Radiology casebook. Intussusception in a premature infant: a case report.
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Diagnosis, Differential↗
Biomedical subjects
A Price
Publications and source records attributed to A Price.
Cortisol response in short synacthen tests.
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Cosyntropin↗
ATLS: are we training the wrong people?
BACKGROUND: Despite the evolution, expansion and popularity of emergency medicine as a medical specialty in the United Kingdom (UK), emergency departments are still primarily staffed by senior house officers (second and third year graduates), particularly at weekends and at night. METHODS: A telephone and postal survey of Advanced Trauma Life Support (ATLS) training completed by this cohort of doctors indicates that UK courses are failing to train adequate numbers. RESULTS: It can thus be argued that ATLS is not being disseminated to the relevant grass-roots of medical care, where it is likely to be of the most benefit. CONCLUSIONS: The present study discusses possible reasons for this and offers constructive solutions to the problem. Although the matters discussed in this study refer to UK medical practice, they may be of relevance and interest to Australasian practitioners. Is EMST in Australasia training the appropriate group of doctors?
Data Collection↗
Hepatic plasmacytomas: case report and review of imaging features.
Extramedullary plasmacytomas are uncommon and have a better prognosis than disseminated myeloma. We describe the second case of hepatic plasmacytomas (multiple) following a solitary bone plasmacytoma. The imaging characteristics of the few reported cases of these rare hepatic tumours are compared. The value of ultrasound in the assessment of liver lesions is emphasized.
Aged↗
Hypofractionated radiotherapy for patients with carcinoma of the bladder.
In order to develop a low toxicity regimen of bladder radiotherapy for the palliation of patients with poor performance status we carried out a Phase II study of weekly 6 Gy fractions to a maximum dose of 30-36 Gy in 65 patients with T(2)-T(4) bladder cancer (median age 81 years). A complete response was obtained in 23/37 (62%) assessable patients at cystoscopy. Local control was achieved in 16/65 (25%) patients. The median survival of all 65 patients was 35 weeks, and the 2-year actuarial survival 21%. The main acute toxicity was urinary frequency as often as hourly at the peak of the reaction (Radiation Therapy Oncology Group (RTOG) grade 3) in seven patients, and urinary obstruction (RTOG grade 4) in one. The reactions may have been compounded by the effects of locally advanced tumour. Late bladder toxicity amongst the 16 patients who were evaluable after 1 year included four patients with persisting frequency, one with severe haematuria (RTOG grade), and one with a bladder capacity <100 ml (RTOG grade 4). One patient experienced RTOG grade 4 late bowel and bladder morbidity. Weekly 6 Gy fractions to a total dose of 30-36 Gy is a satisfactory palliative regimen for patients with advanced bladder cancer who cannot tolerate standard radical radiotherapy, but it may produce significant late bladder morbidity.
Aged↗
Marked inhibition of tumor growth in a malignant glioma tumor model by a novel synthetic matrix metalloproteinase inhibitor AG3340.
Synthetic matrix metalloproteinase (MMP) inhibitors have activity against a variety of tumors in preclinical models but have not been studied in gliomas. We determined the effect of AG3340, a novel synthetic MMP inhibitor with Ki values against gelatinases in the low picomolar range, on the growth of a human malignant glioma cell line (U87) in SCID-NOD mice. Mice were injected s.c. with U87 cells. Tumors were allowed to grow to a size of approximately 0.5 x 0.5 cm (after about 3 weeks), and the mice were randomized to receive either: (a) 100 mg/kg AG3340 in vehicle; or (b) vehicle control (0.5% carboxymethyl cellulose, 0.1% pluronic F68), both given daily i.p. Tumor area was measured twice weekly, and animals were sacrificed when moribund, or earlier if premorbid histology was examined. In vivo inhibition of tumor growth was profound, with AG3340 decreasing tumor size by 78% compared with controls after 31 days (when controls were sacrificed; P < 0.01, Wilcoxon test). Control animals survived 31 days after the i.p. injections began, and AG3340 mice survived 71 days, representing a >2-fold increase in survival associated with tumor growth delay. Histological examination found that AG3340-treated tumors were smaller, had lower rates of proliferation, and significantly less invasion than control-treated tumors. Hepatic or pulmonary metastases were not seen in either group. In a separate experiment, the tumors were smaller and sampled after a shorter duration of treatment; the changes in proliferation were more marked and occurred earlier than differences in tumor invasion between the two groups. Furthermore, in vitro cell growth was not inhibited at AG3340 concentrations of <1 mM. AG3340 plasma concentrations in vivo, 1 h after administration, ranged from 67 to 365 nM. Thus, AG3340 produced a profound inhibition of glioma tumor growth and invasion. AG3340 markedly increased survival in this in vivo glioma model. Treatment with AG3340 may be potentially useful in patients with malignant gliomas.
Animals↗
How accurately do we estimate patients' weight in emergency departments?
OBJECTIVE: To assess the accuracy of estimates of patients' weight made by physicians, nurses, and patients themselves in emergency departments. DESIGN: Observational prospective study. SETTING: Tertiary referral centre in Vancouver, BC. PARTICIPANTS: Eleven attending physicians, 26 nurses, and a convenience sample of 117 patients. INTERVENTIONS: Patients themselves, attending physicians, and nurses independently estimated the weight of 117 patients. An investigator weighed each patient. MAIN OUTCOME MEASURES: Mean error was determined by subtracting actual weight from estimated weight and dividing by actual weight; 95% confidence intervals (CI) were calculated. RESULTS: Mean error in estimates was 3.1% (95% CI 2.7 to 3.5) for patients, 8.4% for nurses (CI 7.6 to 9.2), and 8.1% (CI 7.1 to 9.1) for physicians. Weight was estimated within 5% of actual weight by 32% of nurses, 39% of physicians, and 82% of patients. Weight was estimated within 10% of actual weight by 66% of nurses, 66% of physicians, and 97% of patients. Estimates out by more than 15% were made by 11% of nurses, 16% of physicians, and 1% of patients. CONCLUSIONS: Patient estimates were most accurate. Physician and nurse estimates were unreliable.
Adult↗
Interaction of the baculovirus anti-apoptotic protein p35 with caspases. Specificity, kinetics, and characterization of the caspase/p35 complex.
The anti-apoptotic protein p35 from baculovirus is thought to prevent the suicidal response of infected insect cells by inhibiting caspases. Ectopic expression of p35 in a number of transgenic animals or cell lines is also anti-apoptotic, giving rise to the hypothesis that the protein is a general inhibitor of caspases. We have verified this hypothesis by demonstrating that purified recombinant p35 inhibits human caspase-1, -3, -6, -7, -8, and -10 with kass values from 1.2 x 10(3) to 7 x 10(5) (M-1 s-1), and with upper limits of Ki values from 0.1 to 9 nM. Inhibition of 12 unrelated serine or cysteine proteases was insignificant, implying that p35 is a potent caspase-specific inhibitor. Mutation of the putative inhibitory loop to favor caspase-1 resulted in a substantial decline in caspase-3 inhibition, but minimal changes in caspase-1 inhibition. The interaction p35 with caspase-3, as a model of the inhibitory mechanism, revealed classic slow-binding inhibition, with both active-sites of the caspase-3 dimer acting equally and independently. Inhibition resulted from complex formation between the enzyme and inhibitor, which could be visualized under nondenaturing conditions, but was dissociated by SDS to give p35 cleaved at Asp87, the P1 residue of the inhibitor. Complex formation requires the substrate-binding cleft to be unoccupied. Taken together, these data revealed that p35 is an active-site-directed inhibitor highly adapted to inhibiting caspases.
Apoptosis↗
Training in advanced trauma life support.
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Education, Medical, Continuing↗
Comparison of the diagnostic utility of the simplified and standard i.m. glucagon stimulation test (IMGST).
OBJECTIVE: To compare the peak GH and cortisol responses to the simplified and standard i.m. glucagon stimulation test (IMGST) in order to determine whether the use of a simplified form of this test results in a loss of diagnostic utility. PATIENT AND DESIGN: A retrospective study of 35 consecutive patients with pituitary disease who underwent a standard IMGST to measure GH (n = 34) or cortisol (n = 21) reserve at the programmed investigation unit of the Northern General Hospital, Sheffield. MEASUREMENTS: Cortisol, glucose and GH levels were measured at baseline and 30, 60, 90, 120, 150, 180, 210 and 240 min during the standard IMGST. We used the hormone levels at baseline, 150 and 180 min for the simplified IMGST and compared the cortisol and GH responses achieved. RESULTS: The median (range) peak GH and cortisol responses to simplified and standard IMGST were comparable 4.2 (0.5-47.5) vs 5.4 (0.5-47.5) mU/l (P = 0.75) and 635 (306-1669) vs 647 (306-1669) nmol/l (P = 0.801), respectively. Using the standard 'cut-off' points to assess GH (9 mU/l) or cortisol deficiency (580 nmol/l) there was no significant loss of diagnostic utility (P = 0.98 and P = 1.00, respectively). CONCLUSIONS: The simplified and standard IMGST have a similar diagnostic utility. The simplified IMGST could replace the standard IMGST as a screening test for GH and cortisol reserve in pituitary disease. The insulin-induced hypoglycaemia stress test can be reserved for cases in which a second assessment of pituitary reserve is clinically indicated or because of an indeterminate biochemical result.
Adolescent↗
Amiodarone and the thyroid: a practical guide to the management of thyroid dysfunction induced by amiodarone therapy.
Amiodarone induces predictable changes in thyroid function tests that are largely explicable in terms of the physiological effects of iodide excess and inhibition of deiodinase activity. Clinically relevant thyroid dysfunction is not uncommon during amiodarone therapy, and requires careful diagnosis and treatment. The diagnosis and management of thyrotoxicosis is probably best supervised by a specialist endocrinologist. Control of hypothyroidism can generally be achieved simply by the addition of T4 to the therapeutic regimen, ideally after an initial assessment by an endocrinologist. The frequency with which amiodarone causes thyroid and other complications serves to emphasize the need for rational prescribing and long-term cardiological follow up.
Amiodarone↗
Improving surgical resection rate in lung cancer.
BACKGROUND: Surgical resection is the recognised treatment of choice for patients with stage I or II non-small cell lung cancer (NSCLC). In the UK surgical resection rates have remained far lower (< 10%) than those achieved in Europe and the USA (> 20%), despite the recent introduction of fast access investigation units. It remains unclear therefore why UK surgical resection rates lag so far behind those of other countries. METHODS: A new quick access two stop investigation service was established at Papworth in November 1995 to investigate all patients presenting to any of three surrounding health districts with suspected lung cancer. Once staging was complete, all patients with confirmed lung cancer were reviewed by a multidisciplinary team which included an oncologist and a thoracic surgeon. Time from presentation to definitive treatment and surgical resection rates were reviewed. RESULTS: Two hundred and nine (76%) of a total of 275 consecutive patients investigated had confirmed lung cancer (28 small cell, 181 non-small cell). Of the remainder, eight patients (2%) had metastatic disease, four (1%) had other thoracic malignancy (thymoma, mesothelioma), four patients (1%) had benign thoracic tumours, and 50 (18%) had other non-malignant diseases. Of the 181 patients with non-small cell primary lung cancer, 47 (25%) underwent successful surgical resection, of whom 59% had stage I and 21% stage II disease. The failed thoracotomy rate was 11%. Median time from presentation at the peripheral clinic to surgical resection was 5 weeks (range 1-13). CONCLUSION: Quick access investigation, high histological confirmation rates, routine CT scanning, and review of every patient with confirmed lung cancer by a thoracic surgeon led to a substantial increase in the successful surgical resection rate. These results support the growing concern that many patients with operable tumours are being denied the chance of curative surgery in our present system.
Aged↗
A histochemical examination of the staining of kainate-induced neuronal degeneration by anionic dyes.
Anionic dyes, notably acid fuchsine, strongly stain the nuclei and cytoplasm of neurons severely damaged by injury or disease. We provide detailed instructions for staining nervous tissue with toluidine blue and acid fuchsine for optimal demonstration of injured neurons. Degeneration was induced in the hippocampus of the mouse by systemic administration of kainic acid, and the resulting acidophilia was investigated using paraffin sections of the Carnoy- or Bouin-fixed brains. The affected cells were bright red with the toluidine blue-acid fuchsine sequence. Their nuclei were stainable also with alkaline Biebrich scarlet and with the 1,2-naphthoquinone-4-sulfonic acid-Ba(OH)2 method; all staining was blocked by benzil but was relatively refractory to deamination by HNO2. These properties indicated an arginine-rich protein. The nuclei were strongly acidophilic in the presence of a high concentration of DNA (strong Feulgen reaction), and acidophilia could not be induced in normal neuronal nuclei by chemical extraction of nucleic acids. The cytoplasmic acidophilia of degenerating hippocampal neurons was due to a protein rich in lysine (extinguished by alkalinity, easily prevented by deamination, and unaffected by benzil). Stainable RNA was absent from the perikarya of the affected cells, but normal neuronal cytoplasm did not become acidophilic after extraction of nucleic acids. We suggest that kainate-induced cell death is preceded by increased production of basic proteins, which become concentrated in the nucleus and perikaryon. Groups of small, darkly staining neurons were seen in the cerebral cortex in control and kainate-treated mice. These shrunken cells were purple with the toluidine blue-acid fuchsine stain, and were attributed to local injury incurred during removal of the unfixed brain.
Animals↗
New developments in radiation treatment.
Radiotherapy is a key modality in the treatment of patients with cancer. Recent trials have extended its role. Advances in the technology of radiotherapy delivery and in the molecular basis of radiation treatment offer the prospect of further improvements in treating these patients.
Breast Neoplasms↗
[Surgical treatment of children with brachial plexus paralysis].
OBJECTIVE AND METHODS: A variety of surgical procedures exist for early repair of the nerve injury in obstetrical brachial plexus palsy, including neuroma excision and nerve grafting, neurolysis and neurotization. Secondary deformities of the shoulder, forearm, and hand can similarly be reconstructed using soft tissue and skeletal procedures. This review describes our surgical approach to maximize the ultimate functional outcome in infants and children with obstetrical brachial plexus palsy.
Brachial Plexus↗
Biogenesis of the gram-negative bacterial envelope.
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Bacterial Outer Membrane Proteins↗
Glucocorticoid replacement therapy: are patients over treated and does it matter?
BACKGROUND AND OBJECTIVES: Adequate assessment of patients on glucocorticoid replacement therapy is of great importance to avoid the consequences of under or over treatment, but no simple test is available for this. The aims of this study were (1) to assess adequacy of glucocorticoid replacement in hypoadrenal patients, (2) to correlate serum cortisol levels (cortisol day curve) with 24-hour urine free cortisol excretion and (3) to assess the impact of glucocorticoid dose optimization on markers of bone formation and bone resorption. DESIGN: Cross-sectional study of current replacement therapy and a prospective study of the effect of dose alteration on bone turnover markers. PATIENTS: Thirty-two consecutive patients on replacement glucocorticoid therapy (12 Addison's disease, 20 hypopituitarism) from a University teaching hospital out-patient department. MEASUREMENTS: Serum and urinary cortisol, osteocalcin, N-telopeptide of type I collagen (NTX) and bone mineral density. RESULTS: 28/32 (88%) patients required a change of therapy; 24/32 (75%) a total reduction in dose, 18/32 (56%) a change in replacement therapy regimen or drug and 14/32 (44%) both changes. The mean daily dose of hydrocortisone was reduced from 29.5 +/- 1.2 to 20.8 +/- 1.0 mg. A significant correlation was found between peak cortisol and 24-hour urine free cortisol/ creatinine (Spearman correlation r = 0.60, P < 0.0001; n = 51). Following hydrocortisone dose reduction, median osteocalcin increased from 16.7 micrograms/l (range 8.2-65.7) to 19.9 micrograms/l (8.2-56.3); P < 0.01, with no change in the NTX/creatinine ratio. CONCLUSIONS: A high proportion of patients on conventional corticosteroid replacement therapy are over treated or on inappropriate replacement regimens. To reduce the long term risk of osteoporosis, corticosteroid replacement therapy should be individually assessed and over replacement avoided.
Addison Disease↗
Investigation of oestrogen receptors, sex steroids and soluble adhesion molecules in the progression of malignant melanoma.
The question of whether melanoma tumours have classical oestrogen receptors (ERs) is unresolved, but epidemiological data clearly show a survival benefit for female patients with metastatic melanoma. The aims of this study were to examine to what extent the presence of ER in melanoma tumours might relate to disease progression and whether disease progression relates to patients' sex steroid status. Additionally, levels of two soluble adhesion molecules [circulating intercellular adhesion molecule-1 (sICAM-1) and circulating vascular cell adhesion molecule-1 (sVCAM-1)] were examined as independent, possibly prognostic indicators of disease progression. ER immunocytochemical assay identified only two lesions (out of 69 investigated) which had any evidence of the receptors, and staining in these lesions was very modest. No significant changes in oestrone or androstenedione levels were noted for male or female patients with disease progression. As expected, oestradiol levels reflected the menopausal status of the female patients but, for all post-menopausal female patients and male patients, there was no significant relationship to tumour stage. However, a significant decrease in sex hormone-binding globulin occurred with disease progression in male but not female patients, and sex differences in the levels of soluble adhesion molecules were also seen in advanced metastatic disease.
Adolescent↗