In Vitro and in Vivo Evaluation of Whole and Half Tablets of Sustained-Release Adinazolam Mesylate

The mechanism of release from sustained-release adinazolam mesylate tablets was assessed by the Higuchi equation and by analysis of drug release profiles through 60% released using the Peppas equation. Computed values of the diffusional exponent, n, ranged from 0.59 to 0.66. Values of n in this range are consistent with a mixed mechanism of release, with diffusion of drug through the hydrated polymer matrix and relaxation of this matrix being the principal processes controlling release. The rate of in vitro drug release was increased for half tablets relative to whole tablets and is attributed to an increase in the surface to volume ratio of half tablets of about 16%. This increase in surface-to-volume ratio of half tablets was reflected by an increase in the constant, k, from the Peppas equation of 20–23% and by an increase in the slope of Higuchi plots of 12–18% for four lots of tablets. In vivo/in vitro relationships from two bioavailability studies were thoroughly evaluated. Using either a linear or a quadratic relationship, an in vivo/in vitro correlation exists for sustained-release adinazolam mesylate tablets.     

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.     

Hyperprolactinemia as a marker of neurotransmitter imbalance in uremic population

Serum prolactin (PRL) levels are elevated in patients with chronic renal failure (CRF) but the mechanisms responsible for these abnormalities are not fully understood. PRL secretion is undoubtedly influenced by many substances, which can be variously altered in uremia: monoamines, endogenous opiates and PTH. Our data suggest that in early renal failure PRL levels are already significantly high and the 24-h pattern of PRL secretion is significantly different from that in controls. PRL derangements could be due in mild renal failure, to unknown factors (GABA?); in severe CRF, to a major change in dopaminergic activity; in hemodialysis (HD), to a low turnover of monoamines, and in peritoneal dialysis (PD) to increased activity of serotoninergic and dopaminergic systems.     

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.     

Role of cellulosic and noncellulosic membranes in hyperhomocysteinemia and oxidative stress

Hyperhomocysteinemia is an independent risk factor for cardiovascular morbidity and mortality in end-stage renal disease (ESRD) with an increased relative risk (RR) of 1% per micromol/L in total homocysteine concentration. In ESRD patients who undergo hemodialysis (HD), the antioxidant system is largely inadequate in correcting the imbalance between generation and scavenging of reactive oxygen species (ROS). To clarify the role of several cellulosic (CMs) and noncellulosic of synthetic membranes (NCMs) upon hyperhomocysteinemia and the oxidative stress, we measured plasma (P) homocysteine (t-HCY), plasma lipid peroxidation (LPO), and erythrocyte (E) concentration of several antioxidant enzymes in 20 normal subjects, in 35 HD patients treated with CMs, and in 29 patients treated with NCMs. Before, during, and after the first session of the week (at times 0', 120', end, 30' after HD end), blood samples were drawn. Plasma (P) homocysteine (t-HCY), cysteine (CYS), malondialdehyde (MDA), erythrocyte (E)-glutathione (GSH), glucose-6-phosphodehydrogenase (G6PD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), and superoxide-dismutase (SOD) were determined. The dialytic procedure significantly decreased the three plasma parameters, but none normalized (as a mean). The E-enzymes scavenging ROS (lower than normal before session) increased throughout the session, but the normal range of activity was never reached. Different membranes have shown different effects. When these effects on P and E spaces were pooled, we were able to classify the membranes as follows. In a general sense, cellulosic membranes are less effective than synthetic membranes both on lipoperoxides (LPO) and antioxidant activity (AOA). Among synthetic membranes, PMMA is the best membrane both for plasma values and lesser enzymatic derangement during the session. A practical system for classifying the anti-atherosclerotic action and antioxidant activity of dialytic membranes is proposed.     

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.