PubMed Health⌕ Search

Biomedical subjects

W Fang

Publications and source records attributed to W Fang.

At least 109 records · Page 6Linked to original sources
PubMed1994

Cloning and molecular characterization of mouse bcl-x in B and T lymphocytes.

We report the cloning and initial characterization of the mouse homologues of the bcl-2-related gene, bcl-x. We compare these to the two major isoforms of human bcl-x that were previously identified, bcl-xLong (bcl-xL) which has death repressor activity similar to bcl-2, and bcl-xShort (bcl-xS), an alternative mRNA splice product that deletes a highly conserved domain shared by bcl-2 family members and promotes cell death in transfection studies. In addition to murine (m) bcl-xL and mbcl-xS, we have cloned a novel cDNA isoform that we designate mbcl-x delta TM. This cDNA deletes, by means of alternative splicing, the carboxy terminal transmembrane domain of bcl-x and is predicted to be a soluble, rather than membrane-bound, protein. We found that mbcl-x mRNA is highly inducible in splenocytes stimulated with either anti-CD3 Abs or LPS/dextran sulfate, and that the major species of mbcl-x mRNA in a variety of cell lines and tissues was the xL isoform. Transfection of mbcl-xL or mbcl-xS into Hela cells resulted in targeting primarily to mitochondria, whereas mbcl-x delta TM localized diffusely throughout the cytosol. Overexpression of the novel delta TM isoform in an IL-3-dependent cell line delayed the onset of apoptosis induced by growth factor withdrawal. Thus, a naturally-occurring form of mbcl-x present in lymphocytes that does not localize to the mitochondrial membrane is functional in preventing apoptotic cell death. Moreover, these data suggest that bcl-x provides a life signal in activated lymphocytes.

Amino Acid Sequence↗
PubMed1994

Enhanced cancer growth in mice administered daily human-equivalent doses of some H1-antihistamines: predictive in vitro correlates.

BACKGROUND: Present studies of drug-induced tumor growth promotion have evolved from earlier investigations into the mechanism of action of N,N-diethyl-2-[4-(phenylmethyl)phenoxy[ethanamine.HCl, a tamoxifen derivative which potently inhibits lymphocyte mitogenesis in vitro and stimulates tumor growth in vivo. It is thought that potency to bind to intracellular histamine receptors (HIC), some of which are on cytochromes P450, may correlate with tumor growth-promoting activity. PURPOSE: We assessed the effectiveness of five in vitro assays in predicting in vivo tumor growth stimulation by the H1-antihistamines loratadine, astemizole, cetirizine, hydroxyzine, and doxylamine. METHODS: Potency of each agent was ranked 1-5 in each of the following in vitro assays: 1) inhibition of [3H]histamine binding to microsomal HIC, 2) inhibition of histamine binding to microsomal P450, 3) inhibition of the P450-catalyzed demethylation of aminopyrine, 4) inhibition of lymphocyte mitogenesis, and 5) stimulation of tumor colony formation. An overall rank score was assigned to each drug and correlated with tumor growth stimulation in vivo. Two laboratories conducted in vivo studies in a blinded fashion. Female C57BL and C3H mice were given a subcutaneous injection on day 1 of syngeneic B16F10 melanoma cells (5 x 10(5)) or C-3 fibrosarcoma cells (1 x 10(5)), respectively. Mice were randomly assigned to treatment groups, then received a single, daily intraperitoneal injection of an estimated human-equivalent dose (or range of doses) of antihistamine or vehicle control for 18-21 days before being killed. Tumors were surgically removed and wet weights compared statistically among groups. RESULTS: The cumulative potency of each drug in affecting tumor growth or growth mechanisms in the five in vitro assays ranked as follows: Loratidine and astemizole ranked highest and were equally potent, followed in decreasing order by hydroxyzine, doxylamine, and cetirizine. A significant correlation (r = .97; P < .02) was observed between the rank order of potency of the antihistamines in all five in vitro assays and the rank order to enhance tumor growth in vivo: Loratidine and astemizole significantly (P < .001) promoted the growth of both melanoma and fibrosarcoma, hydroxyzine significantly (P < .001) promoted the growth of melanoma, while doxylamine and cetirizine did not promote the growth of either tumor. CONCLUSION: Data demonstrate that the in vitro assays predicted the propensity of each H1-antihistamine to stimulate cancer growth in vivo. IMPLICATION: These in vitro tests may prove valuable to screen potential tumor growth promoters.

Animals↗
PubMed1994

Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome: report of a Chinese family with mitochondrial DNA point mutation in tRNA(Lys) gene.

We report myoclonic epilepsy with ragged-red fibers (MERRF) syndrome in a Chinese family with confirmed mitochondrial DNA point mutation. Six members of the family including the grandmother, two siblings, and three grandchildren were affected. Among them, action myoclonus was seen in five; short stature, muscle weakness, and mental retardation in four; lactic acidosis, hearing impairment, and ataxia in two; and seizures in one. Muscle biopsy from two affected siblings revealed ragged-red fibers and abundant subsarcolemmal mitochondria with paracrystalline inclusions. Pedigree analysis suggests a maternal transmission. Analysis of mitochondrial DNA showed a point mutation from A to G at the 8344th nucleotide position located in the tRNA(Lys) gene. To our knowledge, this is the first report of MERRF syndrome with such genetic defect from a Chinese family. The present and previous reports support the notion that mitochondrial DNA point mutation at the 8344th nucleotide position is the most common cause of MERRF syndrome.

Adult↗
PubMed1993

Ophthalmologic manifestations in MELAS syndrome.

We describe a 15-year-old boy with full-blown mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and chronic progressive external ophthalmoplegia (CPEO). He presented with visual disturbance, hearing impairment, continuous partial epilepsy on the right aspect of the face, and right hemiparesis since the age of 13. Four months later, he experienced another strokelike episode with continuous partial epilepsy on the left hand. Serial computed tomographic scans revealed bilateral parieto-occipital hypodense lesions with gyral enhancement and an additional low-density lesion in the right frontal area 4 months later, respectively. Results of laboratory examinations disclosed lactic acidosis and mitochondrial myopathy with many ragged-red fibers. To identify the defective gene in mitochondrial DNA, a simple molecular test was performed by using restriction endonuclease Apa I. A transition from A to G was found at nucleotide position 3243 of the tRNA(Leu) gene. Interestingly, the patient also had marked external ophthalmoplegia and ptosis commonly found in patients with CPEO. Therefore, we suggest that ophthalmoplegia also occurs in the MELAS syndrome.

Adolescent↗
PubMed1993

Growth of lactobacilli, Staphylococcus aureus and Escherichia coli in normal and mastitic milk and whey.

The growth of three lactobacilli (Lactobacillus acidophilus, L. bulgaricus and L. casei), Staphylococcus aureus and Escherichia coli was followed in normal and mastitic milk and whey using the standard plate count method. L. acidophilus, L. bulgaricus 6032 and L. casei 6028 grew well in normal milk, but had decreased growth in mastitic milk if not pre-adapted in mastitic whey. S. aureus 26003 and E. coli 44102 showed enhanced growth in mastitic milk as compared with their growth in normal milk. These mastitis pathogens grew faster than the lactobacilli in both the normal milk and the mastitic milk. Among the lactobacilli, L. acidophilus and L. bulgaricus grew faster than L. casei in both types of milk samples. All the bacteria tested grew well in the normal and mastitic whey samples. However, they seemed to have enhanced growth in mastitic whey with the exception of L. casei. Pre-adaptation of the bacteria in mastitic whey in subculture markedly improved the growth of both pathogenic and non-pathogenic bacteria in mastitic milk. All the bacteria showed decreased replication in mastitic milk as compared with mastitic whey.

Animals↗
PubMed1992

Pleiotrophin stimulates fibroblasts and endothelial and epithelial cells and is expressed in human cancer.

Previously we reported the purification of the heparin-binding growth factor pleiotrophin (PTN) from supernatants of the human breast cancer cell line MDA-MB-231. To investigate further the biological activities of PTN and its potential role in cancer, we cloned a PTN cDNA and expressed the gene in a human kidney and in a human adrenal carcinoma cell line (SW-13). The supernatants harvested from cells transfected with PTN contained a heparin-binding specific protein of an apparent molecular mass of 18 kDa. These supernatants stimulated the proliferation of endothelial cells as well as the anchorage-independent growth of SW-13 cells and of normal rat kidney fibroblasts. Furthermore, SW-13 cells transfected with PTN acquired autonomous growth in soft agar and were tumorigenic in athymic nude mice. In contrast to these results with PTN from human cells, PTN obtained from insect cells (Sf9) using recombinant baculovirus as a vector was biologically inactive. We detected high levels of PTN mRNA in 16 of 27 primary human breast cancer samples (62%) as well as in 8 of 8 carcinogen-induced rat mammary tumors. Furthermore, 9 of 34 human tumor cell lines of different origin showed detectable PTN mRNA. We conclude that PTN may function as a tumor growth and angiogenesis factor in addition to its role during embryonic development.

Adrenal Gland Neoplasms↗
PubMed1992

Stimulation of malignant growth in rodents by antidepressant drugs at clinically relevant doses.

Tricyclic antidepressants, such as amitriptyline (Elavil), and the nontricyclic agent, fluoxetine (Prozac), bind to growth-regulatory intracellular histamine receptors, associated with anti-estrogen binding sites in microsomes and nuclei. The prototype anti-estrogen binding site/intracellular histamine receptor ligand, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl, inhibits normal cell proliferation in vitro but stimulates tumor growth in vivo. Because of their structural similarity to N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl, we carried out studies to determine whether amitriptyline and fluoxetine stimulate tumor growth and/or development in rodents at concentrations relevant to the treatment of human depression (equivalent human dose range, approximately 100-150 mg/day for amitriptyline and approximately 20-80 mg/day for fluoxetine). All experiments were performed blinded. In studies of growth stimulation of transplantable syngeneic tumors, groups of mice were inoculated s.c. with C-3 fibrosarcoma cells or given i.v. or s.c. injections of B16f10 melanoma cells, followed 24 h later by daily i.p. injections of saline, amitriptyline, or fluoxetine. Tumor latency (fibrosarcoma), aggregate tumor weight (s.c. injected melanoma), or time to death from pulmonary metastasis (i.v. injected melanoma) was determined; drug-induced stimulation of DNA synthesis in C-3 fibrosarcoma cells in vitro was correlated with tumor growth acceleration in vivo. In a mammary carcinogenesis model, the effects of chronic saline, amitriptyline, or fluoxetine administration on the rate and frequency of development of mammary tumors in rats fed dimethylbenzanthracene (DMBA) were compared. Eight of 20 amitriptyline- or fluoxetine-treated mice developed fibrosarcoma tumors by day 5, as compared to none of 20 saline controls (P less than 0.002). Similarly, 20 of 21 DMBA-treated rats receiving the antidepressant drugs developed 33 mammary tumors by week 15 as compared to 5 tumors in 4 of 7 DMBA-treated rats receiving saline (P less than 0.001). For both models, tumor latency decreased 30-40% and, in the DMBA model, tumor frequency increased greater than 2-fold in the antidepressant-treated rats as compared to controls. Stimulation of fibrosarcoma growth in vivo correlated with a corresponding bell-shaped drug-induced increase in DNA synthesis in vitro. While the median time to death from pulmonary metastases did not differ among groups given i.v. injections of melanoma cells, a significant (P less than 0.01) stimulation of growth of s.c. injected melanoma was observed in mice receiving the antidepressants.(ABSTRACT TRUNCATED AT 400 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Plasma bactericidal activity of a new C-5 methyl fluoroquinolone after oral doses of 400 and 800 mg.

The plasma bactericidal activity of a new C-5 methyl fluoroquinolone, OPC-17116, was determined after once-daily oral ingestion of 400 mg and 800 mg in normal, healthy volunteers. OPC-17116 at a 400-mg dose produced plasma bactericidal titers greater than or equal to 1:16 at 12 hours against Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Haemophilus influenzae, and Moraxella catarrhalis. OPC-17116 bactericidal titers against Pseudomonas aeruginosa were 1:2 or 1:4 at 6 and 12 hours. The plasma bactericidal titers against Streptococcus pyogenes and Streptococcus pneumoniae were 1:4 or greater, but bactericidal titers against Staphylococcus aureus were 1:2 at 12 hours and less than 1:2 at 24 hours. The 800-mg dose of OPC-17116 produced bactericidal titers of at least 1:32 at 12 hours for the Enterobacteriaceae, Haemophilus, and Moraxella, and 1:4 for S. pyogenes and S. pneumoniae, but bactericidal titers against S. aureus were 1:2. These data would suggest that an 800-mg dose of OPC-17116 taken orally once daily would provide adequate concentrations to treat infections due to the pathogens examined in this study.

Administration, Oral↗
PubMed1992

In vitro activity of OPC-17116.

The in vitro activity of OPC-17116, a new C-5 methyl fluoroquinolone, was compared with the activities of other fluoroquinolones. OPC-17116 inhibited 50% of the members of the family Enterobacteriaceae tested and 90% of Haemophilus influenzae, Neisseria species, and Moraxella catarrhalis isolates at less than or equal to 0.25 microgram/ml. At less than or equal to 2 micrograms/ml, 90% of the Enterobacteriaceae were inhibited, which was comparable to or better than the activities of fleroxacin, ofloxacin, and lomefloxacin but less than the activity of ciprofloxacin. OPC-17116 inhibited 90% of the staphylococci tested at less than or equal to 0.25 micrograms/ml, but it did not inhibit methicillin-resistant, ciprofloxacin-resistant Staphylococcus aureus or Staphylococcus epidermidis. Group A, B, C, F, and G streptococci and Streptococcus pneumoniae were inhibited by less than or equal to 0.5 microgram/ml, being four-fold more active than ciprofloxacin and ofloxacin. Tosufloxacin was the most active agent tested against gram-positive cocci. OPC-17116 inhibited Bacteroides fragilis at 4 micrograms/ml. There was a minimal effect of inoculum size on MIC, and the MBCs were within 1 dilution of the MICs. The activity of OPC-17116 was decreased at pH 6 and in the presence of high Mg2+ concentrations, but it was unaffected by human serum. OPC-17116 showed a postantibiotic effect against Pseudomonas aeruginosa and Staphylococcus aureus similar to the postantibiotic effects reported for other fluoroquinolones. The frequency of spontaneous single-step resistance was low (less than 10(-9)), but repeated passage of organisms in the presence of OPC-17116 resulted in the selection of resistant isolates.

Anti-Infective Agents↗
PubMed1992

In vitro activity and susceptibility to hydrolysis of S-1006.

The in vitro activity of S-1006, the active component of a new orally absorbed cephalosporin, S-1108, inhibited 90% of Staphylococcus aureus isolates at less than or equal to 2 micrograms/ml, 90% of group A, B, C, F, and G streptococci and Streptococcus pneumoniae isolates at less than or equal to 0.12 microgram/ml, and all Haemophilus influenzae isolates at less than or equal to 0.06 microgram/ml. Although 50% of the members of the family Enterobacteriaceae were inhibited by less than or equal to 2 micrograms of S-1006 per ml, Enterobacter spp. and Citrobacter freundii resistant to ceftriaxone were resistant to S-1006. The MICs of S-1006 for approximately 20% of Providencia, Proteus vulgaris, and Serratia isolates were 4 micrograms/ml. S-1006 was hydrolyzed by the plasmid TEM-3, TEM-5, PSE-1, and PSE-4 beta-lactamases and by the chromosomal beta-lactamase of Enterobacter and Morganella spp. and P. vulgaris.

Bacteria↗
PubMed1992

In vitro activity and beta-lactamase stability of LJC 10,627.

The in vitro activity of LJC 10,627, a new carbapenem, was compared with those of imipenem, cefotaxime, ceftazidime, and gentamicin. LJC 10,627 inhibited 90% of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Hafnia alvei, Citrobacter freundii, Citrobacter diversus, Proteus mirabilis, Morganella morganii, Proteus rettgeri, Serratia marcescens, Pseudomonas cepacia, salmonellae, shigellae, aeromonas, and yersiniae at less than or equal to 2 micrograms/ml. Haemophilus influenzae was inhibited by 0.5 microgram/ml, and moraxellae were inhibited by 0.12 microgram/ml. LJC 10,627 was twofold more active than imipenem against aerobic gram-negative organisms and inhibited ceftazidime-, cefotaxime-, and gentamicin-resistant members of the genera Klebsiella, Enterobacter, Citrobacter, and Serratia at less than or equal to 2 micrograms/ml. Xanthomonas maltophilia strains were resistant to the drug. Imipenem was two- to fourfold more active than LJC 10,627 against Staphylococcus aureus and Staphylococcus epidermidis. LJC 10,627 did not inhibit most methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis strains. LJC 10,627 inhibited Streptococcus pyogenes and Streptococcus pneumoniae at 0.06 and 0.12 microgram/ml, respectively. Bacteroides fragilis and other Bacteroides spp. were inhibited by 0.5 microgram of LJC 10,627 per ml. Serum (50%) did not affect the MICs. LJC 10,627 was not hydrolyzed by plasmid-mediated beta-lactamases of Bush types 2b, 2b', TEM-1, TEM-2, TEM-3, TEM-5, TEM-7, TEM-9, and SHV-1; the chromosomal beta-lactamases of Bush type 1; P-99; a Morganella enzyme; or a Citrobacter freundii enzyme. The Bush type 2c and 2d enzymes OXA-1, OXA-2, PSE-1, PSE-2, and PSE-4 did not hydrolyze LJC 10,627, nor did the beta-lactamases of Staphylococcus aureus, Moraxella spp., Bacteroides fragilis, and Proteus vulgaris. The beta-lactamase of Xanthomonas hydrolyzed LJC 10,627, albeit at approximately one-third the rate that imipenem was hydrolyzed.

Carbapenems↗
PubMed1992

[Studies on the tissue schizonticide of malaria parasite: synthesis of 5-trieluoroacetyl-primaquine and its derivatives].

Primaquine was acylated with trifluoroacetic anhydride to give 6-methoxy-8-(4-trifluoroacetamido-1-methylbutyl) aminoquinoline (compound 2 in Table) and 5-trifluoro-acetyl-6-methoxy-8-(4-trifluoroacetamido-1-methylbutyl )- aminoquinoline (compound 6), bis (trifluoroacetyl) primaquine, which was subsequently hydrolyzed to yield 5-trifluoroacetyl-6-methoxy-8-(4-amino-1-methylbutyl)-aminoquinoline (compound 11), 5-trifluoroacetyprimaquine or trifluoroacetoprimaquine, coded M8506. Similarly, compounds 1, 3-5 and 7-10 were also prepared. Among them, compound 11 appeared to be the most effective by evaluation in mice infected with sporozoites of Plamodium yoelii. With intragastrical dosage of 0.75 mg/kg/d x 3 d of compound 11 to monkeys infected with sporozoites of P. cynomolgi, the radical cure rate of the compound was 92.3%, while that of primaquine was 55.6%. The acute toxicity of compound 11 was two times a low as that of primaquine in mice. The compound did not appear to have mutagenicity, embryotoxicity and chromosomal aberration. When rats received intragastrical doses of 15, 30 and 60 mg/kg/d of compound 11 for 14 and 28 consecutive days respectively, no change was found in histopathological examination at the two lower doses. However, reversible changes were observed at the highest dose. Compound 11, trifluoroacetoprimaquine, was shown to be a promising tissue schizonticide of malaria parasite.

Aminoquinolines↗
PubMed1991

In vitro activity of Ro 09-1428 compared to other cephalosporins.

The in vitro activity of Ro 09-1428, a new catechol-type parenteral cephalosporin, was compared to that of ceftazidime, E-1040, cefpirome and cefepime against gram-positive and gram-negative organisms. Ro 09-1428 inhibited group A streptococci at less than or equal to 0.12 micrograms/ml, and group B, C and G streptococci and Streptococcus pneumoniae at 0.5 micrograms/ml, whereas for Staphylococcus aureus Ro 09-1428 had MICs of 8-16 micrograms/ml similar to ceftazidime and E-1040. Against Pseudomonas aeruginosa Ro 09-1428 was the most active agent, inhibiting isolates at less than or equal to 0.12-2 micrograms/ml, and inhibited ceftazidime-resistant isolates. The majority of Escherichia coli, Klebsiella spp., Proteus mirabilis, Citrobacter diversus, Providencia, Salmonella and Shigella were inhibited by less than or equal to 0.5 micrograms/ml as with the other cephalosporins. For most Citrobacter freundii and Enterobacter cloacae Ro 09-1428 had higher MICs of 4-16 micrograms/ml; most ceftazidime-resistant isolates of these species were resistant. Anaerobes, enterococci and Listeria monocytogenes were resistant to Ro 09-1428. Ro 09-1428 was not hydrolyzed by TEM-1, TEM-2, Staphylococcus aureus PC-1, Moraxella catarrhalis Bro-1, Enterobacter P-99, Pseudomonas aeruginosa Sabath-Abraham or Klebsiella beta-lactamases, but was hydrolyzed by TEM-3, TEM-7 and TEM-9. Ro 09-1428 was markedly less active at an acid pH.

Cephalosporins↗
PubMed1991

In vitro activity and beta-lactamase stability of GR69153, a new long-acting cephalosporin.

GR69153, a new parenteral cephalosporin, inhibited 90% of Escherichia coli, Klebsiella oxytoca, Proteus mirabilis, Citrobacter diversus, shigellae, and salmonellae at less than 0.25 micrograms/ml (MIC90). It had activity comparable to those of ceftazidime, cefpirome, cefepime, and E-1040. Against cephalosporinase-producing Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens, MICs ranged from 0.12 to greater than 32 micrograms/ml, and cefpirome and cefepime were the most active agents against these species. Pseudomonas aeruginosa was highly susceptible to GR69153, and for this organism the MIC90 was less than or equal to 2 micrograms/ml, which was similar to the E-1040 MIC90, but most Pseudomonas cepacia and Xanthomonas maltophilia isolates were resistant. GR69153 inhibited Haemophilus influenzae and Moraxella branhamella at less than or equal to 0.5 micrograms/ml. For Staphylococcus aureus GR69153 MICs were similar to those of ceftazidime and E-1040. Enterococci and listeriae were resistant to GR69153, but Streptococcus pyogenes and Streptococcus pneumoniae were inhibited by 0.5 micrograms/ml. The activity of GR69153 was not affected by serum. GR69153 was not inactivated by the beta-lactamases of Staphylococcus aureus, TEM-1, TEM-2, SHV-1, and BRO-1, but it was hydrolyzed by TEM-3, TEM-9, and morganellae. GR69153 had overall activity comparable to those of commercially available parenteral cephalosporins or those found in clinical investigations. It is more active against bacteroides than most available aminothiazolyl parenteral cephalosporins are. GR69153 is hydrolyzed by the new plasmid beta-lactamases, and thus, its primary value may be related to its pharmacological properties.

Cephalosporins↗
PubMed1991

Indoor air pollution in four cities in China.

The study reports the investigation of indoor air pollution carried out in four cities in China (Chengde, Shanghai, Shenyang and Wuhan). The concentrations of RP, SO2, CO and NO2 were measured in kitchens and bedrooms, both in summer and in winter. The results showed that indoor air pollution, as measured by RP, SO2, CO, was heavy when coal was used as domestic fuel. This was particularly severe in winter. For example, the concentrations of SO2 in homes with coal stoves were more than 10 times higher than those in homes with gas or LPG in Shanghai. The concentrations of pollutants in kitchens were higher than those in bedrooms. The source of pollutants was fuel combustion from kitchen. The highest concentrations in kitchen could reach 665 micrograms/m3 (RP), 860 micrograms/m3 (SO2) and 14.07 mg/m3 (CO). The concentrations in bedrooms were up to 270 micrograms/m3, 502 micrograms/m3, and 13.67mg/m3, respectively.

Air Pollution, Indoor↗
PubMed1984

Adverse reactions to protamine sulfate following cardiac surgery.

We report four patients who developed severe adverse reactions to protamine sulfate following cardiac surgery. Two types of reactions were seen. First, an immediate anaphylaxis which is a complement-dependent IgG antibody-mediated reaction. In the literature, 80% of patients who had similar reactions have had previous exposure to protamine. All patients adequately tested had positive skin tests and there is 6% mortality. The second reaction to protamine during cardiac surgery is characterized by delayed onset and profound vascular damage presenting as noncardiogenic pulmonary edema or total vascular collapse with prolonged hypotension and anasarca. These patients have negative skin tests and in our studies, no evidence of antibody mediated reaction, suggesting some other mechanisms may play a part. The mortality is high (30% of patients reported) and survivors have significant morbidity.

Aged↗