Proceedings of The National Academy of Sciences, 1997
Fluoxetine (Prozac), a widely used antidepressant, is said to exert its medicinal effects almost ... more Fluoxetine (Prozac), a widely used antidepressant, is said to exert its medicinal effects almost exclusively by blocking the serotonin uptake systems. The present study shows that both muscle and neuronal nicotinic acetylcholine receptors are blocked, in a noncompetitive and voltage-dependent way, by fluoxetine, which also increases the rate of desensitization of the nicotinic receptors. Because these receptors are very widely distributed in the both central and peripheral nervous systems, the blocking action of fluoxetine on nicotinic receptors may play an important role in its antidepressant and other therapeutical effects. Our findings will help to understand the mode of action of fluoxetine, and they may also help to develop more specific medicinal drugs.
Three patients are reported on who suffered anaphylactic reactions after amoxycillin (AX) treatme... more Three patients are reported on who suffered anaphylactic reactions after amoxycillin (AX) treatment and challenge but tolerated benzylpenicillin (BP) parenterally and orally. Two of the three patients had positive skin tests and RAST to AX reagents but negative responses to benzyl penicilloyl (BPO) specific skin tests and RAST and the minor determinant mixture (MDM) skin test reagent. The third case was negative to all skin tests and RAST. RAST and RAST inhibition on the two positive sera suggest that the response is related to the acyl side chain of AX.
Nineteen well-characterized penicillin-allergic patients were investigated for their seasitivity ... more Nineteen well-characterized penicillin-allergic patients were investigated for their seasitivity to cephalosporins containing potentially cross-reactive side chains. All patients were administered cephamandole parenterally and, if this was tolerated, a course of oral cephaloridine was administered. Only two patients responded to the cephamandole; none of the remaining patients reacted to cephaloridine. Benzylpenicilloyl RAST-inhibition studies with sera from three subjects who had not reacted to the cephalosporins demonstrated that cephamandole linked to proteins was capable of recognizing benzylpenicilloyl-specific IgE antibody. it is concluded that consideration of side chain structures can help to predict possible cross-reactions between penicillins and cephalosporins, but carefully controlled challenge tests are advisable before penicillin-allergic patients are treated with cephalosporins. In relation to cross-reacting potential, in vitro experimental studies are d#icult to interpret and may in some circumstances overestimate the risk. (J ALLERGY CLIN IMMUNOL 1989;83:381-5.) From the
In patients treated with penicillins, adverse cutaneous reactions can occur within minutes or may... more In patients treated with penicillins, adverse cutaneous reactions can occur within minutes or may take several days to develop. IgE antibody-mediated reactions are well documented, but other mechanisms may also be involved. In particular, nonimmediate reactions have not been studied extensively, and the purpose of the present work was to establish the incidence of such reactions among a large group of patients and to study the penicillins involved. A total of 380 subjects with a history of a cutaneous reaction following administration of a penicillin antibiotic was included in the study. Skin tests and specific IgE measurements (RAST) were carried out using various penicillins and penicillin-related reagents, and patients were also challenged with various penicillins. In some patients with delayed skin test responses, skin biopsies were carried out. The tests confirmed that 74 subjects (19.4% of total investigated) had suffered a cutaneous reaction to a penicillin derivative, and 29 of these subjects (7.6%, of total or 39% of confirmed) showed evidence of having suffered a nonimmediate reaction. The latter group were identified by giving a positive delayed direct challenge, and in 65% of the cases a delayed skin test response was detected. In most cases, these responses were to amino penicillins. Skin biopsies showed a lymphomonocytic cell infiltrate. Nonimmediate reactions to penicillins are a reproducible phenomenon, suggesting that a specific mechanism is responsible. By direct challenge, 93 Q of responders were positive to amino penicillins (10.3% ampicillin, 82.7% amoxicillin), indicating a major role for these penicillins in nonimmediate reactions. The high percentage (65%) of subjects in this group who showed delayed skin test responses, taken together with the biopsy results, suggests that a lymphocyte-mediated reaction occurred. However, the possibility that other mechanisms may also have been involved cannot be ruled out
Two hundred and eighty-eight subjects with a history of allergy to penicillin were studied for ob... more Two hundred and eighty-eight subjects with a history of allergy to penicillin were studied for objective proof of their allergy. On the basis of skin tests, specific IgE antibody measurements and direct challenge tests, 64 patients (22%) were shown objectively to be allergic to one or more penicillins. The following tests were carried out: skin tests to benzyl-penicilloyl poly-L-lysine (BPO-PLL), minor determinant mixture (MDM), amoxycillin (AX) and ampicillin (AMP), in-vitro IgE antibody measurement to benzyl-penicilloyl (BPO) and AX and challenge with benzylpenicillin (BP), phenoxymethyl-penicillin (PV) and amoxycillin. Forty-four cases were found to respond to benzyl or phenoxymethyl-penicillin, however, 20 were shown to be sensitive to amoxycillin and unresponsive to tests with other penicillins. The contribution that any individual test gave for establishing the diagnosis was 21·8% for skin testing with BPO-PLL, 9·3% with MDM and 12·5% with AX, Nine point three per cent were RAST positive to BPO and 1·5% to AX; 7·8% developed a positive response after challenge to BP, 7·8% to PV and 14% to AX. In 16% of the 64 positive cases more than one test was found to be positive. The challenge tests suggested that not all the penicillin-sensitive subjects had IgE-mediated reactions implying other immunological mechanisms. These results clearly demonstrate the importance of side chain-specific diagnostic reagents and challenge tests. Thirty-one per cent of the positive group or 6·9% of the total group would have been missed in this study using benzyl or phenoxymethyl-penicillin diagnostic reagents alone.
Three patients are reported on who suffered anaphylactic reactions after amoxycillin (AX) treatme... more Three patients are reported on who suffered anaphylactic reactions after amoxycillin (AX) treatment and challenge but tolerated benzylpenicillin (BP) parenterally and orally. Two of the three patients had positive skin tests and RAST to AX reagents but negative responses to benzyl penicilloyl (BPO) specific skin tests and RAST and the minor determinant mixture (MDM) skin test reagent. The third case was negative to all skin tests and RAST. RAST and RAST inhibition on the two positive sera suggest that the response is related to the acyl side chain of AX.
Nineteen well-characterized penicillin-allergic patients were investigated for their seasitivity ... more Nineteen well-characterized penicillin-allergic patients were investigated for their seasitivity to cephalosporins containing potentially cross-reactive side chains. All patients were administered cephamandole parenterally and, if this was tolerated, a course of oral cephaloridine was administered. Only two patients responded to the cephamandole; none of the remaining patients reacted to cephaloridine. Benzylpenicilloyl RAST-inhibition studies with sera from three subjects who had not reacted to the cephalosporins demonstrated that cephamandole linked to proteins was capable of recognizing benzylpenicilloyl-specific IgE antibody. it is concluded that consideration of side chain structures can help to predict possible cross-reactions between penicillins and cephalosporins, but carefully controlled challenge tests are advisable before penicillin-allergic patients are treated with cephalosporins. In relation to cross-reacting potential, in vitro experimental studies are d#icult to interpret and may in some circumstances overestimate the risk. (J ALLERGY CLIN IMMUNOL 1989;83:381-5.) From the
In patients treated with penicillins, adverse cutaneous reactions can occur within minutes or may... more In patients treated with penicillins, adverse cutaneous reactions can occur within minutes or may take several days to develop. IgE antibody-mediated reactions are well documented, but other mechanisms may also be involved. In particular, nonimmediate reactions have not been studied extensively, and the purpose of the present work was to establish the incidence of such reactions among a large group of patients and to study the penicillins involved. A total of 380 subjects with a history of a cutaneous reaction following administration of a penicillin antibiotic was included in the study. Skin tests and specific IgE measurements (RAST) were carried out using various penicillins and penicillin-related reagents, and patients were also challenged with various penicillins. In some patients with delayed skin test responses, skin biopsies were carried out. The tests confirmed that 74 subjects (19.4% of total investigated) had suffered a cutaneous reaction to a penicillin derivative, and 29 of these subjects (7.6%, of total or 39% of confirmed) showed evidence of having suffered a nonimmediate reaction. The latter group were identified by giving a positive delayed direct challenge, and in 65% of the cases a delayed skin test response was detected. In most cases, these responses were to amino penicillins. Skin biopsies showed a lymphomonocytic cell infiltrate. Nonimmediate reactions to penicillins are a reproducible phenomenon, suggesting that a specific mechanism is responsible. By direct challenge, 93 Q of responders were positive to amino penicillins (10.3% ampicillin, 82.7% amoxicillin), indicating a major role for these penicillins in nonimmediate reactions. The high percentage (65%) of subjects in this group who showed delayed skin test responses, taken together with the biopsy results, suggests that a lymphocyte-mediated reaction occurred. However, the possibility that other mechanisms may also have been involved cannot be ruled out
Two hundred and eighty-eight subjects with a history of allergy to penicillin were studied for ob... more Two hundred and eighty-eight subjects with a history of allergy to penicillin were studied for objective proof of their allergy. On the basis of skin tests, specific IgE antibody measurements and direct challenge tests, 64 patients (22%) were shown objectively to be allergic to one or more penicillins. The following tests were carried out: skin tests to benzyl-penicilloyl poly-L-lysine (BPO-PLL), minor determinant mixture (MDM), amoxycillin (AX) and ampicillin (AMP), in-vitro IgE antibody measurement to benzyl-penicilloyl (BPO) and AX and challenge with benzylpenicillin (BP), phenoxymethyl-penicillin (PV) and amoxycillin. Forty-four cases were found to respond to benzyl or phenoxymethyl-penicillin, however, 20 were shown to be sensitive to amoxycillin and unresponsive to tests with other penicillins. The contribution that any individual test gave for establishing the diagnosis was 21·8% for skin testing with BPO-PLL, 9·3% with MDM and 12·5% with AX, Nine point three per cent were RAST positive to BPO and 1·5% to AX; 7·8% developed a positive response after challenge to BP, 7·8% to PV and 14% to AX. In 16% of the 64 positive cases more than one test was found to be positive. The challenge tests suggested that not all the penicillin-sensitive subjects had IgE-mediated reactions implying other immunological mechanisms. These results clearly demonstrate the importance of side chain-specific diagnostic reagents and challenge tests. Thirty-one per cent of the positive group or 6·9% of the total group would have been missed in this study using benzyl or phenoxymethyl-penicillin diagnostic reagents alone.
Proceedings of The National Academy of Sciences, 1997
Fluoxetine (Prozac), a widely used antidepressant, is said to exert its medicinal effects almost ... more Fluoxetine (Prozac), a widely used antidepressant, is said to exert its medicinal effects almost exclusively by blocking the serotonin uptake systems. The present study shows that both muscle and neuronal nicotinic acetylcholine receptors are blocked, in a noncompetitive and voltage-dependent way, by fluoxetine, which also increases the rate of desensitization of the nicotinic receptors. Because these receptors are very widely distributed in the both central and peripheral nervous systems, the blocking action of fluoxetine on nicotinic receptors may play an important role in its antidepressant and other therapeutical effects. Our findings will help to understand the mode of action of fluoxetine, and they may also help to develop more specific medicinal drugs.
Three patients are reported on who suffered anaphylactic reactions after amoxycillin (AX) treatme... more Three patients are reported on who suffered anaphylactic reactions after amoxycillin (AX) treatment and challenge but tolerated benzylpenicillin (BP) parenterally and orally. Two of the three patients had positive skin tests and RAST to AX reagents but negative responses to benzyl penicilloyl (BPO) specific skin tests and RAST and the minor determinant mixture (MDM) skin test reagent. The third case was negative to all skin tests and RAST. RAST and RAST inhibition on the two positive sera suggest that the response is related to the acyl side chain of AX.
Nineteen well-characterized penicillin-allergic patients were investigated for their seasitivity ... more Nineteen well-characterized penicillin-allergic patients were investigated for their seasitivity to cephalosporins containing potentially cross-reactive side chains. All patients were administered cephamandole parenterally and, if this was tolerated, a course of oral cephaloridine was administered. Only two patients responded to the cephamandole; none of the remaining patients reacted to cephaloridine. Benzylpenicilloyl RAST-inhibition studies with sera from three subjects who had not reacted to the cephalosporins demonstrated that cephamandole linked to proteins was capable of recognizing benzylpenicilloyl-specific IgE antibody. it is concluded that consideration of side chain structures can help to predict possible cross-reactions between penicillins and cephalosporins, but carefully controlled challenge tests are advisable before penicillin-allergic patients are treated with cephalosporins. In relation to cross-reacting potential, in vitro experimental studies are d#icult to interpret and may in some circumstances overestimate the risk. (J ALLERGY CLIN IMMUNOL 1989;83:381-5.) From the
In patients treated with penicillins, adverse cutaneous reactions can occur within minutes or may... more In patients treated with penicillins, adverse cutaneous reactions can occur within minutes or may take several days to develop. IgE antibody-mediated reactions are well documented, but other mechanisms may also be involved. In particular, nonimmediate reactions have not been studied extensively, and the purpose of the present work was to establish the incidence of such reactions among a large group of patients and to study the penicillins involved. A total of 380 subjects with a history of a cutaneous reaction following administration of a penicillin antibiotic was included in the study. Skin tests and specific IgE measurements (RAST) were carried out using various penicillins and penicillin-related reagents, and patients were also challenged with various penicillins. In some patients with delayed skin test responses, skin biopsies were carried out. The tests confirmed that 74 subjects (19.4% of total investigated) had suffered a cutaneous reaction to a penicillin derivative, and 29 of these subjects (7.6%, of total or 39% of confirmed) showed evidence of having suffered a nonimmediate reaction. The latter group were identified by giving a positive delayed direct challenge, and in 65% of the cases a delayed skin test response was detected. In most cases, these responses were to amino penicillins. Skin biopsies showed a lymphomonocytic cell infiltrate. Nonimmediate reactions to penicillins are a reproducible phenomenon, suggesting that a specific mechanism is responsible. By direct challenge, 93 Q of responders were positive to amino penicillins (10.3% ampicillin, 82.7% amoxicillin), indicating a major role for these penicillins in nonimmediate reactions. The high percentage (65%) of subjects in this group who showed delayed skin test responses, taken together with the biopsy results, suggests that a lymphocyte-mediated reaction occurred. However, the possibility that other mechanisms may also have been involved cannot be ruled out
Two hundred and eighty-eight subjects with a history of allergy to penicillin were studied for ob... more Two hundred and eighty-eight subjects with a history of allergy to penicillin were studied for objective proof of their allergy. On the basis of skin tests, specific IgE antibody measurements and direct challenge tests, 64 patients (22%) were shown objectively to be allergic to one or more penicillins. The following tests were carried out: skin tests to benzyl-penicilloyl poly-L-lysine (BPO-PLL), minor determinant mixture (MDM), amoxycillin (AX) and ampicillin (AMP), in-vitro IgE antibody measurement to benzyl-penicilloyl (BPO) and AX and challenge with benzylpenicillin (BP), phenoxymethyl-penicillin (PV) and amoxycillin. Forty-four cases were found to respond to benzyl or phenoxymethyl-penicillin, however, 20 were shown to be sensitive to amoxycillin and unresponsive to tests with other penicillins. The contribution that any individual test gave for establishing the diagnosis was 21·8% for skin testing with BPO-PLL, 9·3% with MDM and 12·5% with AX, Nine point three per cent were RAST positive to BPO and 1·5% to AX; 7·8% developed a positive response after challenge to BP, 7·8% to PV and 14% to AX. In 16% of the 64 positive cases more than one test was found to be positive. The challenge tests suggested that not all the penicillin-sensitive subjects had IgE-mediated reactions implying other immunological mechanisms. These results clearly demonstrate the importance of side chain-specific diagnostic reagents and challenge tests. Thirty-one per cent of the positive group or 6·9% of the total group would have been missed in this study using benzyl or phenoxymethyl-penicillin diagnostic reagents alone.
Three patients are reported on who suffered anaphylactic reactions after amoxycillin (AX) treatme... more Three patients are reported on who suffered anaphylactic reactions after amoxycillin (AX) treatment and challenge but tolerated benzylpenicillin (BP) parenterally and orally. Two of the three patients had positive skin tests and RAST to AX reagents but negative responses to benzyl penicilloyl (BPO) specific skin tests and RAST and the minor determinant mixture (MDM) skin test reagent. The third case was negative to all skin tests and RAST. RAST and RAST inhibition on the two positive sera suggest that the response is related to the acyl side chain of AX.
Nineteen well-characterized penicillin-allergic patients were investigated for their seasitivity ... more Nineteen well-characterized penicillin-allergic patients were investigated for their seasitivity to cephalosporins containing potentially cross-reactive side chains. All patients were administered cephamandole parenterally and, if this was tolerated, a course of oral cephaloridine was administered. Only two patients responded to the cephamandole; none of the remaining patients reacted to cephaloridine. Benzylpenicilloyl RAST-inhibition studies with sera from three subjects who had not reacted to the cephalosporins demonstrated that cephamandole linked to proteins was capable of recognizing benzylpenicilloyl-specific IgE antibody. it is concluded that consideration of side chain structures can help to predict possible cross-reactions between penicillins and cephalosporins, but carefully controlled challenge tests are advisable before penicillin-allergic patients are treated with cephalosporins. In relation to cross-reacting potential, in vitro experimental studies are d#icult to interpret and may in some circumstances overestimate the risk. (J ALLERGY CLIN IMMUNOL 1989;83:381-5.) From the
In patients treated with penicillins, adverse cutaneous reactions can occur within minutes or may... more In patients treated with penicillins, adverse cutaneous reactions can occur within minutes or may take several days to develop. IgE antibody-mediated reactions are well documented, but other mechanisms may also be involved. In particular, nonimmediate reactions have not been studied extensively, and the purpose of the present work was to establish the incidence of such reactions among a large group of patients and to study the penicillins involved. A total of 380 subjects with a history of a cutaneous reaction following administration of a penicillin antibiotic was included in the study. Skin tests and specific IgE measurements (RAST) were carried out using various penicillins and penicillin-related reagents, and patients were also challenged with various penicillins. In some patients with delayed skin test responses, skin biopsies were carried out. The tests confirmed that 74 subjects (19.4% of total investigated) had suffered a cutaneous reaction to a penicillin derivative, and 29 of these subjects (7.6%, of total or 39% of confirmed) showed evidence of having suffered a nonimmediate reaction. The latter group were identified by giving a positive delayed direct challenge, and in 65% of the cases a delayed skin test response was detected. In most cases, these responses were to amino penicillins. Skin biopsies showed a lymphomonocytic cell infiltrate. Nonimmediate reactions to penicillins are a reproducible phenomenon, suggesting that a specific mechanism is responsible. By direct challenge, 93 Q of responders were positive to amino penicillins (10.3% ampicillin, 82.7% amoxicillin), indicating a major role for these penicillins in nonimmediate reactions. The high percentage (65%) of subjects in this group who showed delayed skin test responses, taken together with the biopsy results, suggests that a lymphocyte-mediated reaction occurred. However, the possibility that other mechanisms may also have been involved cannot be ruled out
Two hundred and eighty-eight subjects with a history of allergy to penicillin were studied for ob... more Two hundred and eighty-eight subjects with a history of allergy to penicillin were studied for objective proof of their allergy. On the basis of skin tests, specific IgE antibody measurements and direct challenge tests, 64 patients (22%) were shown objectively to be allergic to one or more penicillins. The following tests were carried out: skin tests to benzyl-penicilloyl poly-L-lysine (BPO-PLL), minor determinant mixture (MDM), amoxycillin (AX) and ampicillin (AMP), in-vitro IgE antibody measurement to benzyl-penicilloyl (BPO) and AX and challenge with benzylpenicillin (BP), phenoxymethyl-penicillin (PV) and amoxycillin. Forty-four cases were found to respond to benzyl or phenoxymethyl-penicillin, however, 20 were shown to be sensitive to amoxycillin and unresponsive to tests with other penicillins. The contribution that any individual test gave for establishing the diagnosis was 21·8% for skin testing with BPO-PLL, 9·3% with MDM and 12·5% with AX, Nine point three per cent were RAST positive to BPO and 1·5% to AX; 7·8% developed a positive response after challenge to BP, 7·8% to PV and 14% to AX. In 16% of the 64 positive cases more than one test was found to be positive. The challenge tests suggested that not all the penicillin-sensitive subjects had IgE-mediated reactions implying other immunological mechanisms. These results clearly demonstrate the importance of side chain-specific diagnostic reagents and challenge tests. Thirty-one per cent of the positive group or 6·9% of the total group would have been missed in this study using benzyl or phenoxymethyl-penicillin diagnostic reagents alone.
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