Biomedical subjects

J M Morgan

Publications and source records attributed to J M Morgan.

At least 55 records · Page 3Linked to original sources

PubMed2000

A multifilamented electrode in the middle cardiac vein reduces energy requirements for defibrillation in the pig.

OBJECTIVE: To compare the defibrillation efficacy of a novel lead system placed in the middle cardiac vein with a conventional non-thoracotomy lead system. METHODS: In eight pigs (weighing 35-71 kg), an electrode was advanced transvenously to the right ventricular apex (RV), with the proximal electrode in the superior caval vein (SCV). Middle cardiac vein (MCV) angiography was used to delineate the anatomy before a three electrode system (length 2 x 25 mm + 1 x 50 mm) was positioned in the vein. An active housing (AH) electrode was implanted in the left pectoral region. Ventricular fibrillation was induced and biphasic shocks were delivered by an external defibrillator. The defibrillation threshold was measured and the electrode configurations randomised to: RV-->AH, RV+MCV-->AH, MCV-->AH, and RV-->SCV+AH. RESULTS: For these configurations, mean (SD) defibrillation thresholds were 27.3 (9.6) J, 11.9 (2.9) J, 15.2 (4.3) J, and 21.8 (9.3) J, respectively. Both electrode configurations incorporating the MCV had defibrillation thresholds that were significantly less than those observed with the RV-->AH (p < 0.001) and RV-->SCV+AH (p < 0.05) configurations. Necropsy dissection showed that the MCV drained into the coronary sinus at a location close to its orifice (mean distance = 2.7 (2.2) mm). The MCV bifurcated into two main branches that drained the right and left ventricles, the left branch being the dominant vessel in the majority (6/7) of cases. CONCLUSIONS: Placement of specialised defibrillation electrodes within the middle cardiac vein provides more effective defibrillation than a conventional tight ventricular lead.

Analysis of Variance↗

PubMed2000

Consistency in the observation of features used to classify duct carcinoma in situ (DCIS) of the breast.

AIM: To determine interobserver and intra-observer agreement in the assessment of cytological grade and intraduct necrosis in pure duct carcinoma in situ (DCIS) of the breast. METHODS: Sixty unselected cases with illustrated diagnostic criteria were circulated to 19 practising histopathologists. RESULTS: Overall agreement was moderate for cytological grade in three categories: 71% agreement; weighted kappa (kappa w), 0.36; intraduct necrosis in three categories (absent, present, extensive): 76% agreement; kappa w, 0.57; and the Van Nuys classification system: 73% agreement; kappa w, 0.48. Agreement was no better among observers participating in the National External Quality Assurance Programme. Intra-observer agreement for cytological assessment (69.6% agreement; kappa w, 0.52) and intraduct necrosis (68.3% agreement; kappa w, 0.48) was moderate, suggesting that individual variation rather than precision of criteria contributes to the lack of agreement. CONCLUSIONS: Moderate agreement on observations can be achieved by non-specialist pathologists, with better agreement on necrosis than cytological grade. There was evidence of consistent individual bias towards over or under scoring cytological grade, which could be corrected with adequate and prompt feedback.

Breast Neoplasms↗

PubMed2000

Calcaneocuboid joint pressure after lateral column lengthening in a cadaveric planovalgus deformity model.

The purpose of this study is twofold: first, to measure the joint contact pressure across the calcaneocuboid joint in a planovalgus deformity and compare the results to pressures measured in a normal foot; and second, to determine the change in pressure across the calcaneocuboid joint after an Evan's-type calcaneal lengthening osteotomy. The effect of this procedure on the calcaneocuboid joint was evaluated using seven cadaver feet to measure peak pressure across the calcaneocuboid joint under a constant load. Each foot was sectioned medially to reproduce a deformity consistent with an adult, acquired flatfoot. Each flatfoot deformity was then corrected using a ten-millimeter lateral column lengthening osteotomy. Joint pressures were measured in the normal foot, the created flatfoot and then in the corrected flatfoot. Peak pressures across the joint increased significantly from baseline in the flatfoot (p <0.05). However, the change in pressure from the flatfoot to the corrected foot was not significant, and in some cases peak pressures in the corrected foot were actually lower than in the flatfoot. These findings indicate that calcaneal lengthening through an Evan's osteotomy does not increase pressure across the calcaneocuboid joint beyond physiologic loads in the flatfoot.

Arthritis↗

PubMed1999

Neurons bearing NK(3) tachykinin receptors in the guinea-pig ileum revealed by specific binding of fluorescently labelled agonists.

The localisation of NK(3) tachykinin receptors in guinea-pig ileum was studied using the fluorescently labelled agonists, Cy3. 5-neurokinin A and Cy3.5-kassinin. Binding to nerve cell bodies in the myenteric and submucosal plexuses was visualised using confocal microscopy. Binding to NK(1) receptors was blocked by the NK(1) receptor antagonist, CP-99994. NK(3) receptors, demonstrated by binding in the presence of CP-99994, occurred in 72% of myenteric and 38% of submucosal neurons. Colocalisation with other markers was examined to deduce the classes of neurons with NK(3) receptors. In myenteric ganglia, NK(3) receptors were present on the following: 73% of calbindin-immunoreactive (IR) intrinsic primary afferent neurons, 63% of calretinin-IR excitatory motor neurons and ascending interneurons, 63% of nitric oxide synthase-IR inhibitory motor neurons and descending interneurons, 79% of strongly neuropeptide Y (NPY)-IR secretomotor neurons, 67% of weakly NPY-IR descending interneurons and motor neurons, and 46% of NK(1) receptor-IR neurons. In submucosal ganglia, NK(3) receptors were on 65% of calretinin-IR secretomotor/vasodilator neurons, 81% of NPY-IR cholinergic secretomotor neurons, 2% of vasoactive intestinal peptide-IR non-cholinergic secretomotor neurons and were completely absent from substance P-IR intrinsic primary afferent neurons. The results support physiological studies suggesting that NK(3) receptors mediate tachykinin transmission between myenteric sensory neurons and to interneurons and/or motor neurons in descending inhibitory and ascending excitatory pathways.

Animals↗

PubMed1999

The middle cardiac vein--a novel pathway to reduce the defibrillation threshold.

UNLABELLED: Defibrillation energy requirements of epicardial implantable cardioverter defibrillator systems are generally lower than endovascular systems currently used. The former has the disadvantage of requiring a thoracotomy and so has a greater morbidity and mortality than an endovascular procedure. The middle cardiac vein (MCV) is an epicardial structure that is accessible by a non-thoracotomy approach. This study investigated the merits of ventricular defibrillation from the middle cardiac vein. METHODS AND RESULTS. Defibrillation thresholds (DFT) were measured in 10 anesthetized pigs, weighing 34.5 +/- 44.1 kg (mean 39 kg). An Angeflex electrode (1.7 mm x 50 mm) was introduced via the left external jugular vein to the right ventricular apex. The MCV was identified with standard angiography techniques and a 4080 (Angeion Corp.) defibrillation electrode (1.6 mm x 65 mm) introduced into the vein. An active can was implanted in the left subpectoral region. The defibrillation thresholds (DFT) of the following defibrillation configurations were assessed using a modified four-reversal binary search: RV-->Can, RV + MCV-->Can and MCV-->Can. The DFT's for the three configurations were 15.5 +/- 2.8 J, 10.8 +/- 3.4 J and 13.7 +/- 2.4 J. Analysis of variance showed that the DFT with the RV + MCV combination was significantly less than the RV alone (p < 0.05) CONCLUSIONS: Defibrillation is possible through the MCV and that incorporating an electrode in the MCV with RV-Can configuration can reduce the DFT by 30%.

Animals↗

PubMed1999

A systematic evaluation of conventional and novel transvenous pathways for defibrillation.

INTRODUCTION: Conventional implantable cardioverter defibrillators employ endocardial (shock) electrodes with a lead located in the right ventricular apex (RV) and a "hot-can" electrode located subcutaneously in the left pectoral region. In the event of a high defibrillation threshold (DFT) a third electrode is frequently employed in the superior vena cava (SVC). We report the comparison of conventional and novel locations of additional electrodes with the RV/Can configuration, in a porcine model. METHOD: In 12 anesthetized pigs (30-45 kg), endocardial defibrillation electrodes were randomized to the following locations: RV/Can, RV/Can + SVC, RV/Can + main pulmonary artery (MPA) and RV/Can + left pulmonary artery wedge position (PAW), RV/Can + high inferior vena cava (HIVC), RV/Can + Low inferior vena cava (LIVC). Ventricular fibrillation (VF) was induced using 60 Hz alternating current. After 10 seconds VF a rectangular biphasic shock was delivered by the ARD9000 (Angeion Corp). The DFT was determined for each configuration using a modified four-reversal binary search. All configurations were compared using a repeated measures analysis of variance (ANOVA) statistical test and the five 3-electrode configurations were compared to the RV/Can position using a Dunnett test. RESULTS: Mean DFTs: RV = 21.5 +/- 4.8 J, SVC = 16.8 +/- 4.7 J (p < 0.05 vs. RV), HIVC = 21.1 +/- 4.7 J (p <. 0.05), LIVC = 19.1 +/- 5.7 J (p <. 0.05 vs. RV), MPA = 16.0 +/- 5.8 J (p < 0.01), PAW = 17.5 +/- 4.6 J (p < 0.05 vs. RV). CONCLUSIONS: Relative to the RV/can configuration the addition of a third electrode in the PA, PAW or SVC significantly reduces the DFT in the pig. The addition of an electrode to the IVC did not significantly reduce the DFT in our model.

Animals↗

PubMed1999

Improved efficacy of anodal biphasic defibrillation shocks following a failed defibrillation attempt.

Although it is generally assumed that defibrillation becomes more difficult when the duration of VF is prolonged, after a failed defibrillation attempt, there is little information on the defibrillation efficacy of multiple shocks delivered at the same energy. The purpose of this study was to systematically examine the efficacy of a second shock delivered at the same or reversed polarity after a failed first shock. Defibrillation was attempted after 10 seconds of VF in 12 pigs (30-56 kg) using biphasic waveforms and a nonthoracotomy lead system. Shock energy was held constant for the first and second shocks at 50%-90% of the DFT. The second shock was delivered 10 seconds after a failed first shock. First and second shock polarity (first phase) was randomized to (+, +), (+, -), (-, -), (-, +). The incidence of successful defibrillation (for all polarities) was 12.3% for first and 49.1% for second shocks (P < 0.0001). Anodal first shocks had a 17.2% incidence of success as opposed to a 7.4% incidence of success with cathodal first shocks (P = 0.001). Anodal second shocks had a 55.5% incidence of success compared to a 42.7% incidence of success with cathodal second shocks (P = 0.008). There was no significant benefit from polarity reversal after a failed first shock (P = 0.29). In conclusion, less energy is required for successful defibrillation by a second shock after a failed first. The optimal configuration for first and second shocks is with the RV as anode. Polarity reversal of a second shock after a failed first does not affect the probability of second shock success.

Animals↗

PubMed1999

Catheter mounted coaxially moveable ablation electrode for the creation of linear transmural endocardial lesions.

INTRODUCTION: Use of a novel ablation catheter for the creation of linear transmural endocardial lesions, which uses a coaxially moving ablation electrode mounted on the terminal portion of a catheter shaft and able to move axially for a distance of up to 4 cm, is reported. METHODS AND RESULTS: The coaxially moving ablation electrode is moved by a sliding mechanism in the catheter handle. The distal portion of the catheter shaft is steerable. Bipolar or unipolar electrograms can be recorded from electrodes on the catheter tip and the coaxially moving ablation. Radiofrequency (RF) current is delivered to the coaxially moving ablation electrode with thermocouple temperature control. This ablation catheter was evaluated in five (30 to 65 kg) anesthetized pigs and introduced via the venous/arterial systems into the right and left atrium (1 lesion) (using the retrograde aortic approach). The catheter was maneuvered to bring the slide range into apposition with atrial endocardium. The coaxially moving ablation electrode was deployed to the terminal portion of the catheter's slide range and then withdrawn in 2-mm steps. RF current was delivered to the coaxially moving ablation electrode at each point (maximum temperature 70 degrees C). Postmortem examination of eight endocardial linear lesions (2.2 to 4.1 cm length) was made 1 to 3 hours after creation. Histopathologic examination confirmed transmural myocyte necrosis along the length of the lesion, that included the trabeculated right atrium. CONCLUSION: We conclude that a catheter using a moveable electrode creates continuous linear transmural lesions and could find clinical application in the therapy of a variety of reentry tachycardia mechanisms.

Animals↗

PubMed1998

Efficacy and safety of an extended-release niacin (Niaspan): a long-term study.

Crystalline nicotinic acid (immediate-release niacin) is effective therapy for lipoprotein regulation and cardiovascular risk reduction. However, inconvenient regimens and unpleasant side effects decrease compliance. Sustained-release formulations designed to circumvent these difficulties increase hepatotoxicity. Niaspan, a new US Food and Drug Administration (FDA)-approved, once-daily, extended-release form, has been found effective and safe in short-term trials. The long-term efficacy and safety of Niaspan lipid monotherapy was studied in 517 patients (aged 21-75 years) for < or =96 weeks in dosages < or =3,000 mg/day. Primary efficacy endpoints were low-density lipoprotein (LDL) cholesterol and apolipoprotein B (apo B) changes from baseline; secondary efficacy endpoints were changes in total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, lipoprotein(a), and total cholesterol/HDL-cholesterol ratio; safety data included adverse events and laboratory values over the 2-year study period. LDL-cholesterol levels decreased significantly: 18% at week 48 and 20% at week 96; apo B reduction was similar (16% decrease at week 48 and 19% at week 96). Large elevations in HDL cholesterol (26%, week 48; 28%, week 96) allowed only modest decreases in total cholesterol (12% and 13%, respectively), whereas total cholesterol/HDL-cholesterol ratio decreased by almost one third. Triglyceride and lipoprotein(a) levels were decreased by 27% and 30%, respectively (week 48), and by 28% and 40%, respectively (week 96). All changes from baseline were significant (p <0.001). Niaspan was generally well tolerated, although flushing was common (75%); however, there was a progressive decrease in flushing with time from 3.3 episodes in the first month to < or = 1 episode by week 48. Aspirin was used by one third of patients before Niaspan dosing to minimize flushing episodes. Although serious adverse events occurred in about 10% of patients, none were considered probably or definitely related to Niaspan. Adverse events in general varied widely, but their true relation to the study drug is difficult to ascertain without a placebo (control) group. No deaths occurred. There were statistically significant changes in hepatic transaminases, alkaline phosphatase, direct bilirubin, phosphorus, glucose, amylase, and uric acid. However, these changes were mostly small and are not likely to be biologically or clinically significant (the decrease in phosphorus is a new finding in niacin therapy). No myopathy was observed. Thus, this long-term study confirms the earlier short-term findings that Niaspan is safe and effective as monotherapy in plasma lipoprotein regulation.

Adult↗

PubMed1998

A new extended-release niacin (Niaspan): efficacy, tolerability, and safety in hypercholesterolemic patients.

Immediate-release niacin manifests beneficial effects in cardiovascular disease with respect to dyslipidemic states. It lowers low-density lipoprotein (LDL) cholesterol, triglycerides, lipoprotein(a), and apoprotein B; at the same time, it increases high-density lipoprotein (HDL) cholesterol, HDL2, and apoprotein A-I. However, use of crystalline niacin has drawbacks: therapy requires multidose regimens, and side effects include flushing and pruritus. Slowing absorption with sustained-release formulations succeeds in decreasing flushing and increasing tolerance, but increases in hepatic enzyme levels have raised safety concerns. A new extended-release, once-daily formulation of niacin (Niaspan) shows promise in minimizing flushing while avoiding hepatotoxicity. A multicenter, randomized, double-blind clinical trial of Niaspan enrolled 122 patients with confirmed diagnosis of primary dyslipidemia (LDL cholesterol >4.14 mmol/L [160 mg/dL] and triglycerides <9 mmol/L [800 mg/dL]) into 3 treatment groups: (1) Niaspan 1,000 mg/day; (2) Niaspan 2,000 mg/day; and (3) placebo. The primary treatment endpoint was LDL-cholesterol level. This endpoint was not significantly affected by placebo (0.2% increase), but Niaspan decreased LDL cholesterol by 5.8% (1,000 mg/day) and 14.6% (2,000 mg/day) (p <0.001). Likewise, with placebo there were significant changes in total cholesterol, triglycerides, lipoprotein(a), and apoprotein B, whereas both Niaspan 1,000 and 2,000 mg/day significantly (p <0.001) decreased these parameters. In addition, both Niaspan groups showed significant (p <0.001) increases in HDL cholesterol (17% and 23%, respectively), including HDL subfractions. With respect to flushing, 20% of the placebo group reported at least 1 episode, whereas 88% and 83% of the Niaspon 1,000- and 2,000-mg/day groups, respectively, reported episodes. There was no hepatotoxicity as liver enzyme levels remained within clinically accepted limits in all treatment groups. However, Niaspan 2,000 mg/day showed a significant increase in aspartate aminotransferase compared with baseline and placebo. This trial demonstrated a cholesterol-modifying effect of Niaspan consistent with those reported for niacin, but demonstrated a better tolerance for flushing. Moreover, in contrast to sustained-release formulations, Niaspan showed relatively mild hepatic effects.

Cholesterol, LDL↗

PubMed1998

Preliminary single center clinical experience of the use of a new implantable cardioverter defibrillator.

We report a single center's preliminary clinical experience of the Sentinel (Angeion, Minneapolis, MN) implantable cardioverter defibrillator (ICD), which employs novel technologies that offer the potential for significant reduction in ICD size. Thirty-three patients have received Sentinel ICDs with a mean follow-up of 450 (range 150-1023) days. Device shock therapy has been used to defibrillate/cardiovert 43 spontaneous episodes of malignant ventricular arrhythmia and 510 episodes of hemodynamically well tolerated ventricular arrhythmia have been pace-terminated (pace-termination failed in 6 episodes with subsequent delivery of appropriate shock therapy). There has been no arrhythmic death in this patient population. There have been 9 inappropriate shocks in 6 patients (in 2 patients for atrial fibrillation which had satisfied the algorithm detection criteria for high zone ventricular arrhythmia, in 3 for sinus tachycardia [rate greater than 180 beats per min] and in 1 due to device capacitor malfunction). Device replacement has been required for component malfunction in 3 patients. There have been no other major complications. Follow-up time to date is short and longterm device efficacy and performance remain unproven. However, our early clinical experience suggests that the innovations used to manufacture the Sentinel ICD have facilitated reduction in ICD size without compromising therapeutic efficacy.

Adolescent↗

PubMed1998

Role of octreotide on release of intact 1-84 parathyroid hormone from human parathyroid cells.

BACKGROUND: Octreotide has been shown to lower urinary calcium in primary hyperparathyroidism although the mechanism remains unclear. This study examined the effect of octreotide on parathyroid hormone (PTH) secretion from human parathyroid cells in culture and as isolated cells. Additionally in situ hybridization was performed for somatostatin receptor messenger RNA (mRNA) and immunocytochemistry for somatostatin in eight parathyroid adenomas. METHODS: Tissue from three hyperplastic glands and three adenomas was studied as dispersed cell suspensions. Incubation was in buffers containing high (2.0 mmol/l) and low (0.5 mmol/l) calcium concentrations, with or without octreotide 200 ng/ml. Cells were also seeded into tissue culture wells for 24 h to allow receptors to regenerate. Supernatant was removed at regular intervals and PTH levels were estimated using a two-site chemiluminescent assay. RESULTS: Mean(s.e.m.) PTH secretion at 90 min in hyperplastic cells was 445(75) pmol/l in low calcium and 160(42) pmol/l in high calcium (P< 0.02), and in adenoma cells was 170(21) pmol/l in low calcium and 137(27) pmol/l in high calcium (P=0.37). There was no significant difference in secretion of PTH from cells incubated with octreotide either in culture or as dispersed cells. In situ hybridization failed to demonstrate any mRNA for the somatostatin receptors and no somatostatin was detected in any cells with immunocytochemistry. CONCLUSION: Somatostatin has no direct action on PTH production and release from human parathyroid cells and is unlikely to be of any therapeutic value in the treatment of hyperparathyroidism.

Adenoma↗

PubMed1998

Intracoronary Multi-link stents: experience in 218 patients using aspirin alone.

OBJECTIVES: To assess procedural outcome, complications, and clinical follow up in 218 patients who underwent treatment with 297 Multi-link (Guidant) stents implanted without the use of intravascular ultrasound (IVUS) or quantitative coronary angiography (QCA), and using aspirin alone as antiplatelet therapy. METHODS: The case records and angiograms were reviewed and the patients were contacted by telephone to determine their symptoms and any adverse events at follow up. Data were analysed using Fisher's exact test. RESULTS: Of the 218 patients included in the study, 45 had multivessel intracoronary intervention, and 55 had unstable angina. The mean (SD) length of hospital stay following the procedure was 2.0 (2.1) days. There were two early deaths at less than 30 days, and two deaths during follow up at more than 100 days. Ten patients suffered complications during the first 30 days: four had subacute stent thrombosis, of whom two died and two were treated successfully with coronary artery bypass grafting; five had a non-Q wave myocardial infarction; and one had a femoral false aneurysm. Patient outcome was analysed according to stent diameter (3.0 mm or less, or 3.5 mm or more) and by angina status (stable or unstable). In patients in whom at least one stent was 3.0 mm diameter, four of 86 patients suffered acute stent occlusion, whereas in the 132 patients in whom all stents were at least 3.5 mm diameter there were no cases of stent occlusion (p = 0.02). In the unstable angina group two of 55 patients suffered acute stent occlusion compared to two of 163 patients in the stable angina group (NS). In patients with unstable angina and at least one stent of 3.0 mm diameter, the acute occlusion rate was 7.1% (two of 28 patients). Three of the four patients with stent occlusion had undergone complex procedures. Twenty eight patients were restudied for recurrent symptoms during the follow up period. Of these, eight patients had restenosis within their stent. In seven of these patients the stent size was 3.0 mm diameter, and in the remaining patient the stent size was 4.0 mm diameter. Three of the 28 patients restudied had developed new disease remote from the stented site, and 17 had patent stents and no significant other coronary lesion. CONCLUSIONS: This study suggests that coronary intervention using the Multi-link stent is safe and effective using aspirin alone, without IVUS or QCA, when stent diameter is greater than 3.0 mm. All cases of stent occlusion in this series occurred in patients in whom at least one stent was 3.0 mm diameter, with stent occlusion being higher in patients with unstable angina compared to those with stable angina. Additional antiplatelet therapy may be beneficial in those patients in whom Multi-link stent diameter is less than 3.5 mm, particularly in those with unstable angina, but is not necessary for patients receiving Multi-link stents of 3.5 mm diameter or greater.

Adult↗

PubMed1998

Evidence of effectiveness of clinical audit in improving histopathology reporting standards of mastectomy specimens.

AIM: To assess the effectiveness of clinical audit in improving standards in histopathological reporting of mastectomy specimens. METHODS: Reports on mastectomy specimens containing tumour issued by non-specialist histopathologists in 1990, 1992, 1994, and 1996 were scored for their information content. There were 10 reports evaluated from each year. Before 1990 no reporting guidelines had been formulated within the department. The audits in 1992 and 1994 were performed after agreed written guidelines (including the establishment of six essential pieces of information), and in 1996 the specimens were reported using a proforma. RESULTS: There was a significant increase in information after the introduction of written guidelines but there was a reduction in information over time. In 1990 none of the 10 reports included all six pieces of mandatory information; in 1992 four of the reports contained all mandatory information; in 1994 only one report contained all mandatory information. The introduction of a proforma for reporting resulted in further significant improvement with all 10 reports in 1996 containing all mandatory information. CONCLUSIONS: Successive rounds of audit increases the standard of reporting in histopathology. There is a need for continuing monitoring of standards as these may deteriorate over time. Reporting complex specimens on a proforma has a significant beneficial effect on information content.

Breast Neoplasms↗

PubMed1998

Stress fracture of the fifth metatarsal after Evans' calcaneal osteotomy: a report of two cases.

The Evans calcaneal lengthening osteotomy has gained popularity in recent years for the treatment of symptomatic flexible pes planus deformity. To our knowledge, the occurrence of a stress fracture of the fifth metatarsal has not been reported after this procedure. We report two such cases and discuss the probable mechanism of this problem, a relative overloading of the lateral aspect of the foot. Both cases were treated successfully with immobilization. Clinicians should be aware of this possible problem and treat it appropriately.

Adolescent↗

PubMed1997

The clinical behavior of breast carcinoma is probably determined at the preinvasive stage (ductal carcinoma in situ).

BACKGROUND: Mammography has greatly increased the number of women diagnosed with ductal carcinoma in situ (DCIS) of the breast. New classifications of DCIS recently have been proposed. In this study, these classifications were applied to DCIS associated with invasive tumors and correlated with patient prognosis. METHODS: Three hundred cases of infiltrating ductal carcinoma of the breast in which there was associated DCIS in the surrounding breast were studied. The DCIS was classified as well, moderately, or poorly differentiated, according to two recently published systems using the cytonuclear features of the malignant cells (Holland classification) and cytology and the presence of necrosis (Van Nuys classification). RESULTS: The differentiation of DCIS was significantly correlated with the grade of the invasive carcinoma (P < 0.0001), the Nottingham prognostic index (P < 0.0001), and the clinical outcomes of the patients (P < 0.0001). CONCLUSIONS: These findings indicate that a model in which there is increasing in situ dysplasia before the development of stromal invasion is incorrect for breast carcinoma. Rather, in most cases, well-differentiated DCIS probably gives rise to low grade invasive breast carcinoma with a better long term clinical outcome. These data suggest that many of the important prognostic biologic and genetic characteristics of breast carcinoma are already established in the neoplastic clones of malignant cells at the preinvasive stage of the disease.

Breast Neoplasms↗

PubMed1997

Differential expression of ryanodine receptor RyR2 mRNA in the non-pregnant and pregnant human myometrium.

We describe here the expression of the ryanodine receptor isoforms RyR2 and RyR3 in human non-pregnant and pregnant (non-labouring) myometrium, and in isolated cultured myometrial cells. The mRNA encoding the RyR3 isoform was found in both non-pregnant and pregnant myometrial tissue samples; however, the mRNA for RyR2 was found only in pregnant samples. It can be speculated that the appearance of this additional isoform in the pregnant myometrium may increase the ability of this tissue to contract at term. Control of expression of the RyR2 gene may therefore be another example of an up-regulated signalling system in pregnancy. Although the mRNA for RyR3 was expressed in cultured myometrial cells, the mRNA for RyR2 could not be detected. Thus cultured myometrial cells appear to be similar to the non-pregnant myometrium. The cytokine transforming growth factor beta (TGF-beta) has been reported to alter RyR mRNA expression in many cell types. After treatment with TGF-beta, both RyR2 and RyR3 mRNAs could be detected in cultured myometrial cells. These observations support the idea that the expression of the RyR2 isoform is up-regulated both in pregnancy and in TGF-beta-treated cultured myometrial cells. Using measurements of 45Ca2+ release, we have further demonstrated that cultured human myometrial cells show a significant augmentation of both the Ca2+-induced Ca2+ release (CICR) mechanism and ryanodine-induced Ca2+ release after treatment with TGF-beta. Additionally, caffeine was able to induce Ca2+ release and sensitize the CICR mechanism to ryanodine. Thus we suggest that the appearance of RyR2 mRNA leads to the expression of this receptor/channel protein with identifiable pharmacological characteristics. These results are discussed in the context of the potential role of gene activation in the process of maturation of the human myometrium during pregnancy.

Adult↗

PubMed1997

Role of calcium chelation in high-temperature antigen retrieval at different pH values.

Recent work by Shi et al. on the mechanism of high-temperature antigen retrieval has claimed that the antigen retrieval process is pH-dependent, with different antigens benefitting at high or low pH values of antigen retrieval solutions. It has previously been claimed that chelation of Ca2+ at high temperature is an essential feature of the antigen retrieval process. In order to resolve this apparent dichotomy, the relative antigen retrieval effects were analysed using the buffers employed by Shi et al. in both a facilitating and an inhibitory mode. The results show that calcium-related effects are optimal at high pH values and do not operate at very low pH. The relative antigen retrieval effectiveness of hydrochloric acid and its metal halide solutions were also investigated in relation to pH. The results of these experiments showed that whilst HCl alone produced antigen retrieval (AR), it also produced severe tissue damage, which was reduced by the inclusion of inorganic salts. These results suggest that antigen retrieval at low pH may be achieved through the dissociation of Ca2+ complexes by high concentrations of H+ ions and/or the breaking up of cross-links from formalin fixation. Results are also presented to show that chaotropic denaturants such as urea and guanidine hydrochloride also function principally through calcium chelation, whilst detergents have no role to play in high-temperature retrieval.

Calcium↗