A Chinese adolescent girl with Fechtner-like syndrome

We describe a 15-y-old girl with Fechtner-like syndrome, who is the first Chinese reported to have this rare syndrome. She presented with left homonymous hemianopia and neuroimaging revealed haemorrhage in both parietal and occipital lobes. Peripheral blood smear showed macrothrombocytopenia and intracytoplasmic inclusion bodies inside leucocytes. Thrombocytopenia and proteinuria responded to intravenous immunoglobulin and pulsed methylprednisolone. This case illustrates that life-threatening haemorrhage can occur in patients with Fechtner syndrome. Although there was no effective treatment reported in the literature, high dose steroid and immunoglobulin seemed to be useful in our patient. Our patient also had nephritic-nephrotic syndrome with renal insufficiency, which is unusual in adolescent female patients.     

SUICIDE ATTEMPT DUE TO METOCLOPRAMIDE-INDUCED AKATHISIA

Akathisia as a side-effect of metoclopramide has received increasing attention in consultation-liaison psychiatry in recent years. A case of metoclopramide-induced akathisia resulting in a suicide attempt is reported in order to highlight the suffering of such patients and the factors that lead to misdiagnosis.     

Predictive value of normal sperm morphology: a structured literature review

The aim of the study was to conduct a structured review of theliterature published on the use of normal sperm morphology,as an indicator of male fertility potential in the in-vitrofertilization (IVF) situation, and to establish the universalpredictive value of this semen parameter. Published literaturein which normal sperm morphology was used to predict fertilizationand pregnancy, during the period 1978-1996, was reviewed. Atotal of 216 articles were identified by the sourcing methodology,but only 49 provided data that could be tabulated and analysed.Of these, only 18 provided sufficient data for statistical analysis.Fifteen studies used the strict criteria to evaluate sperm morphology,two used World Health Organization (WHO) guidelines and oneused both the strict criteria and the WHO guidelines. All thestudies (n=10) using the 5 and 14% normal sperm morphology thresholds(strict criteria) produced positive predictive values for IVFsuccess. In the prediction of pregnancy, 82% (9/11) and 75%(6/8) of the studies produced positive predictive values whenusing the 5% and 14% thresholds respectively. Aggregating thedata produced around the 5% normal sperm morphology threshold(strict criteria), the overall fertilization rates were 59.3%(1979/3337; per oocyte) for the 4% group and 77.6% (10345/13327;per oocyte) for the >4% group, and the overall pregnancyrates were 15.2% (60/395; per cycle) and 26.0% (355/1368; percycle) respectively. The no-transfer rates across the 5% thresholdwere 24.0% (86/359; per cycle) in the 4% group compared to 7.4%(80/1088; per cycle) in the >4% group. The inclusion of anaccurately evaluated normal sperm morphology count as an integralpart of the standard semen analysis makes this analysis stillthe most cost-effective means of evaluating the male factor.     

Treatment of intracranial gliomas with bone marrow-derived dendritic cells pulsed with tumor antigens.

OBJECT: An approach toward the treatment of intracranial gliomas was developed in a rat experimental model. The authors investigated the ability of "professional" antigen-presenting cells (dendritic cells) to enhance host antitumor immune responses when injected as a vaccine into tumor-bearing animals. METHODS: Dendritic cells, the most potent antigen-presenting cells in the body, were isolated from rat bone marrow precursors stimulated in vitro with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4. Cultured cell populations were confirmed to be functional antigen-presenting cells on the basis of expressed major histocompatibility molecules, as analyzed by fluorescence-activated cell sorter cytofluorography. These dendritic cells were then pulsed (cocultured) ex vivo with acid-eluted tumor antigens from 9L glioma cells. Thirty-eight adult female Fischer 344 rats harboring 7-day-old intracranial 9L tumors were treated with three weekly subcutaneous injections of either control media (10 animals), unpulsed dendritic cells (six animals), dendritic cells pulsed with peptides extracted from normal rat astrocytes (10 animals), or 9L tumor antigen-pulsed dendritic cells (12 animals). The animals were followed for survival. At necropsy, the rat brains were removed and examined histologically, and spleens were harvested for cell-mediated cytotoxicity assays. The results indicate that tumor peptide-pulsed dendritic cell therapy led to prolonged survival in rats with established intracranial 9L tumors implanted 7 days prior to the initiation of vaccine therapy in vivo. Immunohistochemical analyses were used to document a significantly increased perilesional and intratumoral infiltration of CD8+ and CD4+ T cells in the groups treated with tumor antigen-pulsed dendritic cells compared with the control groups. In addition, the results of in vitro cytotoxicity assays suggest that vaccination with these peptide-pulsed dendritic cells can induce specific cytotoxic T lymphocytes against 9L tumor cells. CONCLUSIONS: Based on these results, dendritic antigen-presenting cells pulsed with acid-eluted peptides derived from autologous tumors represent a promising approach to the immunotherapy of established intracranial gliomas. which may serve as a basis for designing clinical trials in patients with brain tumors.     

Comparing sulindac with indomethacin for closure of ductus arteriosus in preterm infants

Objectives: A prospective study comparing the efficiacy and side-effects of oral sulindac with intravenous indomethacin in clinically stable preterm infants (<1750 g) requiring non-invasive closure of haemodynamically significant patent ductus arteriosus.
Methodology: As maturity and birthweight are the two major determinants of ductal closure, infants were matched as closely as possible for these parameters. An eligible patient was first assigned to the sulindac group and a subsequent patient with similar gestational age (± 1 week) and birthweight (±100 g) to the previously recruited infant would automatically receive indomethacin. A total of eight infants were enrolled in each group.
Results: The ductus arteriosus was successfully closed in all eight infants receiving indomethacin, and in seven of eight infants receiving sulindac. No significant differences were found with regards to the ductal size between the two groups at diagnosis or on each of the consecutive days of treatment ( P >0.25). More renal adverse effects were encountered in the indomethacin group. Significant differences in changes from baseline value for urine output, plasma sodium, urea and creatinine concentrations were noted at 24, 48 and 72 h after commencement of treatment between the two groups ( P <0.05). All the parameters returned to normal or pre-treatment levels 48 h after stopping therapy. Unexpectedly, severe gastrointestinal complications were encountered in the sulindac group.
Conclusions: Sulindac is capable of promoting ductal constriction in clinically stable preterm infants without compromising the renal function. The spectrum of gastrointestinal complications observed in sulindac treated infants were similar to those described for indomethacin. The use of sulindac for ductal closure in the preterm infant should remain experimental.     

Erythromycin treatment for gastrointestinal dysmotility in preterm infants

To report our clinical experience on the use of oral erythromycin for the treatment of severe gastrointestinal dysmotility in preterm infants.

Methodology:

A case series study of seven preterm infants (six were very low birthweight) with severe intestinal dysmotility in a tertiary neonatal centre.

Results:

All responded favourably without adverse effects and tolerated full enteral feeding within 1–2 weeks of the commencement of the drug.

Conclusions:

As prolonged total parenteral nutrition carries significant risk of complications, this therapy could be considered in selected preterm infants who fail to establish enteral feeding after an extended period, and in whom an anatomically obstructive lesion of the gastrointestinal tract has been excluded. Meanwhile, we would caution against the widespread implementation of this therapeutic approach until formal evaluation by randomized controlled trials have established the exact role of erythromycin, or its analogues, in the treatment of intestinal dysmotility in preterm infants.     

Phase I trial of tipifarnib in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs: a North American Brain Tumor Consortium Study.

PURPOSE: To determine the maximum-tolerated dose (MTD), toxicities, and clinical effect of tipifarnib, a farnesyltransferase (FTase) inhibitor, in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs (EIAEDs). This study compares the pharmacokinetics and pharmacodynamics of tipifarnib at MTD in patients on and off EIAEDs. PATIENTS AND METHODS: Recurrent malignant glioma patients were treated with tipifarnib using an interpatient dose-escalation scheme. Pharmacokinetics and pharmacodynamics were assessed. RESULTS: Twenty-three assessable patients taking EIAEDs received tipifarnib in escalating doses from 300 to 700 mg bid for 21 of 28 days. The dose-limiting toxicity was rash, and the MTD was 600 mg bid. There were significant differences in pharmacokinetic parameters at 300 mg bid between patients on and not on EIAEDs. When patients on EIAEDs and not on EIAEDs were treated at MTD (600 and 300 mg bid, respectively), the area under the plasma concentration-time curve (AUC)(0-12 hours) was approximately two-fold lower in patients on EIAEDs. Farnesyltransferase inhibition was noted at all tipifarnib dose levels, as measured in peripheral-blood mononuclear cells (PBMC). CONCLUSION: Toxicities and pharmacokinetics differ significantly when comparing patients on or off EIAEDs. EIAEDs significantly decreased the maximum concentration, AUC(0-12 hours), and predose trough concentrations of tipifarnib. Even in the presence of EIAEDs, the levels of tipifarnib were still sufficient to potently inhibit FTase activity in patient PBMCs. The relevance of these important findings to clinical activity will be determined in ongoing studies with larger numbers of patients.