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Biomedical subjects

M A Henderson

Publications and source records attributed to M A Henderson.

At least 37 records · Page 2Linked to original sources
PubMed1995

Proteolytic activation of bacterial toxins by eukaryotic cells is performed by furin and by additional cellular proteases.

Before intoxication can occur, anthrax toxin protective antigen (PA), Pseudomonas exotoxin A (PE), and diphtheria toxin (DT) must be activated by proteolytic cleavage at specific amino acid sequences. Previously, it was shown that PA and DT can be activated by furin. In Chinese hamster ovary (CHO) cells, wild-type (RKKR) and cleavage site mutants of PA, each administered with a modified form of anthrax toxin lethal factor (the N terminus of lethal factor fused to PE domain III), had the following potencies: RKKR (wild type) (concentration causing 50% cell death [EC50] = 12 ng/ml) > or = RAAR (EC50 = 18 ng/ml) > FTKR (EC50 = 24 ng/ml) > STRR (EC50 = 49 ng/ml). In vitro cleavage of PA and cleavage site mutants of PA by furin demonstrated that native PA (RKKR) and PA with the cleavage sequence RAAR are substrates for furin. To characterize eukaryotic proteases that play a role in activating bacterial toxins, furin-deficient CHO cells were selected after chemical mutagenesis. Furin-deficient cells were resistant to PE, whose cleavage site, RQPR, constitutes a furin recognition site and to all PA cleavage site mutants, but were sensitive to DT (EC50 = 2.9 ng/ml) and PA (EC50 = 23 ng/ml), whose respective cleavage sites, RKKR and RVRR, contain additional basic residues. Furin-deficient cells that were transfected with the furin gene regained sensitivity to PE and PA cleavage site mutants. These studies provide evidence that furin can activate the three toxins and that one or more additional proteases contribute to the activation of DT and PA.

ADP Ribose Transferases↗
PubMed1995

A salaried compensation model for postanesthesia nurses.

Health care organizations involved in innovative and creative work redesign projects may find traditional pay structures inadequate to meet the needs of the changing environment. The idea of salaried compensation for registered nurses is not unprecedented. However, few salaried compensation models for nurses are described in the literature. This article presents a model that we believe will be of particular interest to nurses in PACUs, because its design allows for adequate call coverage plus flexibility in scheduling. In addition, this compensation model eliminates incidental overtime, thus allowing for a more predictable salary budget.

Humans↗
PubMed1995

Use of a laryngeal mask airway in an adult patient with the Hunter syndrome.

The mucopolysaccharidoses are a rare group of diseases. The Hunter Syndrome (mucopolysaccharidosis II) has been classified into severe and mild forms with presentation between the years 2 and 4. Enzyme assays provide the definitive diagnosis. An outstanding concern for the anaesthetist is airway management. The management of a patient with this condition is illustrated with a case report.

Abscess↗
PubMed1993

Extracorporeal shock wave lithotripsy combined with litholytic therapy in the treatment of patients with symptomatic gallstones--the Melbourne experience.

OBJECTIVE: To investigate the role of extracorporeal shock wave lithotripsy using the Dornier MPL9000 lithotripter and adjuvant litholytic therapy in the treatment of symptomatic gallbladder stones. PATIENTS AND METHODS: Between August 1989 and March 1991, 399 patients had their one to three gallbladder stones fragmented by the Dornier MPL9000 lithotripter. Chenodeoxycholic acid alone was used as adjuvant litholytic therapy in the majority. A minority received a combination of chenodeoxycholic acid and ursodeoxycholic acid or ursodeoxycholic acid alone. Patients who died, had cholecystectomies or failed to complete the treatment program were excluded from analysis, leaving a cohort of 287 patients with a follow-up of at least 12 months. This cohort comprised 173 patients with single small stones (20 mm or less in diameter), 32 patients with single large stones (21 mm to 30 mm in diameter) and 82 patients with two to three stones. OUTCOME MEASURES: Patients were followed up by repeated ultrasound examination to monitor the disappearance of fragments from the gallbladder. Stone-free rates, recurrences and complications of treatment were determined. RESULTS: The stone-free rate 12 months after treatment was 37.6% for patients with a single small stone, 3.1% for patients with a single large stone and 18.3% for patients with two to three stones. Of 70 patients with a single small stone who had become stone free at some time during the 12 months after treatment, five (7.1%) experienced recurrence, as did one of the 16 patients (6.9%) with two to three stones. Some 179 patients (44.9%) experienced biliary colic after lithotripsy. Most attacks were mild. Eleven patients (2.8%) developed cholecystitis and nine (2.3%) became jaundiced. Five patients (1.3%) suffered from pancreatitis, of whom one died from severe necrotising pancreatitis. Treatment mortality was 0.25%. Cholecystectomy was needed in 44 patients (11.9%). CONCLUSIONS: Only about 15%-20% of all patients with symptomatic gallbladder stones are suitable for lithotripsy. In this study, only about 28% were stone free after 12 months. As the gallbladder is not removed, stones may re-form. Laparoscopic cholecystectomy and open cholecystectomy by comparison will produce a "stone-free state" in 100% of patients, no matter how many stones are present in the gallbladder, their size, or whether the gallbladder is non-functioning. Consequently, lithotripsy and litholytic therapy are now reserved for those few patients who are unable to tolerate general anaesthesia and cholecystectomy and those who refuse surgery. Even in centres showing the most favourable results, lithotripsy and litholytic therapy will have at best a minor role to play in the overall management of symptomatic gallbladder stones.

Adult↗
PubMed1993

Detection and significance of occult metastases in node-negative breast cancer.

The clinical value of lymph node immunohistochemistry was assessed in 343 consecutive patients with apparently node-negative breast cancer using antimucin monoclonal antibodies BC2, BC3 and 3E1.2. Occult metastases were detected in 41 patients (12 per cent). Although most of these were micrometastatic (< 2 mm in diameter), larger or diffuse deposits were found in ten patients. Blind assessment of repeat haematoxylin and eosin stained sections detected metastases in ten of the 41 patients with occult metastases. After a median follow-up of 79 months, patients with occult metastases had a shorter time to disease recurrence (P < 0.05) but not to death. After adjustment for other prognostic factors, the presence of occult metastases in two or more nodes was the most significant predictor of both disease recurrence (P < 0.01) and death (P < 0.01). When the ten patients with positive haematoxylin and eosin sections were excluded from the analysis, the presence of occult metastases in two or more nodes was still associated with a reduced disease-free interval (P < 0.05) and survival (P < 0.05). Lymph node immunohistochemistry is a simple technique affording more accurate definition of nodal involvement than conventional methods.

Adult↗
PubMed1993

Parental attitudes to presence at induction of paediatric anaesthesia.

Previous studies of parental presence at induction of anaesthesia in children have examined parental reaction to being present and the benefits gained from their presence. This study was undertaken specifically to assess parents' attitudes to being present at induction of their child's anaesthetic. A total of 154 questionnaires were distributed over a two-week period to parents of children presenting to the Day Stay Unit for procedures requiring general anaesthesia. Eighty-eight percent would have liked to be present at induction. Only 41% of parents expected to be present and only 40% of parents were actually present for their child's induction. Of those parents present, 94% felt it helpful to their child, 65% helpful to themselves and 41% helpful to the anaesthetist. No-one felt their presence to have been unhelpful. These results may provide an incentive for anaesthetists to review their current paediatric anaesthetic practices.

Anesthesia↗
PubMed1993

Parathyroid hormone related protein in breast cancers of widely varying prognosis.

Parathyroid hormone related protein (PTHrP) is a novel calcium regulating hormone that may have a significant role in the pathophysiology of breast cancer. We have previously demonstrated a relationship between immunohistochemically detectable PTHrP in primary breast tumours and the subsequent development of bone metastases and hypercalcaemia. The aim of this study was to compare the PTHrP status in the primary tumours from three groups of patients with widely varying prognosis. (1) The favourable outcome group; all patients had a favourable prognosis and minimum 3 years disease free follow up (n = 30). (2) The unfavourable outcome group; all patients presented with localized breast cancer but developed distant disease within 3 years (n = 26). (3) The unfavourable presentation group; all had distant disease at first presentation (n = 26). No differences in PTHrP status of the primary tumour amongst the three patient groups were found (66%, 65% and 61% positive respectively). The development of bone with liver metastases and hypercalcaemia was associated with increased positive PTHrP status of the primary tumor.

Bone Neoplasms↗
PubMed1992

Needle core biopsy of the breast with a spring-loaded device.

Over a 2-year period, 151 outpatients with a palpable breast lump requiring needle core biopsy were randomized to a Tru-Cut 14-G (T14), Bioptycut 14-G (B14) or Bioptycut 18-G (B18) needle. Use of a Biopty gun resulted in less pain than a Tru-Cut needle. An inadequate sample was obtained after two needle passes in 11 of 49 (T14), none of 51 (B14) and two of 51 (B18) patients (chi 2 = 14.6, 2 d.f., P = 0.0007). Tissue samples were assessed by a single pathologist for tissue volume and overall diagnostic value; the B14 group scored better than the B18 and T14 for both of these parameters (P < 0.003). The sensitivities were 68 (T14), 88 (B14) and 96 (B18) per cent (overall chi 2 = 7.3, 2 d.f., P = 0.026). The Biopty gun with a 14-G needle results in a higher sampling success rate, greater diagnostic sensitivity and a better specimen quality than the Tru-Cut, and is much easier to use.

Adult↗
PubMed1992

Breast cancer in the elderly: treatment of operable disease.

Between 1976 and 1985 122 elderly patients aged 70 years and over, were treated for 'operable' invasive breast cancer (UICC stage I-IIB). A tendency towards less aggressive investigation and treatment was noted in the elderly. Of 117 patients undergoing surgery, 79 (68%) had 'full' conventional treatment, either mastectomy with axillary clearance, sampling or radiotherapy, or local excision with radiotherapy. In 38 patients (32%) management of the breast or axilla was considered to have been less complete than the usual practice for younger patients ('limited' treatment group), either local excision without radiotherapy or simple mastectomy alone. The 'limited' treatment group were significantly older than the 'full' treatment group but were comparable for tumour size, clinical nodal status and oestrogen and progesterone receptor levels. Although there was no survival difference between the groups, those in the 'limited' treatment group were more likely to develop locoregional recurrence (chi 1(2) = 9.2, P = 0.002, log rank test). In practice, management of the elderly often appears to be influenced by chronological age rather than clinical or biological factors. It is suggested that elderly patients sufficiently fit to undergo surgery should be treated along the lines applicable to younger patients.

Age Factors↗
PubMed1991

Localization of parathyroid hormone-related protein in breast cancer metastases: increased incidence in bone compared with other sites.

Parathyroid hormone-related protein (PTHrP) has recently been identified in 60% of a series of primary breast cancers. The detection of a bone-resorbing factor in tumors with a propensity to metastasize to bone prompted study of PTHrP in breast cancer metastasis. PTHrP was localized by immunohistology in 12 of 13 (92%) breast cancer metastases in bone and in 3 of 18 (17%) metastases in non-bone sites. The statistical difference was highly significant (P less than 0.0001). Production of PTHrP as a bone-resorbing agent may contribute to the ability of breast cancers to grow as bone metastases.

Bone Neoplasms↗
PubMed1991

Breast cancer in the elderly: pattern of disease.

The elderly (aged 70 years or more) constituted 201 (37%) of 548 first-time admissions to a single institution for breast cancer between 1976 and 1985. The pattern of disease was studied and contrasted with that seen in younger patients (less than 70 years old). Currently, 5000 new breast cancers are diagnosed in Australia each year. It is projected that the proportion of new breast cancer patients who are elderly will rise from 37 to 60% by the year 2031. In general, the disease was similar to that seen in younger patients. Minor histological differences occurred and there were tendencies towards late presentation and clinically less aggressive disease. Tumour size, the presence of metastases and UICC staging were useful predictors of outcome but nodal status and hormone receptor levels did not discriminate. An unexpected finding was the relative longevity of elderly patients with breast cancer. The stage-specific 5-year survival rates (UICC stages: I--73%; II--65%; III--42%; IV--10%;) did not differ significantly from those seen in younger patients.

Aged↗
PubMed1991

Oestrogen receptor assay of breast cancer by immunocytochemistry of fine needle aspirates.

Sixty-five patients with operable breast cancer were studied to assess the reliability of immunocytochemical analysis of oestrogen receptor (ER-ICA) in specimens obtained by percutaneous fine needle aspiration. Results obtained with the commercially available ER-ICA kit were compared with those obtained by the routine biochemical radioligand assay of oestrogen receptor (ER) on excised tumour specimens. Fifty-two of 65 percutaneous aspirates were evaluable. Of these, thirty-five (67%) were ER positive by the radioligand method. ER-ICA was found to be a reliable method for oestrogen receptor assay, with a high concordance (90.4%) between it and the radioligand essay. The ER-ICA assay had a sensitivity of 89%, specificity of 94%, positive predictive value of 97% and negative predictive value of 80%. ER-ICA assay performed on material obtained by fine-needle aspiration is a reliable method of ER assay. It can replace formal biopsy for patients with inoperable primary tumours or accessible metastases.

Adenocarcinoma, Mucinous↗
PubMed1991

Comparison of EGFR, c-erbB-2 product and ras p21 immunohistochemistry as prognostic markers in primary breast cancer.

In a prospective study of 75 breast carcinomas, monoclonal antibodies EGFR1, Anti-serum 21N (As21N) and RAP-5 were used to assess immunohistochemically expression of Epidermal Growth Factor Receptor (EGFR), c-erbB-2 oncoprotein and ras protein p21. A careful comparison was made of their relative prognostic significance. Positive staining was seen with EGFR1 in 12/71 cancers (17%) and with As21N in 16/75 cancers (21%). Positive staining with RAP-5 occurred in all cancers and benign breast tissue, but varied in intensity. EGFR expression correlated with the number of involved lymph nodes, histological grade, estrogen and progesterone receptor (ER, PR) levels and the Melbourne Prognostic Index. C-erbB-2 and ras expression both correlated with ER levels and EGFR, but not with the Prognostic Index. Based on an immunohistochemical technique, EGFR expression emerges as the parameter with strongest prognostic associations.

Biomarkers, Tumor↗