789
WET VERSUS DRY VACUUM-CLEANING
Paired t-test, baseline
vs
day 42
or
182, *p < 0’02,
tp < 01, :t:p < 05
times in the first 8 weeks and three times in the next 6 months. Dust from the total area of 2 carpets in each house was collected in separate bags, sieved, weighed, and extracted. Der pl was measured in an ELISA.3 Both wet and dry vacuum-cleaning reduced total recoverable dust by 69% on day 42 and 61 % on day 182, both times being 4 weeks after the last cleaning. The failure of dry vacuuming to reduce allergen concentrations (ie, Der p1 per g fine dust) presumably reflected the equal removal of both allergen bearing and nonallergen bearing dust particles (table). However, the total allergen recoverable was decreased, but the reduction failed to reach statistical significance. The wet procedure reduced the mean recoverable allergen per square metre vacuumed by two-thirds (table). But there was less reduction in mite allergen per g of recovered dust, by about one-third. When all time points were considered, the maximum reduction of Der pl per m2 vacuumed by the wet procedure increased to 76% (p < 0-005, best time vs baseline), compared with 54% when measured as Der pl per g of dust. The ability of the wet procedure to reduce recoverable allergen and hence patients’ exposure by 75% indicates that high-surfactant solutions can dislodge mite faecal particles (95% of accumulated allergen is in this form). The rapid fall in concentrations supports cleaning as the predominant mechanism of action, although enhanced mite removal must lead to decreased allergen production over the longer term. Residual solvent could also have a direct effect on the mite, although the solution is dilute and most is recovered. Allergen concentration in dust (Der p 1) is the measurement used in clinical studies. We believe that exposure cannot be assessed as Jlgfg because total recoverable dust is ignored. Certainly cleaning cannot be studied in this way. Overall exposure can be assessed only as total recoverable dust (ie, g/m2). This measurement is most likely to correlate with airborne allergen concentrations, probably the best index of natural exposure4 but one that has practical difficulties. Allergy Clinic, Acland Hospital, PETER FELL
Oxford Blackrock Clinic,
Blackrock,
BRUCE MITCHELL
Dublin
Department of Immunology, Middlesex Hospital, London W1N 8AA, UK
JONATHAN BROSTOFF
appropriately orientated MR images. The quantification of T2 relaxation times, available on most commercial MRI systems, similarly enhances identification of HS.2 Although a single MR feature ofHS can be used to diagnose most cases of HS, undue reliance on any one can be misleading. Hippocampal atrophy (although possibly not asymmetry) is a feature of several neurological diseases, including Huntington’s disease, amnesic states,3 and Alzheimer’s disease,’ and HS can exist without measurable hippocampus asymmetry. Similary, T2 signal can be increased in the hippocampus in situations other than HS-for example, foreign tissue lesions, and hamartomas- and care should be taken to minimise partial volume effects. It is the concordance of features of HS, either assessed qualitatively or quantitatively, which helps to achieve the best MRI-based diagnosis and enables its detection in difficult cases. Hippocampal size varies greatly between healthy individuals. In consequence, bilateral abnormalities, which are present in a high proportion of histologically verified hippocampal sclerosismay never be detectable by measurement of hippocampal volumes alone. By contrast, the range of normal hippocampal T2 relaxation times is small. This potentially enables identification of subtle and bilateral hippocampal abnormalities.7 Although conceding the close relation between increased T2 signal and HS, you state "gliosis per se does not result in prolonged T2 relaxation". The relation between gliosis and T2 signal is more controversial than this statement would imply. In rats treated with vigabatrin, T2 relaxation times were prolonged by an average of 7 ms (about 10%) in vivo in areas of cortical gliosis, where no other histopathological change was present.8 Bames and co-workers’ data9 also show a trend towards prolonged T2 relaxation times within the areas of gliosis in their experimental model of cortical injury. We suggest that gliosis may itself prolong T2 relaxation, and that this is a probable explanation for raised T2 signal in features associated with gliosis such as HS, brain scars, and gliotic hamartomas. Research Group, Institute of Neurology, National Hospitals for Nervous Diseases, London WC1N 3BG, UK, and NMR Unit, Institute of Child Health, Hospital for Sick Children, London WC1
Epilepsy
R. A. GRÜNEWALD G. D. JACKSON J. S. DUNCAN
Jackson GD, Berkovic SF, Duncan JS, Connelly A. Four criteria for the diagnosis of hippocampal sclerosis using MRI. Presented at Society of Magnetic Resonance in Medicine meeting; 11th annual scientific meeting, 1992 (abstr 505). 2. Jackson GD, Duncan JS, Connelly A, Shepherd JK. Intractable complex partial seizures assessed by magnetic resonance imaging and quantitative T1 and T2 mapping. Epilepsia 1991; 32 (suppl 1) 12. 3. Press GA, Amaral DG, Squire LR. Hippocampal abnormalities in amnesic patients revealed by high resolution magnetic resonance imaging. Nature 1989; 341: 54-57. 4. Jack CR, Petersen RC, O’Brien P, Tangalos MD. MR-based hippocampal volumetry in the diagnosis of Alzheimer’s disease. Neurology 1992; 42: 183-88. 5. Jackson GD, Kuzniecky R, Cascino G. Normal hippocampal volumes in hippocampal sclerosis; MRI diagnosis based on other features. Epilepsia (in press). 6. Margerison JH, Corsellis JAN. Epilepsy and the temporal lobes Brain 1966; 89: 1.
499-530.
Jackson GD, Duncan JS, Connelly A, Shepherd JK, Powell S. Detection of bilateral hippocampal pathology in intractable temporal lobe epilepsy using magnetic resonance imaging. Presented at Society of Magnetic Resonance in Medicine meeting; 1991 (abstr 910). 8 Jackson GD, Williams SR, van Bruggen N, Williams SCR, Duncan JS. Vigabatrin induced cerebellar and cortical lesions are demonstrated by quantitative MRI. Epilepsia 1991; 32 (suppl 1): 13. 9. Barnes D, McDonald WI, Landon DN, Johnson G. The characterisation of experimental gliosis by quantitative nuclear magnetic resonance imaging. Brain 1988; 222: 83-94. 7.
1. Platts-Mills
TAE, de Weck AL Dust mite allergens and asthma. J Allergy Clin Immunol 1989; 83: 416-27. 2. Sears MR, Hervison GP, Holdaway MD, Hewitt CJ, Flannery EM, Silva PA. The relative risks of sensitivity to grass pollen, house dust mite, and cat dander in the development of childhood asthma, Clin Exp Allergy 1989; 19: 419-24. 3. Chapman MD, Heymann PW, Wilkins SR, Brown MB, Plates-Mills TAE Monoclonal immunoassay for the major dust mite (Dermatophagoides) allergens. J Allergy Clin Immunol 1987; 80: 184-94. 4. Price JA, Pollock I, Little SA, Longbottom JL, Warner JO. Measurement of airborne mite allergen in homes of asthmatic children. Lancet 1990; 336: 895-97.
Improvement in seizures after ivermectin
Magnetic
resonance
SIR,-Your Aug
8 editorial
imaging
in
epilepsy
discusses the assessment of
hippocampal sclerosis (HS) by magnetic resonance imaging (MRI), and concentrates on techniques for quantification of hippocampal volume. In addition to volume assymetry, three other MRI features of HS have been reported: loss or disruption of internal structure, decrease in signal on T1weighted images, and increase in signal on T2 weighted images.1 Quantification improves the estimation of hippocampal asymmetry which is often visible to the naked eye on
SiR,—After the first round of ivermectin mass treatment for onchocerciasis in Kabarole district, Uganda, some epileptics from two communities reported improvements in seizure patterns. To follow up these reports, all epileptics in these communites were asked to come for examination, and 91 met criteria for inclusion in this survey (48 men). The mean age was 15-9years (range 6-50) and, on average, 41 months had elapsed between ivermectin treatment and examination (25—13-0). Grand mal seizures were present in 69 and petit mal in 22.
790
After ivermectin, 34 (37%) of the 91 reported some improvement in either the frequency or severity of seizures. 13 had had no seizures after ivermectin (14%) during, on average, 3-7 months (1-6). In these, the usual frequency of seizures had ranged from six times weekly to once monthly. 7 (8%) noted a transient freedom from seizures after treatment and 14 (15%) reported seizures to be less frequent or intense. Seizures were unchanged in 51 (56%), and worse in 6 (7%). Was the improvement in seizure patterns noted by the 34 subjects due to anticonvulsant properties of ivermectin or was this a spurious observation arising from inaccurate recall of patient or unrepresentative selection? Avermectins produce a sustained increase in gamma-aminobutyric acid release from brain synaptosomes,’ which may explain ivermectin’s anticonvulsant effects in animals stUdies.2 Lamotrigine3 and benzodiazepines’ exert anticonvulsant actions through a similar mechanism. But with a tissue half-life of 2-8 days,s ivermectin’s anticonvulsant actions alone would seem incapable of producing the sustained improvements reported by these 34 epileptics. Could onchocerciasis itself contribute to seizure disorders? Microfilariae of Onchocerca volvulus are found in cerebrospinal fluid6 and optic nerved Marshall and Cherry8 postulated that microfilariae caused Nakalanga dwarfism in Uganda by affecting the pituitary gland. If inflammation evoked by dying microfilariae in the central nervous system did contribute to seizures, clearance of microfilariae by ivermectins might explain the improvements. Basic Health Services, Western Fort Portal, Uganda
Stimulated salivary flow indicates the glands’ ability to respond to a standard gustatory stimulus and was considered abnormal if less than 4 ml per 10 min. We used thet test to compare mean salivary flow. The mean resting whole salivary flow rate for patients on didanosine was 1-6 ml per 5 min (SD 1-05) and 3-8 (1 21) ml per 5 min in patients not taking this drug (p = 0-0002). The mean stimulated salivary flows were 3-49 (2-65) and 4-13 (2-38) ml per 10 min (not significant). Thus we found that didanosine affected the resting but not the stimulated flow rate, which suggests that the drug does not interfere with the parasympathetic reflex stimulation of salivation after mastication, oral or pharyngeal stimulation, taste, and smell. However, didanosine may interfere with the sympathetic impulses that maintain unstimulated saliva production. Xerostomia may lead to appetite and weight loss, dental decay, periodontal infections, and fungal infections such as candidosis. Patients on didanosine who have xerostomia may benefit from the use of salivary stimulants, such as sugarless chewing gum or confectionery. Topical fluoride, oral hygiene instruction and antifungals should be prescribed as necessary. Oral AIDS Center, Department of Stomatology, University of California San Francisco, San Francisco, California 94143-0512, USA 1
Uganda,
W. KIPP
School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
G. BURNHAM
Ministry of Health, Entebbe, Uganda
J. KAMUGISHA
CAROLINE L. DODD DEBORAH GREENSPAN JANICE L. WESTENHOUSE MITCHELL H. KATZ
Cooley TP, Kunches LM, Saunders CA, et al Once-daily administration of 2’,3’-dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS-related complex: results of a phase I trial. N Engl J Med 1990; 322: 1340-45.
Pong S-S, Wang CC, Fritz LC. Studies on the mechanism of action of avermectin B1a stimulation of release of gamma-aminobutyric acid from brain synaptosomes. J Neurochem 1980; 34: 351-58. 2. Mayer TW, Horton ML. Modulation of monomethylhydrazine-induced seizures by ivermectin. Toxicol Lett 1991; 57: 167-73. 3. Brodie MJ. Lamotrigine Lancet 1992; 339: 1397-400. 4. Laukamm-Josten U. The paralyzing effect of midazolam on Onchocerca volvulus microfilariae in vitro. Am J Trop Med Hyg 1987; 37: 152-56. 5. Bennett JL, Williams JF, Dave V. Pharmacology of ivermectin. Parasitol Today 1988; 1.
4: 226-28. 6. Mazzotti L. Presencia de microfilarias de Onchocerca volvulus en el liquido cefalorraquideo de enfermos tratados con hetrazan. R Inst Salubr Enferm Trop Méx
1959; 19: 1-5 Roger FC. The pathogenesis and pathology of ocular onchocerciasis: part IV, the pathology. Am J Ophthalmol 1960; 49: 560-90. 8. Marshall AJ, Cherry JKT. Endocrine dysfunction in a Nakalanga dwarf. Trans R Soc Trop Med Hyg 1961; 55: 188-91 7.
Xerostomia associated with didanosine SiR,—Phase I studies have reported several adverse effects associated with didanosine (2’,3’-dideoxyinosine, ddl) including pancreatitis, peripheral neuropathy, elevations in hepatic transminase levels, serum triglycerides, and creatinine kinase, abnormalities in cardiac conduction, rash, headache, restlessness, insomnia, seizures, and symptomless hyperuricaemia.1-s Xerostomia has not been reported; however, clinicians involved in phase II studies tell us that about 35 % of patients taking didanosine have subjective xerostomia. We used objective criteria to assess whether xerostomia is related to didanosine therapy in HIVinfected patients. We evaluated 14 HIV-infected patients receiving didanosine and 10 HIV-infected patients not receiving the drug. Patients were excluded if they were taking other medications known to cause xerostomia, if they had been given radiation therapy to the head or neck, or if they had a history of HIV-associated salivary gland disease or Sjogren’s syndrome.Patients were asked about any symptoms of dry mouth, such as a need to use salivary stimulants or a frequent need to quench thirst. Objective evaluation consisted of oral examination and sialometry to measure resting whole saliva and stimulated parotid salivary flow. Resting whole saliva is a measure of total basal saliva, including the minor salivary gland secretions, and was regarded as abnormal if it was less than 05 ml per 5 min.
2. Lambert JS, Seidlin M, Reichman RC, et al. 2’,3’-Dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS-related complex a phase I trial. N Engl J Med 1990; 322: 1333-40. 3. Yarchoan R, Mitsuya H, Pluda JM, et al. The National Cancer Institute phase I study of 2’,3’-dideoxyinosine administration in adults with AIDS or AIDS-related complex: analysis of activity and toxicity profiles. Rev Infect Dis 1990; 12 (suppl
S5): S522-33. Rozencweig M, McLaren C, Beltangady M, et al. Overview of phase I trials of 2’,3’-dideoxyinosine (ddI) conducted on adult patients. Rev Infect Dis 1990; 12 (suppl S5): S570-75. 5. Yarchoan R, Pluda JM, Thomas RV, et al. Long-term toxicity/activity profile of 2’,3’-dideoxyinosine in AIDS or AIDS-related complex Lancet 1990; 336: 4.
526-29
Novel delivery system for continuous desferrioxamine infusion in iron-overloaded
patients SiR,—To prevent and treat iron overload after long-term blood transfusion desferrioxamine is given as a slow (8-10 h) subcutaneous infusion 5-6 days a week or intravenously, either with the transfusions or through indwelling cannula. 1.2 The subcutaneous route is time-consuming, painful, and cumbersome; compliance is variable and patients may die young with cardiomyopathy.3 The administration of continuous intravenous desferrioxamine can be difficult. The patient has to reconstitute the drug daily, self-administer it, and carry a battery-operated pump, often strapped to the body. Compliance is better than with the subcutaneous route. However, failure can occur because of the time necessary to prepare the drug and the pump’s noise. In addition, self-preparation increases the risk of infection. We have introduced a new delivery system, which is based around a light, disposable, and silent balloon. When the balloon is filled with 40-60 ml solution, the infusor operates with internal pressure. It has no mechanical device or battery. The contents are delivered via a filter and flow restrictor. This device provides a continuous flow of medication
half, whole, Infusor (Baxter).
as a
or
over
different times and is available the Singleday
multi-day infusor. We used
Desferrioxamine in different doses was diluted in 40-43 ml water for injection and connected to a Port-A-Cath infusion site. Five whole-day infusions are delivered to the patient’s home every 5 days and the used containers are collected. The patient connects the balloon to the infusion set every 24 h. The infusor is compact, and can easily be concealed either in a pocket or in an attractive leather bag that protects the balloon from sunlight when carried outside clothing. We have treated four patients (one female, mean age 22
WET VERSUS DRY VACUUM-CLEANING
Paired t-test, baseline
vs
day 42
or
182, *p < 0’02,
tp < 01, :t:p < 05
times in the first 8 weeks and three times in the next 6 months. Dust from the total area of 2 carpets in each house was collected in separate bags, sieved, weighed, and extracted. Der pl was measured in an ELISA.3 Both wet and dry vacuum-cleaning reduced total recoverable dust by 69% on day 42 and 61 % on day 182, both times being 4 weeks after the last cleaning. The failure of dry vacuuming to reduce allergen concentrations (ie, Der p1 per g fine dust) presumably reflected the equal removal of both allergen bearing and nonallergen bearing dust particles (table). However, the total allergen recoverable was decreased, but the reduction failed to reach statistical significance. The wet procedure reduced the mean recoverable allergen per square metre vacuumed by two-thirds (table). But there was less reduction in mite allergen per g of recovered dust, by about one-third. When all time points were considered, the maximum reduction of Der pl per m2 vacuumed by the wet procedure increased to 76% (p < 0-005, best time vs baseline), compared with 54% when measured as Der pl per g of dust. The ability of the wet procedure to reduce recoverable allergen and hence patients’ exposure by 75% indicates that high-surfactant solutions can dislodge mite faecal particles (95% of accumulated allergen is in this form). The rapid fall in concentrations supports cleaning as the predominant mechanism of action, although enhanced mite removal must lead to decreased allergen production over the longer term. Residual solvent could also have a direct effect on the mite, although the solution is dilute and most is recovered. Allergen concentration in dust (Der p 1) is the measurement used in clinical studies. We believe that exposure cannot be assessed as Jlgfg because total recoverable dust is ignored. Certainly cleaning cannot be studied in this way. Overall exposure can be assessed only as total recoverable dust (ie, g/m2). This measurement is most likely to correlate with airborne allergen concentrations, probably the best index of natural exposure4 but one that has practical difficulties. Allergy Clinic, Acland Hospital, PETER FELL
Oxford Blackrock Clinic,
Blackrock,
BRUCE MITCHELL
Dublin
Department of Immunology, Middlesex Hospital, London W1N 8AA, UK
JONATHAN BROSTOFF
appropriately orientated MR images. The quantification of T2 relaxation times, available on most commercial MRI systems, similarly enhances identification of HS.2 Although a single MR feature ofHS can be used to diagnose most cases of HS, undue reliance on any one can be misleading. Hippocampal atrophy (although possibly not asymmetry) is a feature of several neurological diseases, including Huntington’s disease, amnesic states,3 and Alzheimer’s disease,’ and HS can exist without measurable hippocampus asymmetry. Similary, T2 signal can be increased in the hippocampus in situations other than HS-for example, foreign tissue lesions, and hamartomas- and care should be taken to minimise partial volume effects. It is the concordance of features of HS, either assessed qualitatively or quantitatively, which helps to achieve the best MRI-based diagnosis and enables its detection in difficult cases. Hippocampal size varies greatly between healthy individuals. In consequence, bilateral abnormalities, which are present in a high proportion of histologically verified hippocampal sclerosismay never be detectable by measurement of hippocampal volumes alone. By contrast, the range of normal hippocampal T2 relaxation times is small. This potentially enables identification of subtle and bilateral hippocampal abnormalities.7 Although conceding the close relation between increased T2 signal and HS, you state "gliosis per se does not result in prolonged T2 relaxation". The relation between gliosis and T2 signal is more controversial than this statement would imply. In rats treated with vigabatrin, T2 relaxation times were prolonged by an average of 7 ms (about 10%) in vivo in areas of cortical gliosis, where no other histopathological change was present.8 Bames and co-workers’ data9 also show a trend towards prolonged T2 relaxation times within the areas of gliosis in their experimental model of cortical injury. We suggest that gliosis may itself prolong T2 relaxation, and that this is a probable explanation for raised T2 signal in features associated with gliosis such as HS, brain scars, and gliotic hamartomas. Research Group, Institute of Neurology, National Hospitals for Nervous Diseases, London WC1N 3BG, UK, and NMR Unit, Institute of Child Health, Hospital for Sick Children, London WC1
Epilepsy
R. A. GRÜNEWALD G. D. JACKSON J. S. DUNCAN
Jackson GD, Berkovic SF, Duncan JS, Connelly A. Four criteria for the diagnosis of hippocampal sclerosis using MRI. Presented at Society of Magnetic Resonance in Medicine meeting; 11th annual scientific meeting, 1992 (abstr 505). 2. Jackson GD, Duncan JS, Connelly A, Shepherd JK. Intractable complex partial seizures assessed by magnetic resonance imaging and quantitative T1 and T2 mapping. Epilepsia 1991; 32 (suppl 1) 12. 3. Press GA, Amaral DG, Squire LR. Hippocampal abnormalities in amnesic patients revealed by high resolution magnetic resonance imaging. Nature 1989; 341: 54-57. 4. Jack CR, Petersen RC, O’Brien P, Tangalos MD. MR-based hippocampal volumetry in the diagnosis of Alzheimer’s disease. Neurology 1992; 42: 183-88. 5. Jackson GD, Kuzniecky R, Cascino G. Normal hippocampal volumes in hippocampal sclerosis; MRI diagnosis based on other features. Epilepsia (in press). 6. Margerison JH, Corsellis JAN. Epilepsy and the temporal lobes Brain 1966; 89: 1.
499-530.
Jackson GD, Duncan JS, Connelly A, Shepherd JK, Powell S. Detection of bilateral hippocampal pathology in intractable temporal lobe epilepsy using magnetic resonance imaging. Presented at Society of Magnetic Resonance in Medicine meeting; 1991 (abstr 910). 8 Jackson GD, Williams SR, van Bruggen N, Williams SCR, Duncan JS. Vigabatrin induced cerebellar and cortical lesions are demonstrated by quantitative MRI. Epilepsia 1991; 32 (suppl 1): 13. 9. Barnes D, McDonald WI, Landon DN, Johnson G. The characterisation of experimental gliosis by quantitative nuclear magnetic resonance imaging. Brain 1988; 222: 83-94. 7.
1. Platts-Mills
TAE, de Weck AL Dust mite allergens and asthma. J Allergy Clin Immunol 1989; 83: 416-27. 2. Sears MR, Hervison GP, Holdaway MD, Hewitt CJ, Flannery EM, Silva PA. The relative risks of sensitivity to grass pollen, house dust mite, and cat dander in the development of childhood asthma, Clin Exp Allergy 1989; 19: 419-24. 3. Chapman MD, Heymann PW, Wilkins SR, Brown MB, Plates-Mills TAE Monoclonal immunoassay for the major dust mite (Dermatophagoides) allergens. J Allergy Clin Immunol 1987; 80: 184-94. 4. Price JA, Pollock I, Little SA, Longbottom JL, Warner JO. Measurement of airborne mite allergen in homes of asthmatic children. Lancet 1990; 336: 895-97.
Improvement in seizures after ivermectin
Magnetic
resonance
SIR,-Your Aug
8 editorial
imaging
in
epilepsy
discusses the assessment of
hippocampal sclerosis (HS) by magnetic resonance imaging (MRI), and concentrates on techniques for quantification of hippocampal volume. In addition to volume assymetry, three other MRI features of HS have been reported: loss or disruption of internal structure, decrease in signal on T1weighted images, and increase in signal on T2 weighted images.1 Quantification improves the estimation of hippocampal asymmetry which is often visible to the naked eye on
SiR,—After the first round of ivermectin mass treatment for onchocerciasis in Kabarole district, Uganda, some epileptics from two communities reported improvements in seizure patterns. To follow up these reports, all epileptics in these communites were asked to come for examination, and 91 met criteria for inclusion in this survey (48 men). The mean age was 15-9years (range 6-50) and, on average, 41 months had elapsed between ivermectin treatment and examination (25—13-0). Grand mal seizures were present in 69 and petit mal in 22.
790
After ivermectin, 34 (37%) of the 91 reported some improvement in either the frequency or severity of seizures. 13 had had no seizures after ivermectin (14%) during, on average, 3-7 months (1-6). In these, the usual frequency of seizures had ranged from six times weekly to once monthly. 7 (8%) noted a transient freedom from seizures after treatment and 14 (15%) reported seizures to be less frequent or intense. Seizures were unchanged in 51 (56%), and worse in 6 (7%). Was the improvement in seizure patterns noted by the 34 subjects due to anticonvulsant properties of ivermectin or was this a spurious observation arising from inaccurate recall of patient or unrepresentative selection? Avermectins produce a sustained increase in gamma-aminobutyric acid release from brain synaptosomes,’ which may explain ivermectin’s anticonvulsant effects in animals stUdies.2 Lamotrigine3 and benzodiazepines’ exert anticonvulsant actions through a similar mechanism. But with a tissue half-life of 2-8 days,s ivermectin’s anticonvulsant actions alone would seem incapable of producing the sustained improvements reported by these 34 epileptics. Could onchocerciasis itself contribute to seizure disorders? Microfilariae of Onchocerca volvulus are found in cerebrospinal fluid6 and optic nerved Marshall and Cherry8 postulated that microfilariae caused Nakalanga dwarfism in Uganda by affecting the pituitary gland. If inflammation evoked by dying microfilariae in the central nervous system did contribute to seizures, clearance of microfilariae by ivermectins might explain the improvements. Basic Health Services, Western Fort Portal, Uganda
Stimulated salivary flow indicates the glands’ ability to respond to a standard gustatory stimulus and was considered abnormal if less than 4 ml per 10 min. We used thet test to compare mean salivary flow. The mean resting whole salivary flow rate for patients on didanosine was 1-6 ml per 5 min (SD 1-05) and 3-8 (1 21) ml per 5 min in patients not taking this drug (p = 0-0002). The mean stimulated salivary flows were 3-49 (2-65) and 4-13 (2-38) ml per 10 min (not significant). Thus we found that didanosine affected the resting but not the stimulated flow rate, which suggests that the drug does not interfere with the parasympathetic reflex stimulation of salivation after mastication, oral or pharyngeal stimulation, taste, and smell. However, didanosine may interfere with the sympathetic impulses that maintain unstimulated saliva production. Xerostomia may lead to appetite and weight loss, dental decay, periodontal infections, and fungal infections such as candidosis. Patients on didanosine who have xerostomia may benefit from the use of salivary stimulants, such as sugarless chewing gum or confectionery. Topical fluoride, oral hygiene instruction and antifungals should be prescribed as necessary. Oral AIDS Center, Department of Stomatology, University of California San Francisco, San Francisco, California 94143-0512, USA 1
Uganda,
W. KIPP
School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
G. BURNHAM
Ministry of Health, Entebbe, Uganda
J. KAMUGISHA
CAROLINE L. DODD DEBORAH GREENSPAN JANICE L. WESTENHOUSE MITCHELL H. KATZ
Cooley TP, Kunches LM, Saunders CA, et al Once-daily administration of 2’,3’-dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS-related complex: results of a phase I trial. N Engl J Med 1990; 322: 1340-45.
Pong S-S, Wang CC, Fritz LC. Studies on the mechanism of action of avermectin B1a stimulation of release of gamma-aminobutyric acid from brain synaptosomes. J Neurochem 1980; 34: 351-58. 2. Mayer TW, Horton ML. Modulation of monomethylhydrazine-induced seizures by ivermectin. Toxicol Lett 1991; 57: 167-73. 3. Brodie MJ. Lamotrigine Lancet 1992; 339: 1397-400. 4. Laukamm-Josten U. The paralyzing effect of midazolam on Onchocerca volvulus microfilariae in vitro. Am J Trop Med Hyg 1987; 37: 152-56. 5. Bennett JL, Williams JF, Dave V. Pharmacology of ivermectin. Parasitol Today 1988; 1.
4: 226-28. 6. Mazzotti L. Presencia de microfilarias de Onchocerca volvulus en el liquido cefalorraquideo de enfermos tratados con hetrazan. R Inst Salubr Enferm Trop Méx
1959; 19: 1-5 Roger FC. The pathogenesis and pathology of ocular onchocerciasis: part IV, the pathology. Am J Ophthalmol 1960; 49: 560-90. 8. Marshall AJ, Cherry JKT. Endocrine dysfunction in a Nakalanga dwarf. Trans R Soc Trop Med Hyg 1961; 55: 188-91 7.
Xerostomia associated with didanosine SiR,—Phase I studies have reported several adverse effects associated with didanosine (2’,3’-dideoxyinosine, ddl) including pancreatitis, peripheral neuropathy, elevations in hepatic transminase levels, serum triglycerides, and creatinine kinase, abnormalities in cardiac conduction, rash, headache, restlessness, insomnia, seizures, and symptomless hyperuricaemia.1-s Xerostomia has not been reported; however, clinicians involved in phase II studies tell us that about 35 % of patients taking didanosine have subjective xerostomia. We used objective criteria to assess whether xerostomia is related to didanosine therapy in HIVinfected patients. We evaluated 14 HIV-infected patients receiving didanosine and 10 HIV-infected patients not receiving the drug. Patients were excluded if they were taking other medications known to cause xerostomia, if they had been given radiation therapy to the head or neck, or if they had a history of HIV-associated salivary gland disease or Sjogren’s syndrome.Patients were asked about any symptoms of dry mouth, such as a need to use salivary stimulants or a frequent need to quench thirst. Objective evaluation consisted of oral examination and sialometry to measure resting whole saliva and stimulated parotid salivary flow. Resting whole saliva is a measure of total basal saliva, including the minor salivary gland secretions, and was regarded as abnormal if it was less than 05 ml per 5 min.
2. Lambert JS, Seidlin M, Reichman RC, et al. 2’,3’-Dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS-related complex a phase I trial. N Engl J Med 1990; 322: 1333-40. 3. Yarchoan R, Mitsuya H, Pluda JM, et al. The National Cancer Institute phase I study of 2’,3’-dideoxyinosine administration in adults with AIDS or AIDS-related complex: analysis of activity and toxicity profiles. Rev Infect Dis 1990; 12 (suppl
S5): S522-33. Rozencweig M, McLaren C, Beltangady M, et al. Overview of phase I trials of 2’,3’-dideoxyinosine (ddI) conducted on adult patients. Rev Infect Dis 1990; 12 (suppl S5): S570-75. 5. Yarchoan R, Pluda JM, Thomas RV, et al. Long-term toxicity/activity profile of 2’,3’-dideoxyinosine in AIDS or AIDS-related complex Lancet 1990; 336: 4.
526-29
Novel delivery system for continuous desferrioxamine infusion in iron-overloaded
patients SiR,—To prevent and treat iron overload after long-term blood transfusion desferrioxamine is given as a slow (8-10 h) subcutaneous infusion 5-6 days a week or intravenously, either with the transfusions or through indwelling cannula. 1.2 The subcutaneous route is time-consuming, painful, and cumbersome; compliance is variable and patients may die young with cardiomyopathy.3 The administration of continuous intravenous desferrioxamine can be difficult. The patient has to reconstitute the drug daily, self-administer it, and carry a battery-operated pump, often strapped to the body. Compliance is better than with the subcutaneous route. However, failure can occur because of the time necessary to prepare the drug and the pump’s noise. In addition, self-preparation increases the risk of infection. We have introduced a new delivery system, which is based around a light, disposable, and silent balloon. When the balloon is filled with 40-60 ml solution, the infusor operates with internal pressure. It has no mechanical device or battery. The contents are delivered via a filter and flow restrictor. This device provides a continuous flow of medication
half, whole, Infusor (Baxter).
as a
or
over
different times and is available the Singleday
multi-day infusor. We used
Desferrioxamine in different doses was diluted in 40-43 ml water for injection and connected to a Port-A-Cath infusion site. Five whole-day infusions are delivered to the patient’s home every 5 days and the used containers are collected. The patient connects the balloon to the infusion set every 24 h. The infusor is compact, and can easily be concealed either in a pocket or in an attractive leather bag that protects the balloon from sunlight when carried outside clothing. We have treated four patients (one female, mean age 22
