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Biomedical subjects

A Fowler

Publications and source records attributed to A Fowler.

At least 37 records · Page 2Linked to original sources

Argument for the surgical staging of apparent early endometrial cancer.

Cancer of the uterine corpus, commonly referred to as cancer of the endometrium or cancer of the uterus, continues to be the most common pelvic genital malignancy affecting western women (1). In 1998 in the United States 36,100 women were diagnosed with this cancer, and there were 6,300 deaths from this condition in that year. Of concern is that despite a relatively stable incidence over the last decade, the annual number of deaths since 1987 from endometrial cancer has more than doubled (2). Many controversies exist in the management of apparent early endometrial cancer. These include: 1. The role of surgical staging which includes pelvic lymphadenectomy. 2. The role of the subspecialist gynaecological oncologist in primary surgical treatment. 3. Indications for vaginal and external beam radiotherapy. 4. Who is at risk for recurrence? 5. The role of laparoscopic approach to the management of this disease. Despite their importance, these and other issues have not been appropriately addressed by prospective randomized studies. Treatment strategies and algorithms have thus been based upon a combination of clinicopathological studies and uncontrolled reviews. The views expressed in this clinical opinion are those of the Sydney Gynaecologic Oncology Group and reflect our philosophy on the current management of this tumour, supported by recent and appropriate peer reviewed scientific literature.

Brachytherapy↗

High-dose-rate brachytherapy alone post-hysterectomy for endometrial cancer.

PURPOSE: To evaluate the outcome of post-hysterectomy adjuvant vaginal high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: A retrospective analysis was performed on a series of 143 patients with endometrial cancer treated with HDR brachytherapy alone post-hysterectomy from 1985 to June 1993. Of these patients, 141 received 34 Gy in four fractions prescribed to the vaginal mucosa in a 2-week period. The median follow-up was 6.9 years. Patients were analyzed for treatment parameters, survival, local recurrence, distant relapse, and toxicity. RESULTS: Five-year relapse free survival and overall survival was 100% and 88% for Stage 1A, 98% and 94% for Stage IB, 100% and 86% for Stage IC, and 92% and 92% for Stage IIA. The overall vaginal recurrence rate was 1.4%. The overall late-toxicity rate was low, and no RTOG grade 3, 4, or 5 complications were recorded. CONCLUSION: These results are similar to reported international series that have used either low-dose-rate or HDR brachytherapy. The biological effective dose was low for both acute and late responding tissues compared with some of the HDR brachytherapy series, and supports using this lower dose and possibly decreasing late side-effects with no apparent increased risk of vaginal recurrence.

Adult↗

Haemodialysis dose is independent of type of surgically-created vascular access.

BACKGROUND: In the United States, the use of polytertraflouroethylene (PTFE) graft compared with native arteriovenous fistula (AVF) for haemodialysis vascular access has been increasing despite a greater than twofold higher incidence of thrombosis and infection associated with PTFE grafts. METHODS: We studied 214 haemodialysis patients with not more than two revisions of their vascular access, to determine whether any relationship exists between the type of haemodialysis vascular access and dialysis dose assessed primarily by urea reduction ratio (per cent reduction in blood urea nitrogen concentration after a dialysis session). Serum albumin concentration was used as a secondary outcome measure of dialysis adequacy. Urea reduction ratio and predialysis serum albumin concentration were measured at onset of study and at 4-week intervals and mean values were calculated for each subject. RESULTS: The 214 patients (118 males, 96 females) included 173 Blacks (81%), 26 Whites (15%), and 15 Hispanics (7%), of mean (+/-SD) age 55.6+/-15.5 years. Of these 214 subjects, 111 (52%) had a native AVF, while 103 (48%) had a PTFE graft. Both mean urea reduction ratio (native AVF=69 +/-6.7% vs PTFE graft=70+/-7.3%; P=0.31), and mean serum albumin concentration (native AVF=4.02+/-0.39 g/dl vs PTFE graft=4+/-0.33 g/dl; P= 0.59) were equivalent in both groups. Separate multiple logistic regression analyses with type of vascular access as one of the independent variables, found no significant relationship between type of vascular access and either a urea reduction ratio > 65% (P= 0.67), or a serum albumin concentration >4g/dl (P=0.89), after adjustment for age of vascular access, access revision, location of access, dialyser urea clearance, length of dialysis treatment, body weight, and age. CONCLUSION: We conclude that PTFE grafts do not permit delivery of better dialysis than native AVF. The increasing use of PTFE grafts in the United States does not have any clinical justification.

Adult↗

Desialylation of peripheral blood mononuclear cells promotes growth of HIV-1.

Activation of peripheral blood CD4+ helper T lymphocytes establishes a permissive state for growth of HIV-1. Activated T lymphocytes expressed increased sialidase (neuraminidase) activity and were hyposialylated. Treatment of freshly isolated peripheral blood mononuclear cells (PBMCs) with microbial neuraminidase (NANase) or phytohemagglutinin (PHA) prior to infection at low multiplicity with T cell line-adapted HIV-1IIIB resulted in production of large amounts of p24 antigen and reverse transcriptase. In contrast, neither viral component was detected in the medium of mock-treated cells infected at a similar multiplicity through 21 days in culture. The titer of a stock solution of HIV-1IIIB was 1.4 +/- 0.18 log10 greater in NANase-treated PBMCs than in mock-treated cells; the titer was similarly raised 1.5 to 1.76 +/- 0.18 log10 in PHA-treated cells. Growth of the primary isolate HIV-1(91/US/056) was also enhanced in NANase-treated PBMCs; the titer of a stock solution of HIV-1(91/US/056 was 1.0 +/- 0.16 log10 greater in NANase-treated PBMCs than in mock-treated cells 7 days after infection. No enhancement of viral growth in PBMCs was detected when NANase was heat-inactivated or specifically inhibited with 2,3-dehydro-2-desoxy-N-acetyl-neuraminic acid prior to use. Treatment of PBMCs with NANase did not alter the distribution of lymphocyte subsets nor change the density of CD4 antigen per cell after 7 days in culture. Whereas PHA treatment of PBMCs was mitogenic, pretreatment with NANase was not; the amount of [3H]thymidine incorporated into DNA and culture growth characteristics were similar for NANase- and mock-treated cells. Thus, desialylation of PBMCs promoted a permissive state for growth of HIV-1 without affecting the rate of DNA synthesis or relative number of target CD4+ cells.

Antigens, CD↗

High-dose-rate brachytherapy in the management of high-grade intraepithelial neoplasia of the vagina.

The majority of women with high-grade intraepithelial neoplasia (VAIN 3) are over 60 years of age and have a history of premalignant or malignant disease of the cervix. Although the natural history of VAIN is not well defined, high-grade lesions are premalignant. Ablative treatment with laser or 5-fluorouracil cream is commonly unsatisfactory. Several series have reported a low rate of recurrence and complications if VAIN 3 is treated with low-dose-rate brachytherapy. This retrospective review reports the outcome of 14 patients treated with high-dose-rate brachytherapy, with a dose of 34 to 45 Gy in 4.5- to 8.5-Gy fractions. Treatment was well tolerated with no severe early or late toxicity observed. At a median follow-up of 46 months 1 patient progressed to invasive carcinoma of the vagina; in another patient VAIN 3 persisted.

Adult↗

High-dose-rate brachytherapy in the management of carcinoma of the cervix: an 8-year Australian experience.

High-dose-rate brachytherapy was introduced at this hospital for the treatment of gynaecological malignancy in 1985. A retrospective analysis was performed of 103 patients with cervix cancer treated with this technique from 1985 to June, 1993. The patients were analyzed for treatment parameters, response, survival, relapse and toxicity. Five-year survival was 78% for Stage 1B, 72% for Stage 2A, 42% for Stage 2B and 29% for Stage 3B. The severe late toxicity rate was 4.9%. These results are similar to reported international series that have used either low-dose-rate or high-dose-rate brachytherapy.

Actuarial Analysis↗

Diffuse oesophageal spasm: diagnosis by ambulatory 24 hour manometry.

BACKGROUND: Diffuse oesophageal spasm (DOS) is a potential cause of intermittent chest pain and/or dysphagia. In the past, the diagnosis of DOS has relied on criteria obtained from standard oesophageal manometry (more than one simultaneous contraction in a series of 10 wet swallows with the rest being peristaltic). As symptoms are intermittent, however, 24 hour manometry may well be more suited to its investigation. AIMS: To determine the ability of 24 hour manometry to detect the symptomatic contractions of DOS and to compare standard, laboratory based manometry with 24 hour manometry in its diagnosis. PATIENTS: Three hundred and ninety consecutive patients referred with suspected oesophageal disorders. METHODS: Standard laboratory based manometry and 24 hour outpatient manometry. RESULTS: Sixteen patients were classified by 24 hour manometry as having DOS on the basis of painful contractions (spasms) of excessive duration and increased amplitude. Laboratory based manometry failed to detect the majority of these patients with DOS (14/16), and 53/55 were incorrectly labelled as having DOS on the basis of asymptomatic manometric findings. CONCLUSION: The detection of symptomatic DOS requires 24 hour manometry.

Adult↗

Rubisco in marine symbiotic dinoflagellates: form II enzymes in eukaryotic oxygenic phototrophs encoded by a nuclear multigene family.

Genes encoding ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) were cloned from dinoflagellate symbionts (Symbiodinium spp) of the giant clam Tridacna gigas and characterized. Strikingly, Symbiodinium Rubisco is completely different from other eukaryotic (form I) Rubiscos: it is a form II enzyme that is approximately 65% identical to Rubisco from Rhodospirillum rubrum (Rubisco forms I and II are approximately 25 to 30% identical); it is nuclear encoded by a multigene family; and the predominantly expressed Rubisco is encoded as a precursor polyprotein. One clone appears to contain a predominantly expressed Rubisco locus (rbcA), as determined by RNA gel blot analysis of Symbiodinium RNA and sequencing of purified Rubisco protein. Another contains an enigmatic locus (rbcG) that exhibits an unprecedented pattern of amino acid replacement but does not appear to be a pseudogene. The expression of rbcG has not been analyzed; it was detected only in the minor of two taxa of Symbiodinium that occur together in T. gigas. This study confirms and describes a previously unrecognized branch of Rubisco's evolution: a eukaryotic form II enzyme that participates in oxygenic photosynthesis and is encoded by a diverse, nuclear multigene family.

Amino Acid Sequence↗

Structure of the cell wall anchor of surface proteins in Staphylococcus aureus.

Many surface proteins are anchored to the cell wall of Gram-positive bacteria and are involved in the pathogenesis of these organisms. A hybrid molecule was designed that, when expressed in Staphylococcus aureus, was anchored to the cell wall and could be released by controlled enzymatic digestion. By a combination of molecular biology and mass spectrometry techniques, the structure of the cell wall anchor of surface proteins in S. aureus was revealed. After cleavage of surface proteins between threonine and glycine of the conserved LPXTG motif, the carboxyl of threonine is amide-linked to the free amino group of the pentaglycine crossbridge in the staphylococcal cell wall.

Amino Acid Sequence↗