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Hypoglycaemia In paediatric admissions In Mozambique
The Swedish study did not find IHD mortality to be higher than normal in twins, and Vagero and Leon remain unconvinced by the Barker hypothesis on the fetal origin of adult diseases. However, experimental data have shown that intrauterine growth retardation is associated with fetal hypoinsulinism and reduced development of insulin receptors, leading to insulin resistance in later life.2 Growth-retarded newborn babies have a reduced number of B cells and reduced insulin secretion.2,3 Hales and Barker4 suggest that fetal malnutrition is detrimental to the development and function of the insulin-producing B cells and induces adult B-cell dysfunction and insulin resistance, linked with hypertension. Twins, except those with extreme uterine growth retardation as seen in the twin transfusion syndrome, do not have reduced numbers of B cells, nor do they have hypoinsulinism in utero.3 The Barker hypothesis relies on the fact that fetal malnutrition has induced fetal hypoinsulinism. Fetal hypoinsulinism was not sought in the Swedish study, and our data show it to be absent in twins.3 Vagero and Leon’s study would have been a valid test of the Barker hypothesis if IHD in adult life had been investigated in monozygotic twin pairs with a substantial difference in
birthweight.
1
2
3
4
pain Figure: Albumin excretion rate In voided urine Reference albumin excretion <0
5 nmol/min = 33 Jlg/min.
described, died 3 days after admission. The results of
FA Van Assche, L Aerts, K Holemans Department of Obstetrics and 3000 Leuven, Belgium
Hours after onset of
Gynaecology, Universitaire Ziekenhuizen Leuven,
Barker DJP, Gluckman PD, Godfrey KM, Harding YE, Owens JA, Robinson JS. Fetal nutrition and cardiovascular disease in adult life. Lancet 1993; 341: 938-41. Van Assche FA, Aerts L, De Prins F. Degranulation of the insulin producing beta cells in an infant of a diabetic mother: case report. Br J Obstet Gynaecol 1993; 90: 182-85. Van Assche FA, Aerts L, Holemans K. Fetal growth retardation is associated with a reduced function of insulin producing B cells and may explain insulin resistance in later life. Am J Obstet Gynecol 1994; 170: 135 (abstr). Hales CN, Barker DJP. Non-insulin dependent (type II) diabetes mellitus: thrifty phenotype hypothesis. In: Barker DJP, ed. Fetal and infant origins of adult disease. Plymouth: Latimer Trend, 1992: 258-72.
measurements
in urine
shown in the figure. Two episodes The second episode, which coincided
are
of albuminuria are seen. with the second pain attack, preceded thrombolytic treatment. In addition to albumin, the concentrations of al-microglobulin and IgG were raised indicating increased glomerular leakage of proteins. The four patients were monitored as described for a total of thirteen 24 h periods. We have recorded a total of seven albuminuric episodes-between one and three episodes in each patient. The minimum duration of an episode was 30 min, and the maximum rate of albumin excretion was 50 nmol/min (3300
g/min). We conclude that studies of albuminuria in acute disease should be done in urine samples obtained with short intervals in order to avoid loss of information. Knowledge of the mechanisms that cause episodic albuminuria may prove to be of significance for the understanding of microalbuminuria and chronic proteinuria. states
Steen Horne Nielsen, Jens-Erik Beck Jensen, Erik Magid
Episodic
albuminuria in acute ischaemic heart
disease SiR-In the early phase of acute myocardial infarction (AMI) there is a transient increase in urinary excretion of protein similar to that found after trauma, bum injury, surgery, or acute pancreatitis.1 It has been proposed that proteinuria in patients treated with streptokinase may be attributable to the deposition of immune complexes as a result of naturally occurring antibodies to streptokinase.2 Alternatively, transient proteinuria in AMI could be due to glomerular haemodynamic changes caused by, for example, activation of the reninangiotensin system. We report that in patients with AMI large reversible changes in the excretion rate of urinary albumin can take place within 1-2 h, probably even within minutes. In each of four patients monitored from the time of admission for urinary albumin excretion, the time and volume of every amount of urine voided was noted and a 10 mL sample was saved. Albumin was measured by immunoturbidimetry in fresh urine; Cï1-microglobulin and IgG were measured in samples stored at - 20°C. A representative example is provided by a 67-year-old man with AMI (figure). He was admitted 9 h after the onset of severe chest pain. Initial treatment comprised streptokinase, glyceryl trinitrate, and morphine. After a new attack of chest pain thrombolytic treatment was repeated with alteplase at a total dose of 100 mg. The patient, who was neither hypotensive nor hypertensive during the observation period 732
Departments of Clinical Chemistry and Copenhagen S, DK 2300 Denmark
1
Internal Medicine,
Sundby Hospital,
Gosling P, Hughes EA, Reynolds TM, Fox JP. Microalbuminuria is an early response following acute myocardial infarction. Eur Heart J 1991; 12: 508-13.
Lynch M, Pentecost, BL, Littler WA, Stockley RA. Proteinuria with streptokinase. Lancet 1993; 341: 1024. 3 Pickett TM, Hilton PJ. Proteinuria and streptokinase. Lancet 1993; 2
341: 1538.
Hypoglycaemia In paediatric admissions In Mozambique SIR—Solomon and colleagues (Jan 15, p 149) found that 7-1% of children admitted to the emergency unit of Maputo Central Hospital had hypoglycaemia and that these patients had a worse prognosis. They conclude that hypoglycaemia should be looked for in all severely ill children. This conclusion is not
totally justified. Only patients with cerebral malaria or severe protein-energy malnutrition had a significantly high risk of being hypoglycaemic. These risks are recognised1.2 and they are an indication for close monitoring of blood glucose. No conclusion can be drawn about additional mortality risk due to hypoglycaemia by comparing case-fatality rates in those with and without a low blood sugar because of differences in disease
severity between the two groups. The only valid diseasespecific mortality comprison was for children with malaria, and
hypoglycemia made no difference.
A 24-year-old man presented 5 years previously with impotence, which was treated intermittently with monthly intramuscular (IM) depot testosterone injections allowing him to initiate secondary sexual development. At the time of entry
terms of time
told when the blood glucose was measured, in elapsed from admission, or what the frequency of severe hypoglycaemia (under 1-5 mmol/L) was. Moderate very hypoglycaemia could be the effect of inadequate feeding after admission and should be analysed separately. In our experience, only hypoglycaemia due to disease-dependent metabolic impairment (not inability to feed) or to poisoning tends to be very severe. The additional burden of routine glucose screening in severely ill children on busy paediatric wards such as the one in Maputo does not seem to be justified. "Relatively cheap" methods, such as reflectometers and glucose sticks, can end up being more expensive, despite the advantage of immediacy. Many variables should be explored before glucose monitoring is extended to patients other than those with cerebral malaria or very severe malnutrition. One such group might be severely ill children with no obvious diagnosis, especially if accidental poisoning or traditional medications are suspected. 3 out of 7 hypoglycaemic patients who died in the Maputo series fitted this description.
into Serono trial 5844 he was azoospermic with testicular volumes of 10 cm bilaterally. He was euosmic and of normal male karyotype. Serum luteinising hormone (LH) was 0 53 mIU/L, FSH 1 43 mIU/L, and testosterone 1 4 nmol/L. After 6 months pretreatment with incremental doses of twice weekly IM human chorionic gonadotrophin (Profasi), testosterone had risen to 13 3 nmol/L but he remained azoospermic, indicating an absolute gonadotropin deficiency. He was then started on subcutaneous injections of r-hFSH at a dose of 150 IU thrice weekly. 3 months later he had a sperm density of 0-2 x 106/mL (40% normal morphology and 70% progressive motility). At 7 months his wife had a positive pregnancy test. Semen analysis at 9 months showed a sperm density of 2-0 x 106/mL (70% normal morphology and 60% progressive motility). We were able to confirm the presence of a viable 9-week fetus within the gestational sac by transvaginal ultrasound. We report successful induction of fertility in a hypogonadotropic male with r-hFSH.
Giorgio Tamburlini, Marco Rabusin
Richard Quinton, Glenn Matfin, Pierre Bouloux, Ernest Loumaye
Department of Paediatrics and Bureau for International Health, Istituto per l’Infanzia "Burlo Garofolo", 34137 Trieste, Italy
Department of Medicine, Royal Free Hospital School of Medicine, London NW3 2PF,UK;
We
are not
1 Kawo NG, Msengi AE, Swai ABM, et al. Specificity of hypoglycaemia for severe malaria in children. Lancet 1990; 336: 454-57. 2 Wharton B. Hypoglycaemia in children with kwashiorkor. Lancet 1970; i: 171-73.
SiR-Solomon and colleagues show that 7-1% of 603 acutely ill children admitted to hospital in Mozambique were hypoglycaemic. The children had a wide range of conditions. Significant associations were found between hypoglycaemia and cerebral malaria (predictably) and protein-energy malnutrition. Solomon et al conclude that hypoglycaemia is a common accompaniment of severe illness in children in the developing world and may be related either to hepatic glycogen depletion or to endotoxin-induced inhibition of gluconeogenesis. This confirms our suggestion’ based on studies in Tanzania that "hypoglycaemia is not a specific complication of malaria" and "should be sought in all severely sick children". The frequency of hypoglycaemia was similar in children with severe malaria and those with other diseases (5/97 vs 10/89). The only significant correlation was with time since last feeding, supporting the view that hepatic glycogen depletion is the main risk factor. We would add a note of caution about reliance on test-strip glucose values, although often there is no alternative. Erroneously high readings can be obtained in hot humid climates if strips are not stored very carefully, and Solomon et al may even have underestimated the prevalence of hypoglycaemia. K G MM
Alberti, D G McLarty, A B M Swai
Department of Medicine, Muhimbili Medical Centre, PO Box 65243, Dar es Salaam, Tanzania; and Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, UK 1
Kawo Ng, Msengi AE, Swai ABM, Chuwa LM, Alberti KGMM, McLarty DG. Specificity of hypoglycaemia for cerebral malaria in children. Lancet 1990; 336: 454-57.
Successful induction of fertility in a hypogonadotropic male SiR-We are investigating the safety and efficacy of recombinant human follicle-stimulating hormone (FSH) (r-hFSH, Gonal-F) in the induction of spermatogenesis in hypogonadotropic hypogonadism (IHH).
males with isolated
and Ares Services SA, 1202 Geneva, Switzerland
Guillain-Barré syndrome after measles, mumps, and rubella vaccine SIR—Morris and Rylance report (Jan 1, p 60) a 16-year-old girl who developed Guillain-Barre syndrome (GBS) ten days after immunisation with measles, mumps, and rubella vaccine. As they admit, this is a very rare but potentially important association in view of the many children being vaccinated. We are undertaking a case-control study to investigate the association between Campylobacter jejuni and Guillain-Barre syndrome in which only 8 of 89 patients with GBS have reported an immunisation within three months of onset of neuropathic symptoms. This rate was not much more than in 8 of 81 family controls or 2 of 82 hospital controls. In our previous case-control study 6 of 100 GBS patients received immunisations within 3 months of disease onset compared with 5 of 100 hospital controls.1 To identify more accurately the frequency of vaccination as an antecedent event in the aetiology of GBS we are carrying out an epidemiological study of GBS in adults in south-east England over 1 year, in conjunction with the British Neurological Surveillance Unit. A similar study of children possibly under the auspices of the British Paediatric Surveillance Unit would be justified. It would clearly be advantageous to detect any adverse effects of this new vaccine earlier rather than later, to avoid the situation that arose in the USA in 1977 after the swine flu vaccine epidemic.2 An important related issue is whether immunisation might precipitate a relapse of GBS, as has been documented after reimmunisation with tetanus toxoid on three occasions.3
Jeremy Rees,
Richard
Hughes
Department of Neurology, UMDS, Guy’s Hospital, London SE1 9RT, UK
1
JB, Hughes RAC, Anderson MJ, et al. A prospective study of idiopathic neuropathy, II: antecedent events. J Neurol Neurosurg Psychiatry 1988; 51: 613-18. Langmuir AD, Bregman DJ, Kurland LT, et al. An epidemiologic and clinical evaluation of GBS reported in association with administration of swine influenza vaccines. Am J Epidemiol 1984; 119: 841-79. Pollard JB, Selby G. Relapsing neuropathy due to tetanus toxoid.
Winer acute
2
3
J Neurol Sci 1978; 37: 113-25.
733
birthweight.
1
2
3
4
pain Figure: Albumin excretion rate In voided urine Reference albumin excretion <0
5 nmol/min = 33 Jlg/min.
described, died 3 days after admission. The results of
FA Van Assche, L Aerts, K Holemans Department of Obstetrics and 3000 Leuven, Belgium
Hours after onset of
Gynaecology, Universitaire Ziekenhuizen Leuven,
Barker DJP, Gluckman PD, Godfrey KM, Harding YE, Owens JA, Robinson JS. Fetal nutrition and cardiovascular disease in adult life. Lancet 1993; 341: 938-41. Van Assche FA, Aerts L, De Prins F. Degranulation of the insulin producing beta cells in an infant of a diabetic mother: case report. Br J Obstet Gynaecol 1993; 90: 182-85. Van Assche FA, Aerts L, Holemans K. Fetal growth retardation is associated with a reduced function of insulin producing B cells and may explain insulin resistance in later life. Am J Obstet Gynecol 1994; 170: 135 (abstr). Hales CN, Barker DJP. Non-insulin dependent (type II) diabetes mellitus: thrifty phenotype hypothesis. In: Barker DJP, ed. Fetal and infant origins of adult disease. Plymouth: Latimer Trend, 1992: 258-72.
measurements
in urine
shown in the figure. Two episodes The second episode, which coincided
are
of albuminuria are seen. with the second pain attack, preceded thrombolytic treatment. In addition to albumin, the concentrations of al-microglobulin and IgG were raised indicating increased glomerular leakage of proteins. The four patients were monitored as described for a total of thirteen 24 h periods. We have recorded a total of seven albuminuric episodes-between one and three episodes in each patient. The minimum duration of an episode was 30 min, and the maximum rate of albumin excretion was 50 nmol/min (3300
g/min). We conclude that studies of albuminuria in acute disease should be done in urine samples obtained with short intervals in order to avoid loss of information. Knowledge of the mechanisms that cause episodic albuminuria may prove to be of significance for the understanding of microalbuminuria and chronic proteinuria. states
Steen Horne Nielsen, Jens-Erik Beck Jensen, Erik Magid
Episodic
albuminuria in acute ischaemic heart
disease SiR-In the early phase of acute myocardial infarction (AMI) there is a transient increase in urinary excretion of protein similar to that found after trauma, bum injury, surgery, or acute pancreatitis.1 It has been proposed that proteinuria in patients treated with streptokinase may be attributable to the deposition of immune complexes as a result of naturally occurring antibodies to streptokinase.2 Alternatively, transient proteinuria in AMI could be due to glomerular haemodynamic changes caused by, for example, activation of the reninangiotensin system. We report that in patients with AMI large reversible changes in the excretion rate of urinary albumin can take place within 1-2 h, probably even within minutes. In each of four patients monitored from the time of admission for urinary albumin excretion, the time and volume of every amount of urine voided was noted and a 10 mL sample was saved. Albumin was measured by immunoturbidimetry in fresh urine; Cï1-microglobulin and IgG were measured in samples stored at - 20°C. A representative example is provided by a 67-year-old man with AMI (figure). He was admitted 9 h after the onset of severe chest pain. Initial treatment comprised streptokinase, glyceryl trinitrate, and morphine. After a new attack of chest pain thrombolytic treatment was repeated with alteplase at a total dose of 100 mg. The patient, who was neither hypotensive nor hypertensive during the observation period 732
Departments of Clinical Chemistry and Copenhagen S, DK 2300 Denmark
1
Internal Medicine,
Sundby Hospital,
Gosling P, Hughes EA, Reynolds TM, Fox JP. Microalbuminuria is an early response following acute myocardial infarction. Eur Heart J 1991; 12: 508-13.
Lynch M, Pentecost, BL, Littler WA, Stockley RA. Proteinuria with streptokinase. Lancet 1993; 341: 1024. 3 Pickett TM, Hilton PJ. Proteinuria and streptokinase. Lancet 1993; 2
341: 1538.
Hypoglycaemia In paediatric admissions In Mozambique SIR—Solomon and colleagues (Jan 15, p 149) found that 7-1% of children admitted to the emergency unit of Maputo Central Hospital had hypoglycaemia and that these patients had a worse prognosis. They conclude that hypoglycaemia should be looked for in all severely ill children. This conclusion is not
totally justified. Only patients with cerebral malaria or severe protein-energy malnutrition had a significantly high risk of being hypoglycaemic. These risks are recognised1.2 and they are an indication for close monitoring of blood glucose. No conclusion can be drawn about additional mortality risk due to hypoglycaemia by comparing case-fatality rates in those with and without a low blood sugar because of differences in disease
severity between the two groups. The only valid diseasespecific mortality comprison was for children with malaria, and
hypoglycemia made no difference.
A 24-year-old man presented 5 years previously with impotence, which was treated intermittently with monthly intramuscular (IM) depot testosterone injections allowing him to initiate secondary sexual development. At the time of entry
terms of time
told when the blood glucose was measured, in elapsed from admission, or what the frequency of severe hypoglycaemia (under 1-5 mmol/L) was. Moderate very hypoglycaemia could be the effect of inadequate feeding after admission and should be analysed separately. In our experience, only hypoglycaemia due to disease-dependent metabolic impairment (not inability to feed) or to poisoning tends to be very severe. The additional burden of routine glucose screening in severely ill children on busy paediatric wards such as the one in Maputo does not seem to be justified. "Relatively cheap" methods, such as reflectometers and glucose sticks, can end up being more expensive, despite the advantage of immediacy. Many variables should be explored before glucose monitoring is extended to patients other than those with cerebral malaria or very severe malnutrition. One such group might be severely ill children with no obvious diagnosis, especially if accidental poisoning or traditional medications are suspected. 3 out of 7 hypoglycaemic patients who died in the Maputo series fitted this description.
into Serono trial 5844 he was azoospermic with testicular volumes of 10 cm bilaterally. He was euosmic and of normal male karyotype. Serum luteinising hormone (LH) was 0 53 mIU/L, FSH 1 43 mIU/L, and testosterone 1 4 nmol/L. After 6 months pretreatment with incremental doses of twice weekly IM human chorionic gonadotrophin (Profasi), testosterone had risen to 13 3 nmol/L but he remained azoospermic, indicating an absolute gonadotropin deficiency. He was then started on subcutaneous injections of r-hFSH at a dose of 150 IU thrice weekly. 3 months later he had a sperm density of 0-2 x 106/mL (40% normal morphology and 70% progressive motility). At 7 months his wife had a positive pregnancy test. Semen analysis at 9 months showed a sperm density of 2-0 x 106/mL (70% normal morphology and 60% progressive motility). We were able to confirm the presence of a viable 9-week fetus within the gestational sac by transvaginal ultrasound. We report successful induction of fertility in a hypogonadotropic male with r-hFSH.
Giorgio Tamburlini, Marco Rabusin
Richard Quinton, Glenn Matfin, Pierre Bouloux, Ernest Loumaye
Department of Paediatrics and Bureau for International Health, Istituto per l’Infanzia "Burlo Garofolo", 34137 Trieste, Italy
Department of Medicine, Royal Free Hospital School of Medicine, London NW3 2PF,UK;
We
are not
1 Kawo NG, Msengi AE, Swai ABM, et al. Specificity of hypoglycaemia for severe malaria in children. Lancet 1990; 336: 454-57. 2 Wharton B. Hypoglycaemia in children with kwashiorkor. Lancet 1970; i: 171-73.
SiR-Solomon and colleagues show that 7-1% of 603 acutely ill children admitted to hospital in Mozambique were hypoglycaemic. The children had a wide range of conditions. Significant associations were found between hypoglycaemia and cerebral malaria (predictably) and protein-energy malnutrition. Solomon et al conclude that hypoglycaemia is a common accompaniment of severe illness in children in the developing world and may be related either to hepatic glycogen depletion or to endotoxin-induced inhibition of gluconeogenesis. This confirms our suggestion’ based on studies in Tanzania that "hypoglycaemia is not a specific complication of malaria" and "should be sought in all severely sick children". The frequency of hypoglycaemia was similar in children with severe malaria and those with other diseases (5/97 vs 10/89). The only significant correlation was with time since last feeding, supporting the view that hepatic glycogen depletion is the main risk factor. We would add a note of caution about reliance on test-strip glucose values, although often there is no alternative. Erroneously high readings can be obtained in hot humid climates if strips are not stored very carefully, and Solomon et al may even have underestimated the prevalence of hypoglycaemia. K G MM
Alberti, D G McLarty, A B M Swai
Department of Medicine, Muhimbili Medical Centre, PO Box 65243, Dar es Salaam, Tanzania; and Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, UK 1
Kawo Ng, Msengi AE, Swai ABM, Chuwa LM, Alberti KGMM, McLarty DG. Specificity of hypoglycaemia for cerebral malaria in children. Lancet 1990; 336: 454-57.
Successful induction of fertility in a hypogonadotropic male SiR-We are investigating the safety and efficacy of recombinant human follicle-stimulating hormone (FSH) (r-hFSH, Gonal-F) in the induction of spermatogenesis in hypogonadotropic hypogonadism (IHH).
males with isolated
and Ares Services SA, 1202 Geneva, Switzerland
Guillain-Barré syndrome after measles, mumps, and rubella vaccine SIR—Morris and Rylance report (Jan 1, p 60) a 16-year-old girl who developed Guillain-Barre syndrome (GBS) ten days after immunisation with measles, mumps, and rubella vaccine. As they admit, this is a very rare but potentially important association in view of the many children being vaccinated. We are undertaking a case-control study to investigate the association between Campylobacter jejuni and Guillain-Barre syndrome in which only 8 of 89 patients with GBS have reported an immunisation within three months of onset of neuropathic symptoms. This rate was not much more than in 8 of 81 family controls or 2 of 82 hospital controls. In our previous case-control study 6 of 100 GBS patients received immunisations within 3 months of disease onset compared with 5 of 100 hospital controls.1 To identify more accurately the frequency of vaccination as an antecedent event in the aetiology of GBS we are carrying out an epidemiological study of GBS in adults in south-east England over 1 year, in conjunction with the British Neurological Surveillance Unit. A similar study of children possibly under the auspices of the British Paediatric Surveillance Unit would be justified. It would clearly be advantageous to detect any adverse effects of this new vaccine earlier rather than later, to avoid the situation that arose in the USA in 1977 after the swine flu vaccine epidemic.2 An important related issue is whether immunisation might precipitate a relapse of GBS, as has been documented after reimmunisation with tetanus toxoid on three occasions.3
Jeremy Rees,
Richard
Hughes
Department of Neurology, UMDS, Guy’s Hospital, London SE1 9RT, UK
1
JB, Hughes RAC, Anderson MJ, et al. A prospective study of idiopathic neuropathy, II: antecedent events. J Neurol Neurosurg Psychiatry 1988; 51: 613-18. Langmuir AD, Bregman DJ, Kurland LT, et al. An epidemiologic and clinical evaluation of GBS reported in association with administration of swine influenza vaccines. Am J Epidemiol 1984; 119: 841-79. Pollard JB, Selby G. Relapsing neuropathy due to tetanus toxoid.
Winer acute
2
3
J Neurol Sci 1978; 37: 113-25.
733