Cellular rescue in a zebrafish model of congenital muscular dystrophy type 1A.

Laminins comprise structural components of basement membranes, critical in the regulation of differentiation, survival and migration of a diverse range of cell types, including skeletal muscle. Mutations in one muscle enriched Laminin isoform, Laminin alpha2 (Lama2), results in the most common form of congenital muscular dystrophy, congenital muscular dystrophy type 1A (MDC1A). However, the exact cellular mechanism by which Laminin loss results in the pathological spectrum associated with MDC1A remains elusive. Here we show, via live tracking of individual muscle fibres, that dystrophic myofibres in the zebrafish model of MDC1A maintain sarcolemmal integrity and undergo dynamic remodelling behaviours post detachment, including focal sarcolemmal reattachment, cell extension and hyper-fusion with surrounding myoblasts. These observations imply the existence of a window of therapeutic opportunity, where detached cells may be "re-functionalised" prior to their delayed entry into the cell death program, a process we show can be achieved by muscle specific or systemic Laminin delivery. We further reveal that Laminin also acts as a pro-regenerative factor that stimulates muscle stem cell-mediated repair in lama2-deficient animals in vivo. The potential multi-mode of action of Laminin replacement therapy suggests it may provide a potent therapeutic axis for the treatment for MDC1A.

Proof of genetic heterogeneity in X-linked Charcot-Marie-Tooth disease.

OBJECTIVE: To characterize a large family with X-linked Charcot-Marie-Tooth (CMT) neuropathy without mutations in the gap junction protein B1 (GJB1) gene, which has an unusual phenotype that is different in some aspects from classic CMTX1. METHODS: We tested CMT families consistent with X-linked inheritance for GJB1 mutations. We compared the largest family (CMT623) without GJB1 mutation and with linkage excluding the CMTX1 locus to CMTX1 and normal individuals. RESULTS: Only 51% of probable X-linked CMT families had mutations in GJB1. Family CMT623 shows linkage to Xq26.3-q27.1 (lod score z = 6.58), a region within the previously identified locus for CMTX3, Xq26-q28. Unlike CMTX1, affected males in family CMT623 report pain and paraesthesia before the onset of sensory loss, and women are usually asymptomatic. As in CMTX1, affected males have widely ranging intermediate motor conduction velocities. The coding regions of 14 positional candidate genes within the narrowed CMTX3 locus have been excluded for a pathogenic role in the disease. CONCLUSION: This study is the first to confirm the CMTX3 locus and to refine the genetic interval to a 5.7-Mb region flanked by the markers DXS1041 and DXS8106. GJB1 mutation-negative forms of X-linked CMT, such as CMTX3, may account for a significant proportion of X-linked CMT.

Facial sweat gland carcinoma metastasizing to neck nodes: a diagnostic and therapeutic challenge.

We report an unusual case involving a patient with sweat gland carcinoma of the cheek who presented with ipsilateral neck lymph node metastasis 10 years after his initial presentation. Pathological analysis of the surgical specimen revealed a strong reactivity of tumor cells to gross cystic disease fluid protein 15, estrogen receptor protein, and progesterone receptor protein. On the basis of these results, tamoxifen citrate therapy was initiated empirically. Our patient has been disease free for more than 3 years. Based on this and another case reported in the literature, we believe that antiestrogen therapy could prove beneficial in a subset of patients with sweat gland carcinoma. We recommend future multicenter clinical trials to assess the effectiveness of postoperative tamoxifen therapy for patients with estrogen and progesterone receptor protein-positive metastatic sweat gland carcinoma.

Changes of haemostasis in patients undergoing major abdominal surgery--is there a difference between elderly and younger patients?

Many physiological functions are altered in the elderly. It is not clear whether this applies to haemostatic mechanisms in patients undergoing major surgery. Twenty-five consecutive patients <60 yr and 25 consecutive patients >70 yr scheduled for abdominal surgery for malignancies were included in our study. Various standard coagulation variables and specific markers of coagulation were serially measured before surgery (baseline), at arrival on the intensive care unit (ICU), 4 h after arrival on ICU, and on the morning of the first postoperative day. Platelet function was assessed using the Platelet Function Analyser PFA-100 with adenosine diphosphate (ADP) as an inductor. Anaesthesia and surgery were similar between the elderly (76(3) years) and younger (53(5) years) groups. Baseline plasma levels of prothrombin fragments F1+2, thrombin-antithrombin III (TAT) complex, and D-dimers were significantly different between the two groups, indicating thrombin activation and fibrin formation in the elderly. Postoperatively, only F1+2 plasma levels were significantly higher in the elderly (4.0(0.8) nmol/l) than in the younger patients (2.2(0.9) nmol/l), whereas the course of D-dimer and TAT did not differ significantly between the two groups. Endothelial-derived markers of coagulation (von Willebrand factor, collagen-binding activity of von Willebrand factor) were not different between the groups throughout the study period. Platelet function was impaired in the elderly compared with the younger patients. It is concluded that elderly patients showed more prothrombin activation/thrombin generation and increased fibrinolytic activity prior to surgery than younger patients. However, perioperative changes of coagulation in the elderly were similar to those seen in younger patients.

Placebo-controlled comparison of dolasetron and metoclopramide in preventing postoperative nausea and vomiting in patients undergoing hysterectomy.

BACKGROUND AND OBJECTIVE: In a randomized, placebo-controlled, double-blind trial, we compared the efficacy of dolasetron and metoclopramide in preventing postoperative nausea and vomiting in women undergoing hysterectomy. METHODS: Patients were allocated randomly to one of three groups: group A (n = 50) received 50 mg dolasetron orally, group B (n = 50) received 20 mg metoclopramide intravenously and placebo orally, group C (n = 50) received placebo orally. If patients complained of retching or vomiting, or if patients demanded an antiemetic, 1.25 mg droperidol was administrated intravenously. To quantify postoperative nausea and vomiting the following score was used: 0 = no nausea, 1 = nausea, 2 = retching, 3 = single vomiting, 4 = multiple vomiting. The Raatz test was used to analyse postoperative nausea and vomiting (PONV) scores. RESULTS: Dolasetron reduced the postoperative nausea and vomiting score significantly (P < 0.02 vs. metoclopramide; P < 0.0001 vs. placebo). Metoclopramide also reduced the postoperative nausea and vomiting score (P < 0.02 vs. placebo). Fisher's exact test showed a significant reduction of vomiting in the dolasetron group compared with metoclopramide-treated patients (P < 0.007) and placebo-treated patients (P < 0.000006) and a significantly lower rate of nausea in comparison to the placebo group (P < 0.009). There were no significant differences between the metoclopramide and the placebo groups (in Fisher's exact test). The use of postoperative droperidol per patient was significantly lower in the dolasetron group (P < 0.04 vs. metoclopramide; P < 0.0001 vs. placebo) than in the metoclopramide (P < 0.02 vs. placebo) and in the placebo groups. CONCLUSIONS: Oral dolasetron is more effective than either metoclopramide given intravenously or placebo for preventing vomiting after hysterectomy. It also was significantly superior to either metoclopramide or placebo concerning the PONV score and the need for droperidol rescue.

Myxoid leiomyosarcoma of the left atrium: a rare malignancy of the heart and its comparison with atrial myxoma.

Primary tumours of the heart are rare. The majority of these tumours are benign, with myxomas located in the left atrium being the most common form. Almost all malignant tumours are sarcomas and occur preferentially in the right side of the heart. An exception to this rule is leiomyosarcoma, a rare form of primary cardiac sarcoma that occurs predominantly in the left atrium, as does cardiac myxoma. The case of a 53-year-old woman who presented with symptoms of mitral valve stenosis and pulmonary hypertension is reported. Cardiac catheterization, angiography and echocardiography revealed a left atrial mass that was interpreted as atrial myxoma. At the time of operation, the myxoid appearance of the tumour mass further supported this assumption. The tumour, including a wide rim of atrial septum, was removed with cautery. Histopathological examination unexpectedly showed that the tumour was not an atrial myxoma but rather a myxoid variant of a primary leiomyosarcoma. Immunohistochemistry and electron microscopy confirmed the diagnosis. Local radiotherapy was considered but deemed contraindicated in view of the longstanding pulmonary hypertension. Two months after excision, a repeat echocardiogram indicated recurrence of tumour in the left atrium, and the patient died a few days later. The preferential left atrial location and the frequently myxoid appearance of primary leiomyosarcomas of the heart make it particularly difficult to differentiate them preoperatively from atrial myxomas. The authors recommend resection of all atrial myxoid tumours with a wide (at least 1 cm) margin, combined with intraoperative frozen section diagnosis, because complete surgical resection appears to correlate with prolonged survival in the few reported cases of atrial leiomyosarcomas. In cases of incomplete initial resection or local recurrence in the absence of metastatic disease, heart transplantation may be a valid option in appropriately selected patients.

Cerebral effects and blood sparing efficiency of sodium nitroprusside-induced hypotension alone and in combination with acute normovolaemic haemodilution.

The combined reduction of oxygen-carrying capacity and perfusion pressure during the combination of acute normovolaemic haemodilution (ANH) and controlled hypotension (CH) raises concerns of hypoperfusion and ischaemic injury to the brain. Forty-two patients undergoing radical prostatectomy were prospectively allocated to receive CH induced by sodium nitroprusside (mean arterial pressure (MAP) 50 mm Hg), a combination of CH+ANH (post-ANH haematocrit 29%; intraoperative MAP 50 mm Hg), or standard anaesthesia (control). Serum levels of the brain-originated proteins neuron-specific enolase (NSE) and protein S-100, blood loss, transfusion requirements, adverse effects, and postoperative recovery profile were compared among the three groups. Intraoperative blood loss in the CH group (mean (SD)) (788 (193) ml) and CH+ANH group (861 (184) ml) was significantly less than in the control group (1335 (460) ml). Significantly fewer total units of allogeneic packed red blood cells (PRBC) were transfused in the patients receiving hypotensive anaesthesia (CH, 3 units; CH+ANH, 2 units; control, 17 units). There was no difference in immediate postoperative recovery profile among the three groups as determined by the emergence from anaesthesia and time to discharge from the postanaesthesia care unit. Serum S-100 protein concentrations increased significantly in all groups from baseline to peak concentrations 2 h postoperatively (CH 0.25 (0.11) microg litre(-1); CH+ANH 0.31 (0.12) microg litre(-1); control 0.31 (0.10) microg litre(-1)). A return to baseline values was seen within 24 h postoperatively in all patients. No changes in NSE concentrations were seen. Our observations suggest that CH and CH+ANH were effective in reducing blood loss and transfusion requirements in patients undergoing radical prostatectomy. Increased serum S-100 protein concentrations imply a disturbance in astroglial cell membrane integrity and an increased endothelial permeability of the blood-brain barrier. There were no associations between serum S-100 protein or NSE and adverse cognitive effects. Further work needs to be done to determine the prognostic importance of S-100 protein and NSE as surrogate variables of postoperative cerebral complications.

Influence of different colloids on molecular markers of haemostasis and platelet function in patients undergoing major abdominal surgery.

Synthetic colloids have been reported to cause haemorrhagic complications. The effects of perioperative volume replacement with 4% gelatin (n = 20), 6% low-molecular weight (LMW) hydroxyethyl starch (HES) (Mw: 70,000 dalton; HES 70/0.5; n = 20) and 6% medium-molecular weight (MMW) HES (Mw: 200,000 dalton; HES 200/0.5; n = 20) on haemostasis were assessed in patients undergoing major abdominal surgery. Volume was administered to keep central venous pressure (CVP) between 10 and 14 mm Hg. Conventional global coagulation tests, molecular markers of coagulation, and platelet function (using a platelet function analyser (PFA-100) with ADP as inductor) were monitored prior to surgery (T0), at the end of surgery (T1), 4 h after the end of surgery (T2), and on the morning of the first postoperative day (T3). Significantly more gelatin (2900 (SD 320) ml) than HES 200 (2150 (312) ml) was given during the study period. Bleeding and the use of allogeneic blood-blood products were similar in all groups. Markers of thrombin generation (F1 + 2), of thrombin neutralization (TAT III complex), and of fibrin formation and its degradation (D-dimer) increased significantly during and after surgery without showing significant group differences. Factor VIII and von Willebrand factor (vWF) also increased in all groups beyond the normal range, showing the significantly highest increase in the gelatin-treated group (VIII: from 173 (36) to 266 (33) U dl-1; vWF: from 164(33) to 238 (31) U dl-1). Platelet function remained within the normal range and without group differences throughout the study period. We can conclude that all three solutions can be used safely in patients undergoing major abdominal surgery with regard to the haemostatic process.

Structure and calcium-binding properties of Frq1, a novel calcium sensor in the yeast Saccharomyces cerevisiae.

The FRQ1 gene is essential for growth of budding yeast and encodes a 190-residue, N-myristoylated (myr) calcium-binding protein. Frq1 belongs to the recoverin/frequenin branch of the EF-hand superfamily and regulates a yeast phosphatidylinositol 4-kinase isoform. Conformational changes in Frq1 due to N-myristoylation and Ca(2+) binding were assessed by nuclear magnetic resonance (NMR), fluorescence, and equilibrium Ca(2+)-binding measurements. For this purpose, Frq1 and myr-Frq1 were expressed in and purified from Escherichia coli. At saturation, Frq1 bound three Ca(2+) ions at independent sites, which correspond to the second, third, and fourth EF-hand motifs in the protein. Affinity of the second site (K(d) = 10 microM) was much weaker than that of the third and fourth sites (K(d) = 0.4 microM). Myr-Frq1 bound Ca(2+) with a K(d)app of 3 microM and a positive Hill coefficient (n = 1.25), suggesting that the N-myristoyl group confers some degree of cooperativity in Ca(2+) binding, as seen previously in recoverin. Both the NMR and fluorescence spectra of Frq1 exhibited very large Ca(2+)-dependent differences, indicating major conformational changes induced upon Ca(2+) binding. Nearly complete sequence-specific NMR assignments were obtained for the entire carboxy-terminal domain (residues K100-I190). Assignments were made for 20% of the residues in the amino-terminal domain; unassigned residues exhibited very broad NMR signals, most likely due to Frq1 dimerization. NMR chemical shifts and nuclear Overhauser effect (NOE) patterns of Ca(2+)-bound Frq1 were very similar to those of Ca(2+)-bound recoverin, suggesting that the overall structure of Frq1 resembles that of recoverin. A model of the three-dimensional structure of Ca(2+)-bound Frq1 is presented based on the NMR data and homology to recoverin. N-myristoylation of Frq1 had little or no effect on its NMR and fluorescence spectra, suggesting that the myristoyl moiety does not significantly alter Frq1 structure. Correspondingly, the NMR chemical shifts for the myristoyl group in both Ca(2+)-free and Ca(2+)-bound myr-Frq1 were nearly identical to those of free myristate in solution, indicating that the fatty acyl chain is solvent-exposed and not sequestered within the hydrophobic core of the protein, unlike the myristoyl group in Ca(2+)-free recoverin. Subcellular fractionation experiments showed that both the N-myristoyl group and Ca(2+)-binding contribute to the ability of Frq1 to associate with membranes.

Primary right atrial synovial sarcoma manifesting as transient ischemic attacks.

Primary tumors of the heart are rare and most of them benign. The majority of benign cardiac tumors are myxomas while almost all malignant cardiac tumors are sarcomas. We present a case of primary right atrial synovial sarcoma, a form of sarcoma particularly rare in the heart. The tumor manifested clinically as transient ischemic attacks probably related to a patent foramen ovale allowing paradoxical tumor embolization.

Low-flow desflurane and sevoflurane anesthesia minimally affect hepatic integrity and function in elderly patients.

UNLABELLED: Hepatic blood flow is reduced in a dose-related manner by all inhaled anesthetics now in use. We assessed hepatic function in elderly patients anesthetized with desflurane or sevoflurane. We measured the cytosolic liver enzyme alpha glutathione S-transferase (alpha GST), the formation of the lidocaine metabolite monoethylglycinexylidide (MEGX), and gastric mucosal tonometry-derived variables as sensitive markers of hepatic function and splanchnic perfusion. Thirty patients, 70 to 90 yr old, were allocated randomly to receive desflurane or sevoflurane anesthesia. Anesthetic exposure ranged from 2.1-4.5 minimum alveolar concentration hours. No significant changes in standard liver enzyme markers were seen throughout the study. In both anesthetic groups, tonometric measurements showed a significant decrease from baseline in regional PCO(2), regional to arterial difference in PCO(2), and intramucosal pH at 90 min after skin incision. alpha GST concentrations increased significantly in both groups (desflurane: median peak concentrations 5.8 microg/L [25th, 75th percentile 5.3 microg/L, 7.2 microg/L]; sevoflurane: 7.0 microg/L [5.8 microg/L, 7.3 microg/L]) without showing differences between both anesthetic groups. A return to baseline values in tonometric values and alpha GST levels was seen 24 h postoperatively. MEGX formation did not change significantly after surgery. Median MEGX concentrations postoperatively were 70.0 ng/mL (56.2 ng/mL, 102.0 ng/mL) and 70.0 ng/mL (60.0 ng/mL, 94.2 ng/mL) in the desflurane and sevoflurane groups, respectively. We conclude that, overall, liver function in elderly patients is well preserved during desflurane and sevoflurane anesthesia. Increased serum levels of alpha GST and changes of gastric tonometry-derived variables imply a reduction in splanchnic perfusion, leading to a temporary impairment of hepatocyte oxygenation. IMPLICATIONS: We measured the lidocaine metabolite monoethylglycinexylidide, the cytosolic liver enzyme, alpha glutathione S-transferase, and gastric mucosal tonometry-derived variables to evaluate the effects of desflurane and sevoflurane on hepatic function in elderly patients. Liver function was well preserved, whereas increased alpha glutathione S-transferase levels and changes in tonometry-derived variables indicated a reduction in splanchnic blood flow and a temporary impairment of hepatocyte oxygenation for both anesthetics.

Gastric carcinoid tumours and pernicious anemia: case report and review of the literature.

Patients with pernicious anemia are at risk of developing carcinoid tumours of the stomach. A patient with pernicious anemia and multifocal carcinoid tumours of the gastric fundus that regressed after antrectomy is presented. The frequent occurrence of gastric carcinoid tumours in patients with long-standing pernicious anemia suggests that surveillance gastroscopy and biopsies of the fundus might be indicated. Compete functional antrectomy may effectively cause these tumours to regress by removing their excessive gastrin hormonal stimulation. However, incomplete antrectomy can result in persistently elevated serum gastrin and failure of total disappearance of the carcinoid tumours.

Unsuspected intrathyroidal parathyroid adenoma: mimic of lymphocytic thyroiditis in fine-needle aspiration specimens-a case report.

Fine-needle aspirations (FNAs) of parathyroid adenomas (PA) are infrequently encountered, but the scant literature on this topic emphasizes the difficulties in distinguishing them from thyroid neoplasms. We report on a case of an unsuspected intrathyroidal PA whose two FNA specimens mimicked almost perfectly the features of lymphocytic thyroiditis (LT). The smears from two FNAs of a "thyroid nodule" in a 22-yr-old woman were received with a clinical diagnosis of "LT." The cytological features of both specimens were similar and consisted of groups of epithelial cells in a background of numerous "naked" nuclei, interpreted as Hurthle cells and lymphocytes respectively, and leading to a cytological diagnosis of LT. Subsequent surgical excision of the "nodule" revealed a large intrathyroidal PA. The oxyphil cells and chief cells (the latter devoid of cytoplasm) present in the PA resembled Hurthle cells and lymphocytes respectively, in the FNA specimens. In conclusion, PA can give a cytological picture almost identical to that of LT in FNA material. Important clues to the diagnosis of PA in FNA specimens include the presence of prominent capillaries and the knowledge of a clinical history of hyperparathyroidism. Diagn. Cytopathol. 1999;21:276-279.

Fine-needle aspiration cytology of pleomorphic lobular carcinoma of the breast. Comparison with the classic type.

BACKGROUND: The pleomorphic variant of invasive lobular carcinoma shares the typical infiltrating histologic pattern of classic invasive lobular carcinoma, but differs from it in its nuclear pleomorphism and aggressive behavior. The purpose of this study was to describe the fine-needle aspiration (FNA) cytologic findings of the pleomorphic variant of lobular carcinoma and to compare them with those of classic lobular carcinoma. METHODS: Among 405 breast FNA performed in 1995, 7 examples of classic infiltrating lobular carcinoma and 4 cases of this neoplasm's pleomorphic variant were identified; all were histologically confirmed. The FNA from three of the four pleomorphic variant cases and from two of the seven classic lobular carcinoma cases were diagnostic of malignancy; these were evaluated for a variety of cytologic criteria, which were graded from 0 to 3. RESULTS: Although exhibiting many cytologic features in common with the classic type, such as indian files and cytoplasmic vacuoles, the FNA of the pleomorphic variant differed in their tendency to yield greater cellularity, larger cell size, and, particularly, more pleomorphic nuclei. CONCLUSIONS: The FNA cytologic findings of the pleomorphic variant of lobular carcinoma are characteristically hybrid between those of classic lobular carcinoma and ductal carcinoma.

Multicentric epithelioid angiosarcoma of the bone. Pitfalls in clinical and morphological diagnosis.

Epithelioid angiosarcoma of the bone represents a challenging diagnosis by bone marrow biopsy. We present a case of a multicentric high grade angiosarcoma of the bone with epithelioid features. On the basis of the clinical presentation, the radiological findings, and the appearance of loosely clustered tumor cells detected in the initial bone marrow biopsy, the main differential diagnoses considered were a poorly differentiated non-secretory multiple myeloma and metastatic carcinoma. Subsequent morphologic, immunohistochemical and electron microscopic examination of tissue samples clarified the nature of the tumor as epithelioid angiosarcoma. We discuss potential pitfalls in clinical and morphological diagnosis. The strong reactivity of the tumor cells with the nonspecific but ubiquitous mesenchymal marker vimentin in similar cases should direct early attention to the rare malignant bone tumor, epithelioid angiosarcoma, with subsequent confirmation of this diagnosis with specific immunohistochemical endothelial cell markers and/or electron microscopy.

Phenotypic features of smooth muscle cells during the evolution of experimental carotid artery intimal thickening. Biochemical and morphologic studies.

Balloon catheter denudation of rat carotid artery that results in significant medial damage is followed by marked intimal smooth muscle cell (SMC) proliferation associated with limited endothelial regrowth. In this report we demonstrate that: (a) SMC of the carotid media, preceding their intimal proliferation, develop a cytoskeletal profile and morphology consistent with a de-differentiated SMC phenotype; and (b) both medial and intimal SMC subsequently revert to a cytoskeletal profile and morphology reflecting incomplete but significant re-differentiation toward normal SMC phenotype. Specifically, early after balloon injury, SMC of the media and those that have migrated into the intima contain decreased amounts of actin, desmin, and tropomyosin and increased amounts of vimentin; moreover, beta-actin becomes the dominant actin isoform, whereas alpha-actin decreases as compared with that found in normal medial SMC. Late after balloon injury, actin is still less abundant, however, desmin, tropomyosin, and vimentin return toward normal values and both medial and intimal SMC again show a predominance of alpha-actin, although the endothelium does not regenerate over the central surface of intimal thickening in this model. The SMC surface to volume ratio significantly decreases early after balloon injury, whereas it is not significantly different late after balloon injury as compared with that of SMC of the normal carotid media. We demonstrate, furthermore that: (c) adjacent luminal SMC are interconnected by gap junctions and develop focal tight junctions, a feature not reported previously to occur in smooth muscle; these cells however do not form any well defined membrane specialization with the leading edge of endothelium, supporting the view that presence of modified SMC on the luminal surface of chronically denuded vessels is not responsible for the cessation of endothelial regrowth.

Rhabdomyomatosis of newborn lung: a case report with immunohistochemical and electronmicroscopic characterization of striated muscle cells in the lung.

Interstitial proliferation of striated muscle cells in the lung is rare. A few cases in the literature only document infants with associated lung and other major organ anomalies incompatible with long-term survival. In this report we document a case of diffuse patchy interstitial proliferation of striated muscle cells in the left lung and confirm their nature by immunohistochemistry and electron microscopy. In particular, we show that these skeletal muscle cells express alpha-sarcomeric actin, but not alpha-smooth muscle actin, indicating an antigenetically well-developed striated muscle phenotype despite morphologically embryonal features.

Perturbation of the sarcolemmal membrane in isoproterenol-induced myocardial injury of the rat. Permeability and freeze-fracture studies in vivo and in vitro.

The mechanism whereby cardiotoxic doses of isoproterenol (ISO) induces early permeability alteration of the sarcolemmal membrane is unknown; both beta-receptor overstimulation and direct toxic effect of ISO oxidation products have been implicated. There has been no morphologic observation, furthermore, on the structural basis of permeability alteration during this process. The purpose of the present study was to compare the morphology of cardiocyte injury induced by ISO and oxidized ISO (ISO-O2) and to visualize perturbation of the sarcolemma correlating with the leaky membrane. The authors studied the left ventricular myocardium of rats 10 and 60 minutes after subcutaneous administration of 85 mg/kg ISO and isolated perfused rat hearts exposed for 10 minutes either to ISO or ISO-O2 in a dose of 100 mg/l (10(-4) M) to determine the permeability of the sarcolemmal membrane using the extracellular diffusion tracer horseradish peroxidase (HRP) by light and thin section electron microscopy, the morphology of the sarcolemmal membrane by means of freeze-fracture electron microscopy, and the density of intramembrane particles (IMP) in the sarcolemmal membrane by planimetry using freeze-fracture electron microscopy. In in vivo rat hearts both 10 and 60 minutes after ISO and in vitro (isolated perfused) rat hearts exposed to either ISO or ISO-O2 for 10 minutes, HRP labeled the sarcoplasm of focally located cardiocytes implicating leakiness of the sarcolemmal membrane. HRP positive cardiocytes (with the exception of the in vivo 10 minute group) showed characteristic features of contraction band necrosis (both on light and thin-section electron microscopy) in all groups. Freeze-fracture electron microscopy of sarcolemmal protoplasmic (P) membrane faces revealed two populations of cardiocytes in all groups. P-membrane faces in one population of cardiocytes appeared as in the control. In the other population of cardiocytes, P-membrane faces showed irregular tears. Planimetry demonstrated a significant decrease of IMP numerical densities in P-membrane faces with tears in the in vivo 10 minute group and both with or without tears in the in vivo 60 minutes group and the in vitro groups compared with the control values. Furthermore, with the exception of the 10 minute in vivo group, IMP densities significantly decreased in sarcolemmal membranes with tears compared with those without tears in all experimental groups. These observations are consistent with the view that catecholamine induced myocardial injury is, at least partly, related to the direct toxic effect of catecholamine oxidation products on the sarcolemmal membrane.(ABSTRACT TRUNCATED AT 400 WORDS)

Stiff left atrial syndrome.

A 67-year-old female presented seven years after insertion of a mitral prosthesis with mild to moderate pulmonary edema and severe right heart failure with pulmonary and tricuspid insufficiency. Clinical examination and noninvasive tests did not demonstrate prosthetic valve dysfunction. Cardiac catheterization revealed a marked V wave but no mitral regurgitation and no significant mitral diastolic gradient. A clinical diagnosis of a stiff left atrium was made and confirmed at autopsy. The pathophysiology of the syndrome is discussed.