Diagnosis of the acute ischaemic heart by ion elution from myocardium.

The post-mortem diagnosis of acute myocardial ischaemia may be difficult to establish in the absence of morphological changes in the myocardium or recent coronary thrombosis. Ischaemic cell injury leads to potassium (K) efflux and sodium (Na) influx and, if the blood is still circulating, the K:Na ratio of the tissue falls. In this study, the K:Na ratio was measured by eluting the ions from samples of myocardium and assaying the eluate. The method yields similar results to those obtained by a previous method, in which myocardial samples were homogenized. The K:Na ratios on samples of horizontal slices through the heart were plotted on maps of the slices. A low K:Na ratio corresponded to, but extended beyond, areas where there was morphological evidence of ischaemia. The method is simple and may be of use in routine practice.     

Anti-tumor effects of antibody-alkaline phosphatase conjugates in combination with etoposide phosphate.

Two anti-tumor monoclonal antibodies, L6 (anticarcinoma) and 1F5 (anti-B lymphoma), were covalently linked to alkaline phosphatase (AP), forming conjugates that could bind to the surface of antigen-positive tumor cells. The conjugates were capable of converting a relatively noncytotoxic prodrug, etoposide phosphate (EP), into etoposide--a drug with significant antitumor activity. In vitro studies with a human colon carcinoma cell line, H3347, demonstrated that while EP was less toxic than etoposide by a factor of greater than 100, it was equally toxic when the cells were pretreated with L6-AP, a conjugate that bound to the surface of H3347 cells. The L6-AP conjugate localized in H3347 tumor xenografts in nude mice and histological evaluation indicated that the targeted enzyme (AP) was distributed throughout the tumor mass. A strong antitumor response was observed in H3347-bearing mice that were treated with L6-AP followed 18-24 hr later by EP. This response, which included the rejection of established tumors, was superior to that of EP (P less than 0.005) or etoposide (P less than 0.001) given alone. The IF5-AP conjugate did not bind to H3347 cells and did not enhance the toxicity of EP on these cells in vitro. In addition, IF5-AP did not localize to H3347 tumors in nude mice and did not demonstrate enhanced antitumor activity in combination with the prodrug.     

United states non-Hodgkin's lymphoma surveillance by occupation 1984-1989: A twenty-four state death certificate study

Death certificates from 23,890 male and female non-Hodgkin's lymphoma (NHL) cases and 119,450 noncancer controls from 24 states for the period 1984-1989 were used to generate hypotheses regarding occupational associations. Cases were frequency matched by age, race, and gender with five controls per case. Odds ratios were calculated for 231 industries and 509 occupations. Significant associations were observed for a variety of white-collar professionals (i.e., real estate agents, secretaries, bookkeepers, teachers, postal employees, business agents, engineers, chemists, and medical professionals) and blue-collar occupations (i.e., firefighters, farm managers, aircraft mechanics, electronic repairers, mining machine operators, and crane and tower operators). © 1995 Wiley-Liss, Inc.     

The effect of the fiber components cellulose and lignin on experimental colon neoplasia

Sixty Sprague-Dawley rats were pair-fed one of three nutritionally identical diets. One diet contained “low-fiber” (3.8% crude fiber); the others contained “high fiber” (28.7% crude fiber) composed of either cellulose or lignin. Although both “high fiber” diets had similar stool bulking effects, only the cellulose diet was associated with a reduction in 1,2-dimethylhydrazine (DMH)-induced colon neoplasms. The cellulose diet was also associated with distinct changes in the gut bacterial profile and with a lowered serum cholesterol. © 1993 Wiley-Liss, Inc.     

Capillary density and fine structure in rabbit papillary muscles after a high dose of norepinephrine

Two days after an iv infusion of norepinephrine (NE) (4 micrograms.kg-1.min-1 X 60 min) in rabbits, patchy myocardial damage in frozen cross sections of right and left papillary muscles was associated with loss of staining for alkaline phosphatase (ALP), an enzyme present in normal capillary endothelium, whereas a regular pattern of staining was observed in control normal muscles. Semithin cross sections of the same muscles after resin embedment gave comparable estimates of capillary density in control muscles and undamaged regions of norepinephrine-treated muscles. In damaged regions the complete absence of ALP staining corresponded with an apparent reduction in number, but not absence, of capillaries identifiable in semithin sections with light microscopy. Electron microscopy, however, revealed capillaries present in these regions in numbers similar to control undamaged tissue. Around 90% of these capillaries exhibited marked morphological abnormalities, with an 18% increase in endothelial cell volume density and a corresponding reduction in luminal volume density. These changes are similar to those reported after ischemia in cardiac and skeletal muscle. Myocardial damage induced by a high dose of NE is therefore associated 48 hr later with loss of ALP staining and endothelial cell disruption and edema, which may impair capillary perfusion and contribute to limited working cardiac performance observed previously.     

National Committee for Clinical Laboratory Standards agar dilution susceptibility testing of anaerobic gram-negative bacteria.

One hundred nine recent clinical isolates of anaerobic gram-negative bacteria were tested in triplicate by the National Committee for Clinical Laboratory Standards agar dilution procedure for their susceptibility to 32 antimicrobial agents. All isolates were inhibited by imipenem, but there were significant numbers of strains resistant to other beta-lactam drugs, and therefore the in vitro response to these antimicrobial agents cannot be predicted. This was particularly true for the bile-resistant or Bacteroides fragilis group. beta-Lactamase production was detected in 82% of the bacteroides with the nitrocefin test. Clavulanic acid combined with amoxicillin and ticarcillin and sulbactam combined with ampicillin resulted in synergistic activity against all beta-lactamase-positive organisms. Ceftizoxime was the most active of the cephalosporins. Two percent of the isolates were resistant to chloramphenicol and metronidazole. Clindamycin resistance was detected in 38% of the B. fragilis group, which is a marked increase from the 4% detected 10 years ago at this institution.     

1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 1. Synthesis and biological properties of alkyl alcohol and statine derivatives

A series of 1,2,4-triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity, which incorporate (1S,2S)-2-amino-1,3-dicyclohexyl-1-hydroxypropane, statine (Sta), and (3S,4S)-4-amino-5-cyclohexyl-3-hydroxy-pentanoic acid (ACHPA) transition-state mimetics, have been prepared. Structure-activity relationships for renin inhibitory activity in the series are consistent with the 2-[8-isobutyl-6-phenyl-1,2,4-triazolo[4,3-a]pyrazin-3-yl]-3-(3 pyridyl)propionic acid moiety 10b acting as a non-peptidic replacement for the P4-P2 (Pro-Phe-His) residues of the natural substrate angiotensinogen. Compounds 12m, 12o and 12q were potent inhibitors of partially purified human renin (IC50 values 1.7, 6.8, and 3.7 nM, respectively), and also effectively lowered blood pressure in anesthetized, sodium depleted marmosets following intravenous administration. On oral administration however, no blood pressure lowering activity could be detected, and absorption studies in bile duct cannulated rats indicate that this may be due primarily to poor oral absorption, rather than rapid biliary excretion. The reason for the observed poor oral activity is not clear, but it seems unlikely that poor aqueous solubility or metabolic instability to gut enzymes are rate-determining, and other factors such as high molecular weight may also be very important.     

Pulsed ultrasound Doppler velocimetry in the assessment of microvascular hemodynamics

Pulsed ultrasonic Doppler velocimetry (20 MHz) (PUDVM) has evolved considerably in the last 10 years. Engineering development has resulted in a computer-controlled vessel-scanning instrument whose backscattered frequency shift spectra are analyzed using fast Fourier transforms (FFT). Benchtop and theoretic studies indicate accurate (error less than 5%) velocity and volumetric flow rate measurements in vessels with a lumen diameter as small as 1.2 mm. Clinical application of the PUDVM has provided transcutaneous measurements of blood flow variables in normal human digital arteries. Experimental application to arteries 1.0-1.5 mm has provided information on the hemodynamic effects of topical vasodilators, standard microarteriorrhaphy, variations in microvascular technique, interpositional grafts, and early wound repair. With improving computer capabilities and technical modifications, the PUDVM will be an increasingly important tool in clinical and experimental microsurgery.