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Biomedical subjects

M W Reed

Publications and source records attributed to M W Reed.

At least 73 records · Page 4Linked to original sources

Ownership and uses of human tissue: does the Nuffield bioethics report accord with opinion of surgical inpatients?

OBJECTIVE: To compare opinion of surgical inpatients with the conclusions of the report of the Nuffield Council on Bioethics regarding the ownership and uses of human tissue. DESIGN: Survey of results of questionnaires completed by patients. SETTING: Large teaching hospital. SUBJECTS: 384 postoperative adult surgical patients. RESULTS: There was strong support among patients for the use of tissues in medical education, research, and science with the exception of those tissues which may transmit disease to others. Few patients (39; 10%) believed that they retained ownership of tissue removed at surgery. Most believed that the tissue belonged to the hospital (103; 27%), to nobody (103; 27%), or to the laboratory (77; 20%). Most patients had not been given any information about the possible uses of their tissues after removal. CONCLUSIONS: Surgical inpatients seem to endorse the conclusions of the Nuffield report regarding the ownership and uses of human tissue. The recommendations regarding patient information and consent procedures should be implemented at the earliest opportunity.

Adult↗

Randomised, prospective, single-blind comparison of laparoscopic versus small-incision cholecystectomy.

BACKGROUND: We report a prospective randomised comparison between laparoscopic and small-incision cholecystectomy in 200 patients which was designed to eliminate bias for or against either technique. METHODS: Patients were randomised in the operating theatre and anaesthetic technique and pain-control methods were standardised. Four experienced surgeons did both types of procedure. Identical wound dressings were applied in both groups so that carers could be kept blind to the type of operation. FINDINGS: There was no significant difference between the groups for age, sex, body mass index, and American Society of Anaesthesiologists grade. Laparoscopic cholecystectomy took significantly longer than small-incision cholecystectomy (median 65 [range 27-140] min vs 40 [18-142] min, p<0.001). The operating time included operative cholangiography which was attempted in all patients. We found no significant difference between the groups for hospital stay (postoperative nights in hospital, median 3-0 [1-17] nights for laparoscopic vs 3-0 [1-14] nights for small-incision, p=0.74), time back to work for employed persons (median 5-0 weeks vs 4.0 weeks; p=0.39), and time to full activity (median 3-0 weeks vs 3.0 weeks; p=0.15). INTERPRETATION: Laparoscopic cholecystectomy takes longer to do than small-incision cholecystectomy and does not have any significant advantages in terms of hospital stay or postoperative recovery.

Analgesia, Patient-Controlled↗

Prognostic significance of angiogenesis in transitional cell carcinoma of the human urinary bladder.

OBJECTIVES: To quantify tumour angiogenesis in bladder cancer and determine whether it correlates with tumour stage, grade and survival. PATIENTS AND METHODS: Archival samples from a total of 113 patients newly presenting with transitional cell carcinomas of the urinary bladder were graded and staged, and analysed for angiogenic blood vessel density by a double immunohistochemical technique. The findings were correlated with the information obtained during a minimum follow-up of 12 years. RESULTS: Univariate analysis showed that TNM stage (P = 0.02) and mean vessel count (P = 0.01) were significant predictors of death from bladder cancer. Blood vessel density was significantly correlated with tumour stage (P = 0.01) and the presence of vascular invasion (P = 0.007). Trained observers were essential for the accurate counting of blood vessels to prevent excessive inter-observer variability. Multiple regression analysis showed that the combination of mean vessel count and stage was a significant prognostic indicator. CONCLUSION: Angiogenesis in primary bladder cancer is a predictor of death from the disease. Further work to determine whether it predicts invasion and recurrences in superficial tumours may be valuable.

Adult↗

Structure-activity relationships of cytotoxic cholesterol-modified DNA duplexes.

Short DNA duplexes with cholesterol linked at the 3'-terminus of each strand have unique, selective cytotoxic properties. The structural requirements for biological activity were explored through chemical synthesis of analogs and testing in cultured hepatoma cells. Effects of modifications to the sequence, backbone, 3'-sterol, 3'-linker, and 5'-terminus were evaluated. Self-complementary 3'-modified oligodeoxynucleotide (ODN) 10-mers were prepared from solid supports bearing the modification and linker of interest. Any changes to the normal phosphodiester backbone were poorly tolerated. The presence of cholesterol or a closely related sterol was an absolute requirement for activity. The length and position of attachment of the linker to cholesterol was important, with longer linkers showing reduced activity. Large, lipophilic groups at the 5'-terminus gave reduced cytotoxicity and poor solubility properties. The short length and unique structure of these ODNs allowed efficient automated synthesis on a 400 mumol scale and simplified purification.

Antineoplastic Agents↗

Intestinal endometriosis: presentation, investigation, and surgical management.

The study was undertaken to identify the presenting features of intestinal endometriosis and to evaluate its investigation and surgical management. Twenty-six cases of intestinal endometriosis were identified during a fourteen year period. The commonest site of occurrence was the rectosigmoid region (11 cases) followed by the appendix (9 cases), and ileocaecal region (6 cases). Abdominal pain was the main presenting feature in 20 cases, with associated nausea and vomiting in 12 cases and altered bowel habit in ten. Other presenting features included rectal bleeding, abdominal bloating and tenesmus. Endometriosis was not suspected preoperatively in any of the patients without a past history of this condition. Accurate preoperative diagnosis proved very difficult, with only laparoscopy providing definite evidence of intestinal endometriosis prior to formal surgery. Colonic resections were performed in 12 cases, small bowel resection in six cases and appendicectomy in nine cases, together with resection of adjacent adherent structures. This series illustrates the difficulty of establishing an accurate preoperative diagnosis, and the propensity of intestinal endometriosis to mimic other gastrointestinal diseases, particularly carcinoma and inflammatory bowel disease.

Appendix↗

The effect of aminolaevulinic acid-induced, protoporphyrin IX-mediated photodynamic therapy on the cremaster muscle microcirculation in vivo.

The effect of photodynamic therapy on normal striated muscle was investigated using 30 adult male rats. Animals were divided into six groups. Three control groups received phosphate-buffered saline by gavage and violet light at 105, 178 and 300 mW cm-2 respectively. Three experimental groups received aminolaevulinic acid (ALA; 200 mg kg-1) and violet light at 105, 178 and 300 mW cm-2 respectively. After exposure of the cremaster muscle animals were allowed to equilibrate and vessel diameters and bloodflow assessed. Following photoactivation measurements were taken every 10 min over a 2 h period. Photoactivation of experimental groups at the two higher power densities resulted in an initial decrease in both arteriolar and venular diameters, and a concomitant decrease in blood flow. The magnitude of these changes and the degree of recovery by the end of the observation period was related to power density. No effects were observed in the control groups. These results suggest that microcirculatory damage may contribute to the mechanism of action of photodynamic therapy with ALA.

Aminolevulinic Acid↗

Bladder and erectile dysfunction before and after rectal surgery for cancer.

OBJECTIVE: To establish the incidence of bladder and erectile dysfunction after rectal surgery for cancer. PATIENTS AND METHODS: Twenty patients (16 men and four women, median age 66 years, range 36-78) with carcinoma of the rectum were prospectively studied immediately before and 4 months after operation by clinical assessment, uroflowmetry and video-cystometrography. All patients were catheterized routinely at the time of surgery. Those experiencing voiding difficulties after catheter removal were managed by intermittent self-catheterization or an indwelling urethral catheter. RESULTS: Before surgery, only six patients had completely normal bladder function and 13 of the 16 men were at least partially potent. Eight of the 19 patients who eventually had surgery developed identifiable bladder dysfunction, of whom three had urodynamic evidence of complete bladder denervation. Three men who were potent before became impotent after surgery. CONCLUSIONS: Bladder and erectile dysfunction are recognized complications of radical rectal surgery, although there is significant variation in the reported risk; much of this variability is related to the retrospective nature of most previous studies. This study demonstrates the importance of prospective urodynamic evaluation and confirms that the small but significant risk of permanent bladder dysfunction is likely to be related to pelvic nerve injury at the time of surgery.

Adult↗

The value of abdominal exploration during cholecystectomy.

With the advent of 'minimal access' cholecystectomy patients no longer have an exploratory laparotomy at the time of the operation and it is possible that relevant pathology may be missed as a result. This study analyses the findings at exploratory laparotomy in 223 patients undergoing open cholecystectomy. Forty-two patients (19%) were found to have incidental pathology but in only three (1.3%) did this lead to additional operative procedures. We therefore conclude that the loss of exploratory laparotomy at cholecystectomy does not have a significant detrimental effect on patient care.

Adenocarcinoma↗

Discovery of short, 3'-cholesterol-modified DNA duplexes with unique antitumor cell activity.

A new class of modified oligodeoxynucleotides with unique, selective cytotoxic properties has been discovered. Self-complementary, 3'-cholesterol-modified oligodeoxynucleotides caused morphology changes and death in certain cancer cell lines, whereas other cell lines were unaffected. Susceptible cells were killed in a dose-dependent manner at submicromolar concentrations. Optimum potency was exhibited by phosphodiester duplexes approximately 10 base pairs in length, and base composition was important only in the context of duplex stability. Phosphorothioate analogues were less potent. Although the molecular mechanism of action of these unique compounds is not yet known, they offer potential applications in cancer therapy and in studies of cell death. In addition, the path toward elucidation of the structure-based biological activity of these oligonucleotides should be especially instructive for researchers studying sequence-specific effects.

Animals↗

Xanthogranulomatous cholecystitis.

Clinical, radiological and pathological findings in 31 patients with xanthogranulomatous cholecystitis have been reviewed. The spectrum of presentation was similar to that of cholelithiasis but fewer patients had biliary colic (17 per cent) and there were more complications (32 per cent). Four patients had a biliary fistula and four a perforated gallbladder with abscess formation. Patients characteristically had gallstones. Appearances often mimicked carcinoma of the gallbladder at ultrasonography and/or laparotomy, with xanthogranulomatous tissue extending to adjacent structures. Xanthogranulomatous cholecystitis and carcinoma of the gallbladder coexisted in three patients. The possibility should be considered that an 'inoperable tumour' of the gallbladder may in fact be xanthogranulomatous cholecystitis, a benign condition that frozen-section biopsy may confirm.

Adult↗

Advanced gastrointestinal malignancy or benign inflammatory disease? An unusual presentation of sclerosing mesenteritis. Report of a case.

The presentation of change of bowel habit, weight loss, muscle wasting, ascites, and the surgical appearance of "omental cake" are almost pathognomonic of advanced gastrointestinal malignancy. In our case, these symptoms represented a unique presentation of the condition sclerosing mesenteritis. Despite its rarity, the clinician should be aware of this "sheep in wolf's clothing," the clinical importance of which lies in the condition's benign and self-limiting course and imparts to the patient a prognosis and treatment that could not be further removed from that of advanced malignancy. Investigations that may be helpful to the surgeon in distinguishing the condition from carcinomatosis and avoiding unnecessary laparotomy include preoperative colonoscopy, barium enema, cytology of any ascites, and intraoperative frozen section biopsy. Treatment of the condition is conservative unless it has caused extrinsic bowel obstruction.

Ascites↗

Kinetics of endogenous protoporphyrin IX induction by aminolevulinic acid: preliminary studies in the bladder.

Photodynamic therapy (PDT) is an experimental treatment for cancer in which cell damage is achieved by the action of light on a photosensitizing drug. Though an effective treatment for superficial bladder cancer, its use has been limited due to complications relating to laser light dosimetry and the tissue specificity of the photosensitizer hematoporphyrin derivative (HPD). Aminolevulinic acid (ALA), a precursor in the biosynthesis of heme, induces the production of the endogenous photosensitizer protoporphyrin IX (PpIX) in a variety of tissues. We have studied the kinetics of PpIX accumulation in the rat bladder following ALA administration using a fluorimetric porphyrin assay. After oral and intravenous administration of ALA a rapid rise in PpIX content occurs followed by a reduction to control values by 24 hours. No increase in bladder PpIX content was detected after topical administration.

Administration, Oral↗

The effect of cryotherapy on the cremaster muscle microcirculation in vivo.

The effect of cryotherapy on normal striated muscle was investigated using 18 adult male rats. Animals were divided into two groups, an experimental cryotherapy group and a control group receiving sham treatment. After the surgical procedure animals were allowed to equilibrate and vessel diameters, macromolecular leakage and blood flow were assessed before the cremaster muscle was frozen to -60 degrees C. After thawing measurements were taken every 15 min over a 2 h period. Cryotherapy resulted in an initial reduction in blood flow followed by a brief period of reperfusion, with complete vascular stasis eventually observed. Macromolecular leakage occurred from all vessels, which mirrored the fluctuations in blood flow. Transient changes in vessel diameters were also observed. Histology confirmed the in vivo observations of vessel congestion and muscle damage. The data suggest that cessation of flow and increased macromolecular leakage within the muscle may contribute to the cell death and tumour necrosis observed following cryotherapy.

Abdominal Muscles↗

Operating theatre lists--accidents waiting to happen?

Each year the Medical Defence Societies report cases where litigation has arisen due to errors in operating theatres. Incorrect details on operating lists increase the risk of such errors. The Medical Defence Societies, in conjunction with the nursing profession, have produced recommendations to reduce the risks of errors in operating theatres (1). The patient's full name and hospital number should be checked against the theatre list by the receiving nurse. Abbreviations should be avoided and operating lists should be altered as little as possible and never by telephone. Current practice in our hospital is that operating lists are typed by the consultant's secretary, using information drawn from handwritten lists submitted by junior doctors or from admission lists. Currently the final operating list is not routinely double-checked. The possibility that such a system could lead to potentially dangerous errors prompted an audit of operating lists for a one-month period, including all specialties at the Royal Hallamshire Hospital, Sheffield. The aim was to measure the incidence of errors, omissions and alterations in completed operating lists.

Appointments and Schedules↗

Laparoscopic fundoplication for gastro-oesophageal reflux.

The initial teaching and learning experience of four surgeons performing a laparoscopic Nissen fundoplication is reported. A total of 33 patients underwent the laparoscopic approach for Nissen fundoplication. Two patients also underwent concomitant cholecystectomy. A loose 360 degrees fundoplication secured by three or four sutures was performed, with 29 patients also undergoing posterior crural repair. Three operations were converted to open procedures. Two patients required subsequent surgery, one when the fundoplication and proximal stomach slipped into the chest and one for oesophageal obstruction. No other complications occurred. All patients are well and free of reflux symptoms at follow-up ranging up to 10 months (median 5 months). Operating time ranged from 47 min to 154 min (median 81 min) for fundoplication alone. The laparoscopic fundoplications with cholecystectomy required 145 and 170 min. Postoperative stay ranged from 3 to 12 days (median 3 days). Laparoscopic Nissen fundoplication is feasible in the management of gastro-oesophageal reflux disease. These early results demonstrate that this new technique may reduce some of the morbidity associated with open antireflux surgery. A prospective randomised study has been started to assess efficacy and benefits more thoroughly.

Adult↗

Facile preparation of nuclease resistant 3' modified oligodeoxynucleotides.

An efficient chemical procedure for the immobilization of carboxylate containing conjugate groups onto controlled pore glass (CPG) is described. The derivatized supports were used in the automated synthesis of an oligodeoxynucleotide (20-mer ODN) containing a 3' phosphodiester linked hexanol, aminohexyl, acridine, or cholesterol group. The stability of the oligomer in a hepatoma cell culture was found to be prolonged two to three fold by the presence of any of the 3' tails. By contrast, an aminohexyl group appended to the 5' terminus of the ODN only marginally improved its nuclease resistance. These data support the notion that antisense ODNs are primarily degraded by 3' exonucleases. Introduction of simple 3' tails which incorporate a normal phosphodiester linkage can increase ODN stability by interfering with these enzymes.

Base Sequence↗