a group of patients with previously treated superficial TCC.

Administration, Intravesical↗

Semen analysis after vasectomy: when and how many?

OBJECTIVE: To assess patient compliance for semen analysis after vasectomy, and to determine the timing and number of semen analyses required to confirm sterility. PATIENTS AND METHODS: The study included 1321 men who underwent vasectomy between October 1995 and June 1998. They were followed up in two groups; in group 1 (one-test method) 961 consecutive patients were asked to provide a semen sample for analysis 4 months after vasectomy. Sterility was defined as the absence of sperm in one sample. If sperm were present in the sample, the test was repeated at monthly intervals until there were no sperm. In group 2 (two-test method) 360 consecutive patients were advised to provide semen samples 3 and 4 months after vasectomy. The absence of sperm in two consecutive samples was defined as the criterion to declare the man azoospermic. The presence of sperm in one sample required further samples every month until two consecutive azoospermic samples were produced. RESULTS: In group 1, 810 patients provided semen samples, of which 783 (97%) had no sperm and the men were thus declared azoospermic. The remaining 27 (3%) samples contained sperm; six men withdrew from follow-up at various times but 21 patients produced a negative sample at some time within 7 months and were declared azoospermic. At the end of the follow-up, 804 (84%) patients had been declared azoospermic. In group 2, 294 (82%) patients provided a semen sample after 3 months but only 259 (72%) did so after 4 months. Of the patients providing the first sample, 287 (98%) were azoospermic, and after the second 252 (97%) were azoospermic. At the end of the follow-up 255 (71%) patients were declared azoospermic. There was no reported paternity in any of the men. CONCLUSION: These results suggest that compliance was better in group 1; when the patients in group 2 were asked to provide a second sample the compliance decreased significantly. The percentage of patients producing an azoospermic sample was similar for semen provided after 3 and 4 months. Thus, provided that the patient is adequately warned about the risk of failure of the vasectomy at any time during his life, a single semen analysis after 3 months is sufficient grounds for discontinuing other contraceptive precautions.

Follow-Up Studies↗

Assessment of voiding outcome, sexual function and quality of life two years following KTP/YAG hybrid laser prostatectomy.

OBJECTIVE: To assess the long-term outcome of patients undergoing KTP/YAG hybrid laser treatment for bladder outlet obstruction due to benign prostatic enlargement, in terms of symptomatic relief, complications, sexual function, patient satisfaction and acceptance of procedure. PATIENTS AND METHODS: The study recruited 148 patients prospectively. The hybrid laser treatment involved performing an initial bladder neck incision using KTP laser at 34 W followed by 4/6 point coagulation using NdYAG laser at 60 W. Patients were followed up till 2 years and assessed using uroflowmetry, International Prostate Symptom Score (IPSS), Patient Satisfaction Score (PSS), BPH impact index (BII) and the Danish Prostate Symptom Score (DAN-PSS) sexual function questionnaire. RESULTS: 137 patients were followed up for 2 years. There was a significant improvement in the maximum flow rate, IPSS and Quality of Life Scale (QLS). The mean BII (2.9) and the mean PSS (1.9) were low suggesting overall satisfaction with the procedure. The complications included urethral stricture (0.73%), bladder neck obstruction (2.15%) and retreatment (3.6%). 79.4% had a significant decrease in the ejaculate and 32.8% had a significant change in the strength of erections. On comparing the two groups (sexual function affected vs. not affected), the age, BII, IPSS and PSS were significantly higher (p < 0.05) in the group of patients that were affected. CONCLUSIONS: Following KTP/YAG hybrid laser prostatectomy the outcome for voiding is good and durable for up to 2 years. The patient satisfaction level following the procedure is high and the procedure well accepted. However, significant interference with sexual function occurs, which appears to be occurring in tandem with a poor voiding outcome.

Aged↗

Inhibition of sphingolipid synthesis down-modulates CD4 expression by peripheral blood T lymphocytes and T lymphoma cells.

Recent studies have demonstrated that L-cycloserine, an inhibitor of sphingolipid biosynthesis, interferes with the life cycle of HIV. Experiments with human T cells and CD4+ T lymphoma cells were performed to examine possible mechanisms. L-CS selectively down-modulated CD4 expression without affecting the expression of CD3 and CD8. L-cycloserine also inhibited T cell mitogen responses without affecting IL-2 production. Membranes prepared from L-CS-treated T lymphoma cells showed changes in lipid composition that correlated with changes in membrane microviscosity. These results suggest that normal expression of CD4 may depend upon sphingolipid biosynthesis in contrast with the other CD determinants measured. Selective inhibition of CD4 by L-cycloserine together with its antiviral effects may offer a novel approach for interfering with HIV cell binding and infectivity.

Antigens, CD↗

L-cycloserine, an inhibitor of sphingolipid biosynthesis, inhibits HIV-1 cytopathic effects, replication, and infectivity.

Drugs that reduce viral production or prevent viral spread by interference with the host's cellular components are unlikely to induce resistance, in contrast to treatment modalities that interact with the HIV-1 life cycle. Two features make L-cycloserine (L-CS) a candidate drug of this kind: (a) L-CS is a potent inhibitor of the sphingolipid pathway (b) sphingolipids, galactocerebrosides, and sulfatides have been shown, by others, to bind gp120. In a feasibility and efficacy study, we have found that L-CS inhibits HIV-1 replication in a CD4+ lymphoid cell line (CEM) as documented by the reduction of syncytium formation, the number of HIV-1 infected cells, and p24 protein production. This observation may lead to a new strategy for the treatment of HIV-1 infection.

Antimetabolites↗

A neutral galactocerebroside sulfate sulfatidase from mouse brain.

We have described an enzyme in brain that catabolizes galactocerebroside sulfatide with a pH optimum of 7.2. To our knowledge, this is the first description of a catabolic enzyme for sulfatide at a neutral pH. Activity at a neutral pH implies a non-lysosomal location for this sulfatidase. Galactocerebroside sulfate sulfatidase (n-sulfatidase) activity was not apparent in crude microsomal extracts and was detected following partial purification of the enzyme. This enzyme, n-sulfatidase, differs from other arylsulfatases in its M(r), inability to bind to concanavalin A, and substrate specificity; n-sulfatidase was unable to hydrolyze p-nitrocatechol sulfate or estrone sulfate. The molecular mass of n-sulfatidase obtained by Sephacryl S-200 chromatography was 72 kDa, and the active fraction from this procedure was purified > 600-fold by isoelectric focusing. Following SDS-polyacrylamide gel electrophoresis, two bands were obtained with apparent molecular masses of 58 and 66 kDa. Enzyme activity was regenerated from both of these bands, with the 66-kDa band showing greater activity. The Km of the sulfatidase was determined as 5.8 x 10(-5) M. The pI of n-sulfatidase was 7.7 in contrast to the pI of 4.9 for the sulfotransferase. No requirement was found for Mg2+ or ATP for sulfatidase activity; vitamin K1 enhanced sulfatidase activity approximately 3.3-fold. Therefore, this enzyme may have a role in the pathogenesis of metachromatic leukodystrophy in which sulfatides accumulate in the nervous and other tissues and in myelination since sulfatides are an important component of myelin.

Animals↗

Sodium depletion of pregnant ewes and its effects on foetuses and foetal fluids.

1. Some effects of sodium depletion were investigated in sheep at different stages of pregnancy ranging from 55 to 139 days. Sodium depletion was induced by draining the saliva from one parotid gland for a period of 6 days. Foetal samples were collected at the end of the depletion period.2. Sodium depletion of the ewe resulted in a fall in saliva Na(+) level and a rise in saliva K(+) level, a fall in plasma Na(+) and K(+) levels, a 35% reduction in plasma volume and a 16% reduction in body weight.3. In the Na(+) depleted ewes the sodium levels of the foetal plasma and amniotic fluid were lower and the volume of the allantoic fluid greater than those in the control ewes.4. It is concluded that sodium depletion of the ewe leads to a deficiency of sodium in the foetus.5. On the basis of these experiments and other reports it is postulated that a sodium deficient foetus, like a sodium deficient adult, responds to the deficiency by restricting sodium losses in the urine and by excreting water.

Amniotic Fluid↗