- Email: [email protected]
Modulators of nitric oxide synthesis
116
[SD 4-6] years, range 28-44; number of previously attempts 2-5 [1-5], 1--6; number of previously transferred embryos 7-2 ,1-19), which amounts to a clinical pregnancy rate of 67% and an implantation rate of 29%. Tadir and colleagues’ pioneering work was based on experimental research, whereas the erbium-YAG laser has already repeatedly proved its qualities in clinical appliance.
mean
age 35-5
failed IVF
Institute of Sterility Treatment, A-1130 Vienna, Austria
WILFRIED FEICHTINGER HEINZ STROHMER KARL M. RADNER
Kaufmann R, Hibst R. Pulsed Er:YAG- and 308 nm UV-excimer laser: an in vitro and in vivo study of skin-ablative effects. Lasers Surg Med 1989; 9: 132-40. 2. Rasmussen RE, Hammer-Wilson M, Berns MW. Mutation and sister chromatid exchange induction in Chinese hamster ovary (CHO) cells by pulsed excimer laser 1.
radiation at 193 nm and 308 nm and continuous UV radiation at 254 nm. Photochem Photobiol 1989; 49: 413-18. 3. Strohmer H, Feichtinger W. Successful clinical application of laser for micromanipulation in an in vitro fertilization program. Fertil Steril (in press).
Cryopreservation of embryos and
pregnancy
rates after IVF
SIR,-Dr Tan and colleagues (June 6, p 1390) demonstrate that the cumulative pregnancy rate after repeated IVF treatment declines after the female partner reaches the age of 34 years. The cryopreservation of embryos after IVF is a safe and cost-effective 1 way to increase cumulative pregnancy rates per oocyte recovery, do not include this in their results. yet they PREGNANCY RATES PER TRANSFER OF CRYOPRESERVED EMBRYOS IN NATURAL CYCLES (NC) OR CYCLES WITH HORMONE REPLACEMENT THERAPY (HRT).
colleagues in the University of Kansas School of Medicine in the 1920s, and they showed that a bolus injection of 30-50 mg/kg methylguanidine sulphate resulted in a large (greater than 100 mm Hg) sustained rise in blood pressure, similar to that seen with inhibitors of NO synthase.4 The results were consistent in over 200 experiments. These experiments were done to explain why patients with renal disease developed hypertension, the theory being that a pressor product of metabolism may be retained in these patients. Such studies influenced Goldblatt and colleagues,’ who believed that retention of guanidine compounds was one explanation for their observation that renal ischaemia causes hypertension. Since the dose Taylor and colleagues used was only slightly lower than that used by Major it seems that there may be inter-species differences in sensitivity of the endothelial constitutive NO synthase to this substance. Furthermore, the demonstration that aminoguanidine is an effective inhibitor of the inducible NO synthase6 invalidates the presumption that the full aminoacid structure is needed to inhibit NO synthase. Despite the thoughts of Taylor and colleagues, it seems that small molecules that resemble the guanidino end of the arginine molecule may in fact be important modulators of NO synthesis and deserve further study. Departement of Medicine and Therapeutics, University of Aberdeen,
NIGEL BENJAMIN
Foresterhill, Aberdeen AB9 2ZD, UK
Major RH. Relationship between certain products of metabolism and arterial hypertension. JAMA 1924; 83: 81-84. 2. Major RH. The possible relationship between guanidine and high blood pressure. Am J Med Sci 1925; 170: 228-32. 3. Major RH, Weber CJ. The effect of methylguanidine upon the blood pressure of adrenalectomized dogs. J Pharmacol Exp Ther 1929; 35: 351-54. 4. Aisaka K, Gross SS, Steinberg C, Griffith OW, Levi R. NG methylarginine, an inhibitor of endothelium-derived nitric oxide synthesis, is a potent pressor agent m the guinea pig: does nitric oxide regulate blood pressure in vivo? Biochem Biophys 1.
Res Comm 1989; 160: 881 5. Goldblatt H, Lynch J, Hanzal RF, Summerville WW. The production of persistent elevation of systolic blood pressure by means of renal ischaemia. J Exp Med 1934; 59: 347-78. 6. Corbett JA, Tilton RG, Chang K, et al. Aminoguanidine, a novel inhibitor of nitric oxide formation, prevents diabetic vascular dysfunction. Diabetes 1992; 41: 552-56.
*p < 0 05 both
<
34 yr and 35-39 yr groups.
We have found
a
reduced pregnancy
rate
after the transfer of
embryos cryopreserved in propanediol only in women aged 40 years or more (table). This reduction is seen both when embryos are transferred in unstimulated cycles in which replacement is timed relative to the endogenous LH surge, and in cycles in which the endometrium is artificially stimulated by exogenous steroids after pituitary suppression with buserelin therapy, removing the possibility of an impairment of ovarian activity affecting endometrial development. We believe that it is essential to provide cryopreservation facilities in IVF units. Manchester Fertility Services, Manchester BUPA Hospital, Whalley Range, Manchester M168AJ, UK 1.
BRIAN A. LIEBERMAN STEPHEN A. TROUP PHILLIP L. MATSON
Troup SA, Matson PL, Critchlow JD, et al. Cryopreservation of human embryos at the pronucleate, early cleavage or expanded blastocyst stages. Eur J Obstet Gynecol Reprod Biol 1990; 38: 133-39.
Modulators of nitric oxide synthesis SIR,--4Commenting on Dr Vallance and colleagues’ (March 7, 572) discovery of an endogenous inhibitor of nitric oxide (NO) synthesis, Dr Taylor and colleagues (May 16, p 1243) point out the structural similarity of the endogenous metabolite methylguanidine with the guanidino end of the NO synthase inhibitor L-NG monomethyl arginine. They say that there are no reports of methylguanidine having a pressor action. There are in fact many, if somewhat ancient, publications (for example, refs 1-3) on the effects of guanidine compounds, including methylguanidine and dimethylguanidine, on blood pressure in the anaesthetised dog. These experiments were done by Ralph H. Major and his p
Diagnostic difficulties of
HCV serological
tests
SiR,—Dr Allain and colleagues (May 9, p 1171) suggest that "half of all HCV RIBA indeterminate results are likely to be false reactions". Perhaps this is so, depending on the group of patients you choose to examine. A new test (Chiron RIBA HCV SIA prototype) was used to assay 27 samples that had given an indeterminate result by the immunoblot Chiron RIBA HCV test system. This new test uses three recombinant antigens (c33, NS5, and SOD) and two synthetic peptide bands (clOO and c22). According to the manufacturer’s instructions, it should be used only to establish whether indeterminate samples indeed contain specific antibodies to epitopes carried by HCV. The results were: /?/M HCV RIBA C SIA 5M prototype pmfofype PosJindJneg c33 12/1/0 c22 4/7/3 Pos=positme, !nd=!ndetermmate, new= negative
Total 13 14
significant difference between the samples with or c22 (X2 test, p < 0005). reactivity Most patients (10 of 13) included in the c33 group were on haemodialysis and had been transfused several times. It is noteworthy that 7 c22 reactive samples remained indeterminate
There
was
to
a
c33
with the new test, whereas only 1 of c33 reactive samples did so. The c33 band seems to be more specific than the c22 band. c22-only reactivity could be residual,l but in 3 cases it disappeared when the new test was used. Obviously, the difficulty of indeterminate test results persists whichever RIBA is used. The range of such results might increase from 16% with first generation RIBAs2 to 29% with this third generation RIBA. We have to wait for the development of a more
[SD 4-6] years, range 28-44; number of previously attempts 2-5 [1-5], 1--6; number of previously transferred embryos 7-2 ,1-19), which amounts to a clinical pregnancy rate of 67% and an implantation rate of 29%. Tadir and colleagues’ pioneering work was based on experimental research, whereas the erbium-YAG laser has already repeatedly proved its qualities in clinical appliance.
mean
age 35-5
failed IVF
Institute of Sterility Treatment, A-1130 Vienna, Austria
WILFRIED FEICHTINGER HEINZ STROHMER KARL M. RADNER
Kaufmann R, Hibst R. Pulsed Er:YAG- and 308 nm UV-excimer laser: an in vitro and in vivo study of skin-ablative effects. Lasers Surg Med 1989; 9: 132-40. 2. Rasmussen RE, Hammer-Wilson M, Berns MW. Mutation and sister chromatid exchange induction in Chinese hamster ovary (CHO) cells by pulsed excimer laser 1.
radiation at 193 nm and 308 nm and continuous UV radiation at 254 nm. Photochem Photobiol 1989; 49: 413-18. 3. Strohmer H, Feichtinger W. Successful clinical application of laser for micromanipulation in an in vitro fertilization program. Fertil Steril (in press).
Cryopreservation of embryos and
pregnancy
rates after IVF
SIR,-Dr Tan and colleagues (June 6, p 1390) demonstrate that the cumulative pregnancy rate after repeated IVF treatment declines after the female partner reaches the age of 34 years. The cryopreservation of embryos after IVF is a safe and cost-effective 1 way to increase cumulative pregnancy rates per oocyte recovery, do not include this in their results. yet they PREGNANCY RATES PER TRANSFER OF CRYOPRESERVED EMBRYOS IN NATURAL CYCLES (NC) OR CYCLES WITH HORMONE REPLACEMENT THERAPY (HRT).
colleagues in the University of Kansas School of Medicine in the 1920s, and they showed that a bolus injection of 30-50 mg/kg methylguanidine sulphate resulted in a large (greater than 100 mm Hg) sustained rise in blood pressure, similar to that seen with inhibitors of NO synthase.4 The results were consistent in over 200 experiments. These experiments were done to explain why patients with renal disease developed hypertension, the theory being that a pressor product of metabolism may be retained in these patients. Such studies influenced Goldblatt and colleagues,’ who believed that retention of guanidine compounds was one explanation for their observation that renal ischaemia causes hypertension. Since the dose Taylor and colleagues used was only slightly lower than that used by Major it seems that there may be inter-species differences in sensitivity of the endothelial constitutive NO synthase to this substance. Furthermore, the demonstration that aminoguanidine is an effective inhibitor of the inducible NO synthase6 invalidates the presumption that the full aminoacid structure is needed to inhibit NO synthase. Despite the thoughts of Taylor and colleagues, it seems that small molecules that resemble the guanidino end of the arginine molecule may in fact be important modulators of NO synthesis and deserve further study. Departement of Medicine and Therapeutics, University of Aberdeen,
NIGEL BENJAMIN
Foresterhill, Aberdeen AB9 2ZD, UK
Major RH. Relationship between certain products of metabolism and arterial hypertension. JAMA 1924; 83: 81-84. 2. Major RH. The possible relationship between guanidine and high blood pressure. Am J Med Sci 1925; 170: 228-32. 3. Major RH, Weber CJ. The effect of methylguanidine upon the blood pressure of adrenalectomized dogs. J Pharmacol Exp Ther 1929; 35: 351-54. 4. Aisaka K, Gross SS, Steinberg C, Griffith OW, Levi R. NG methylarginine, an inhibitor of endothelium-derived nitric oxide synthesis, is a potent pressor agent m the guinea pig: does nitric oxide regulate blood pressure in vivo? Biochem Biophys 1.
Res Comm 1989; 160: 881 5. Goldblatt H, Lynch J, Hanzal RF, Summerville WW. The production of persistent elevation of systolic blood pressure by means of renal ischaemia. J Exp Med 1934; 59: 347-78. 6. Corbett JA, Tilton RG, Chang K, et al. Aminoguanidine, a novel inhibitor of nitric oxide formation, prevents diabetic vascular dysfunction. Diabetes 1992; 41: 552-56.
*p < 0 05 both
<
34 yr and 35-39 yr groups.
We have found
a
reduced pregnancy
rate
after the transfer of
embryos cryopreserved in propanediol only in women aged 40 years or more (table). This reduction is seen both when embryos are transferred in unstimulated cycles in which replacement is timed relative to the endogenous LH surge, and in cycles in which the endometrium is artificially stimulated by exogenous steroids after pituitary suppression with buserelin therapy, removing the possibility of an impairment of ovarian activity affecting endometrial development. We believe that it is essential to provide cryopreservation facilities in IVF units. Manchester Fertility Services, Manchester BUPA Hospital, Whalley Range, Manchester M168AJ, UK 1.
BRIAN A. LIEBERMAN STEPHEN A. TROUP PHILLIP L. MATSON
Troup SA, Matson PL, Critchlow JD, et al. Cryopreservation of human embryos at the pronucleate, early cleavage or expanded blastocyst stages. Eur J Obstet Gynecol Reprod Biol 1990; 38: 133-39.
Modulators of nitric oxide synthesis SIR,--4Commenting on Dr Vallance and colleagues’ (March 7, 572) discovery of an endogenous inhibitor of nitric oxide (NO) synthesis, Dr Taylor and colleagues (May 16, p 1243) point out the structural similarity of the endogenous metabolite methylguanidine with the guanidino end of the NO synthase inhibitor L-NG monomethyl arginine. They say that there are no reports of methylguanidine having a pressor action. There are in fact many, if somewhat ancient, publications (for example, refs 1-3) on the effects of guanidine compounds, including methylguanidine and dimethylguanidine, on blood pressure in the anaesthetised dog. These experiments were done by Ralph H. Major and his p
Diagnostic difficulties of
HCV serological
tests
SiR,—Dr Allain and colleagues (May 9, p 1171) suggest that "half of all HCV RIBA indeterminate results are likely to be false reactions". Perhaps this is so, depending on the group of patients you choose to examine. A new test (Chiron RIBA HCV SIA prototype) was used to assay 27 samples that had given an indeterminate result by the immunoblot Chiron RIBA HCV test system. This new test uses three recombinant antigens (c33, NS5, and SOD) and two synthetic peptide bands (clOO and c22). According to the manufacturer’s instructions, it should be used only to establish whether indeterminate samples indeed contain specific antibodies to epitopes carried by HCV. The results were: /?/M HCV RIBA C SIA 5M prototype pmfofype PosJindJneg c33 12/1/0 c22 4/7/3 Pos=positme, !nd=!ndetermmate, new= negative
Total 13 14
significant difference between the samples with or c22 (X2 test, p < 0005). reactivity Most patients (10 of 13) included in the c33 group were on haemodialysis and had been transfused several times. It is noteworthy that 7 c22 reactive samples remained indeterminate
There
was
to
a
c33
with the new test, whereas only 1 of c33 reactive samples did so. The c33 band seems to be more specific than the c22 band. c22-only reactivity could be residual,l but in 3 cases it disappeared when the new test was used. Obviously, the difficulty of indeterminate test results persists whichever RIBA is used. The range of such results might increase from 16% with first generation RIBAs2 to 29% with this third generation RIBA. We have to wait for the development of a more