Non-aneurysmal inflammation of the aorta in combination with aortic valve disease.

A 61-year-old man presented with aortic valve stenosis, coronary artery disease in combination with rheumatic arthritis, peri-aortic inflammation and fibrosis with aortitis. In the pathological literature this has been termed chronic periaortitis, while in the surgical literature, non-aneurysmal dilatation of the aorta associated with atherosclerosis and inflammation has been described as aortitis. The name chronic periarteritis refers to the associated involvement of coronary arteries. Although different terminologies have been used, it is suggested that all of them most likely represent the same disease entity.

Leukocyte-depleted secondary blood cardioplegia attenuates reperfusion injury after myocardial ischemia.

BACKGROUND: Activated neutrophils have been implicated in reperfusion injury of the myocardium; leukocyte depletion at the time of reperfusion may contribute to better myocardial protection after cardiac surgery. In the present study, we examined whether leukocyte depletion as an adjunct to terminal blood cardioplegia attenuates reperfusion injury. METHODS: Porcine hearts that had undergone 60 minutes of normothermic ischemia with cardioplegia and 60 minutes of reperfusion under cardiopulmonary bypass were divided into four groups according to the methods of 15 min of controlled initial reperfusion: whole blood reperfusion (n = 6), leukocyte-depleted reperfusion (n = 6), secondary blood cardioplegia (n = 6) and leukocyte-depleted secondary blood cardioplegia (n = 6). At 60 min of reperfusion, hemodynamic recovery, release of malondialdehyde (MDA) as a marker for free oxygen radicals, CK-MB-isoenzyme from the coronary sinus, recovery of adenosine triphosphate, and myocardial water content were evaluated. RESULTS: The group with leukocyte-depleted secondary blood cardioplegia showed the best hemodynamic recovery (Emax and total dp/dt), lowest levels of MDA, CK-MB and myocardial water content, and highest adenosine triphosphate recovery. CONCLUSIONS: These results suggest that controlled reperfusion with leukocyte-depleted secondary blood cardioplegia attenuated severe damage of the myocardium as compared to whole blood reperfusion.

Ruptured papillary muscle after mitral valve replacement with preservation of chordae tendineae.

Many cardiac surgeons believe strongly that every effort should be made to preserve the continuity of the mitral anulus, chordae tendineae, and papillary muscles during mitral valve replacement in order to maximize ventricular function and maintain normal ventricular geometry. We treated a patient with spontaneous papillary muscle rupture after mitral valve replacement in whom efforts had been made to preserve continuity of the mitral mechanism.

[Papillary muscle rupture after mitral valve replacement with preservation of subvalvular structures]. / Papillarmuskelruptur nach Mitralklappenersatz mit erhaltenem subvalvulärem Apparat.

We report a female patient with mitral valve replacement and preservation of subvalvular apparatus in which parts of the papillary muscle ruptured postoperatively. During systole the ruptured papillary muscle prolapsed through the native aortic valve. Echocardiographic documentation and operative procedure were demonstrated.

Petrolatum versus Resurfix ointment in the treatment of pressure ulcers.

This study compares the therapeutic effects of a new topically applied, nonprescription medication that has been introduced for re-epithelialization of ulcers and erosions of the skin, with petrolatum in treating pressure ulcers of shallow depth (Stage I and Stage II). A 6-week, randomized, double-blind study was performed on 19 patients with Stage I or Stage II pressure ulcers. The patients received either the new nonprescription medication or petrolatum, which served as a control. After the course of the study, the study ointment effected resolution in a majority of pressure ulcers (9 out of 10), while only one out of three ulcers treated with petrolatum resolved in the same time period. These preliminary results show that the study ointment is a safe and effective treatment for Stage I and II pressure ulcers.

[Spontaneous dissection of the coronary arteries: a rare cardiologic diagnosis]. / Spontandissektion der Koronararterien: Eine seltene kardiologische Diagnose.

A 55-year-old woman who was admitted to hospital with acute chest pain as a case of emergency suffered from an acute anteroseptal myocardial infarction. Four weeks later coronary angiography revealed a long dissection of the left anterior descending artery (LAD) as well as a significant stenosis of the left main and the proximal circumflex. Cardiovascular surgery was done subsequently. In addition to myocardial revascularization using coronary artery bypass grafts a readaptation of the dissecting artery walls and a proximal ligation of the LAD before anastomosis were performed. Clinical data, pathogenesis, and indications for medical and surgical treatment of spontaneous artery dissection are presented.

Atrial fibrillation after coronary artery bypass surgery: association with changes in G protein levels in mononuclear leukocytes.

Atrial fibrillation (AFib) is a frequent complication of coronary artery bypass grafting (CABG). Its cause, however, is unknown. As the adrenergic system is involved in some types of AFib, we hypothesized that a change in guanine nucleotide-binding protein (G protein) expression plays a role in the development of post-CABG AFib. In 28 patients undergoing CABG surgery, the G(s alpha)/G(i alpha) ratio (stimulatory/inhibitory G protein alpha) at the protein (Western blotting) and mRNA (reverse transcription polymerase chain reaction) levels was measured before and after surgery. As a suitable test system allowing multiple analysis mononuclear leukocytes (MNL) were chosen. The perioperative change of the G(s alpha)/G(i alpha) ratio of protein and mRNA was significantly different in patients who subsequently developed AFib (eight patients) and in patients who did not (20 patients; P<0.01 and <0.001, respectively). On average, the protein G(s alpha)/G(i alpha) ratio decreased from 1.79+/-1.13 (mean+/-SD) to 1.32+/-0.69 in patients without AFib (P=0.1, n.s.) whereas a significant increase from 0.86+/-0.44 to 1.62+/-0.65 (P<0.01) was observed in patients subsequently developing AFib. The mRNA G(s alpha)/G(i alpha) ratio decreased significantly from 0.53+/-0.24 to 0.36+/-0.11 in patients without AFib (P<0.01) whereas a significant increase from 0.31+/-0.14 to 0.47+/-0.13 was observed in those who subsequently developed AFib (P<0.05). These results indicate that an increase of the G(s alpha)/G(i alpha) ratio in MNL is associated with AFib after CABG surgery and possibly may be used as a prognostic indicator of this complication.

Isolation of differentially expressed cDNA clones from salt-adapted Aspergillus nidulans.

Differentially expressed cDNA clones were isolated from salt-adapted Aspergillus nidulans (FGSC #359). Poly (A)+ RNA from adapted mycelia was used to construct a lambda Uni-ZAP cDNA library. The library was screened with mixed subtracted cDNA probes. Three-hundred and fifty-seven positive plaques were isolated in the primary screening. Sixty-two randomly selected plaques were purified and placed into eight different cross-hybridization groups. A representative cDNA from each group was used to study expression under unadapted, salt-adapted and salt-shock conditions. These clones, representing eight different genes, displayed enhanced expression under salt stress. Exploratory nucleotide sequencing was performed, and the predicted amino-acid sequence was compared with known gene sequences in the data-bank. Five of the cDNA clones were identified as a mitochondrial (mt) ATPase beta subunit, a mt ATPase subunit 9, a mt transport protein, a ubiquitin-extension protein and a ribosomal protein. Three cDNA clones could not be identified due to lack of adequate homology with known sequences. These results suggest that at least five genes with known function in cellular processes like ATP generation and protein synthesis, and three other genes of unknown identity, are greatly induced in salt-adapted conditions.

The Thom Award address. Industrial mycology and the new genetics.

The genetic investigation of fungi has been extended substantially by DNA-mediated transformation, providing a supplement to more conventional genetic approaches based upon sexual and parasexual processes. Initial transformation studies with the yeast Saccharomyces cerevisiae provided the model for transformation systems in other fungi with regard to methodology, vector construction and selection strategies. There are, however, certain differences between S. cerevisiae and filamentous fungi with regard to type of genomic insertion and the availability of shuttle vectors. Single-site linked insertions are common in yeast due to the high level of homology required for recombination between vectored and genomic sequences, whereas mycelial fungi often show a high frequency of heterologous and unlinked insertions, often in the form of random and multiple-site integrations. While extrachromosomally-maintained or replicative vectors are readily available for use with yeasts, such vectors have been difficult to construct for use with filamentous fungi. The development of vectors for replicative transformation with these fungi awaits further study. It is proposed that replicative vectors may be inherently less efficient for use with mycelial fungi relative to yeasts, since the mycelium, as an extended and semicontinuous network of cells, may delimit an adequate diffusion of the vector carrying the selectable gene, thus leading to a high frequency of abortive or unstable transformants.

Presence of a P1 bacteriophage sequence in transforming plasmids of Pleurotus ostreatus.

Replicative plasmids pP01 and pP02, recovered from Pleurotus ostreatus transformants, contain an insert of bacteriophage origin. These plasmids have been amplified by the polymerase chain reaction (PCR) and have been shown to represent a low-grade component in the initial preparation of the vector pAN7-1. The pP01 and pP02 plasmids share an insert (P01A) of virtual identity with a SmaI-BamHI genomic fragment of P 1 bacteriophage and retain remnants of a polylinker at the 5' end of this fragment. Such an insert undoubtedly represents an in vitro-generated event and did not arise, as suggested previously, by recombination of pAN7-1 with the P. ostreatus genome. The P. ostreatus transformants, however, do select for the minority pP0 plasmid, apparently recognizing the P01A insert as a heterologous or surrogate replicon.

Fosinoprilate prolongs the action potential: reduction of iK and enhancement of the L-type calcium current in guinea pig ventricular myocytes.

OBJECTIVE: The aim was to study the effect of fosinoprilate, a new ACE inhibitor, on the action potential and plateau currents of cardiac muscle. METHODS: Whole cell patch technique was used to record action potentials (n = 6), the L-type iCa (iCaL; n = 5), in some cases (n = 4) also using Cs+ loaded pipettes; with 5 mM Co2+, the time dependent K+ current (IK) underlying delayed rectification was analysed in guinea pig ventricular myocytes (n = 3). RESULTS: Fosinoprilate prolonged the 50% repolarisation (APD50) from 440(SEM 50) ms to 485(48) ms (0.1 microM), to 525(46) ms (0.3 microM), to 632(58) ms (1 microM), and to 702(69) ms (3.0 microM). The APD90 was delayed from 510(63) ms to 540(45) ms (0.1 microM), to 583(42) ms (0.3 microM), to 702(62) ms (1.0 microM), and to 765(72) ms (3.0 microM). Higher concentrations (10-100 microM) caused early afterdepolarisations, very long action potentials, and irregular oscillations. ICaL was enhanced by up to 183%, showing a Kd of 0.2 microM; in contrast to the steady state activation (d infinity), the inactivation curve f infinity was shifted in the depolarising direction, considerably enlarging the Ca2+ window. Slow inactivation time course was unchanged, whereas the fast time constant (tau f) was accelerated. Fosinoprilate reduced the outward current during depolarising clamps from 1.7(0.2) nA to 1.41(0.11) nA with a 0.1 microM dose, and to 0.54(0.14) nA with a 1.0 microM dose; the tails were decreased from 0.39(0.03) nA to 0.27(0.03) nA with 0.1 microM and to 0.13(0.02) nA with 1.0 microM. Kinetics of IK were unaltered. Computer simulations based on these data using the OXSOFT-HEART program mimicked the results rather closely. CONCLUSIONS: The results suggest that fosinoprilate prolongs the plateau due to a partial block of iK and an extension of the Ca2+ window by 10 mV, causing a class III antiarrhythmic effect. High concentrations further open the Ca2+ window resulting in early afterdepolarisations and plateau oscillations and may cause an inward transport of Ca2+ ions by the Na-Ca exchange.

A nucleotide sequence involved in replicative transformation of a filamentous fungus.

Replicative plasmids generated through in-vivo recombination have been identified among transformants of the fungus Pleurotus ostreatus. In addition to sequences from a standard selection vector (pAN7-1), these recombinant plasmids contain recombined sequences of chromosomal origin conferring replicative potential upon the vector. One such recombined sequence, an 1148-bp insert into plasmid pP01, has been characterized. This sequence has been analyzed for secondary structural features as well as for consensus sites affiliated with origins of replication (ori) in other eukaryotic systems. The 1148-bp insert lacks an ORF and does not contain an acceptable match to the commonly identified 11-bp ars consensus sequence (A/TTTTATA/GTTTA/T) for autonomous replication in the yeast Saccharomyces cerevisiae. The analysis, however, revealed a cluster of three hairpin-loop-forming subsequences with individual delta G25 degrees C free energy values of -7.6, -6.4 and -5.2 kcal mol-1. Also found were two 7-bp analogues to centromere-affiliated sequences recognized in other fungi, as well as several putative gyrase recognition sites comparable to the 9-bp S. cerevisiae/E. coli gyrase-binding consensus sequence. Sequences comparable to the ori of the yeast 2-microns plasmid or to various sequences associated with ori of yeast/fungal mitochondrial DNAs (mtDNA) were not present in the 1148-bp insert. Replication of pP01 appears rather to involve a replication of chromosomal derivation devoid of an ars-type consensus.

Recovery of recombinant plasmids from Pleurotus ostreatus transformants.

A transformation system employing selectable resistance to hygromycin B has been developed for the mushroom-forming fungus, Pleurotus ostreatus. Vector pAN7-1, a commonly used non-replicative vector for integrative transformation in fungi, yielded 5-46 resistant colonies per micrograms of DNA per 10(7) viable protoplasts. Southern blot analysis of certain transformants revealed unexpected replicative plasmids containing pAN7-1 sequences, but modified for size, methylation and restriction enzyme pattern when compared to the initial transforming vector. Two such replicative derivatives of pAN7-1 have been rescued from P. ostreatus by cloning into Escherichia coli. Rescued plasmids have been used to probe DNA from untransformed P. ostreatus in an effort to identify fungal sequences that recombined in vivo with pAN7-1 to form replicative plasmids. Such replicative sequences have been localized in high molecular weight (chromosomal) DNA of wild-type P. ostreatus. Transformation has been obtained for P. ostreatus using a rescued plasmid, thereby confirming the role of this recombinant plasmid as a shuttle vector.

An autistic boy copes with a terminal illness.

David, a 12-year-old boy with autism, developed Ewing's Sarcoma and died 3 months later. This report describes the effects of both illnesses on David, his parents, and his care givers. The difficulties encountered in finding appropriate help in the care of both illnesses and in making difficult decisions are described. The presence of autism can affect medical management and the presence of terminal illness can affect the management of autism. Suggestions are offered for effective medical and psychiatric interventions that include a sensitivity to both illnesses in physicians and other care givers; a case manager to help find appropriate medical and psychiatric services; and the availability of combined medical and psychiatric units.

Direct visual detection of aflatoxin synthesis by minicolonies of Aspergillus species.

Single-spore colonies of Aspergillus flavus and Aspergillus parasiticus, grown for 4 to 5 days at 25 degrees C on a coconut extract agar containing sodium desoxycholate as a growth inhibitor, produced aflatoxin, readily detectable as blue fluorescent zones under long-wave (365 nm) UV light. Over 100 colonies per standard petri dish were scored for aflatoxin production by this procedure. Progeny from some strains remained consistently stable for toxin production after repeated subculture, whereas instability for toxin synthesis was revealed among progeny from other strains. Spore color markers were used to rule out cross-contamination in monitoring strains. A yellow-spored and nontoxigenic strain of A. flavus, reported previously to produce aflatoxin in response to cycloheximide treatment, proved to be toxin negative even after repeated exposure to cycloheximide. Extended series of progeny from another strain of A. flavus and from a strain of A. parasiticus were each compared by this plating procedure and by fluorometric analysis for aflatoxin when grown in a coconut extract broth. Both of these strains showed variation for toxin synthesis among their respective progeny, and specific progeny showed a good correlation for aflatoxin synthesis when examined by the two procedures.

The effect of chronic administration of indomethacin in captopril-treated renal hypertensive rats.

To examine the possible involvement of prostaglandins (PG) in the antihypertensive action of captopril, a PG synthetase inhibitor (indomethacin) was administered to normal and one-kidney renovascular hypertensive rats treated with captopril for 2 weeks. Continuous infusion of captopril (40 micrograms/hr SC) to normal and renal hypertensive (RH) rats via an implantable osmotic pump for 14 days lowered systolic blood pressure (SBP) in RH rats only. However, administration of indomethacin (5 mg/kg SC) 3 times a week to normotensive rats pre-treated with captopril by continuous infusion (40 micrograms/hr SC), lowered SBP significantly 24 hours after the injection of indomethacin. In RH rats pre-treated with captopril, subsequent administration of indomethacin further reduced SBP. In this study, indomethacin given alone to both RH and normal rats produced no significant alteration in SBP. However, indomethacin potentiated the hypotensive effect of captopril. This action may be attributed to inhibition of PG biosynthesis. It has been reported that the effects of PGE2 within the kidneys are species dependent and in the case of the rat, cause vasoconstriction of the renal vasculature. Therefore, administration of indomethacin would attenuate the vasoconstricting effects of PGE2 and thus lower blood pressure. Accordingly, based on these observations, PGs may perhaps play a role in mediating the hypotensive effect of captopril.