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Biomedical subjects

M Manoharan

Publications and source records attributed to M Manoharan.

At least 19 recordsLinked to original sources
PubMed2006

Accuracy of single-photon emission computed tomography in differentiating frontotemporal dementia from Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the commonest causes of presenile dementia. In the absence of a biological marker, diagnosis is reliant on clinical evaluation. Confirmation is often sought from neuroimaging, including single-photon emission computed tomography (SPECT). Most previous SPECT studies lack pathological validation. AIM: To examine the accuracy of SPECT in differentiating FTD from AD in patients with subsequent pathological confirmation. METHODS: Technetium-99-labelled hexamethyl propylene amine oxime SPECT images obtained at initial evaluation in 25 pathologically confirmed cases of FTD were examined. These images were visually rated by an experienced blinded nuclear medicine consultant and compared with those of 31 patients with AD, also with pathological validation. RESULTS: A reduction in frontal cerebral blood flow (CBF) was more common in FTD and was of diagnostic value (sensitivity 0.8, specificity 0.65 and likelihood ratio (LR) 2.25; 95% CI 1.35 to 3.77). A pattern of bilateral frontal CBF reduction without the presence of associated bilateral parietal CBF change is diagnostically more accurate (sensitivity 0.80, specificity 0.81 and +LR 4.13, 95% CI 1.96 to 8.71). Diagnostic categorisation (FTD or AD) on the basis of SPECT alone was less accurate than clinical diagnosis (based on neurology and detailed neuropsychological evaluation). One patient with FTD was initially clinically misdiagnosed as AD, owing to the lack of availability of full neuropsychological assessment. However, SPECT correctly diagnosed this patient, providing a diagnostic gain of 4%. CONCLUSION: Technetium-99-labelled hexamethyl propylene amine oxime SPECT CBF patterns provide valuable information in the diagnosis of FTD and AD. These data can be better used as an adjunct to clinical diagnosis if pathology is to be correctly predicted in life.

Aged↗
PubMed2006

Metastatic adenoid cystic carcinoma to the kidney in a young woman.

The incidence of an adenoid cystic carcinoma on major salivary glands is low, constituting only about 10% to 15% of all parotid malignancies. Cases of delayed metastasis have been reported, but reports of specific renal involvement have not been extensively found. We present the case of a 21-year-old woman with a left renal metastasis from an adenoid cystic carcinoma of the parotid gland that had been surgically treated 7 years previously. The patient underwent successful left radical nephrectomy. During follow-up, the patient developed pulmonary nodules that were metastatic adenoid cystic carcinoma and were surgically excised. At last follow-up, the patient was doing well with no evidence of disease.

Adult↗
PubMed2004

Modified Pfannenstiel approach for radical retropubic prostatectomy.

Radical retropubic prostatectomy is traditionally performed using a vertical midline incision and occasionally using a transverse Pfannenstiel incision. We describe a technique for performing radical retropubic prostatectomy using a modified Pfannenstiel approach. This involves a Y incision of the rectus sheath, instead of a pure transverse incision, and provides both excellent exposure and better cosmetic results.

Esthetics↗
PubMed2004

A reverse perfusion pattern during Technetium-99m stress myocardial perfusion imaging does not predict flow limiting coronary artery disease.

BACKGROUND: A reverse redistribution pattern during myocardial perfusion imaging is most widely described using thallium (Tl-201), when stress images exhibit greater perfusion than rest. Technetium (Tc-99 m) radiopharmaceuticals may also yield a reverse perfusion (RP) pattern, but its significance is uncertain. This study tested the hypothesis that RP correlates with the presence and location of flow limiting coronary stenosis(es). METHOD: We reviewed 842 consecutive Tc-99 m tetrofosmin SPECT stress studies performed at a cardiothoracic centre over a 15 month period. 69 (8.2%) demonstrated RP. Thirty-three patients (age 32-79 mean 56, 17 female) had undergone cardiac catheterisation within 12 months of the scan. Correlation was sought between the presence and location of angiographic stenoses and RP pattern. RESULTS: 10/33 (30.3%) had significant (>60%) coronary stenosis(es); 5 single-vessel, 2 two-vessel and 3 three-vessel disease (3VD). Stenosis location correlated poorly with the RP territory (LAD/Anterior 5/17, RCA/Inferior 1/10, Cx/lateral 0/4 (p = 0.57)). Of the 6 patients with a lesion in the RP territory, 3 had 3VD; 2 of these had a simultaneous reversible defect. All 5 patients with previous myocardial infarction had a simultaneous fixed defect. However only 3/12 with co-existent reversible defects had significant disease. CONCLUSION: The reverse perfusion pattern is a poor predictor of flow limiting coronary disease, and does not correlate with stenosis location in those with significant lesions. Such patients should not undergo invasive investigation purely on the basis of this result.

Adult↗
PubMed2004

Limitations of biopsy Gleason grade: implications for counseling patients with biopsy Gleason score 6 prostate cancer.

PURPOSE: We examined the implications of underestimating Gleason score by prostate biopsy in patients with biopsy Gleason 6 prostate cancer with respect to adverse pathological findings and biochemical recurrence after radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed clinical and pathological data on a cohort of 531 patients with Gleason score 6 on prostate biopsy who underwent radical retropubic prostatectomy between June 1992 and January 2002. Patients were excluded if they received neoadjuvant androgen deprivation. Concordance between biopsy and radical prostatectomy Gleason score was examined. A comparison was made with respect to final radical prostatectomy specimen pathology and the risk of biochemical recurrence between cases that remained Gleason 6 and those with a final grade of 7 or greater. RESULTS: A total of 451 patients were included in the analysis. Mean followup was 55.1 months (range 12 to 123.4). Of the patients 184 (41%) had a Gleason score of 7 or greater after a review of the entire prostate, while 37 (8%) had a score of less than 6 and 230 remained with Gleason 6. Patients who were under graded were more likely to have extraprostatic extension (22% vs 4%, p <0.01), seminal vesicle invasion (9% vs 2%, p <0.01) and biochemical recurrence (10% vs 3%, p <0.01) compared to those who remained with Gleason score 6. CONCLUSIONS: Gleason grade on needle biopsy is an inexact predictor of the final grade following radical prostatectomy. Patients with biopsy Gleason score 6 who are under graded are at significantly higher risk for adverse pathological features and biochemical recurrence than patients who remain with Gleason score 6 or less on final pathology findings.

Aged↗
PubMed2004

Concurrent radical retropubic prostatectomy and inguinal hernia repair through a modified Pfannenstiel incision.

OBJECTIVE: To describe a technique for concurrent radical retropubic prostatectomy (RRP) and inguinal hernioplasty, using a modified Pfannenstiel incision. PATIENTS AND METHODS: RRP is usually done through a midline lower abdominal incision but some patients with localized prostate cancer have an inguinal hernia. Concurrent inguinal hernia repair at the time of RRP with the usual method is only possible by either a preperitoneal mesh repair or formal hernioplasty, requiring an additional incision(s). A 10-12 cm Pfannenstiel incision is made along the pubic hairline centred over the pubic symphysis, and a 'Y'-shaped incision in the rectus sheath. The rectus muscle is split vertically along the midline, followed by RRP. After removing the prostate and completing the anastomosis, the surgeon identifies the inguinal canal along the inferior and lateral aspect of the transverse incision and uses a formal tension-free hernioplasty with a 3 x 5 cm polypropylene mesh. We used this technique in fifteen concurrent inguinal hernioplasties (two bilateral hernias and thirteen unilateral) at the time of RRP, with no additional incisions, using the formal tension-free Lichtenstein technique. One patient with bilateral hernias had a right indirect inguinal hernia, and all the remaining men had a direct inguinal hernia. RESULTS: All patients were discharged 2 days after surgery, with no complications associated with the procedure and no recurrences; however, the follow-up was short (mean 5.5 months). CONCLUSION: A modified Pfannenstiel incision is ideal for concurrent RRP and inguinal hernioplasty, providing excellent exposure of the pelvic structures and allowing the surgeon to use a formal tension-free mesh hernioplasty through the same incision. Wound healing and cosmetic results are excellent.

Hernia, Inguinal↗
PubMed2003

The management of a postdural puncture headache in a child.

We present a case of an 11-year old girl who underwent an elective pyeloplasty and had an epidural catheter placed for per- and postoperative analgesia. Postoperatively she developed a postural headache and severe nausea, and a diagnosis of postdural puncture headache (PDPH) was made. Her symptoms failed to respond to conservative management. An epidural blood patch was performed with immediate and complete resolution of her symptoms. We present this case to highlight the occurrence of PDPH in children and to outline the considerations for management.

Anesthesia↗
PubMed2003

Outcome after radical prostatectomy with a pretreatment prostate biopsy Gleason score of >/=8.

OBJECTIVE: To determine the outcome and predictors of recurrence in patients with a pretreatment prostate biopsy Gleason score (GS) of >/= 8 and treated with radical prostatectomy (RP). PATIENTS AND METHODS: We retrospectively reviewed 1048 consecutive patients who underwent RP by one surgeon (M.S.S.); patients who had a pretreatment biopsy GS of >/= 8 were identified. Information was recorded on patient age, initial prostate specific antigen (PSA) level, clinical stage, biopsy GS, pathology GS, extraprostatic extension (EPE), tumour volume, surgical margin status, seminal vesicle invasion (SVI), and lymph node involvement. The results were assessed statistically using the Kaplan-Meier method, univariate log-rank tests and multivariate analysis using Cox's proportional hazards regression. RESULTS: In all, 123 patients met the initial selection criteria; 44 were excluded from further analyses (five salvage RP, 23 < 1 year follow-up and 16 adjuvant treatment). Thus 79 patients were included in the uni- and multivariate analyses; 25 (31%) patients had a GS of </= 7 in the RP specimen and 54 (69%) remained at GS >/= 8. The mean follow-up was 55 months, the age of the patients 63 years and the mean (sd) initial PSA level 13 (12) ng/mL. The overall biochemical failure rate was 38% (41% if the final GS was >/= 8 and 32% if it was </= 7). For those with a GS of >/= 8 in the RP specimen, 20% (11/54) were organ-confined; two patients (2.5%) in this group developed local recurrence. If the final GS was </= 7, 52% (13/25) were organ-confined. In the univariate analysis, significant risk factors for recurrence were PSA >/= 20 ng/mL, EPE, SVI, a positive surgical margin and tumour volume. Cox's proportional regression indicated that a PSA of >/= 20 ng/mL (hazard ratio 7.9, 95% confidence interval 2.6-24.2, P < 0.001), the presence of EPE (4.2, 1.6-10.9, P = 0.004) and a positive surgical margin (3.8, 1.5-9.7, P = 0.005) were significant independent predictors in a multivariate analysis. CONCLUSION: RP is a reasonable treatment option for patients with a prostate biopsy GS of >/=8 and clinical stage T1-2. These patients have a high chance of remaining disease-free if their PSA level is </= 20 ng/mL. Patients with a pretreatment biopsy GS of >/= 8 should be counselled about the potential differences between the biopsy and the RP specimen GS.

Adult↗
PubMed2003

A pelvic drain may be avoided after radical retropubic prostatectomy.

PURPOSE: We reassessed the role of routine pelvic cavity drainage to prevent complications after radical retropubic prostatectomy (RRP). MATERIALS AND METHODS: RRP was performed in 116 consecutive patients with clinically localized adenocarcinoma of the prostate. Clinical and pathological information was recorded for each patient. After the prostate was removed and the anastomotic sutures were tied the bladder was filled with saline through the urethral catheter. If there was no significant leakage, a drain was not placed. RESULTS: We did not place a drain in 85 of the 116 patients (73%). There were 3 immediate postoperative complications. In a patient without a drain, a urinoma developed that required percutaneous placement of a drain on postoperative day 2. None of the 116 patients had clinical evidence of infection, lymphocele or hematoma. Two patients had hematuria 2 weeks after catheter removal and needed bladder irrigation. Neither patient had a drain. Three patients (drain and no drain in 1 each) were in urinary retention after catheter removal, which required catheter reinsertion for an additional week. None had an anastomotic stricture. CONCLUSIONS: The morbidity of RRP is low when performed by those who regularly perform this procedure. If the bladder neck is preserved or meticulously reconstructed, there may be little or no extravasation and, thus, routine drainage may be unnecessary. In properly selected cases morbidity is not increased by omitting a drain from the pelvic cavity after RRP.

Drainage↗
PubMed2003

Visual estimate of percent of carcinoma predicts recurrence after radical prostatectomy.

PURPOSE: Tumor volume is an important prognosticator for predicting prostate cancer recurrence following radical prostatectomy (RP). We assessed the ability of the visual estimate of the percent of carcinoma (VEPC) to predict recurrence. METHODS AND MATERIALS: As performed by 1 surgeon (MSS), 1,114 men underwent radical prostatectomy between 1992 and February 2002. Patients who had less than 12 months of followup, who underwent salvage RP or in whom VEPC was not assessed in the pathology specimen were excluded. VEPC and other clinical variables were analyzed. We performed univariate analysis using the Kaplan-Meier log rank test. Multivariate analysis using Cox proportional hazards regression was performed. RESULTS: A total of 692 patients with a mean age of 61 +/- 7 years met the criteria for this analysis. Mean followup was 52 +/- 30 months. Of the patients 17% had biochemical recurrence. Mean VEPC was 25% and 13% in those with and without recurrence, respectively. On univariate analysis all variables were significant predictors of recurrence. However, multivariate analysis showed that the only significant predictors of recurrence were patient age, initial prostate specific antigen 10 ng/ml or greater, RP Gleason 8 to 10, extraprostatic extension, seminal vesicle involvement and VEPC. Based on disease-free survival curves patients were stratified into 3 broad groups, namely low, intermediate and high volume. The HR for biochemical recurrence was 2.1 for the intermediate VEPC group (9.1% to 20%) and 2.7 for the high VEPC group (greater than 20%). In the reference group it was less than 9% (low volume). CONCLUSIONS: VEPC is a simple and inexpensive method that is an independent predictor of recurrence after RP.

Follow-Up Studies↗
PubMed2001

The acenes: is there a relationship between aromatic stabilization and reactivity?

[reaction--see text] Despite the increasing reactivity from benzene to heptacene, the acene resonance energies per pi electron are nearly constant. The reactivities (computed activation energies) of the individual acene rings correlate with the reaction energies and depend on the product stabilities. Nucleus-independent chemical shifts (NICS; note the sizes of the red dots, above) indicate that the more reactive inner rings actually are more aromatic than the less reactive outer rings and even more aromatic than benzene itself.

Journal Article↗
PubMed2001

Selective phosphate protection: a novel synthesis of double-labeled oligonucleotides.

[structure: see text] A novel, selective labeling of oligonucleotides with two different reporter groups is described. The oligonucleotide is synthesized using a stable 2-(4-methoxybenzamido)ethyl protection for a selected internucleosidic thiophosphate (PS) and a labile 2-(N-isopropyl-4-methoxybenzamido)ethyl for the 3'-terminal PS and internucleosidic phosphates. The latter group and the base protection are removed, and the 3'-terminal PS is labeled. The former protection is then cleaved by a prolonged ammonolysis, and the second reporter is introduced at the internucleosidic PS.

Fluorescent Dyes↗
PubMed2001

Nuclear antisense effects of neutral, anionic and cationic oligonucleotide analogs.

The antisense activity of oligomers with 2'-O-methyl (2'-O-Me) phosphorothioate, 2'-O-methoxyethyl (2'-O-MOE) phosphorothioate, morpholino and peptide nucleic acid (PNA) backbones was investigated using a splicing assay in which the modified oligonucleotides blocked aberrant and restored correct splicing of modified enhanced green fluorescent protein (EGFP) precursor to mRNA (pre-mRNA), generating properly translated EGFP. In this approach, antisense activity of each oligomer was directly proportional to up-regulation of the EGFP reporter. This provided a positive, quantitative readout for sequence-specific antisense effects of the oligomers in the nuclei of individual cells. Nuclear localization of fluorescent labeled oligomers confirmed validity of the functional assay. The results showed that the free uptake and the antisense efficacy of neutral morpholino derivatives and cationic PNA were much higher than that of negatively charged 2'-O-Me and 2'-O-MOE congeners. The effects of the PNA oligomers were observed to be dependent on the number of L-lysine (Lys) residues at the C-terminus. The experiments suggest that the PNA containing Lys was taken up by a mechanism similar to that of cell-penetrating homeodomain proteins and that the Lys tail enhanced intracellular accumulation of PNA oligomer without affecting its ability to reach and hybridize to the target sequence.

Anions↗
PubMed2001

Adenosine nucleotides in rat bone measured by ion-pair reversed-phase high-performance liquid chromatography: effect of hemorrhagic shock, with and without retransfusion of blood.

The measurement of bone adenosine nucleotides (ATP. ADP. AMP) using a simple HPLC procedure is described for rat tibia; the response to hemorrhagic shock with and without blood retransfusion is also described. With respect to the measurement of nucleotides, a number of validation criteria are met. In the anesthetized intact rat (Normal) there was a declining gradient of the three nucleotides, expressed as nmol per g dry matter, from proximal over middle to distal diaphysis, with the mean ratio ATP/ADP (0.21, 0.20, 0.20) and the mean energy charge (0.34, 0.31, 0.30) being low. Irrespective of the anatomic site, hemorrhagic shock of 30-min duration evoked a further decrease versus Normal of ATP, ATP/ADP and energy charge. Blood retransfusion after shock kept nucleotides and other variables in the proximal and distal, but not the middle, diaphysis within normal limits. It was concluded that: (i) bone nucleotides are reliably measurable by HPLC, allowing the described method to be recommended for wider use in bone research and related areas; (ii) in contrast to more parenchymatous tissues, low ATP, ATP/ADP and energy charge may be characteristic for long bones, pointing towards different energy metabolism; and (iii) bone is a "shock organ", reflecting blood hypoperfusion, O2 deficiency and decreased ATP in this situation.

Adenine Nucleotides↗
PubMed2001

Delivery of cholesteryl-conjugated phosphorothioate oligodeoxynucleotides to Kupffer cells by lactosylated low-density lipoprotein.

The efficacy of antisense oligonucleotides depends on the ability to reach in vivo their target cells. We aim to develop strategies to enhance uptake of phosphorothioate oligodeoxynucleotides by Kupffer cells. To this end, we conjugated cholesterol to ISIS-3082, a phosphorothioate oligodeoxynucleotide specific for intercellular adhesion molecule-1. The cholesterol-conjugated oligonucleotide, denoted ISIS-9388, associated readily with lactosylated low-density lipoprotein (LacLDL), a lipidic carrier that is taken up by galactose receptors on Kupffer cells. Association of up to 10 molecules of ISIS-9388 per LacLDL particle did not induce aggregation. LacLDL-associated [3H]ISIS-9388 was rapidly taken up by the liver after injection into rats (52.9+/-1.8% of the dose within 2 min versus 18.6+/-2.8% for ISIS-3082). N-acetylgalactosamine inhibited hepatic uptake, indicating involvement of galactose-specific receptors. Liver cells were isolated at 60 min after injection of LacLDL-associated [3H]ISIS-9388. Kupffer cells displayed the highest uptake: 88.1+/-24.7 ng of oligonucleotide/mg of cell protein, which is 6-14 times higher than after injection of free ISIS-9388 or ISIS-3082 (15.0+/-3.8 ng and 6.3+/-1.4 ng, respectively). It can be calculated that Kupffer cells contribute 43.9+/-5.4% to the liver uptake (free ISIS-9388 and ISIS-3083 14.5+/-3.1% and 8.3+/-3.2%, respectively). In conclusion, conjugation of a phosphorothioate oligodeoxynucleotide with cholesterol and its subsequent association with LacLDL results in a substantially increased Kupffer cell uptake of the oligonucleotide. As Kupffer cells play a key role in inflammation, our approach may be utilized to improve antisense-based therapeutic intervention during inflammation.

Animals↗
PubMed2001

The referral pattern for undescended testes in Auckland.

AIM: To accurately audit the age at orchiopexy at our institution and then to analyse the referral pattern specially related to the age of the patient. METHODS: A retrospective review of hospital records was performed. Data were obtained from the hospital database based on the procedure code of orchiopexy. Mean and median values were calculated for age at referral, time between clinic visit and referral (T1) and between clinic visit and operation (T2). RESULTS: The mean age at referral was 42.6 months (median 23, range 0 - 179.1 months). The mean time T1 was 2.6 months (median 1.7, range 0 - 16.9 months). The mean time T2 was 7.0 months (median 3.3 months). CONCLUSION: There is a need to increase awareness about undescended testes amongst all parties involved in the health care of children.

Adolescent↗