Autologous bone marrow transplantation in B-cell non-Hodgkin's lymphoma: very low treatment-related mortality in 100 patients in sensitive relapse.

One hundred patients with B-cell non-Hodgkin's lymphoma (NHL) in sensitive relapse or incomplete first remission underwent high-dose chemoradiotherapy and anti-B-cell monoclonal antibody (MAb)-treated autologous bone marrow transplantation (ABMT). These patients demonstrated good performance status with a Karnofsky score of 80% or greater. The majority of these patients had one or more adverse prognostic features including a failure to achieve a complete remission (CR) with conventional combination chemotherapy (37 patients), bone marrow infiltration (69 patients), a history of extranodal disease other than bone marrow infiltration (42 patients), and histologic conversion (18 patients).

Who's in CHARGE? Multidisciplinary management of patients with CHARGE association.

Clinical experience of 50 patients with the CHARGE association is reviewed and problems with management of children born with multiple system involvement is highlighted. It was found that the outlook for survival was poor if more than one of the following three features was present: cyanotic cardiac lesions, bilateral posterior choanal atresia, or tracheo-oesophageal fistula. Mortality was largely due not to the structural heart defects or choanal abnormalities, but reflected underlying pharyngeal and laryngeal incoordination, which resulted in aspiration of secretions.

CHARGE association in two monozygous triplets.

In an unusual set of triplets, two monozygous girls presented with CHARGE association. Dissimilar surgical management of identical cardiovascular lesions has resulted in a disparate effect on their clinical state. Their case poses interesting questions concerning how CHARGE association may develop.

Reticuloendothelial function and plasma fibronectin in a murine model of intra-abdominal sepsis.

The lung is the target organ most frequently involved in the early phase of multiple organ failure. Microembolisation of the pulmonary vasculature by bacterial and non-bacterial particles and debris with failure of the clearance mechanism of the reticuloendothelial system (RES) and depletion of plasma fibronectin have been implicated in the pathogenesis. The present study examined the concurrent changes in plasma fibronectin, RES phagocytic function, organ localisation of bacterial and non-bacterial particles and the levels of circulating endotoxin and fibrin degradation products in a clinically relevant murine model of severe intra-abdominal infection.

Complement-independent neutralising monoclonal antibody with differential reactivity for strains of human cytomegalovirus.

A mouse monoclonal antibody with complement-independent neutralising activity against cytomegalovirus (CMV) and reactive with the 86 kilodalton (kDa) viral glycoprotein H is described. Neutralisation tests against a range of different strains of CMV showed significant crossreactivity, but clear differences were evident between the two prototype viruses AD169 and Davis, and particularly between AD169 and several low-passage recent clinical isolates; CMV present in urine was neutralised weakly if at all.

The postnatal expression of acetylcholinesterase in somatostatin-positive cells of mouse hippocampus.

The neuroanatomical distributions of acetylcholinesterase (AChE) staining and somatostatin-like immunoreactivity (SOMLI) of neurons intrinsic to the mouse hippocampal formation have been evaluated during postnatal development. Besides the progressive development of neuropil staining for AChE, as a consequence of the septohippocampal innervation, intense AChE staining was also expressed in a subpopulation of neurons intrinsic to the stratum oriens and the hilus of dentate gyrus. In the stratum oriens, the number of AChE-positive cells increased between postnatal day (PND) 3 and PND 10 and declined slightly after PND 21.

Use of EDTA derivatization to characterize interactions between oligodeoxyribonucleoside methylphosphonates and nucleic acids.

EDTA-derivatized oligonucleoside methylphosphonates were prepared and used to characterize hybridization between the oligomers and single-stranded DNA or RNA. The melting temperatures of duplexes formed between an oligodeoxyribonucleotide 35-mer and complementary methylphosphonate 12-mers were 4-12 degrees C higher than those of duplexes formed by oligodeoxyribonucleotide 12-mers as determined by spectrophotometric measurements. Derivatization of the methylphosphonate oligomers with EDTA reduced the melting temperature by 5 degrees C.

Angina and vasospasm at rest in a patient with an anomalous left coronary system.

An anomalous left main coronary artery with passage between the right ventricular infundibulum and aortic root has been incriminated as the causation of sudden death in a small number of individuals, many of whom are quite young. Mechanical features such as angulation and compression are most often incriminated. A 59-year-old man with such a coronary anomaly who had chest pain at rest, ST segment elevation, and ventricular tachycardia, but who had no evidence of effort-related myocardial ischemia, is reported.

Modulation of ras expression by anti-sense, nonionic deoxyoligonucleotide analogs.

Anti-ras oligodeoxyribonucleoside methylphosphonates (ONMP's) complementary to the initiation codon region have been synthesized to explore their efficacy and specificity on ras-p21 translation. ONMP (IC-0) precisely complementing the first initial 11 nucleotides of the Balb-ras initiation codon region acts in a dose-dependent manner to inhibit p21 translation by a rabbit reticulocyte lysate. At 100 microM, IC-0 inhibits the cell-free translation of p21 close to completion.

Sequence specific inhibition of in vitro translation of mutated or normal ras p21.

Antisense methylphosphonate-modified oligomers (ONMP) complementary to 8 nucleotides spanning the twelfth amino acid codon of human c-Ha-ras have been synthesized to explore their inhibitory effect on ras p21 translation. The ONMP Ras 0, perfectly complementary to the specific target region in normal c-Ha-ras, inhibits cell-free translation of p21 from a normal c-Ha-ras mRNA template in a dose-dependent manner. At 200uM Ras 0, p21 translation is inhibited by almost 90% in a rabbit reticulocyte lysate; at 100uM, p21 is reduced by over 60%.

Photochemical cross-linking of psoralen-derivatized oligonucleoside methylphosphonates to rabbit globin messenger RNA.

Antisense oligodeoxyribonucleoside methylphosphonates targeted against various regions of mRNA or precursor mRNA are selective inhibitors of mRNA expression both in cell-free systems and in cells in culture. The efficiency with which methylphosphonate oligomers interact with mRNA, and thus inhibit translation, can be considerably increased by introducing photoactivatable psoralen derivatives capable of cross-linking with the mRNA. Oligonucleoside methylphosphonates complementary to coding regions of rabbit alpha- or beta-globin mRNA were derivatized with 4'-(aminoalkyl)-4,5',8-trimethylpsoralens by attaching the psoralen group to the 5' end of the oligomer via a nuclease-resistant phosphoramidate linkage.

Long-segment coronary ulcerations in survivors of sudden cardiac death.

Angiographically irregular coronary stenoses usually represent plaque rupture with or without superimposed thrombi. Long-segment coronary stenoses with diffuse irregularities (type IIB morphology) have been shown to be more prevalent than focal irregular lesions (type IIA morphology) in survivors of cardiac arrest without acute myocardial infarction. To further understand the pathogenetic importance of type IIB morphology, the clinical and angiographic characteristics in 59 such patients were analyzed.

Interaction of psoralen-derivatized oligodeoxyribonucleoside methylphosphonates with synthetic DNA containing a promoter for T7 RNA polymerase.

The interaction of 4'-N(2-aminoethyl)aminomethyl-4,5',8-trimethylpsoralen-modified oligonucleoside methylphosphonates with synthetic ds-DNA containing a T7 RNA polymerase promoter was studied. The oligomers effectively crosslinked with either coding or noncoding ss-DNA when irradiated at 365 nm, but not with ds-DNA. The extent of the crosslinking reaction, which was complete within 16 min: (a) reached its maximum at an oligomer concentration of 3 microM; (b) remained constant below the Tm of the duplex and then rapidly decreased; and (c) appeared to depend upon the sequence surrounding the psoralen crosslinking site.

Relative efficacy of phenytoin and phenobarbital for the prevention of theophylline-induced seizures in mice.

We evaluated the efficacy of pretreatment with phenytoin and phenobarbital to prevent seizures in mice given convulsive doses of theophylline. The control LD50 for theophylline was determined in 48 mice by intraperitoneal injections of increasing doses without anticonvulsant treatment. Anticonvulsant effects were determined in 105 additional mice pretreated with either phenytoin 30 mg/kg (n = 35), phenobarbital 35 mg/kg (n = 30), or phenobarbital 60 mg/kg (n = 40) one hour before theophylline administration.

Interaction of psoralen-derivatized oligodeoxyribonucleoside methylphosphonates with single-stranded DNA.

Oligodeoxyribonucleoside methylphosphonates derivatized at the 5' end with 4'-(amino-alkyl)-4,5',8-trimethylpsoralen were prepared. The interaction of these psoralen-derivatized methylphosphonate oligomers with synthetic single-stranded DNAs 35 nucleotides in length was studied. Irradiation of a solution containing the 35-mer and its complementary methylphosphonate oligomer at 365 nm gave a cross-linked duplex produced by cycloaddition between the psoralen pyrone ring of the derivatized methylphosphonate oligomer and a thymine base of the DNA.

Death of a child associated with multiple overdoses of acetaminophen.

A case of long-term acetaminophen overdosage in a six-year-old child, which contributed to her death despite optimal medical management including oral acetylcysteine therapy, is reported. Acetaminophen 325 mg every six hours was prescribed for fever associated with measles. Believing that acetaminophen was nontoxic, the child's mother progressively increased the dose over three days, first in response to fever and subsequently for abdominal pain probably secondary to unrecognized acetaminophen toxicity.

Angiographic coronary morphology in survivors of cardiac arrest.

Autopsy studies in victims of sudden coronary death revealed intramyocardial platelet aggregates with microscopic myonecrosis downstream from ruptured atherosclerotic plaques. Ruptured plaques usually manifest angiographically as irregularly bordered (type II) lesions. To investigate the possible pathogenic role of ruptured plaques in arrhythmic death, we analyzed clinical, angiographic, and electrophysiologic data from 49 survivors of cardiac arrest without acute myocardial infarction.

Mechanism of depolarization in the ischaemic dog heart: discrepancy between T-Q potentials and potassium accumulation.

1. To study the origin of ischaemic myocardial depolarization, the diastolic surface potential - T-Q depression-was correlated with subepicardial extracellular K+ accumulation during serial episodes of widespread ischaemia in open-chest dogs, and in isolated, blood-perfused canine hearts. Placement of the reference electrode on a small island of non-ischaemic myocardium simplified the interpretation of the T-Q potentials.

Electropharmacology of flestolol for supraventricular tachycardia without associated structural heart disease.

Flestolol is an ultrashort-acting beta-blocking drug with a half-life of 6.9 minutes. Its antiarrhythmic efficacy was studied in 21 patients with spontaneous and inducible supraventricular tachycardia: atrioventricular (AV) nodal tachycardia in 6 patients and orthodromic AV reciprocating tachycardia in 15.