1479
1957 but subsequently a further 11individuals have been affected, 5 of whom developed retinal angiomatosis.’ In the large family reported by Green et al phaeochromocytoma was the most frequent manifestation. Although renal cell carcinoma was not apparent at the time of the original report further follow-up has revealed renal cell carcinoma in several family members.8 Although well-defined examples of extensive VHL families with phaeochromocytoma and no renal involvement do occur,9 they are unusual. The molecular basis for interfamilial differences in predisposition to phaeochromocytoma remains to be explained. Our clinical and molecular studies do not provide evidence for the linear arrangement of discrete genes suggested by Neumann and Wiestler (such an arrangement might be expected to produce families manifesting a single complication of VHL disease, and no evidence for this has been produced). So far there is no evidence for locus heterogeneity in VHL diseases,lo and allelic heterogeneity would appear to be the most likely explanation. The isolation and characterisation of the VHL disease gene may allow the expression of specific VHL disease mutations to be predicted. In the meantime it is important that Neumann and Wiestler’s speculations do not influence the screening of families. Renal cell carcinoma is now the most frequent cause of death in patients with VHL disease,3 and all patients and relatives at risk for VHL disease must be screened for both phaeochromocytoma and renal cell carcinoma. Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK
E. R. MAHER
1. Maher ER, Iselius L, Yates JRW, et al. Von Hippel-Lindau disease: a genetic study. J Med Genet (in press). 2. Piotrowski W, Rohrborn G. Eme familienstudie des klassischen falles von v. Hippel-Lindau-syndrom. Langenbecks Arch Klin Chir 1965; 311: 310-22. 3. Maher ER, Harries R, Yates JRW, et al. Clinical features and natural history of von Hippel-Lindau disease. Q J Med 1990; 77: 1151-63. 4 Maher ER, Bentley E, Yates JRW, et al. Mapping of von Hippel-Lindau disease to chromosome 3p confirmed by genetic linkage studies. J Neurol Sci 1990; 100: 27-30. 5. Maher ER, Bentley E, Yates JRW, et al. Mapping of the von Hippel-Lindau disease locus to a small region of chromosome 3p by genetic linkage analysis. Genomics (in
press). 6. Nicol AAM, Lindau’s disease in five generations. Ann Hum Genet 1957; 22: 7-15. 7. Green JS, Bowmer MI, Johnson GJ. Von Hippel-Lindau disease in a Newfoundland kindred. Can Med Assoc J 1986; 134: 133-46. 8. Lamiell JM, Salazar FG, Hsia YE. Von Hippel-Lindau disease affecting 43 members of a single kindred. Medicine 1989; 68: 1-29. 9. Glenn GM, Daniel LN, Chokye P, et al. von Hippel-Lindau disease: distinct phenotypes suggest more than one mutant allele at the VHL locus. Hum Genet (in
press). 10. Hosoe S, Brauch H, Latif F, et al. Localization of the von Hippel-Lindau disease gene to a small region of chromosome 3. Genomics 1990; 8: 634-40.
SIR,-Dr Neumann and Dr Wiestler report a striking pattern of Hippel-Lindau syndrome (VHL), features which call for practical application in the medical care and surveillance of affected families. If the pattern reflects a real biological mechanism, members of family 1 and their doctors (table II) should not be concerned too much with a risk for CNS haemangioblastoma or renal cysts or cancer-in striking contrast to family 22, for example, where some of the members are already known to bear such von
manifestations of VHL disease. In fig 1 of the paper it is tacitly assumed that (eg, family 22) all affected members are prone to the full spectrum except for phaeochromocytoma. The families in table u indicate that this is a working hypothesis, yet a medically very important one. The Freiburg data allow for alternative genetic hypotheses: the explanation of the pattern of familial associations as due to a linear array of independent transcription units calls for deletions of different extent as the cause of VHL disease and its interfamilial variability. Not according with such a model are the apparent "gaps" (CNS haemangioblastoma in families 14-16 and renal cysts or cancer in families 21 and 29). These gaps, if real, require linked or unlinked protective factors which must be constantly present in all affected members, and this is not in accordance with the principles of genetic segregation. Instead of invoking very closely linked protective factors, it appears more conservative to postulate distinct pathogenetic factors-ie, different mutants which affect the different target
differently. The associations of VHL features could also be explained by a non-random topology of these mutants. However, such an explanation would not relate to different transcription units but to the topology of different functional domains of a single
organs
tumour
suppressor protein. gene syndromes1
are of major interest in contemporary human genetics, and the WAGR complex of Wilms’ tumour, aniridism, genitourinary malformations, and mental retardation (with unrelated component features and genes) is but one example from a growing list. DNA analysis will finally tell whether VHL disease must be included too but the odds, I feel, are against it.
Contiguous
Institute of Human Genetics,
University Hospital, D-6000 Frankfurt/Main 70,
1. Human gene mapping 10.
Malaria
Germany
ULRICH LANGENBECK
Cytogenet Cell Genet 1989; 51:
589-90.
chemoprophylaxis with mefloquine
MR,—Fetersen and colleagues’ have questioned World Health
Organisation (WHO) and US Centers for Disease Control (CDC) recommendations that mefloquine be used for chemoprophylaxis for travellers to sub-Saharan Africa, where there is a high transmission rate of chloroquine-resistant Plasmodium falcipar-um (CRPF). Recommendations by international experts have to weigh the risks for malaria infection, the protective efficacy of antimalarial drugs, the risks for adverse reactions, and the availability of drugs (proguanil, for instance, is not marketed in all countries). Some of the most relevant data, partly still unpublished, are summarised in the table. These studies, both retrospective2 and follow Up,3-5 include information on tolerance and efficiency of chemoprophylactic regimens in non-immune travellers. The risk for P falciparum malaria infection in sub-Saharan Africa without chemoprophylaxis is crudely estimated to be 0-5-2-5% per travellers and the case fatality rate is 1-2%. The protective efficiency of proguanil/ chloroquine is estimated to be about 60% in CRPF areas of Africa (table). A significant decline of the efficacy suggested by the eight fold increase of P falciparum malaria in British travellers, despite proguanil/chloroquine prophylaxis and taking account of denominators, ie, travellers at risk.2 The efficiency of mefloquine, in the 95% range in East Africamay be slightly lower in West Africa. The low efficiency in the American study (table) prompted the suggestion that dosing every second week beyond the first four weeks may not be enough.3 However, the main problem may have been compliance. Thus, mefloquine seems to be more effective than other current regimens for short-term travellers visiting tropical Africa. No fatal reactions have been reported to proguanil/chloroquine or mefloquine, despite wide use of the former combination and over one million prescriptions of mefloquine for prophylaxis.6 Although suicide or a fatal accident secondary to neuropsychiatric events may be unrecognised and so unreported, the records suggest a very low risk of death with either regimen. Neuropsychiatric side-effectsabout 50 cases of psychosis, seizures, or severe dizziness having been reported to Hoffmann-La Roche-are the main drawback to mefloquine, although they occur at a significantly lower frequency with prophylaxis than following full-dose treatment.’ The table suggests 2 neuropsychiatric reactions resulting in hospital admission and probably caused by mefloquine in prospective surveys of 30 000 recipients. 1 patient, with a history of posttraumatic epilepsy, had epileptic seizures; 1 had a psychosis. Also, 2 patients in about 30000 on chloroquine prophylaxis had a psychosis.5 Although some serious reactions may have been missed among non-respondents or those that could not be traced, there is evidence from the travellers’ surveys of an increased risk of serious adverse reactions in mefloquine users. Mild adverse events also seem to be similar for the different prophylactic regimens. Petersen and colleagues suggest that a randomised trial is needed to detect serious side-effects and refer to a previous study with less than 400 patients on each regimen. However, at least 5000 recipients
no
1480
SUMMARY OF FOUR RECENT STUDIES (A-D)* ON MALARIA CHEMOPROPHYLAXIS REGIMENSt fOR TRAVELLERS TO WEST AND/OR EAST AFRICA
Endoscopic ligation of perforator leg veins iJllB.,-olUB...VJUpC:lC:oln....c:
m
mc
Ycmuam
vcma
y v Liao
vccu
identified as a major cause of stasis dermatitis and leg utceration, ulceration, and several procedures have been devised to obliterate these vessels.l-4 Linton’s procedureor Cockett’s4 modification are among the most effective and widely used. Unfortunately, both involve a vertical incision on the medial aspect of the leg, through affected skin or even through the ulcers themselves, resulting in a high incidence of wound infection, dehiscence, and flap necrosis.s To avoid these problems, DePalma6 recommends multiple skin incisions, in Langer’s lines, over the perforator veins; Edwards7 developed a method of destroying the perforators through subfascial shearing; and Fegan8 introduced the injection/ compression technique. However, all these methods have their complications and rates of failure. The anatomy of the veins and of the posterior compartment of the leg lends itself to an endoscopic
approach. We report here
on our
experience with this new technique in ten
cases.
*A=American travellers to West Africa (n=526) 3 B=British to East Africa (n=2948), C=French to West (C,) or West+East (C2) Africa (n=20848);’ D,=Sw!SS to East Africa (n =44472),’ updated as D(n= 45 542).°e tM=mef!oqu!ne, C + P = chloroquine plus proguanil, C = chloroquine 300-700 mg
weekly. tAttack rates per journey. §Known post-traumatic
epilepsy (mefloquine clearly contraindicated) and psychosis Gastro!ntest!na! (5), rash (4), psychosis (2), visual problems, muscular pain, thrombocytopenia.
side-effects (such as skin reactions to sulfadoxine/pyrimethamine or neutropenia from amodiaquine) are to be picked up. If a significant difference between proguanil/ chloroquine and mefloquine in respect of one severe adverse reaction, such as seizures or psychosis, are to be detected, huge numbers are required and a randomised trial would not be practicable. Trials on protective efficacy do not need such large numbers. We think it correct to recommend mefloquine as chemoprophylaxis for people who have no contraindications and who are travelling to sub-Saharan Africa, where malaria transmission is high and CRPF common. Travellers should be made aware of the possibility of rare neuropsychiatric reactions and further detailed inquiry is required to establish the severity of relatively common and reportedly "mild" events such as dizziness. may be needed if
rare
Department of Infectious Diseases, Roslagstull Hospital, S-114 89 Stockholm, Sweden
ANDERS
Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland
ROBERT STEFFEN
Infectious Diseases Clinic, CHU Purpan, Toulouse, France
MAXIME ARMENGAUD NICOLE PICOT SYLVIE PICCOLI
BJÖRKMAN
1. Petersen E. Malaria
chemoprophylaxis: why mefloquine? Lancet 1990; 336: 811 Phillips-Howard PA, Radalowicz A, Mitchel J, et al. Risk of malaria in British residents returning from malarious areas. Br Med J 1990; 300: 499-503. 3. Lobel HO, Bernard KW, Williams SL, et al. Effectiveness and tolerance of long-term malaria prophylaxis with mefloquine: need for a better dosing regimen. JAMA (in press). 4. Picot N, Piccoli S, Armengaud M. Malaria protection by chloroquine and mefloquine. International Congress for Infectious Diseases (Montreal, 1990); abstr 302. 5. Steffen R, Heusser R, Machler R, et al. Malaria chemoprophylaxis among European tourists in tropical Africa use, adverse reactions, and efficacy. Bull WHO 1990; 68:
The posterior compartment, which extends from the tibia to the posterior fascial septum, is easily entered through a small incision on the medial aspect of the leg at the level of the tibial tuberosity, and can be explored under direct vision with an endoscope (we have used a rigid bronchoscope). The perforators are ligated with metal clips. Blood loss is slight, which contrasts very favourably with the traditional procedures. When difficulty is encountered we resort to ligation through separate small incisions, as was necessary in two cases. Before surgery, all patients undergo doppler flow mapping of their incompetent perforator veins, which facilitates endoscopic location. In these ten consecutive cases we have achieved 100% obliteration of the perforator veins detected with the doppler flow probe, with no morbidity. This was confirmed by repeat doppler studies at 1 and 3 months postoperatively. All the patients were walking by the second postoperative day and the mean hospital stay was 2-5 days. The procedure takes from 45 min to 1 h, and the operative time could probably be shortened with the development of specialised endoscopes. This approach to perforator vein ligation saves the patient unnecessary incisions in precarious skin and can greatly decrease the morbidity associated with the treatment of venous ulceration. Department of Surgery, University of Oporto, Grupo de Médicos Especialistas do Porto, Av da Boavista, 80-2ª 4000 Porto, Portugal
1. Linton RR The communicating veins of the lower leg and the operative techniques for their ligation. Ann Surg 1938; 107: 582-93. 2. Cockett FB, Jones DEE. The ankle blow-out syndrome. Lancet 1953; 1 17-22. 3. Linton RR. The postphlebitic ulceration of the lower extremity: its etiology and surgical treatment. Ann Surg 1953; 138: 415. 4. Cockett FB. The pathology and treatment of venous ulcers of the legs. Br J Surg 1955, 43: 280-88. 5. Nielubowicz J, Szostek M. Recurrences after Linton flap operation. J Cardiowasc Surg (Torino) 1979; 20: 49. 6 DePalma RG. Surgical therapy for venous stasis. Surgery 1974, 76: 910. 7. Edwards JM. Shearing operation for incompetent perforating veins. Br J Surg 1976; 63: 885-86. 8. Fegan WG. Continuous compression technique of injecting varicose veins. Lancet
1963; i: 109-12.
2.
313-22. 6. Sturchler D, Handschin J, Kaiser D, et al. Neuropsychiatric side effects of mefloquine. N Engl J Med 1990; 322: 1752-53. 7. World Health Organisation. Central nervous system reactions related to the antimalarial drug, mefloquine (WHO/MAL/89/1054). Geneva. WHO, 1989: 1-18. 8. Steffen R, Machler R, Phillips-Howard P, et al. Mefloquine. safety and efficacy in European tourists visiting East Africa International Congress for Infectious Diseases (Montreal, 1990); abstr 202.
JOAQUIM S. COUTO ANTONIO L. BAPTISTA
Chorionic villus sampling for Down’s
syndrome SIR,-Professor Lilford and colleagues (April 6, p 861) report a of Down’s syndrome missed on short-term culture (direct preparation) of chorion, an event that highlights an important anxiety for those adopting chorion villus sampling as a method to allow early fetal diagnosis of cytogenetic abnormalities. Although case
Lilford et al advocate routine use of a culture step, in addition to direct preparation of chorion, they also suggest that early amniocentesis could avoid this difficulty, provided that any effects on fetal lung development are not strongly gestational-age
dependent.
1957 but subsequently a further 11individuals have been affected, 5 of whom developed retinal angiomatosis.’ In the large family reported by Green et al phaeochromocytoma was the most frequent manifestation. Although renal cell carcinoma was not apparent at the time of the original report further follow-up has revealed renal cell carcinoma in several family members.8 Although well-defined examples of extensive VHL families with phaeochromocytoma and no renal involvement do occur,9 they are unusual. The molecular basis for interfamilial differences in predisposition to phaeochromocytoma remains to be explained. Our clinical and molecular studies do not provide evidence for the linear arrangement of discrete genes suggested by Neumann and Wiestler (such an arrangement might be expected to produce families manifesting a single complication of VHL disease, and no evidence for this has been produced). So far there is no evidence for locus heterogeneity in VHL diseases,lo and allelic heterogeneity would appear to be the most likely explanation. The isolation and characterisation of the VHL disease gene may allow the expression of specific VHL disease mutations to be predicted. In the meantime it is important that Neumann and Wiestler’s speculations do not influence the screening of families. Renal cell carcinoma is now the most frequent cause of death in patients with VHL disease,3 and all patients and relatives at risk for VHL disease must be screened for both phaeochromocytoma and renal cell carcinoma. Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK
E. R. MAHER
1. Maher ER, Iselius L, Yates JRW, et al. Von Hippel-Lindau disease: a genetic study. J Med Genet (in press). 2. Piotrowski W, Rohrborn G. Eme familienstudie des klassischen falles von v. Hippel-Lindau-syndrom. Langenbecks Arch Klin Chir 1965; 311: 310-22. 3. Maher ER, Harries R, Yates JRW, et al. Clinical features and natural history of von Hippel-Lindau disease. Q J Med 1990; 77: 1151-63. 4 Maher ER, Bentley E, Yates JRW, et al. Mapping of von Hippel-Lindau disease to chromosome 3p confirmed by genetic linkage studies. J Neurol Sci 1990; 100: 27-30. 5. Maher ER, Bentley E, Yates JRW, et al. Mapping of the von Hippel-Lindau disease locus to a small region of chromosome 3p by genetic linkage analysis. Genomics (in
press). 6. Nicol AAM, Lindau’s disease in five generations. Ann Hum Genet 1957; 22: 7-15. 7. Green JS, Bowmer MI, Johnson GJ. Von Hippel-Lindau disease in a Newfoundland kindred. Can Med Assoc J 1986; 134: 133-46. 8. Lamiell JM, Salazar FG, Hsia YE. Von Hippel-Lindau disease affecting 43 members of a single kindred. Medicine 1989; 68: 1-29. 9. Glenn GM, Daniel LN, Chokye P, et al. von Hippel-Lindau disease: distinct phenotypes suggest more than one mutant allele at the VHL locus. Hum Genet (in
press). 10. Hosoe S, Brauch H, Latif F, et al. Localization of the von Hippel-Lindau disease gene to a small region of chromosome 3. Genomics 1990; 8: 634-40.
SIR,-Dr Neumann and Dr Wiestler report a striking pattern of Hippel-Lindau syndrome (VHL), features which call for practical application in the medical care and surveillance of affected families. If the pattern reflects a real biological mechanism, members of family 1 and their doctors (table II) should not be concerned too much with a risk for CNS haemangioblastoma or renal cysts or cancer-in striking contrast to family 22, for example, where some of the members are already known to bear such von
manifestations of VHL disease. In fig 1 of the paper it is tacitly assumed that (eg, family 22) all affected members are prone to the full spectrum except for phaeochromocytoma. The families in table u indicate that this is a working hypothesis, yet a medically very important one. The Freiburg data allow for alternative genetic hypotheses: the explanation of the pattern of familial associations as due to a linear array of independent transcription units calls for deletions of different extent as the cause of VHL disease and its interfamilial variability. Not according with such a model are the apparent "gaps" (CNS haemangioblastoma in families 14-16 and renal cysts or cancer in families 21 and 29). These gaps, if real, require linked or unlinked protective factors which must be constantly present in all affected members, and this is not in accordance with the principles of genetic segregation. Instead of invoking very closely linked protective factors, it appears more conservative to postulate distinct pathogenetic factors-ie, different mutants which affect the different target
differently. The associations of VHL features could also be explained by a non-random topology of these mutants. However, such an explanation would not relate to different transcription units but to the topology of different functional domains of a single
organs
tumour
suppressor protein. gene syndromes1
are of major interest in contemporary human genetics, and the WAGR complex of Wilms’ tumour, aniridism, genitourinary malformations, and mental retardation (with unrelated component features and genes) is but one example from a growing list. DNA analysis will finally tell whether VHL disease must be included too but the odds, I feel, are against it.
Contiguous
Institute of Human Genetics,
University Hospital, D-6000 Frankfurt/Main 70,
1. Human gene mapping 10.
Malaria
Germany
ULRICH LANGENBECK
Cytogenet Cell Genet 1989; 51:
589-90.
chemoprophylaxis with mefloquine
MR,—Fetersen and colleagues’ have questioned World Health
Organisation (WHO) and US Centers for Disease Control (CDC) recommendations that mefloquine be used for chemoprophylaxis for travellers to sub-Saharan Africa, where there is a high transmission rate of chloroquine-resistant Plasmodium falcipar-um (CRPF). Recommendations by international experts have to weigh the risks for malaria infection, the protective efficacy of antimalarial drugs, the risks for adverse reactions, and the availability of drugs (proguanil, for instance, is not marketed in all countries). Some of the most relevant data, partly still unpublished, are summarised in the table. These studies, both retrospective2 and follow Up,3-5 include information on tolerance and efficiency of chemoprophylactic regimens in non-immune travellers. The risk for P falciparum malaria infection in sub-Saharan Africa without chemoprophylaxis is crudely estimated to be 0-5-2-5% per travellers and the case fatality rate is 1-2%. The protective efficiency of proguanil/ chloroquine is estimated to be about 60% in CRPF areas of Africa (table). A significant decline of the efficacy suggested by the eight fold increase of P falciparum malaria in British travellers, despite proguanil/chloroquine prophylaxis and taking account of denominators, ie, travellers at risk.2 The efficiency of mefloquine, in the 95% range in East Africamay be slightly lower in West Africa. The low efficiency in the American study (table) prompted the suggestion that dosing every second week beyond the first four weeks may not be enough.3 However, the main problem may have been compliance. Thus, mefloquine seems to be more effective than other current regimens for short-term travellers visiting tropical Africa. No fatal reactions have been reported to proguanil/chloroquine or mefloquine, despite wide use of the former combination and over one million prescriptions of mefloquine for prophylaxis.6 Although suicide or a fatal accident secondary to neuropsychiatric events may be unrecognised and so unreported, the records suggest a very low risk of death with either regimen. Neuropsychiatric side-effectsabout 50 cases of psychosis, seizures, or severe dizziness having been reported to Hoffmann-La Roche-are the main drawback to mefloquine, although they occur at a significantly lower frequency with prophylaxis than following full-dose treatment.’ The table suggests 2 neuropsychiatric reactions resulting in hospital admission and probably caused by mefloquine in prospective surveys of 30 000 recipients. 1 patient, with a history of posttraumatic epilepsy, had epileptic seizures; 1 had a psychosis. Also, 2 patients in about 30000 on chloroquine prophylaxis had a psychosis.5 Although some serious reactions may have been missed among non-respondents or those that could not be traced, there is evidence from the travellers’ surveys of an increased risk of serious adverse reactions in mefloquine users. Mild adverse events also seem to be similar for the different prophylactic regimens. Petersen and colleagues suggest that a randomised trial is needed to detect serious side-effects and refer to a previous study with less than 400 patients on each regimen. However, at least 5000 recipients
no
1480
SUMMARY OF FOUR RECENT STUDIES (A-D)* ON MALARIA CHEMOPROPHYLAXIS REGIMENSt fOR TRAVELLERS TO WEST AND/OR EAST AFRICA
Endoscopic ligation of perforator leg veins iJllB.,-olUB...VJUpC:lC:oln....c:
m
mc
Ycmuam
vcma
y v Liao
vccu
identified as a major cause of stasis dermatitis and leg utceration, ulceration, and several procedures have been devised to obliterate these vessels.l-4 Linton’s procedureor Cockett’s4 modification are among the most effective and widely used. Unfortunately, both involve a vertical incision on the medial aspect of the leg, through affected skin or even through the ulcers themselves, resulting in a high incidence of wound infection, dehiscence, and flap necrosis.s To avoid these problems, DePalma6 recommends multiple skin incisions, in Langer’s lines, over the perforator veins; Edwards7 developed a method of destroying the perforators through subfascial shearing; and Fegan8 introduced the injection/ compression technique. However, all these methods have their complications and rates of failure. The anatomy of the veins and of the posterior compartment of the leg lends itself to an endoscopic
approach. We report here
on our
experience with this new technique in ten
cases.
*A=American travellers to West Africa (n=526) 3 B=British to East Africa (n=2948), C=French to West (C,) or West+East (C2) Africa (n=20848);’ D,=Sw!SS to East Africa (n =44472),’ updated as D(n= 45 542).°e tM=mef!oqu!ne, C + P = chloroquine plus proguanil, C = chloroquine 300-700 mg
weekly. tAttack rates per journey. §Known post-traumatic
epilepsy (mefloquine clearly contraindicated) and psychosis Gastro!ntest!na! (5), rash (4), psychosis (2), visual problems, muscular pain, thrombocytopenia.
side-effects (such as skin reactions to sulfadoxine/pyrimethamine or neutropenia from amodiaquine) are to be picked up. If a significant difference between proguanil/ chloroquine and mefloquine in respect of one severe adverse reaction, such as seizures or psychosis, are to be detected, huge numbers are required and a randomised trial would not be practicable. Trials on protective efficacy do not need such large numbers. We think it correct to recommend mefloquine as chemoprophylaxis for people who have no contraindications and who are travelling to sub-Saharan Africa, where malaria transmission is high and CRPF common. Travellers should be made aware of the possibility of rare neuropsychiatric reactions and further detailed inquiry is required to establish the severity of relatively common and reportedly "mild" events such as dizziness. may be needed if
rare
Department of Infectious Diseases, Roslagstull Hospital, S-114 89 Stockholm, Sweden
ANDERS
Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland
ROBERT STEFFEN
Infectious Diseases Clinic, CHU Purpan, Toulouse, France
MAXIME ARMENGAUD NICOLE PICOT SYLVIE PICCOLI
BJÖRKMAN
1. Petersen E. Malaria
chemoprophylaxis: why mefloquine? Lancet 1990; 336: 811 Phillips-Howard PA, Radalowicz A, Mitchel J, et al. Risk of malaria in British residents returning from malarious areas. Br Med J 1990; 300: 499-503. 3. Lobel HO, Bernard KW, Williams SL, et al. Effectiveness and tolerance of long-term malaria prophylaxis with mefloquine: need for a better dosing regimen. JAMA (in press). 4. Picot N, Piccoli S, Armengaud M. Malaria protection by chloroquine and mefloquine. International Congress for Infectious Diseases (Montreal, 1990); abstr 302. 5. Steffen R, Heusser R, Machler R, et al. Malaria chemoprophylaxis among European tourists in tropical Africa use, adverse reactions, and efficacy. Bull WHO 1990; 68:
The posterior compartment, which extends from the tibia to the posterior fascial septum, is easily entered through a small incision on the medial aspect of the leg at the level of the tibial tuberosity, and can be explored under direct vision with an endoscope (we have used a rigid bronchoscope). The perforators are ligated with metal clips. Blood loss is slight, which contrasts very favourably with the traditional procedures. When difficulty is encountered we resort to ligation through separate small incisions, as was necessary in two cases. Before surgery, all patients undergo doppler flow mapping of their incompetent perforator veins, which facilitates endoscopic location. In these ten consecutive cases we have achieved 100% obliteration of the perforator veins detected with the doppler flow probe, with no morbidity. This was confirmed by repeat doppler studies at 1 and 3 months postoperatively. All the patients were walking by the second postoperative day and the mean hospital stay was 2-5 days. The procedure takes from 45 min to 1 h, and the operative time could probably be shortened with the development of specialised endoscopes. This approach to perforator vein ligation saves the patient unnecessary incisions in precarious skin and can greatly decrease the morbidity associated with the treatment of venous ulceration. Department of Surgery, University of Oporto, Grupo de Médicos Especialistas do Porto, Av da Boavista, 80-2ª 4000 Porto, Portugal
1. Linton RR The communicating veins of the lower leg and the operative techniques for their ligation. Ann Surg 1938; 107: 582-93. 2. Cockett FB, Jones DEE. The ankle blow-out syndrome. Lancet 1953; 1 17-22. 3. Linton RR. The postphlebitic ulceration of the lower extremity: its etiology and surgical treatment. Ann Surg 1953; 138: 415. 4. Cockett FB. The pathology and treatment of venous ulcers of the legs. Br J Surg 1955, 43: 280-88. 5. Nielubowicz J, Szostek M. Recurrences after Linton flap operation. J Cardiowasc Surg (Torino) 1979; 20: 49. 6 DePalma RG. Surgical therapy for venous stasis. Surgery 1974, 76: 910. 7. Edwards JM. Shearing operation for incompetent perforating veins. Br J Surg 1976; 63: 885-86. 8. Fegan WG. Continuous compression technique of injecting varicose veins. Lancet
1963; i: 109-12.
2.
313-22. 6. Sturchler D, Handschin J, Kaiser D, et al. Neuropsychiatric side effects of mefloquine. N Engl J Med 1990; 322: 1752-53. 7. World Health Organisation. Central nervous system reactions related to the antimalarial drug, mefloquine (WHO/MAL/89/1054). Geneva. WHO, 1989: 1-18. 8. Steffen R, Machler R, Phillips-Howard P, et al. Mefloquine. safety and efficacy in European tourists visiting East Africa International Congress for Infectious Diseases (Montreal, 1990); abstr 202.
JOAQUIM S. COUTO ANTONIO L. BAPTISTA
Chorionic villus sampling for Down’s
syndrome SIR,-Professor Lilford and colleagues (April 6, p 861) report a of Down’s syndrome missed on short-term culture (direct preparation) of chorion, an event that highlights an important anxiety for those adopting chorion villus sampling as a method to allow early fetal diagnosis of cytogenetic abnormalities. Although case
Lilford et al advocate routine use of a culture step, in addition to direct preparation of chorion, they also suggest that early amniocentesis could avoid this difficulty, provided that any effects on fetal lung development are not strongly gestational-age
dependent.
