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Biomedical subjects

I Ross

Publications and source records attributed to I Ross.

At least 19 recordsLinked to original sources

Hereditary hyperferritinaemia-cataract syndrome and differential diagnosis of hereditary haemochromatosis.

Hereditary hyperferritinaemia-cataract syndrome (HHCS) is a rare differential diagnosis of hereditary haemochromatosis. It should be suspected in patients with raised ferritin levels, but no evidence of iron overload, and in the absence of mutations in the HFE gene. Awareness of this condition prevents unnecessary liver biopsies and allows accurate genetic counselling since HHCS is an autosomal dominant disorder. The danger of treating these patients by phlebotomy in the same manner as those with hereditary haemochromatosis is highlighted.

Adult↗

Somatostatin enhances cAMP-dependent short-circuit current in human colon via somatostatin receptor subtype-2.

Somatostatin inhibits colonic ion secretion in animal models and cultured intestinal cell lines via somatostatin receptor subtype 2 and subtype 1, respectively. In a recent in vitro ion transport study of the human colon, somatostatin was shown to stimulate short-circuit current, a measure of electrogenic ion transport. In this study we have used the reverse-transcription polymerase chain reaction (RT-PCR) and measurements of changes in short-circuit current (Isc) in response to receptor subtype-specific analogs of somatostatin, to define the somatostatin receptor subtype responsible for the stimulation of short-circuit current in human colon. Somatostatin receptor subtypes 1, 2, and 5, but not 3 and 4, were detected in the human colonic epithelium. Measurements of short-circuit current showed somatostatin and octreotide (1 micromol/liter) increased the prostaglandin stimulated short-circuit current by 12.3+/-1 and 11.0+/-1 microA/cm2, respectively. Similarly, analogs selective for somatostatin receptor subtypes 2 and 5 (1 micromol/liter) produced an increase of short-circuit current of 11.7+/-1 and 13.2+/-1 microA/cm2, respectively. However, at a concentration (10 nmol/liter) near the EC50, the somatostatin receptor subtype 2 analog increased short-circuit current by 9+/-1 microA/cm2, whereas the receptor subtype 5 analog had no effect. There was no difference in receptor expression or effect of the peptides related to the anatomical site of tissue collection. In conclusion, human colonic mucosa expresses multiple somatostatin receptor subtypes, of which subtype 2 mediates the stimulatory effect of somatostatin on ion transport.

Colon↗

A prospective study to evaluate the role of complexed prostate specific antigen and free/total prostate specific antigen ratio for the diagnosis of prostate cancer.

PURPOSE: Patients are increasingly undergoing prostatic biopsy to identify localized prostate cancer. The decision to perform a biopsy is often made on the basis of total prostate specific antigen (PSA). However, this value lacks adequate specificity for this task. We evaluate the role that a number of these tests, including the Bayer complexed PSA (Bayer Diagnostics, Tarrytown, New York) and free/total PSA ratio, may have in our clinical practice. MATERIALS AND METHODS: A total of 160 consecutive patients attending a prostate assessment clinic were enrolled during an 18-month period in our study. All patients had a previously recorded total PSA (range 2.6 to 20.0 ng./ml.). Before transrectal ultrasound biopsy of the prostate gland, a blood sample was taken with patient consent. The findings on ultrasound were then recorded, including prostate volume. Serum samples were immediately sent for subsequent storage and analysis. RESULTS: Of the patients enrolled 109 had benign histology while 51 had prostatic carcinoma. The 2 patient groups were well matched for age. In our series patients with prostate cancer had significantly smaller prostates and higher mean total PSA. At a high sensitivity, such as 95%, it appeared that Bayer complexed PSA performed better than the other tests and ratios, with an estimated specificity of 24.8% compared with 17.4% for Bayer total PSA and 15.6% for Abbott free/total PSA (Abbott Laboratories, Abbott Park, Illinois). Receiver operator characteristics curves were drawn, and when the areas under them were calculated, we demonstrated that the area under the curve for Bayer complexed PSA (0.706) was between the values for total PSA (0.671) and free/total PSA ratio (0.731). However, the only statistically significant improvement in performance was in Bayer complexed PSA over the total PSA assays. CONCLUSIONS: Our study revealed that the overall diagnostic performance of Bayer complexed PSA appears to be better than the other PSA tests and ratios studied. The use of Bayer complexed PSA may lead to a reduction in the number of men undergoing unnecessary prostatic biopsy.

Aged↗

Cardiovascular disease and outcome of acute stroke: influence of pre-existing cardiac failure.

BACKGROUND AND AIMS: Whilst a number of variables, mostly a consequence of a stroke, are known to predict mortality of acute stroke there is limited information on the significance of pre-existing cardiovascular variables on stroke mortality. We have investigated the influence of pre-existing cardiovascular factors in one cohort of stroke patients. METHODS: We studied 295 patients, mean age 74+/-10 (range 34-96) years; 133 males, presenting with acute stroke for pre-existing cardiovascular disease (CVD) defined as hypertension, atrial fibrillation (AF), ischaemic heart disease (IHD) and cardiac failure (CF). In addition, data were collected on epidemiological and neurological variables known to influence stroke mortality. The most significant of the cardiovascular factors was further investigated against all the other cardiovascular groups together and against those without any CVD. Outcome was measured as their influence on acute phase and 3-month mortality. RESULTS: There was no significant difference in 3-month mortality with hypertension (P=0.62) and IHD (P=0.33) but there was a significant higher mortality in patients with AF (P=0.05) and CF (P <0.001). CF was more significant than all other CVD (hypertension+AF+IHD) together without the failure (P<0.001); odds ratio of 4.5 (95% CI 2.28-9.07). Partial correlation coefficient revealed CF to be an independent significant variable to influence stroke mortality when controlled with AF, stroke syndromes, age, incontinence, pyrexia, dysphagia and Glasgow coma score. CONCLUSIONS: Pre-existing CF has an adverse influence on stroke mortality independent of other known factors. Cardiovascular factors without failure do not have such an effect except the marginal effect of AF.

Adult↗

Somatostatin and octreotide stimulate short-circuit current in human colonic epithelium.

In vitro somatostatin is a potent inhibitor of intestinal ion secretion in animal models and cultured human cell lines, providing a rationale for its use in secretory diarrheas. However, the effects of somatostatin on ion transport in native human colonic epithelium have not been reported. In this study the effects of somatostatin and octreotide on the basal short-circuit current and the cAMP- and Ca2+-stimulated short-circuit current were studied in isolated human colonic mucosa mounted in Ussing chambers. Under basal conditions somatostatin and octreotide (1 micromol/liter) stimulated a small, bumetanide-sensitive increase in short-circuit current. Following stimulation of secretion with prostaglandin E2, somatostatin and octreotide further increased the short-circuit current in a dose dependent fashion (ED50 approximately 10 nmol/liter for both). This stimulation of short-circuit current was not affected by pretreatment of the tissue with basolateral tetrodotoxin (1 micromol/liter) or mucosal amiloride (10 micromol/liter). In contrast, somatostatin and octreotide had no effect when secretion was stimulated with 8-bromo-cAMP, and pretreatment of the tissue with somatostatin and octreotide (0.1 micromol/liter) did not alter the secretory response to carbachol. The absence of any inhibitory effect of somatostatin and octreotide on electrogenic secretion in the human colon may explain the variable results obtained when somatostatin or octreotide are used for the treatment of secretory diarrheas.

Animals↗

Simultaneous changes in bone mineral density and articular cartilage in a rabbit meniscectomy model of knee osteoarthrosis.

OBJECTIVE: It was hypothesized that increased bone mineral density of the medial proximal tibia would precede or coincide with the development of more severe cartilage changes after meniscectomy. METHODS: In a rabbit knee model, mineral density of subchondral bone and changes of articular cartilage were monitored 13 to 40 weeks after medial meniscectomy or a sham operation. RESULTS: Both procedures resulted in a decrease of bone mineral density, especially of the medial proximal tibia, which persisted up to 40 weeks (P< 0.02-0.0007). Meniscectomy induced cartilage changes typical for osteoarthrosis (P< 0.009), which progressed over time on the posterior aspect of the medial tibial plateau (P< 0.009), which is physiologically covered by the meniscus, but the procedure also induced iatrogenic changes which were located mainly on the anterior aspect of the concerned compartment, and which did not progress or develop to osteoarthrosis. CONCLUSIONS: The data suggest that the cartilage changes after meniscectomy in this animal model are caused by the surgical trauma, subsequent limb misuse, and altered load distribution, and initially associated by a decrease not an increase in bone mineral density of the proximal tibia. Moreover, the cartilage changes progressed without a simultaneous increase of the bone mineral density at corresponding sites.

Animals↗

Prognostic value of CT scan features in acute ischaemic stroke and relationship with clinical stroke syndromes.

The aim of this prospective study was to investigate the value of CT scan in prognosis of acute ischaemic stroke patients as a variable additional to clinical stroke syndromes to develop a simple classification of CT scan features to provide a practical approach to prognosticate and manage such patients. One hundred and eight nine patients admitted with ischaemic stroke were investigated with a CT scan. CT scan features were classified into two groups: large infarct, LI (across more than one lobe) and non-large infarcts (N-LI) for all other features. Patients were also studied for clinical syndromes, analysing results for total anterior circulation syndrome (TACS). Outcome was measured as early post stroke Barthel index, acute phase and 3-month mortality. Patients with LI had features of severe strokes and had a lower Barthel index (p < 0.001), lower Glasgow coma score (p < 0.001), more association with incontinence (p < 0.001), pyrexia (p = 0.007) and dysphagia (p < 0.001). LI patients required higher level of care in acute wards and had a higher length of stay (p = 0.01). Both the LI and TACS individually had a significantly higher mortality (p < 0.001) and similar positive predictive value, sensitivity and specificity for 3-month mortality. While the combined factor of 'large infarct and TACS' provided the highest likelihood ratio (3.1) for mortality, the factor of 'large infarct or TACS' was the most sensitive (85%) to identify majority of patients at a risk of mortality. N-LI patients had a better prognosis. Classification of cerebral infarcts into large and non-large categories identifies patients who require higher level of care in acute wards and have a higher mortality. Combined factor of 'large infarct and/or TACS' identifies the majority of patients at risk of 3-month mortality as compared to either variable taken individually. CT scan features are complimentary to clinical syndromes for managing acute stroke patients.

Adult↗

Bone mineral density in normal Swedish women.

We examined 429 women, aged 20-80 years, randomly selected from the population register to establish normal values for bone mineral density (BMD) in Swedish women. BMD of the spine and hip was measured by dual-energy X-ray absorptiometry (DEXA; Hologic QDR 1000) and in the forearm by single photon absorptiometry (SPA; Molsgaard ND-1100). The recalled age of menarche was negatively correlated to BMD at all ages. There was no significant change in BMD from 20-49 years at any site except a slight decline at Ward's triangle. Bone loss was rapid at all sites during the first decade after menopause. Thereafter, BMD declined slowly in the trochanter and total hip but more rapidly in the forearm, femoral neck, and Ward's triangle. BMD in the spine even increased in the eighth decade probably due to osteoarthritis. The average change in forearm BMD during the 15 perimenopausal years comprising mean age for menopause +/- 2 SD (43-57 years) was -0.4% per year in premenopausal females and -1.6% per year in postmenopausal females. The corresponding annual percental change was, for the spine, +0.2 and -1.7; neck, -0.7 and -1.7; trochanter, +0.5 and -1.5; and Ward's triangle, -0.1% and -2.2%, respectively. Our normal values for lumbar spine BMD prior to menopause did not differ from published values or the manufacturer's normal values; however, our spine BMD values for the first decade after menopause were significantly lower (approximately 10%) than in other studies. Our femoral neck BMD values for younger women were, like those of several other groups, significantly lower than the manufacturer's normal values, but our sample of young women in this study was small. The prevalence of osteoporosis, if defined as t score < -2.5 is highly dependent on the sampling of the reference population of young adult women, and also on the choice of skeletal site. Further studies on bone mineral density in healthy young adult women are needed.

Absorptiometry, Photon↗

Periodontoid synovial cyst causing cervico-medullary compression.

BACKGROUND: Periodontoid synovial cysts are rare lesions which may produce symptomatic cervico-medullary compression. METHOD: We report such a patient, whose progressive neurological deterioration required surgical treatment by transoral odontoidectomy and decompression. RESULTS: The diagnostic and theraputic interventions are described, including a lumbar puncture which precipitated a transient loss of consciousness and respiratory arrest. Surgery achieved clinical improvement, without complications or need for operative stablization. Detailed neuropathology is presented, as well as a literature review. CONCLUSION: Appropriate neuroradiological assessment is required in patients with suspected cervico-medullary compression, and symptomatic periodontoid synovial cysts may respond well to transoral surgical decompression.

Cervical Vertebrae↗

Diffuse leiomyomatosis of the uterus.

The clinical and pathological features of four cases of the rare entity diffuse leiomyomatosis of the uterus are described. The patients, who ranged in age from 28 to 35 years, presented with a six month to ten year history of abnormal uterine bleeding, dysmenorrhoea and an enlarged uterus. Hysterectomy in each case revealed a symmetrically enlarged uterus containing numerous small ill-defined leiomyomatous nodules. On microscopic examination the nodules were composed of compact fascicles and interweaving bundles of plump uniform benign smooth muscle cells. The nodules blended with each other and merged imperceptibly with the surrounding less cellular normal myometrium. The four patients are alive and well without further treatment. The follow-up period ranged from six months to twelve years.

Adult↗

Expression of somatostatin receptor genes and their role in inhibiting Cl- secretion in HT-29cl.19A colonocytes.

Recent studies in a cultured model of the intestinal epithelium (HT-29cl.19A) have shown that somatostatin-14 (SS-14) inhibits the Cl- secretory process by acting at multiple G protein-dependent sites. These actions may underlie the antidiarrheal properties of SS peptides. This study has investigated the expression of specific SS receptor subtypes (SSTR) in HT-29cl.19A and examined their role in mediating SS antisecretory actions. Two predominant SSTR, SSTR1 and SSTR2, were identified by reverse transcriptase-polymerase chain reaction (RT-PCR) of mRNA from polarized HT-29cl.19A monolayers. Receptor binding studies showed evidence of two distinct populations of binding sites consistent with the known properties of SSTR1 and SSTR2. The role of SSTR in inhibition of secretion was investigated by comparing the effectiveness of native and synthetic SS peptides on adenosine 3',5'-cyclic monophosphate (cAMP)-dependent Cl- secretion. Secretion stimulated by the receptor-mediated agonist prostaglandin E2 (PGE2) was inhibited > 70% by SS-14 with a 50% effective concentration (EC50) of 32 nM. In contrast, SMS-201-995 (SMS) and RC-160 exhibited little or no antisecretory activity (maximum inhibition of 15 +/- 1.9 and 2.8 +/- 1.9%, respectively, at 100 microM; EC50 > 1.5 microM). Similar effects on PGE2-stimulated cAMP accumulation were also observed. SS-14, but not SMS, also inhibited secretion stimulated by dibutyryl cAMP, which acts independently of changes in cellular cAMP. Pretreatment with pertussis toxin reversed the antisecretory effects of SS peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

The effect of allowing clinical discretion in ordering biochemical tests. Evaluation by complementary methods.

We describe the effects on costs, working patterns, and clinical behavior of installing a DAX "discretionary" biochemistry analyzer. Use of the new analyzer encouraged doctors to be more specific in requesting biochemical tests, which substantially reduced the number of tests requested and slightly reduced overall costs. Doctors preferred being able to order tests in this more specific way.

Autoanalysis↗

Comparison of the value of novel rapid measurement of myoglobin, creatine kinase, and creatine kinase-MB with the electrocardiogram for the diagnosis of acute myocardial infarction.

OBJECTIVE: To determine whether serum myoglobin, creatine kinase, and creatine kinase-MB measured at admission by rapid, compact, and easy to use automated quantitative analysers (results within 10 min) helped the early identification of acute myocardial infarction. The results were compared with the data obtained from the electrocardiograms recorded at admission. DESIGN: A prospective study. SETTING: Coronary care unit. PATIENTS: 94 consecutive patients with suspected myocardial infarction. Myocardial infarction was subsequently confirmed in 44 patients and excluded in 50. METHODS: All admission serum myoglobin, creatine kinase, and creatine kinase-MB were measured by clinical staff using analysers in the coronary care unit. An admission electrocardiogram was obtained from all patients. RESULTS: The sensitivity, specificity, and predictive accuracy for diagnosing myocardial infarction were: electrocardiogram 68%, 100%, and 85%; myoglobin 57%, 100%, and 80%; creatine kinase (threshold of 190 U/l) 34%, 98%, and 68%; creatine kinase-MB (threshold of 25 U/l) 43%, 100%, and 73%. When the electrocardiographic and myoglobin data were combined the sensitivity improved to 91%, diagnostic accuracy to 96%, with specificity of 100%. The results for the electrocardiogram and creatine kinase-MB were 80%, 90%, 100% respectively and those for the electrocardiogram with creatine kinase were 80%, 89%, 98% respectively. CONCLUSIONS: Admission myoglobin, creatine kinase, and creatine kinase-MB measurements were not as useful as the electrocardiogram for the diagnosis of acute myocardial infarction. Combining the electrocardiogram and myoglobin data substantially improved the sensitivity and predictive accuracy for the diagnosis of acute myocardial infarction.

Blood Chemical Analysis↗

Bone mineral density in coeliac disease.

Patients with coeliac disease may have osteomalacia or osteoporosis, even in the absence of abdominal symptoms. Little is known about the effects of a gluten-free diet and villous restitution on the bone mineral density in adult patients with coeliac disease. Of the 288 patients with coeliac disease in our unit, 13 (5%) had persistent villous atrophy of the small bowel despite dietary recommendations over at least the previous 4 years. For each of these 13 patients, 1 or 2 controls with coeliac disease, matched for age, gender, menopausal state, and dermatitis herpetiformis, whose intestinal mucosa had normalized at least 4 years earlier, were identified (n = 17). Bone mineral density was measured in the forearm using single-photon absorptiometry and in the femoral neck and trochanter using dual-energy X-ray absorptiometry. Bone mineral density was reduced at all sites in patients with persistent villous atrophy compared with patients responsive to diet and healthy controls. Bone mineral density in patients responsive to diet did not differ from that in healthy controls. Persistent villous atrophy is associated with low bone mineral density, underlining the importance of keeping to a proper diet.

Adult↗

Purification and properties of a catechol oxidase from blood cells of the ascidian Pyura stolonifera.

A catechol oxidase (EC 1.10.3.1) was purified to homogeneity from blood cells of the ascidian Pyura stolonifera using gel filtration on Sephadex G-50 and hydrophobic interaction chromatography on PhenylSuperose. Two peaks of activity were eluted from PhenylSuperose, one with a decreasing salt gradient and the other with nonionic detergent. The latter represents an aggregated form of the enzyme. The enzyme has a molecular weight of 56 kd and shows a preference for catechols with uncharged hydrophobic side chains (e.g., 4-t-butylcatechol) but does not hydroxylate free tyrosine. Inhibition of the enzyme by diethyldithiocarbamic acid and thiol reagents implicate copper at the active site. Sequence analysis of a peptide generated by incubation with Staphylococcus aureus V8 protease demonstrated considerable homology to one of the conserved copper binding regions of tyrosinases. This enzyme is found in the same cells as the dopa-containing protein ferreascidin. When ferreascidin is incubated with the enzyme, its spectrum changes rapidly, indicating that the catechol oxidase uses it as a substrate. The P. stolonifera enzyme differs from an enzyme involved in adhesion, isolated from the mussels, M. edulis and G. demissa: it is isolated as a soluble enzyme that does not appear to exist as a latent precursor.

Amino Acid Sequence↗

Tissue heating effect of pulsed Doppler ultrasound in the live fetal lamb brain.

A series of experiments in fetal lambs investigated the heating effects of pulsed Doppler ultrasound on fetal brain tissue. In dead lamb brain, tissue heating was observed at the skull bone-to-brain interface. Minimal or no temperature rise was found in the live lamb, suggesting that the intact circulation conducts away any potential heating. The choice of animal model and the state of the circulation influence the results obtained. This will of course have implications for clinical practice.

Animals↗