Enantiomeric Resolution of Drug Compounds by Liquid Chromatography

Novel techniques have recently emerged to separate chiral drug compounds into pure enantiomers. The mechanism, experimental difficulties, and applicability of these methods can vary greatly, and the choices involved are not straightforward. The most significant new advances in the field of chiral separations have come from work done with liquid chromatographic systems and chiral stationary-phase columns. This review describes several commonly used approaches to chiral separation, diastereomeric derivatization, chiral mobile-phase additives, and three major types of chiral stationary phases. Although no single method can be judged superior for every drug application, it appears that chiral stationary phases have received the most attention recently and they are emphasized here.     

Quantitative comparison of magnetic resonance imaging (MRI) and histologic analyses of focal ischemic damage in the rat

Hemispheric swelling and area of infarction, two parameters of cerebral focal ischemic damage, were identified and quantified from T2-weighted magnetic resonance imaging (MRI) two days after occlusion of the middle cerebral artery (MCAO) in spontaneously hypertensive rat (SHR) brains. Results were compared with these measures quantified from 2,3,5-triphenyltetrazolium hydrochloride (TTC)- and hematoxylin and eosin (H&E)-stained histologic sections in the same brains. The degree of hemispheric swelling and infarct size determined by MRI were highly correlated to the measurements as determined in the TTC- and H&E-stained tissues. These results demonstrate that the focal ischemic damaged area and associated tissue swelling identified by MRI is quantitatively similar to, and thus, is representative of actual tissue damage/changes that can be identified by gross or histologic examination.     

Mortality in neonatal septicemia with involvement of mother in management.

In most Special Care Neonatal Units (SCNUs) in India, mothers are excluded from the care of their sick babies for fear of over-crowding and dislocation. We have attempted to study the feasibility of involving mothers in the care of their babies admitted for neonatal septicemia and to analyse whether this changed the sepsis related case fatality rate. The study material consisted of 158 neonates with blood culture positive neonatal septicemia whose mothers were actively involved in their care during their stay in the SCNU of LNJPN Hospital throughout 1987-88. The mothers lived in with their sick neonates and were extremely useful in feeding, cleaning, and monitoring for some important signs and symptoms. There were no epidemics of infection in the nursery during this period. All the babies discharged were receiving breast feeds, and the mothers were confident in taking care of them before discharge. The mortality in this group was 43%. The onset of septicemia was most often in the first week (36%) being 25.9% in second week, 26.6% in the third, and 11.4% in the fourth. Mortality was maximum (64.5%) when the onset of illness was in the first 3 days. Klebsiella and S. aureus were commonly isolated organisms (38.6 and 21.5%, respectively). Gram negative organisms were isolated in 66.5% cases with higher mortality in this group. Nearly 46% of the babies weighed 2 kg or less, with a mortality of 60.2% compared to 28.2% in those more than 2 kg. Only 3 to 5% and 40 to 66.7% of Gram negative and 23 and 70% of Gram positive organisms were sensitive to ampicillin and gentamicin, respectively.     

Effect on fetal mouse development of exposure to MR imaging and gadopentetate dimeglumine

Pregnant mice were exposed to one of five regimens at 9.5 days of gestation: no treatment (group 1), intraperitoneal injection of normal saline (group 2), intraperitoneal injection of gadopentetate dimeglumine (group 3), intraperitoneal injection of gadopentetate dimeglumine and magnetic resonance (MR) exposure (group 4), and MR exposure alone (group 5). At 18 days of gestation, the mice were sacrifice and fetuses were removed and examined for the following end points: litter size, number alive or dead, fetal weight, extremity morphology, eye and ear development, and appearance of the head. A total of 739 fetuses were analyzed: group 1 (n = 161), group 2 (n = 149), group 3 (n = 142), group 4 (n = 136), and group 5 (n = 151). The only statistically significant difference was a lower mean fetal weight in the saline-injection group compared with the control group. The results show that MR exposure with and without gadopentetate dimeglumine had no adverse effect on the end points analyzed.     

A group intervention to reduce smoking in individuals with psychiatric disorder: brief report of a pilot study

Objectives: To evaluate a group intervention to help individuals with psychiatric disorder stop smoking.
Method: A waitlist-treatment crossover design. Outcome measures included smoking cessation, motivation to stop, the Fagerstrom Test for Nicotine Dependence (FTND), urinary cotinine and psychiatric symptoms on the General Health Questionnaire.
Results: 38 subjects participated, of whom 19 completed the waitlist and intervention phases. There were no significant differences between subjects and dropouts. During the waitlist period there were no significant changes in tobacco use. At the end of the intervention, almost a quarter had stopped smoking, ( z = -2.24, p =0.02). Subjects also showed significant improvements on state of change, FTND score and urinary cotinine levels. These improvements were maintained at three-month follow-up (n=10). Psychiatric morbidity showed no change.
Conclusions: It is possible to reduce smoking in individuals with psychiatric disorder.
Implications: Larger randomised controlled trials are indicated to determine the relative contributions of nicotine replacement, bupropion and group interventions to smoking cessation in this population.     

Polyclonal and monoclonal antibodies monospecific to MMTV LTR orf protein produced in E. coli.

Monoclonal and polyclonal antibodies specific to an open reading frame of the mouse mammary tumor virus long terminal repeat were generated using an open reading frame-beta-galactosidase fusion protein produced in E. coli. Both antibodies reacted with the open reading frame-beta-galactosidase fusion protein but not with beta-galactosidase alone using an immunoblotting technique. It is concluded that these antibodies were specific for the protein encoded by the open reading frame of the mouse mammary tumor virus long terminal repeat.     

The Value of Lung Injury Score in Assessing the Outcome of Patients with Rib Fracture

Background and Purpose:   

Management of rib fractures constitutes a major part of the trauma workload of any unit. Rib fractures result in disrupted chest wall mechanics and ventilatory insufficiency. The ability of a lung injury scoring system to predict the degree of respiratory dysfunction after rib fractures was evaluated.     

Low sodium haemodialysis reduces interdialytic fluid consumption but paradoxically increases post-dialysis thirst.

BACKGROUND: Interdialytic weight gain (IDWG) can be reduced by lowering the dialysate sodium concentration ([Na]) in haemodialysis patients. It has been assumed that this is because thirst is reduced, although this has been difficult to prove. We compared thirst patterns in stable haemodialysis patients with high and low IDWG using a novel technique and compared the effect of low sodium dialysis (LSD) with normal sodium dialysis (NSD). METHODS: Eight patients with initial high IDWG and seven with low IDWG completed hourly visual analogue ratings of thirst using a modified palmtop computer during the dialysis day and the interdialytic day. The dialysate [Na] was progressively reduced by up to 5 mmol/l over five treatments. Dialysis continued at the lowest attained [Na] for 2 weeks and the measurements were repeated. The dialysate [Na] then returned to baseline and the process was repeated. RESULTS: Baseline interdialytic day mean thirst was higher than the dialysis day mean for the high IDWG group (49.9+/-14.0 vs 36.2+/-16.6) and higher than the low weight gain group (49.9+/-14.0 vs 34.1+/-14.6). This trend persisted on LSD, but there was a pronounced increase in post-dialysis thirst scores for both groups (high IDWG: 46+/-13 vs 30+/-21; low IDWG: 48+/-24 vs 33+/-18). The high IDWG group demonstrated lower IDWG during LSD than NSD (2.23+/-0.98 vs 2.86+/-0.38 kg; P<0.05). CONCLUSIONS: Our results indicate that patients with high IDWG experience more intense feelings of thirst on the interdialytic day. LSD reduces their IDWG, but paradoxically increases thirst in the immediate post-dialysis period.