Morpho-functional differentiation in lobular carcinoma of the breast

Lobular carcinoma of the breast has been studied using histochemical methods for mucosubstances; immunocytochemical methods for casein and actin; the ruthenium red electronycytochemical method for acid glycoproteins and an immunoelectroncytochemical method for casein. Mucosubstances and casein showed a similar cytoplasmic localization, but casein production was much more intense and also showed a more diffuse cytoplasmic localization. Occasionally casein assumed the form of target-like 'inclusions' as seen characteristically with the mucosubstances. The neoplastic cells were not stained by antisera against actin. Ultrastructurally, some cells showed an intracytoplasmic lumen with microvilli and/or an irregular outline at one extremity which was covered by microvilli. An electron-dense 'fuzz' and casein coated the microvilli of cells exposed respectively to ruthenium red and an anticasein serum followed by peroxidase--anti-peroxidase complexes. It is concluded that lobular carcinoma shows evidence of epithelial rather than myoepithelial differentiation with the emphasis on epithelial secretory cells engaged in intensive milk protein production. All 10 tumours tested for oestrogen receptors were positive in contradistinction to ductal carcinoma with a lower incidence of positivity. It appears that, in addition to distinctive histological and histochemical features, lobular carcinoma has an almost constant endocrine pattern in respect of its oestrogen receptor content.     

A Novel Glycine Mutation in the Col7a1 Gene Leading to Dominant Dystrophic Epidermolysis Bullosa with Intra-Familial Phenotypical Heterogeneity

Abstract:   Dystrophic epidermolysis bullosa (DEB) represents a group of inherited skin disorders characterized by sublamina densa blister formation. We resent the case of a 16-year old girl with DEB, who had a 10-year-history of recurrent pruritic skin lesions. Despite misleading biopsy results, the correct diagnosis was suspected by examination of other family members. Finally, mutational analysis revealed a novel glycine substitution mutation in the COL7A1 gene in three affected family members.     

Comparative study on the effects of intracoronary nicorandil and nitroglycerin in ischaemic, reperfused porcine hearts

The direct cardioprotective properties of nitroglycerin andnicorandil were compared in regionally ischaemic (45 min), reperfused(24 h) porcine hearts. Intracoronary treatments, which werestarted 15 min prior to occlusion of the distal left anteriordescending coronary artery (LAD), were continuously administeredfor 105min. The following equi-hypotensive drug dosages wereused in nine pigs each; nitroglycerin 6 fig. kg^–1 x minbefore ischaemia and during 45 min of reperfusion, 0.6 µg.kg^–1x min during ischaemia; nicorandil 5 fig. kg^–1x min before ischaemia and during 45 min of reperfusion, and0.5 fig. kg^–1 x min during ischaemia. Nine control animalswere treated with isotonic sodium hydrochloride solution (1ml. min^–1). Despite comparable effects on blood pressure, intracoronarynicorandil, in contrast to intracoronary nitroglycerin, didnot increase heart rate. Although neither drug affected coronaryblood flow significantly, nicorandil substantially reduced regionalmyocardial oxygen consumption before coronary artery occlusion( – 37±22%, P=0003 vs control group, P=0.01 vsnitroglycerin treatment). Infarct sizes (tetrazolium method)after 45 min of ischaemia and 24 h of reperfusion were significantlydecreased by nicorandil (control group 76.9 ± 19%, nicorandilgroup 49.3 ± 24%, P=0.012)whereas nitroglycerin exhibiteda borderline effect (62.5 ± 15%, P=0.054). Both treatmentsresulted in improved regional systolic shortening of the reperfusedsegment at the end of the experiments but this was not significant.At these drug dosages the direct cardioprotective action ofnicorandil is slightly superior to nitroglycerin. This may beascribed to its K-channel opening property associated with reducedregional myocardial oxygen consumption before the onset of ischaemia.     

Relationship between plasma atrial natriuretic factor and opioid peptide levels in healthy subjects and in patients with acute congestive heart failure

We evaluated plasma atrial natriuretic factor (ANF), ß-endorphin,met-enkephalin, dynorphin and noradrenaline levels in 20 healthysubjects and 20 acute congestive heart failure (CHF) patients.In all acute CHF patients plasma values of these hormones werehigher than in healthy subjects. The hormonal pattern differedin patients with the more severe acute CHF (group 1) from patientswith less severe acute CHF (group 2) (ANF 53.8 ± 1.0vs 34.6 ± 1.5 pg.ml^–1, noradrenaline 563.8 ±13.4 vs 202.4 ± 10.6 pg.ml^–1, met-enkephalin 41.0± 3.2 vs 17.0 ± 1.6 fmol. ml^–1, dynorphin46.8 ± 3.7 vs 25.2 ± 2.0 fmol. ml^–1, P <0.01;ß-endorphin 50.6 ± 5.2 vs 41.8 ± 4.1fmol. ml^–1, ns). Administration of an opioid antagonist(naloxone, 8 mg i.v.) did not modify ANF or noradrenaline concentrationin healthy subjects. in group 1 naloxone administration significantlyraised ANF (68.0 ± 1.4 pg. ml^–1), noradrenaline(776.6 ± 18.7 pg. ml^–1), blood pressure and heartrate, whereas in group 2 it significantly decreased ANF values(21.9 ± 0.5 pg. ml^–1)and did not modify the otherparameters. Our findings suggest that the opioid system affectsANF release in acute CHF. In patients with severe CHF opioidpeptides may attenuate ANF secretion reducing noradrenergicstimulation. On the other hand, when CHF is less severe andthe sympathetic activity is moderate, opioid peptides may directlystimulate ANF secretion.     

Total Arterial Revascularization of the Heart using both Mammary Arteries and the Right Gastroepiploic Artery

From April 1988 to April 1989, nine patients (seven men and two women) with coronary three-vessel disease and disabling angina underwent elective myocardial revascularization. None of the patients had available veins because of previous bypass procedures (three) or extensive varicosis (six). On standard cardiopulmonary bypass and cardioplegic arrest the right and the left mammary arteries (RIMA, LIMA) and the right gastroepiploic artery (RGEA) were anastomosed each to a major coronary branch (none of them as free graft) in each patient. All patients survived the operation but one, who died 2 weeks after the operation of a bilateral pneumonia. Autopsy revealed patent anastomoses. One patient had to be reexplored for bleeding. Two patients required temporary inotropic support. There was no perioperative myocardial infarction. All survivors were discharged home in an average of 18.7 days after the operation, are free from angina, and all have negative stress tests (mean follow-up 7.7 months) but one with severe coronary atherosclerosis who experiences slight exertional angina despite good patency of the grafts. Five patients were recatheterized after a mean interval of 5.4 months after operation revealing in all cases patent anastomoses. Total revascularization of the heart with arterial grafts is feasible, safe, and it could become the method of choice if patency persists in the long run.     

Chronic uridine treatment reduces the level of [3H]spiperone-labelled dopamine receptors and enhances their turnover rate in striatum of young rats: relationship to dopamine-dependent behaviours

The effect was studied of chronic uridine treatment on the recovery of striatal D-2 dopamine (DA) receptors after their irreversible blockade by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) in young (40 days old) and adult (14 months old) male rats using [³H]spiperone as radioligand. Chronic uridine treatment (15 mg kg^-1 day^-1, i.p., 14 days) causes a reduction of [³H]spiperone binding sites in striatum of young rats. This treatment also produces an increase in the rate of recovery of striatal [³H]spiperone-labelled DA receptors in young, but not in adult rats. Catalepsy and exploratory locomotor activity, two behaviours associated with blockade versus activation of DA receptors, were evaluated in the same rats. The behavioural recovery from the EEDC^induced syndrome is more rapid in the young rats treated with uridine than in the saline-treated group. The behavioural recovery in old rats was not affected by chronic uridine treatment. Thus, in young rats the pyrimidine nucleoside uridine may modulate the steady state and the turnover rate of striatal D-2 DA receptors.     

Comparative Effects of Immunotoxic Chemicals on in Vitro Proliferative Responses of Human and Rodent Lymphocytes

Comparative Effects of Immunotoxic Chemicals on in Vitro ProliferativeResponses of Human and Rodent Lymphocytes. LANG, D. S., MEIER,K. L., AND LUSTER, M. I. (1993). Fundam. Appl. Toxicol. 21,5357–545. In order to determine the comparability of human and rodentin vitro systems, the direct effects of various therapeuticor environmental chemicals on proliferative responses of lymphocytesof mouse, rat, and human origins were examined and analyzedby a detailed statistical approach. Four compounds of diversestructure and mechanism of action which are known to impairlymphocyte transformation, such as hydroquinone, T-2 toxin,lead nitrate, as well as the widely used immunosuppressive drugcyclosporin A, were chosen as model test substances. T cellswere stimulated by phytohaemagglutinin as well as monoclonalantibodies directed at the T cell receptor/CD3 complex, whileB cells were activated by the T-independent mitogens, includingStaphylococcus aureus cells, Escherichia coli lipopolysaccharide,and Salmonella typhimuriummitogen with specificity for human,mouse, and rat lymphocytes, respectively. In almost all casesthe chemicals altered lymphoproliferative responses in a concentration-relatedmanner in all three species. In general, overall similaritiesin the relative sensitivity of lymphoblastogenesis were obtainedwhen the human dose-response curves were compared to the rodentresponse curves. Frequent, statistically significant species-dependentdiscrepances of the overall response curves between mice andrats were observed. Large, statistically significant differenceswere observed for inorganic lead, revealing obvious divergencesof the effect patterns in all cases, across all species. Inthis case, rodent species, especially the rat, were very sensitiveto immunomodulation by lead, whereas human cells were relativelyresistant. It is suggested that direct interspecies comparisonsof immunological effects due to chemical treatment in vitrocan provide a greater understanding of the relationship betweenanimal and human data, which will improve the confidence ofextrapolation from findings in laboratory animals to human healthrisk.     

Iterative Cardiac Output Measurement for Optimizing Cardiac Resynchronization Therapy: A Randomized,Blinded, Crossover Study

Background: Many invasive and noninvasive methods have been proposed for guiding optimal programming of cardiac resynchronization therapy (CRT) devices. However, results are not satisfying. Preliminary results suggest that cardiac output (CO) measurements using inert gas rebreathing (IGR) might be an eligible method to tailor atrioventricular (AV) and ventriculo‐ventricular (VV) programming. The aims of the present study were: (1) to evaluate whether an optimization of CRT can be obtained by noninvasive CO measurements and (2) to evaluate whether acute hemodynamic improvements obtained by this approach relate into increase in cardiac exercise capacity. Methods: In 24 patients on CRT, iterative VV‐ and AV‐delay optimization was done using the IGR method. This blinded, randomized, crossover study compared the responses to optimization during two periods: a 4‐week optimized and a 4‐week standard programming. Exercise capacity after optimization was assessed after each period by New York Heart Association (NYHA) classification, a 6‐minute walking test, and quality of life (QoL) questionnaire. Results: CO could be determined by IGR in all patients. The NYHA class decreased by 17.8% (2.8 ± 0.3 vs 2.3 ± 0.4, P < 0.001), the mean (± standard deviation) distance walked in 6 minutes was 9.3% greater after optimization (456 ± 140 m vs 417 ± 134 m, P < 0.001), and the QoL improved by 14.5% (41.8 ± 10.4 vs 36.5 ± 9.5, P < 0.001). The portion of responders to CRT increased from 66.5% to 87.5%. Conclusion: CRT optimization by iterative CO measurements leads to an increase in CO and an improvement of exercise capacity. Our results suggest that this method might become an important additive tool to adjust CRT programming. (PACE 2010; 33:1188–1194)     

Eosinophilic granuloma of lymph nodes—a variant of histiocytosis X

A clinicopathologic study of histiocytosis X in lymph nodes disclosed a special variant: primary eosinophilic granuloma of lymph nodes. This variant involves one or more lymph nodes, but does not infiltrate any other organs. Histologically, the infiltration of lymph nodes by histiocytosis X cells and eosinophils is similar to that seen in disseminated or metastatic histiocytosis X. Most cases of eosinophilic granuloma of lymph nodes are recognizable as primary, however, by the heavy infiltration of the surrounding tissue. The predominant proliferating cells are histiocytosis X cells ('Langerhans cells'), which contain Birbeck granules on electron microscopy and are lysozyme-negative. The disease was found in 30 patients among a total of 64 cases of histiocytosis X collected at the Lymph Node Registry in Kiel. Primary eosinophilic granuloma of lymph nodes occurs predominantly in children and young adults and shows a slight preponderance of males. Clinically, the patients present with mostly afcbrile and sometimes painful lymphadenopathy, which is more often solitary (in the cervical or inguinal region) than widespread. The erythrocyte sedimentation rate and/or serum α₂-globulin level are elevated in many patients. There may also be an increase in the number of leucocytes, especially eosinophils, in the blood. The prognosis is favourable: the lymphadenopathy disappeared spontaneously in most patients and only one patient developed two recurrences. Thus, primary eosophilic granuloma of lymph nodes is interpreted as a benign lesion. It might be a special reaction of the T cell system.