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Menstrual variations influence theophylline clearance
THE LANCET
SCIENCE AND MEDICINE
etabolic changes associated with the menstrual cycle may affect theophylline clearance, say Japanese researchers (J Allergy Clin Immunol 1997; 100: 39–43). After observing that an asthmatic patient whose theophylline values fell almost out of the therapeutic range just before menstruation was prone to premenstrual asthma attacks, the authors studied the influence of the menstrual cycle on serum theophylline values in seven nonasthmatic women. They report that theophylline clearance was significantly higher during the menstrual phase than during the follicular phase. The researchers conclude that, when prescribing theophylline for asthmatic women, “ . . . it is important that one consider the menstrual cycle”. And, if a woman complains of worsening asthma symptoms before her menstrual period, her serum theophylline values should be checked. The study is valid as far as it goes, says Marianne Frieri, associate professor of medicine and pathology at the State University of New York (Stony Brook, NY, USA), but more women should probably be studied for greater statistical significance. Frieri also notes that the authors did not rigorously control for factors such as smoking, consumption of barbecued meat, or a high-protein, low-carbohydrate diet, all of which can affect theophylline clearance. Nevertheless, she says, this article is significant in that it makes allergists aware that they should consider menstrual variations when prescribing theophylline.
M
Norra Macready
Little to celebrate on the malaria centenary today than even a decade ago”, century after Ronald Ross found acknowledged John Horton, head of malaria parasites in mosquitos, SmithKline Beecham’s Tropical “The mosquito remains the big Therapeutics division. Dwindling hero”, declared V P Sharma, chairprofits and investment recovery are man of the Ronald Ross Centenary key factors behind the decline. Malaria Meeting (2nd Global Meet Military interest and funding remains on Parasitic Diseases, Hyderabad, an important driving India; Aug 18–22). force behind drug After intensive eradidevelopment. Wilbur cation efforts in the Milhouse, Experimental 1950s, complacency set Therapeutics director at in and the mosquitos the Walter Reed Army have fought back Institute of Research, ingeniously. Malaria (Washington, DC, now kills some 3 milUSA) said that the need lion people and causes for new compounds is 500 million acute cases critical from the US annually, 90% of which national security vieware in Africa. point—with the number Experts at the of US peacekeeping meeting lamented that Ronald Ross: 100 years on missions in malarial simple, low-cost preregions escalating and deaths occurventive strategies—eg, improved saniring among soldiers, despite available tation—have received scant attention. chemoprophylaxis. New drugs remain “This is a seriously neglected aspect too expensive for poor countries. of Ross’s legacy”, said David Bradley, Serious lack of a work ethic, ramdirector of the Ross Institute, pant corruption, and mismanagement London, UK. Almost one-third of remain the real forces derailing the Indian malaria is “man-made”, added best of malaria-control efforts in Sharma, who advocates bioenvirondeveloping countries across the board mental mosquito-control methods in Asia, Africa, and Latin America—a and impregnated bednets. fact acknowledged by key officials and Sharma said that he remained scepscientists, but not much discussed at tical about stable control of malaria conferences. “Malaria exists not situations which he believed would merely because of vector or drug require a vaccine. Despite important resistance but because the publicadvances, experts at the meeting sughealth system is resistant to gested that it will be at least 10 years real malaria-control issues”, said before any affordable and long-acting Ravi Narain, coordinator at the vaccine against both Plasmodium Community Health Cell, Bangalore, falciparum and P vivax is available. India. If these core issues are evaded, Drug resistance is widespread, but even with the best of scientific breakinterest in new antimalarial drugs has throughs, malaria will still dog us a seriously declined. “Investment in 100 years hence, he said. antimalarials has been falling steadily, and the number of pharmaceutical companies involved is much lower Sanjay Kumar
A
The Wellcome Institute Library
Menstrual variations influence theophylline clearance
Molecular messengers mapped in living cells
T
he chain of phosphorylations that occur inside cells when a hormone binds to its receptor can now be visualised in real time, report scientists at the Weizmann Institute, Rehovot, Israel (Science 1997; 277: 1103–06). This should “prove invaluable in deciphering . . . how the signalling process goes awry in diseases, such as cancer, and during precise moments of abnormal development”, says team leader Ben-Zion Shilo.
644
When certain hormones bind to their cell-surface receptors, a chain of phosphorylation reactions is triggered in the cell which culminates in a change in gene expression. By using monoclonal antibodies that react specifically with the phosphorylated (active) form of one of the enzymes in this signalling pathway, the Israeli team mapped signal transmission in fruit flies. Shilo notes that the same enzyme pathways are conserved in human beings so it should be
possible to use the technique to study signalling pathways in man. In many types of cancer, it is “deregulated phosphorylation that causes uncontrolled cell growth”, explains Shilo, so “tracking the phosphorylation pattern in disease states could prove a useful diagnostic tool. If you can see where pathologies develop, you can start to find specific means to stop or prevent them”. Rachelle H B Fishman
Vol 350 • August 30, 1997
SCIENCE AND MEDICINE
etabolic changes associated with the menstrual cycle may affect theophylline clearance, say Japanese researchers (J Allergy Clin Immunol 1997; 100: 39–43). After observing that an asthmatic patient whose theophylline values fell almost out of the therapeutic range just before menstruation was prone to premenstrual asthma attacks, the authors studied the influence of the menstrual cycle on serum theophylline values in seven nonasthmatic women. They report that theophylline clearance was significantly higher during the menstrual phase than during the follicular phase. The researchers conclude that, when prescribing theophylline for asthmatic women, “ . . . it is important that one consider the menstrual cycle”. And, if a woman complains of worsening asthma symptoms before her menstrual period, her serum theophylline values should be checked. The study is valid as far as it goes, says Marianne Frieri, associate professor of medicine and pathology at the State University of New York (Stony Brook, NY, USA), but more women should probably be studied for greater statistical significance. Frieri also notes that the authors did not rigorously control for factors such as smoking, consumption of barbecued meat, or a high-protein, low-carbohydrate diet, all of which can affect theophylline clearance. Nevertheless, she says, this article is significant in that it makes allergists aware that they should consider menstrual variations when prescribing theophylline.
M
Norra Macready
Little to celebrate on the malaria centenary today than even a decade ago”, century after Ronald Ross found acknowledged John Horton, head of malaria parasites in mosquitos, SmithKline Beecham’s Tropical “The mosquito remains the big Therapeutics division. Dwindling hero”, declared V P Sharma, chairprofits and investment recovery are man of the Ronald Ross Centenary key factors behind the decline. Malaria Meeting (2nd Global Meet Military interest and funding remains on Parasitic Diseases, Hyderabad, an important driving India; Aug 18–22). force behind drug After intensive eradidevelopment. Wilbur cation efforts in the Milhouse, Experimental 1950s, complacency set Therapeutics director at in and the mosquitos the Walter Reed Army have fought back Institute of Research, ingeniously. Malaria (Washington, DC, now kills some 3 milUSA) said that the need lion people and causes for new compounds is 500 million acute cases critical from the US annually, 90% of which national security vieware in Africa. point—with the number Experts at the of US peacekeeping meeting lamented that Ronald Ross: 100 years on missions in malarial simple, low-cost preregions escalating and deaths occurventive strategies—eg, improved saniring among soldiers, despite available tation—have received scant attention. chemoprophylaxis. New drugs remain “This is a seriously neglected aspect too expensive for poor countries. of Ross’s legacy”, said David Bradley, Serious lack of a work ethic, ramdirector of the Ross Institute, pant corruption, and mismanagement London, UK. Almost one-third of remain the real forces derailing the Indian malaria is “man-made”, added best of malaria-control efforts in Sharma, who advocates bioenvirondeveloping countries across the board mental mosquito-control methods in Asia, Africa, and Latin America—a and impregnated bednets. fact acknowledged by key officials and Sharma said that he remained scepscientists, but not much discussed at tical about stable control of malaria conferences. “Malaria exists not situations which he believed would merely because of vector or drug require a vaccine. Despite important resistance but because the publicadvances, experts at the meeting sughealth system is resistant to gested that it will be at least 10 years real malaria-control issues”, said before any affordable and long-acting Ravi Narain, coordinator at the vaccine against both Plasmodium Community Health Cell, Bangalore, falciparum and P vivax is available. India. If these core issues are evaded, Drug resistance is widespread, but even with the best of scientific breakinterest in new antimalarial drugs has throughs, malaria will still dog us a seriously declined. “Investment in 100 years hence, he said. antimalarials has been falling steadily, and the number of pharmaceutical companies involved is much lower Sanjay Kumar
A
The Wellcome Institute Library
Menstrual variations influence theophylline clearance
Molecular messengers mapped in living cells
T
he chain of phosphorylations that occur inside cells when a hormone binds to its receptor can now be visualised in real time, report scientists at the Weizmann Institute, Rehovot, Israel (Science 1997; 277: 1103–06). This should “prove invaluable in deciphering . . . how the signalling process goes awry in diseases, such as cancer, and during precise moments of abnormal development”, says team leader Ben-Zion Shilo.
644
When certain hormones bind to their cell-surface receptors, a chain of phosphorylation reactions is triggered in the cell which culminates in a change in gene expression. By using monoclonal antibodies that react specifically with the phosphorylated (active) form of one of the enzymes in this signalling pathway, the Israeli team mapped signal transmission in fruit flies. Shilo notes that the same enzyme pathways are conserved in human beings so it should be
possible to use the technique to study signalling pathways in man. In many types of cancer, it is “deregulated phosphorylation that causes uncontrolled cell growth”, explains Shilo, so “tracking the phosphorylation pattern in disease states could prove a useful diagnostic tool. If you can see where pathologies develop, you can start to find specific means to stop or prevent them”. Rachelle H B Fishman
Vol 350 • August 30, 1997