- Email: [email protected]
Recovery from extreme hypercalcaemia
hypnotic effect, the patient had experienced abstinence phenomena (sweating, tachycardia, tachypnoea, tremors, and severe anxiety) during the day. Interpreting these symptoms as anxiety, she tried to control them by taking zolpidem also during daytime. Soon she reached 70-80 mg per 24 h because abstinence phenomena needed an increasing dose to be controlled. When musclar twitches and myoclonic jerks appeared, the patient called her psychiatrist for help. Diazepam 4 mg daily and gradual zolpidem tapering (1 month) resolved the symptoms. These two cases presented common features and risk factors for benzodiazepine tolerance-related eventseven if the severe withdrawal symptoms could be linked to the high non-clinical doses.
Raymond P Warrell Jr Memorial
Warrell RP Jr, Heller G, Murphy WP, Schulman P, O’Dwyer P. A randomized double-blind study of gallium nitrate compared to etidronate for acute control of cancer-related hypercalcemia. J Clin
1
Regazzetti, Giampiero Covelli
Psychiatry Unit, Bolognini Hospital, Seriate, Italy
Enrico Smeraldi
1 Perrault G, Morel E,
Sanger DJ, Zivkovic B. Lack of tolerance and physical dependence upon repeated treatment with the novel hypnotic zolpidem. J Pharmacol Exp Ther 1992; 263: 298-303. Attali P, Morselli PL. The therapeutic and safety profile of zolpidem. In: Racagni G, Brunello N, Fukuda T, eds. Biological psychiatry. Vol
1. Amsterdarn: Elsevier, 1991: 860-62. 3 Griffith RR, Sannerud CA, Ator NA, Brady JV. Zolpidem behavioural pharmacology in baboons: self-injection, discrimination, tolerance and withdrawal. J Pharmacol Exp Ther 1992; 260: 1199-208. 4 Monti JM. Problems related to long-term use of hypnotics. In: Racagni G, Brunello N, Fukuda T, eds. Biological psychiatry. Vol 1. Amsterdam: Elsevier, 1991: 867-70.
Recovery from extreme hypercalcaemia interested in the report by Gurney and 26, (June p 1611) on the high incidence of failure in colleagues hypercalcaemic patients with high serum concentrations of parathyroid hormone (PTH)-related protein treated with pamidronate. Before the introduction of radioimmunoassays for PTH-related protein, we1 and others2 were impressed that patients with hypercalcaemia associated with epidermoid carcinomas fared poorly when treated with hydration, calcitonin, and biphosphonates. Others have noted poorer responses with equivalent doses of pamidronate in patients with higher concentrations of serum calcium.3 Since gallium nitrate has proved an effective treatment for hypercalcaemia irrespective of tumour histology and the degree of calcium
elevation,
were
we
Oncol 1991; 9: 1467-75. Jaeger P, Burckhardt P. Response to retreatment of malignant hypercalcemia with the biphosphonate AHPrBP (APD): respective role of kidney and bone. J Bone Min Res 1990; 5: 221-26. 3 Gucalp R, Ritch P, Wiernik PH, et al. Comparative study of pamidronate disodium and etidronate disodium in the treatment of cancer-related hypercalcemia. J Clin Oncol 1992; 10: 134-42.
2
Department of Neuropsychiatric Sciences, San Raffaele Hospital, Milan
SiR-We
wish
New York, NY 10021, USA
St Vincent’s Hospital, Dublin 4, Ireland
Department of Neuropsychiatric Sciences, San Raffaele Hospital, IRCCS, University of Milan School of Medicine, Milano 20127, Italy
2
Sloan-Kettering Cancer Center,
John P Crown
Roberto Cavallaro
Maria Grazia
doxorubicin without response, and (due to the investigational status of gallium nitrate which precluded retreatment) recurrent hypercalcaemic episodes of a milder degree were managed with mithramycin, etidronate, calcitonin, and fluids. Antitumour treatment was changed to medroxyprogesterone; she eventually recovered fully and was discharged from hospital after 4 months. She remained stable as an outpatient for 6 months, then developed recurrent hypercalcaemia and died. We believe that the early response in this patient was due to the combined effect of calcitonin plus hydration, whereas the sustained effect was due to gallium nitrate.
to
report the
most
extreme
case
of
hypercalcaemia that we have yet encountered. A 42-year-old woman with breast metastases in bone, skin, and marrow presented with fever and neutropenia. 2 years previously, she had undergone a modified radical mastectomy for stage II cancer with uncertain receptor status, and received 6 months of adjuvant chemotherapy (cyclophosphamide, methotrexate, fluorouracil). 1 week before hospital admission she developed weakness, bone pain, and hypercalcaemia (45 mmolL) managed with parenteral hydration and doxorubicin. She was subsequently readmitted with fever, neutropenia, and a normal serum calcium. Over the next several days, her serum calcium increased despite hydration reaching 8-1 mmol/L (rechecked and found correct). Parenteral hydration was increased, an infusion of gallium nitrate was started (200 mg/m2 per day for 5 days), and she was given 4 doses of salmon calcitonin (8 IU/kg 6 h apart). Although by now she was in coma, her serum calcium fell to normal. She again received
Thiebaud D,
Purkinje cell antibody in lupus ataxia SiR-Neuropsychiatric manifestations are common in systemic lupus erythematosus (SLE), but cerebellar ataxia is seen in less than 2% of SLE patients with central nervous system (CNS) involvement.1,2 We report a 47-year-old woman diagnosed with SLE in 1978 (positive ribonucleoprotein, Sm, and skin-sensitising antibodies). She had been receiving corticosteroids continuously. In May, 1992, she was admitted with dizziness and unstable gait. She was treated with methylprednisolone 1000 mg per day for 3 days (methylprednisolone pulse therapy) and prednisolone 30 mg daily with improvement over the next month, and was
discharged.
In
December, 1992, while on prednisolone 25 mg daily, she noticed gait disturbance and dysarthria gradually returning, and was admitted. Neurological examination demonstrated saccadic ocular pursuit, scanning speech, dysphagia, bilateral ataxia of limbs and ataxic gait. Blood pressure was normal. Laboratory studies showed persistent proteinuria, but lupus coagulant and cardiolipin antibodies were absent. Evoked potentials, electroencephalogram, and cranial computed tomography (CT) revealed no changes. Cerebrospinal fluid had increased protein (56 mg/mL), normal cell count, and positive oligoclonal IgG band. A magnetic resonance image (MRI) revealed no abnormal lesions in the cerebellum. The patient was started on methylprednisolone pulse therapy and then
prednisolone. Her neurological condition improved slightly. In February, 1993, a second MRI showed progression of atrophic change in the cerebellum. Serum contained specific antibody to human Purkinje cells. Immunoblotting analysis showed specific IgG antibody to the 75 kDa protein in the cerebellar cortex (figure). The patient still had cerebellar ataxia and dysarthria. Lupus coagulant and cardiolipin antibodies are associated with various neurological manifestations.3 Guranieri et al4 and Lafer et als explored cross-reactions of phospholipid antibodies with epitopes on CNS phospholipids such as sphingomyelin.4,5The presence of neural antibodies is related to diffuse 50 mg
CNS involvement.6 In
our
patient, Purkinje-cell antibody
or
375
Raymond P Warrell Jr Memorial
Warrell RP Jr, Heller G, Murphy WP, Schulman P, O’Dwyer P. A randomized double-blind study of gallium nitrate compared to etidronate for acute control of cancer-related hypercalcemia. J Clin
1
Regazzetti, Giampiero Covelli
Psychiatry Unit, Bolognini Hospital, Seriate, Italy
Enrico Smeraldi
1 Perrault G, Morel E,
Sanger DJ, Zivkovic B. Lack of tolerance and physical dependence upon repeated treatment with the novel hypnotic zolpidem. J Pharmacol Exp Ther 1992; 263: 298-303. Attali P, Morselli PL. The therapeutic and safety profile of zolpidem. In: Racagni G, Brunello N, Fukuda T, eds. Biological psychiatry. Vol
1. Amsterdarn: Elsevier, 1991: 860-62. 3 Griffith RR, Sannerud CA, Ator NA, Brady JV. Zolpidem behavioural pharmacology in baboons: self-injection, discrimination, tolerance and withdrawal. J Pharmacol Exp Ther 1992; 260: 1199-208. 4 Monti JM. Problems related to long-term use of hypnotics. In: Racagni G, Brunello N, Fukuda T, eds. Biological psychiatry. Vol 1. Amsterdam: Elsevier, 1991: 867-70.
Recovery from extreme hypercalcaemia interested in the report by Gurney and 26, (June p 1611) on the high incidence of failure in colleagues hypercalcaemic patients with high serum concentrations of parathyroid hormone (PTH)-related protein treated with pamidronate. Before the introduction of radioimmunoassays for PTH-related protein, we1 and others2 were impressed that patients with hypercalcaemia associated with epidermoid carcinomas fared poorly when treated with hydration, calcitonin, and biphosphonates. Others have noted poorer responses with equivalent doses of pamidronate in patients with higher concentrations of serum calcium.3 Since gallium nitrate has proved an effective treatment for hypercalcaemia irrespective of tumour histology and the degree of calcium
elevation,
were
we
Oncol 1991; 9: 1467-75. Jaeger P, Burckhardt P. Response to retreatment of malignant hypercalcemia with the biphosphonate AHPrBP (APD): respective role of kidney and bone. J Bone Min Res 1990; 5: 221-26. 3 Gucalp R, Ritch P, Wiernik PH, et al. Comparative study of pamidronate disodium and etidronate disodium in the treatment of cancer-related hypercalcemia. J Clin Oncol 1992; 10: 134-42.
2
Department of Neuropsychiatric Sciences, San Raffaele Hospital, Milan
SiR-We
wish
New York, NY 10021, USA
St Vincent’s Hospital, Dublin 4, Ireland
Department of Neuropsychiatric Sciences, San Raffaele Hospital, IRCCS, University of Milan School of Medicine, Milano 20127, Italy
2
Sloan-Kettering Cancer Center,
John P Crown
Roberto Cavallaro
Maria Grazia
doxorubicin without response, and (due to the investigational status of gallium nitrate which precluded retreatment) recurrent hypercalcaemic episodes of a milder degree were managed with mithramycin, etidronate, calcitonin, and fluids. Antitumour treatment was changed to medroxyprogesterone; she eventually recovered fully and was discharged from hospital after 4 months. She remained stable as an outpatient for 6 months, then developed recurrent hypercalcaemia and died. We believe that the early response in this patient was due to the combined effect of calcitonin plus hydration, whereas the sustained effect was due to gallium nitrate.
to
report the
most
extreme
case
of
hypercalcaemia that we have yet encountered. A 42-year-old woman with breast metastases in bone, skin, and marrow presented with fever and neutropenia. 2 years previously, she had undergone a modified radical mastectomy for stage II cancer with uncertain receptor status, and received 6 months of adjuvant chemotherapy (cyclophosphamide, methotrexate, fluorouracil). 1 week before hospital admission she developed weakness, bone pain, and hypercalcaemia (45 mmolL) managed with parenteral hydration and doxorubicin. She was subsequently readmitted with fever, neutropenia, and a normal serum calcium. Over the next several days, her serum calcium increased despite hydration reaching 8-1 mmol/L (rechecked and found correct). Parenteral hydration was increased, an infusion of gallium nitrate was started (200 mg/m2 per day for 5 days), and she was given 4 doses of salmon calcitonin (8 IU/kg 6 h apart). Although by now she was in coma, her serum calcium fell to normal. She again received
Thiebaud D,
Purkinje cell antibody in lupus ataxia SiR-Neuropsychiatric manifestations are common in systemic lupus erythematosus (SLE), but cerebellar ataxia is seen in less than 2% of SLE patients with central nervous system (CNS) involvement.1,2 We report a 47-year-old woman diagnosed with SLE in 1978 (positive ribonucleoprotein, Sm, and skin-sensitising antibodies). She had been receiving corticosteroids continuously. In May, 1992, she was admitted with dizziness and unstable gait. She was treated with methylprednisolone 1000 mg per day for 3 days (methylprednisolone pulse therapy) and prednisolone 30 mg daily with improvement over the next month, and was
discharged.
In
December, 1992, while on prednisolone 25 mg daily, she noticed gait disturbance and dysarthria gradually returning, and was admitted. Neurological examination demonstrated saccadic ocular pursuit, scanning speech, dysphagia, bilateral ataxia of limbs and ataxic gait. Blood pressure was normal. Laboratory studies showed persistent proteinuria, but lupus coagulant and cardiolipin antibodies were absent. Evoked potentials, electroencephalogram, and cranial computed tomography (CT) revealed no changes. Cerebrospinal fluid had increased protein (56 mg/mL), normal cell count, and positive oligoclonal IgG band. A magnetic resonance image (MRI) revealed no abnormal lesions in the cerebellum. The patient was started on methylprednisolone pulse therapy and then
prednisolone. Her neurological condition improved slightly. In February, 1993, a second MRI showed progression of atrophic change in the cerebellum. Serum contained specific antibody to human Purkinje cells. Immunoblotting analysis showed specific IgG antibody to the 75 kDa protein in the cerebellar cortex (figure). The patient still had cerebellar ataxia and dysarthria. Lupus coagulant and cardiolipin antibodies are associated with various neurological manifestations.3 Guranieri et al4 and Lafer et als explored cross-reactions of phospholipid antibodies with epitopes on CNS phospholipids such as sphingomyelin.4,5The presence of neural antibodies is related to diffuse 50 mg
CNS involvement.6 In
our
patient, Purkinje-cell antibody
or
375