228
for oxygen carrying capacity. Further studies should be done under controlled conditions that include these indices, which we think are important for the outcome of the patients. A. BENZER
G. LUZ M. GOTTARDIS F. PÜHRINGER
Department of Anaesthesia, University Hospital, A-6020 Innsbruck, Austria
1.
2.
Chapler CK, Cain SM. The pshysiologic reserve in oxygen carrying capacity: studies in experimental hemodilution. Can J Physiol Pharmacol 1986; 64: 7-12. Severinghaus JW. Simple, accurate equations for human blood O2 dissociation computations. J Appl Physiol 1979; 46: 599-602.
Central
system involvement in infantile botulism
nervous
SIR,-We report an infant with botulism caused by botulinum toxin type B who recovered from progressive paralysis, but showed
persistent neurological changes. She is a second child with no family history of neurological or neuromuscular disease. Birth was normal at full-term. She thrived and had full motor function of her limbs until two months of age when progressive hypotonia and muscle weakness developed over four days, followed by severe constipation, difficulty with sucking and swallowing, and bilateral ptosis. She gradually improved over the following three weeks, but she was left with a residual weakness of the left arm and hand. She had intermittent brief episodes of apnoea and was placed on a respiratory monitor; ventilation was not needed. Laboratory tests, including lumbar puncture, were normal, and no viruses were cultured. Electromyographic nerve conduction and edrophonium tests were also normal. Two electroencephalographic (EEG) recordings taken during the acute illness showed bursts of spikes and excessive theta waves bilaterally, mainly over the posterior and temporal regions. A third taken while on treatment with sodium valproate was normal. Two specimens of stool contained Clostridium botulinum toxin type B, as shown by mouse inoculation. The organism was not detected in stool or feeds. A virus antibody screen (by Dr John Coleman) was negative. A computed tomographic (CT) scan taken during the recovery phase showed attenuation of cortical thickness over the frontal and temporal lobes, especially on the left side. Gautier et all have reported a male infant similarly affected by C botulinum toxin type A. He had a dysrhythmic EEG associated with abnormal auditory evoked responses with implied brain stem dysfunction. Similar EEG abnormalities were also reported by Smith et al.2 Gautier and colleagues proposed that the toxin had affected central neurological processes, having penetrated into the infant’s developing brain. Previous pathological reports in adults suggested that neuropathological changes had been caused by anoxia, but our patient showed no evidence of this condition. Black and Dolly’ have reported receptors for botulinum neurotoxin A at cholinergic sites in rat brain. The receptors were mainly seen in the rat temporal hom, a site where atrophy was noted on the CT scan in our
patient.
The child had no neurological defect initially. There may have been a pre-existing minor cerebral defect not evident clinically, which could have allowed the entrance of toxin thus causing persistent changes. We suggest that in our patient toxin did enter the nervous system causing semi-permanent or permanent damage to the cerebral cortex which had not fully recovered.
Westminster Children’s Hospital, London SW1 P 2NS, UK
S. JONES C. HAUGH F. STARER
Z. HUMA Y. YOUNG L. SINCLAIR
1. Gautier E, Gallusser A, Despland PA. Botulisme infantile. Helv Paediatr Acta 1988; 43: 521-30. 2. Smith GE, Hinde F, Westmorland D, Berry PN, Gilbert RJ. Infantile botulism. Arch Dis Child 1989; 64: 871-72. 3. Black JP, Dolly JO. Selective acceptors for Botulinum neutotoxin A in the central and
peripheral nervous systems. Neuroscience 1987; 23: 767-79.
More in
spider venom than venom?
SIR,-A 40-year-old guitarist spent the night in a London hotel mainly frequented by foreign, particularly Australian, students. The next morning he noted a small bite on the dorsum of the second web space of his right hand. This became painful and his hand and forearm began to swell. At the local casualty department he was given antibiotics and painkillers but his condition deteriorated and he was admitted to another hospital that night with an acute hand infection. He was treated with systemic antibiotics, and debridement and drainage were required on the following day and some 3 days later. He also underwent a short course of hyperbaric oxygen. 2 weeks after the initial injury he was transferred to our hospital with extensive skin loss of the dorsum of his hand, index, middle and ring fingers. He underwent a further debridement, and skin cover was attempted with a left lateral arm pedicle flap. Just before the flap was to be divided he had a severe cellulitis; it was noted that there was no skin take and the flap was returned to its original site. The next 2 months saw little change with periods of healing followed by areas of breakdown despite intensive dressings. Multiple swabs and wound scrapings yielded either no significant bacterial growth or, on two occasions, a scanty growth of Pseudomonas aeruginosa. It was at this point that blisters developed over his elbow. We sought advice from experts in Australia and were informed of similar cases thought to follow venomous spider bites where acid-fast bacilli had been found in chronic progressive lesions; formal investigations into the flora of spider venoms is underway (S. Sutherland, personal communication). We aspirated one blister, and Ziehl-Neelsen staining revealed acid-fast bacilli. He was put on clofazimine and rifabutin, and over the next 2 months the raw areas progressively healed. Despite prolonged culture of the aspirated material on Lowenstein-Jensen slopes and in Kirchner’s medium at 37°C and 30°C, mycobacteria were not isolated. The antimycobacterial agents were discontinued after 3 months. The patient now has complete skin cover and, with the aid of physiotherapy, has returned to his profession. Departments of Microbiology and Plastic Surgery, Withington Hospital, Manchester M20 8LR, UK
BERYL A. OPPENHEIM IAN TAGGART
Rheumatoid arthritis, diabetes, and
schizophrenia p 1214) reports a negative association and insulin-dependent diabetes mellitus (IDDM) in Sweden. He concludes that in schizophrenics the autoimmune form of diabetes is rarer whereas the non-insulindependent type is more common than expected. We have reviewed publications on the association between schizophrenia and another autoimmune disease, rheumatoid arthritis (RA).’ At least ten such investigations have been done, including two record linkage studies. Although some of the early studies were flawed methodologically, all showed a consistent negative association between rheumatoid arthritis and schizophrenia. Overall, schizophrenics had a four-fold to six-fold reduction in the risk of having RA. Both RA and schizophrenia have a strong genetic component, and one possible explanation for the negative association is that the inheritance of genes for susceptibility to one disease protects against the development of the other. The location and nature of any such genes are uncertain. In common with other autoimmune diseases, RA is strongly associated with human leucocyte antigen (HLA), specifically with the class II antigens HLA DR1 and DR4, the molecular genetic basis for which has lately been clarified.2 Although offspring of schizophrenics have a ten-fold risk of disease, and twin concordance rates of 30-75% are seen, the associations with HLA antigens are much less clear. However, some degree of HLA association has been shown when the disease is subdivided into paranoid (HLA-A9) and hebephrenic (severe) forms (HLA-A1 and HLA-B8).3 Two investigations have shown that the antigens HLA-A1 and HLA-A1/B8 are also negatively associated with RA.4,s
SiR,—Dr Finney (Nov 18,
between
schizophrenia
for oxygen carrying capacity. Further studies should be done under controlled conditions that include these indices, which we think are important for the outcome of the patients. A. BENZER
G. LUZ M. GOTTARDIS F. PÜHRINGER
Department of Anaesthesia, University Hospital, A-6020 Innsbruck, Austria
1.
2.
Chapler CK, Cain SM. The pshysiologic reserve in oxygen carrying capacity: studies in experimental hemodilution. Can J Physiol Pharmacol 1986; 64: 7-12. Severinghaus JW. Simple, accurate equations for human blood O2 dissociation computations. J Appl Physiol 1979; 46: 599-602.
Central
system involvement in infantile botulism
nervous
SIR,-We report an infant with botulism caused by botulinum toxin type B who recovered from progressive paralysis, but showed
persistent neurological changes. She is a second child with no family history of neurological or neuromuscular disease. Birth was normal at full-term. She thrived and had full motor function of her limbs until two months of age when progressive hypotonia and muscle weakness developed over four days, followed by severe constipation, difficulty with sucking and swallowing, and bilateral ptosis. She gradually improved over the following three weeks, but she was left with a residual weakness of the left arm and hand. She had intermittent brief episodes of apnoea and was placed on a respiratory monitor; ventilation was not needed. Laboratory tests, including lumbar puncture, were normal, and no viruses were cultured. Electromyographic nerve conduction and edrophonium tests were also normal. Two electroencephalographic (EEG) recordings taken during the acute illness showed bursts of spikes and excessive theta waves bilaterally, mainly over the posterior and temporal regions. A third taken while on treatment with sodium valproate was normal. Two specimens of stool contained Clostridium botulinum toxin type B, as shown by mouse inoculation. The organism was not detected in stool or feeds. A virus antibody screen (by Dr John Coleman) was negative. A computed tomographic (CT) scan taken during the recovery phase showed attenuation of cortical thickness over the frontal and temporal lobes, especially on the left side. Gautier et all have reported a male infant similarly affected by C botulinum toxin type A. He had a dysrhythmic EEG associated with abnormal auditory evoked responses with implied brain stem dysfunction. Similar EEG abnormalities were also reported by Smith et al.2 Gautier and colleagues proposed that the toxin had affected central neurological processes, having penetrated into the infant’s developing brain. Previous pathological reports in adults suggested that neuropathological changes had been caused by anoxia, but our patient showed no evidence of this condition. Black and Dolly’ have reported receptors for botulinum neurotoxin A at cholinergic sites in rat brain. The receptors were mainly seen in the rat temporal hom, a site where atrophy was noted on the CT scan in our
patient.
The child had no neurological defect initially. There may have been a pre-existing minor cerebral defect not evident clinically, which could have allowed the entrance of toxin thus causing persistent changes. We suggest that in our patient toxin did enter the nervous system causing semi-permanent or permanent damage to the cerebral cortex which had not fully recovered.
Westminster Children’s Hospital, London SW1 P 2NS, UK
S. JONES C. HAUGH F. STARER
Z. HUMA Y. YOUNG L. SINCLAIR
1. Gautier E, Gallusser A, Despland PA. Botulisme infantile. Helv Paediatr Acta 1988; 43: 521-30. 2. Smith GE, Hinde F, Westmorland D, Berry PN, Gilbert RJ. Infantile botulism. Arch Dis Child 1989; 64: 871-72. 3. Black JP, Dolly JO. Selective acceptors for Botulinum neutotoxin A in the central and
peripheral nervous systems. Neuroscience 1987; 23: 767-79.
More in
spider venom than venom?
SIR,-A 40-year-old guitarist spent the night in a London hotel mainly frequented by foreign, particularly Australian, students. The next morning he noted a small bite on the dorsum of the second web space of his right hand. This became painful and his hand and forearm began to swell. At the local casualty department he was given antibiotics and painkillers but his condition deteriorated and he was admitted to another hospital that night with an acute hand infection. He was treated with systemic antibiotics, and debridement and drainage were required on the following day and some 3 days later. He also underwent a short course of hyperbaric oxygen. 2 weeks after the initial injury he was transferred to our hospital with extensive skin loss of the dorsum of his hand, index, middle and ring fingers. He underwent a further debridement, and skin cover was attempted with a left lateral arm pedicle flap. Just before the flap was to be divided he had a severe cellulitis; it was noted that there was no skin take and the flap was returned to its original site. The next 2 months saw little change with periods of healing followed by areas of breakdown despite intensive dressings. Multiple swabs and wound scrapings yielded either no significant bacterial growth or, on two occasions, a scanty growth of Pseudomonas aeruginosa. It was at this point that blisters developed over his elbow. We sought advice from experts in Australia and were informed of similar cases thought to follow venomous spider bites where acid-fast bacilli had been found in chronic progressive lesions; formal investigations into the flora of spider venoms is underway (S. Sutherland, personal communication). We aspirated one blister, and Ziehl-Neelsen staining revealed acid-fast bacilli. He was put on clofazimine and rifabutin, and over the next 2 months the raw areas progressively healed. Despite prolonged culture of the aspirated material on Lowenstein-Jensen slopes and in Kirchner’s medium at 37°C and 30°C, mycobacteria were not isolated. The antimycobacterial agents were discontinued after 3 months. The patient now has complete skin cover and, with the aid of physiotherapy, has returned to his profession. Departments of Microbiology and Plastic Surgery, Withington Hospital, Manchester M20 8LR, UK
BERYL A. OPPENHEIM IAN TAGGART
Rheumatoid arthritis, diabetes, and
schizophrenia p 1214) reports a negative association and insulin-dependent diabetes mellitus (IDDM) in Sweden. He concludes that in schizophrenics the autoimmune form of diabetes is rarer whereas the non-insulindependent type is more common than expected. We have reviewed publications on the association between schizophrenia and another autoimmune disease, rheumatoid arthritis (RA).’ At least ten such investigations have been done, including two record linkage studies. Although some of the early studies were flawed methodologically, all showed a consistent negative association between rheumatoid arthritis and schizophrenia. Overall, schizophrenics had a four-fold to six-fold reduction in the risk of having RA. Both RA and schizophrenia have a strong genetic component, and one possible explanation for the negative association is that the inheritance of genes for susceptibility to one disease protects against the development of the other. The location and nature of any such genes are uncertain. In common with other autoimmune diseases, RA is strongly associated with human leucocyte antigen (HLA), specifically with the class II antigens HLA DR1 and DR4, the molecular genetic basis for which has lately been clarified.2 Although offspring of schizophrenics have a ten-fold risk of disease, and twin concordance rates of 30-75% are seen, the associations with HLA antigens are much less clear. However, some degree of HLA association has been shown when the disease is subdivided into paranoid (HLA-A9) and hebephrenic (severe) forms (HLA-A1 and HLA-B8).3 Two investigations have shown that the antigens HLA-A1 and HLA-A1/B8 are also negatively associated with RA.4,s
SiR,—Dr Finney (Nov 18,
between
schizophrenia
