Brain uptake of iomazenil in cirrhotic patients: a single photon emission tomography study.

Brain uptake of 123I-iomazenil was studied in seven cirrhotic patients and eight normal controls using single photon emission computerized tomography. The highest concentration of the ligand was found in the occipital cortex, which corresponds to the brain region with the highest concentration of benzodiazepine receptors. The peak uptake was delayed in patients across all brain regions. The uptake in occipital cortex was higher in low albumin cirrhotics. Patients with low albumin also presented a more delayed peak uptake in occipital cortex and a higher volume of distribution of iomazenil in plasma, compared to patients with normal albumin levels and controls. The changes in brain uptake (delayed peak uptake and increased maximal uptake in occipital cortex) appears to reflect changes in the pharmacokinetics of the ligand, particularly in cirrhotics with low levels of plasma albumin. The curve of brain uptake of the tracer was modelled into a two compartments equation, which seems to provide a practical and reliable method to calculate the slopes of acquisition and decay, time to peak and maximal acquisition.     

Pharmacodynamics of doxacurium during cardiac surgery with hypothermic cardio-pulmonary bypass

Purpose

To determine the characteristics of neuromuscular block produced by two and three times the 95% effective dose (ED₉₅) of doxacurium in patients undergoing coronary artery surgery with hypothermic cardiopulmonary bypass.

Methods

In a prospective non randomized study, ten patients received doxacurium 0.05 mg·kg^?1 (Group 1) and ten others received 0.075 mg · kg^?1 (Group 2) with midazolam and sufentanil. The mechanomyographic response of the adductor pollicis muscle after supramaximal train-of-four (TOF) stimulation of the ulnar nerve was recorded intraoperatively and postoperatively. Additional doxacurium (10% of the initial dose) was administered until sternal closure whenever the first twitch (T₁) had recovered to 25% of control.

Results

The onset time (time to maximal T₁ depression) of doxacurium was 390 ± 148 sec in Group 1 and 370 ± 74 sec in Group 2 (P = 0.71). The clinical duration of neuromuscular block (time to 25% T₁ recovery) was 165 ± 90 min in Group 1 and 258 ± 86 min in Group 2 (P = 0.03). On arrival to recovery room the mean T₁ was 57 ± 23% in Group 1 and 24 ± 21% in Group 2(P = 0.003); the mean T₄/T₁ ratio was 0.25 ± 0.15 for five patients of Group 1 with four responses to TOF stimulation and 0.10 for the only patient of Group 2 with four twitches.

Conclusion

In contrast with findings in patients without cardiac disease, this study shows comparable onset times of doxacurium with doses of two and three times ED₉₅. The clinical duration of doxacurium is 60 to 100% longer than previously reported in noncardiac surgery.     

Memory functions, alertness and mood of long-term benzodiazepine users: a preliminary investigation of the effects of a normal daily dose

The effects of a normal daytime dose of a benzodiazepine (BZ) on memory functions and mood were assessed in 20 out-patients who had taken BZs regularly for an average of 10 years. The results implied that these chronic users may have developed tolerance differentially to the sedative, anxiolytic and amnesic effects of one dose of BZ. A daytime dose did not produce subjective sedation. Lack of change in psychomotor performance and certain memory measures may either show tolerance or imply that the drug counteracts a possible practice effect. Anxiety levels decreased markedly after a daily dose, but this does not necessarily imply a purely pharmacological effect. Memory impairments were apparent in terms of increased susceptibility to proactive interference. This impairment was significantly correlated with the dosage of BZ taken.     

Parvovirus B19 in kidney transplant patients

Renal transplant patients were screened for the presence of parvovirus B19, before transplantation and monthly for 4 months after transplantation, by means of a sensitive nested PCR assay. Upon screening plasma from 110 patients, we found that two asymptomatic patients were B19 DNA positive. One of these patients was PCR positive in the plasma sample taken 2 months after transplantation; the plasma contained anti-B19 IgG antibodies before transplant and throughout the follow-up period, with an increase in the IgG level in the second posttransplant sample coinciding with the detection of B19 DNA. IgM antibodies to B19 were not detected in this patient. Because, for this patient, the donor's spleen DNA was also B19 DNA positive, we suspect B19 transmission from the donor and limited B19 replication, inasmuch as this patient already had a primed immune response to B19. The other patient was PCR positive in the pretransplant and in the plasma sample taken 1 month after transplant and contained a strong anti-B19 IgG response in the pretransplant sample and throughout the follow-up period-and anti-B19 IgM antibodies were not detected before or after transplantation. By testing samples taken from this patient at 2 weeks, 2 months, and 3 months before transplantation, we were able to determine that the infection occurred shortly before transplantation. Unexpectedly, this graft failed and was removed 2 days after transplantation despite a negative cross-match. A pathological examination of the kidney indicated acute vascular rejection, suggesting a possible role for B19 in this complication.     

RSR13 plus cranial radiation therapy in patients with brain metastases: comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database.

PURPOSE: This phase II, open-label, multicenter study assessed the efficacy and safety of the potential radiation enhancer RSR13 plus cranial radiation therapy (RT) in patients with brain metastases. The primary end point was patient survival in comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database (RTOG RPA BMD). PATIENTS AND METHODS: Eligibility criteria were age > or = 18 years, Karnofsky performance score > or = 70, and brain metastases with solid tumor histology. Patients received cranial RT, 30 Gy in 10 fractions of 3 Gy each, preceded by RSR13, 50 to 100 mg/kg intravenously over 30 minutes. Univariate and multivariate comparisons of survival and cause of death were made between class II study patients and RTOG BMD patients. RESULTS: Fifty-seven RPA class II patients were enrolled. With a minimum follow-up of 24 months, the median survival time and 1- and 2-year survival rates were 6.4 months, 23%, and 11% for the RSR13-treated patients compared with 4.1 months, 15%, and 3% for the RTOG BMD patients (P =.0174). In an exact-matched case analysis (n = 38), median survival time for RSR13 patients was 7.3 months versus 3.4 months for the RTOG BMD patients (P =.006). There was a 54% reduction in the risk of death for RSR13 patients (P =.0267). RSR13-related adverse events of greater than or equal to grade 3 toxicity that occurred in more than one patient included hypoxia, headache, anemia, fatigue, hypertension, and intracranial hypertension. CONCLUSION: RSR13 plus cranial RT resulted in a significant improvement in survival, as well as a reduction in death due to brain metastases, compared with class II patients in the RTOG BMD.     

Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases.

PURPOSE: This phase III randomized trial evaluated survival as well as neurologic and neurocognitive function in patients with brain metastases from solid tumors receiving whole-brain radiation therapy (WBRT) with or without motexafin gadolinium (MGd). PATIENTS AND METHODS: Patients were randomly assigned to 30 Gy of WBRT +/- 5 mg/kg/d MGd. Survival and time to neurologic progression determined by a blinded events review committee (ERC) were coprimary end points. Standardized investigator neurologic assessment and neurocognitive testing were evaluated. RESULTS: Four hundred one (251 non-small-cell lung cancer) patients were enrolled. There was no significant difference by treatment arm in survival (median, 5.2 months for MGd v 4.9 months for WBRT; P =.48) or time to neurologic progression (median, 9.5 months for MGd v 8.3 months for WBRT; P =.95). Treatment with MGd improved time to neurologic progression in patients with lung cancer (median, not reached for MGd v 7.4 months for WBRT; P =.048, unadjusted). By investigator, MGd improved time to neurologic progression in all patients (median, 4.3 months for MGd v 3.8 months for WBRT; P =.018) and in lung cancer patients (median, 5.5 months for MGd v 3.7 months for WBRT; P =.025). MGd improved neurocognitive function in lung cancer patients. CONCLUSION: The overall results did not demonstrate significant differences by treatment arm for survival and ERC time to neurologic progression. Investigator neurologic assessments demonstrated an MGd treatment benefit in all patients. In lung cancer patients, ERC- and investigator-determined time to neurologic progression demonstrated an MGd treatment benefit. MGd may improve time to neurologic and neurocognitive progression in lung cancer.     

Auditing paediatric diabetes care and the impact of a specialist nurse trained in paediatric diabetes

AIMS: To define outcome measures for auditing the clinical care of children and adolescents with insulin dependent diabetes mellitus (IDDM) and to assess the benefit of appointing a dedicated paediatric trained diabetes specialist nurse (PDSN). METHODS: Retrospective analysis of medical notes and hospital records. Glycaemic control, growth, weight gain, microvascular complications, school absence, and the proportion of children undergoing an annual clinical review and diabetes education session were assessed. The effect of the appointment of a PDSN on the frequency of hospital admission, length of inpatient stay, and outpatient attendance was evaluated. RESULTS: Children with IDDM were of normal height and grew well for three years after diagnosis, but grew suboptimally thereafter. Weight gain was above average every year after diagnosis. Glycaemic control was poor at all ages with only 16% of children having an acceptable glycated haemoglobin. Eighty five per cent of patients underwent a formal annual clinical review, of whom 16% had background retinopathy and 20% microalbuminuria in one or more samples. After appointing the PDSN the median length of hospital stay for newly diagnosed patients decreased from five days to one day, with 10 of 24 children not admitted. None of the latter was admitted during the next year. There was no evidence of the PDSN affecting the frequency of readmission or length of stay of children with established IDDM. Non-attendance at the outpatient clinic was reduced from a median of 19 to 10%. CONCLUSIONS: Outcome measures for evaluating the care of children with IDDM can be defined and evaluated. Specialist nursing support markedly reduces the length of hospital stay of newly diagnosed patients without sacrificing the quality of care.     

Inflammatory bowel disease and predisposition to osteopenia

The prevalence of osteopenia in children with inflammatory bowel disease (IBD) is unknown. The effect of nutritional state, disease activity, and steroid therapy on bone mineral content (BMC) of whole body, lumbar spine, and left femoral neck measured by dual energy x ray absorptiometry in 32 children with IBD was assessed by comparison with 58 healthy local school children. Using the control data, a predicted BMC was calculated taking into account bone area, age, height, weight, and pubertal stage. The measured BMC in children with IBD was expressed as a percentage of this predicted value (% BMC). Mean (SD) % BMC was significantly reduced for the whole body and left femoral neck in the children with IBD (97.0 (4.5)% and 93.1 (12.0)% respectively, p < 0.05). Of the children with IBD, 41% had a % BMC less than 1 SD below the mean for the whole body and 47% at the femoral neck. Reduction in % BMC was associated with steroid usage but not with the magnitude of steroid dose, disease activity, or biochemical markers of bone metabolism. In conclusion, osteopenia is relatively common in childhood IBD and may be partly related to the previous use of steroids.     

Phenotypic diversity in siblings with partial androgen insensitivity syndrome

The androgen insensitivity syndrome is a heterogeneous disorder with a wide spectrum of phenotypic abnormalities, ranging from complete female to ambiguous forms that more closely resemble males. The primary abnormality is a defective androgen receptor protein due to a mutation of the androgen receptor gene. This prevents normal androgen action and thus leads to impaired virilisation. A point mutation of the androgen receptor gene affecting two siblings with partial androgen insensitivity syndrome is described. One had cliteromegaly and labial fusion and was raised as a girl, whereas the other sibling had micropenis and penoscrotal hypospadias and was raised as a boy. Both were shown to have the arginine 840 to cysteine mutation. The phenotypic variation in this family is thus dependent on factors other than abnormalities of the androgen receptor gene alone.     

Ploidy profile of morphologically normal squamous epithelium adjacent to high grade cervical intraepithelial neoplasia

We have investigated the ploidy profile of morphologically normal mucosa adjacent to high grade CIN (   n = 16  ) and also from normal cervix ( n = 18). DNA ploidy was assessed using flow cytometry and image analysis. All cases were diploid by both modalities. Our results show that morphologically normal squamous mucosa has a stable ploidy profile even when it lies adjacent to high grade CIN. This finding supports the view that high grade CIN is a neoplastic expansion of transformed cells rather than the result of a field change effect.