Reversible cerebral vasoconstriction syndrome associated with autonomic dysreflexia

A 32-year-old man with a residual spastic quadriparesis from a traumatic C5–C6 fracture experienced a severe thunderclap headache. The medical history revealed an episode of autonomic dysreflexia (AD) due to neurogenic bladder/urinary tract infection (UTI). Blood pressure monitoring at admission revealed hypertension; blood pressure reaching 160/100 mmHg (average blood pressure in these patients and also in this patient being 90/60 mmHg). CT scan of the head, cerebrospinal fluid examination, CT angiography and MR angiography of the brain vessels were normal. Another UTI and a subsequent spell of AD were diagnosed. The patient continued to experience recurrent thunderclap headaches. Selective catheter cerebral angiography revealed multiple calibre changes in the intracranial blood vessels. A diagnosis of reversible cerebral vasoconstriction syndrome (RCVS) due to AD was considered. A magnetic resonance imaging (MRI) of the brain after 2 weeks revealed ischaemic changes in the left hemisphere. Follow-up brain MRI after 3 weeks showed reduction in size of the ischaemic changes, and catheter angiography after 6 weeks demonstrated improvement/normalization. A diagnosis of RCVS could be established. Repeated MRI/CT of the brain after 6 months demonstrated a large infarction in the left hemisphere. RCVS has been reported to occur in various clinical settings. It can occur in the setting of AD in patients with traumatic cervical cord injury. Prompt recognition of RCVS may be of vital importance to avoid further morbidity in patients with spinal cord injury.     

Identification of a cellulose synthase-associated protein required for cellulose biosynthesis

Cellulose synthase-interactive protein 1 (CSI1) was identified in a two-hybrid screen for proteins that interact with cellulose synthase (CESA) isoforms involved in primary plant cell wall synthesis. CSI1 encodes a 2,150-amino acid protein that contains 10 predicted Armadillo repeats and a C2 domain. Mutations in CSI1 cause defective cell elongation in hypocotyls and roots and reduce cellulose content. CSI1 is associated with CESA complexes, and csi1 mutants affect the distribution and movement of CESA complexes in the plasma membrane.     

Mortality risk up to 25 years after initiation of treatment among 420 Swedish women with alcohol addiction

Aims   Women treated for alcohol addiction have mortality rates three to five times those of women from the general population (GP). However, these figures may be inflated because socially disadvantaged women with advanced drinking careers are over-represented in previous studies. Our aim was to study the long-term mortality of socially relatively well-functioning patients coming to their first treatment, compared to matched GP controls.
Design   The mortality rates and causes of death were compared between patients and their matched GP controls, using data from the Causes of Death Register throughout the follow-up period (0–25 years).
Setting   A specialized treatment programme for women only, called 'Early treatment for Women with Alcohol Addiction' (EWA) at the Karolinska Hospital, Stockholm, Sweden.
Participants   Subjects ( n  = 420) receiving their first treatment at the EWA programme, compared to a group of matched GP women ( n  = 2037).
Findings   The women patients had significantly higher mortality than matched GP controls throughout the whole follow-up period, with a relative risk of 2.4. However, the younger women had four times higher mortality than their matched controls. The peak of deaths occurred during the first 5 years, and alcohol-related causes of death were highly over-represented, as were uncertain suicides and accidents.
Conclusions   First-time-treated women with alcohol addiction have a substantially lower mortality than reported previously from clinical samples, except for the youngest group. Our figures were corrected for confounding factors such as socio-demographic status. We believe our results could apply to broader groups of heavy drinking women, inside or outside specialized treatment settings.     

Associations between venous thromboembolism and antipsychotics. A study of the WHO database of adverse drug reactions

BACKGROUND: Concern has been raised about the occurrence of venous thromboembolism (VTE) during treatment with antipsychotics. However, to date, clozapine is the only antipsychotic agent for which recurring evidence supports an association with VTE. Therefore, the aim of this study was to investigate the association between antipsychotic drugs, including clozapine and VTE. STUDY DESIGN AND METHODS: Data mining of the WHO database of adverse drug reactions (ADRs) using Bayesian statistics is in routine use for early alerting to possible ADRs. An information component measure was used to investigate the association between antipsychotic drugs and VTE reactions in the database. RESULTS: A total of 754 suspected cases of VTE related to treatment with antipsychotics had been reported. After excluding cases related to clozapine, 379 cases remained. A robust association was found for the second-generation antipsychotics group but not for the high-potency, first-generation antipsychotics group or the low-potency first-generation antipsychotics group. The individual compounds with statistically significant associations were olanzapine, sertindole and zuclopenthixol. A time-dependent analysis showed that the associations were positive for these drugs in 2002, 2001 and 2003, respectively. Case analyses were undertaken after excluding ten suspected duplicate reports. Of the remaining 369 cases, 91 cases were associated with olanzapine, 9 with zuclopenthixol and 6 with sertindole. CONCLUSIONS: VTE was more often reported with the antipsychotic drugs olanzapine, sertindole and zuclopenthixol than with other drugs in the WHO database. Further studies are warranted to explain this disproportional reporting. Since the associations found were based on incomplete clinical data, the results should be considered as preliminary and interpreted cautiously.     

Postoperative outcome of caesarean sections and other major emergency obstetric surgery by clinical officers and medical officers in Malawi

Background  

Clinical officers perform much of major emergency surgery in Malawi, in the absence of medical officers. The aim of this study was to validate the advantages and disadvantages of delegation of major obstetric surgery to non-doctors.     

Diagnostic considerations of tongue-base malignancies

Summary Forty-two patients with malignancies localized to the base of the tongue were treated at Sahlgrenska Hospital between 1971 and 1980. These patients were re-analyzed with respect to symptomatology and clinical outcome. Pain in the mouth, throat, and ears as well as swallowing difficulties were the most frequent overt symptoms of disease. In general, patients experienced symptoms for at least 3 months before a positive tumor diagnosis was made. In all, 75% of the patients were found to have large tumors which extended beyond the base of the tongue. Most of the patients were treated with irradiation. The overall 3-year survival rate was 28%, while individual patient survival was related to the size of the primary tumor and to the occurrence of lymph node metastases. Careful attention to symptomatology may reduce delays in establishing an accurate diagnosis and consequently improve the prognosis for patients with these cancers.     

A limited sampling strategy for estimation of the cladribine plasma area under the concentration versus time curve after intermittent i.v. infusion,s.c. injection,and oral administration

 Cladribine is a newly developed antimetabolite with promising activity in lymphoproliferative disorders. Recent pharmacokinetics investigations have suggested that there is a relationship between its plasma area under the concentration versus time curve (AUC) and the degree of neutropenia posttreatment as well as the therapeutic outcome in hairy-cell leukemia. To enable a simple estimation of the plasma AUC, a limited sampling strategy was developed. Stepwise linear regression was used to determine which were the most important data points for estimation of the plasma AUC after 2-h i.v. infusion, s.c. injection (5 mg/m²), and oral administration (10 mg/m²) in 27 patients. The most important data points after i.v. infusion in 12 patients were 1, 4, and 24 h, in order of importance. The AUC could be estimated as 2.9081×C _1h ⁺5.1851×C _4h ⁺20.3265×C _24h .The accuracy and precision (mean value±SD for the determined/estimated AUC was 0.99±0.053) of the model could not be increased by the addition of more data points. A somewhat lower accuracy and precision (0.96± 0.089) was seen with the 2-, 4-, and 24-h data points. These were used to test the regression technique prospectively for the estimation of the AUC after i.v. administration in another set of 10 patients. The accuracy and precision of the estimation of the AUC was similar in this group (1.01±0.109). In all, 11 patients were treated orally (10 mg/m²) and 10 patients were treated by s.c. injection (5 mg/m²). The most important data points for estimation of the AUC were 2.5, 24, and 0.5 h after oral administration (AUC=0.8630×C _0.5 h+ 4.2337×C _2.5h ⁺45.4364×C _24h ) and 9, 1, and 16 h after s.c. injection (AUC=1.8821×C _1h +16.4256×C _9h ⁺ 25.4518×C _16h ). The accuracy and precision were 1.01±0.064 after oral dosing and 0.99±0.11 after s.c. injection. The derived mathematical models are reliable for estimation of the plasma AUC of cladribine after 2-h i.v. infusion, oral administration, and s.c. injection. Received: 8 October 1995/Accepted: 1 March 1996     

Synthesis of a small library of 3-(carboranylalkyl)thymidines and their biological evaluation as substrates for human thymidine kinases 1 and 2

A small library consisting of two series of thymidine derivatives containing o-carboranylalkyl groups at the N-3 position was prepared. In both series, alkyl spacers of 2-7 methylene units were placed between the o-carborane cage and the thymidine scaffold. In one series, an additional dihydroxypropyl substituent was introduced at the second carbon atom of the carborane cage. In the series of N-3-substituted carboranyl thymidines without additional dihydroxypropyl substituent, three steps were required to obtain the target compounds in overall yields as high as 75%, while in the series of N-3-substituted carboranyl thymidines with additional dihydroxypropyl substituent, 9-10 steps were necessary with significantly lower overall yield. All target compounds were good substrates of human cytosolic thymidine kinase 1 while they were, if at all, poor substrates of the mitochondrial thymidine kinase 2. There was only a minor difference in phosphorylation rates between N-3-substituted carboranyl thymidines with additional dihydroxypropyl substituents with thymidine kinase 1 (range: 13-49% relative to thymidine) and their counterparts lacking this group (range: 11-57% relative to thymidine). Tether lengths of two and five methylene groups in both series gave the highest enzyme activities in the present study. A hypothesis for this result is presented.