Comparison of the precision of two standardized co-ordinate systems for the quantitation of brain anatomy: preliminary results

We assessed reproducible definition of two standardized co-ordinate systems for intersubject analysis of brain images. The baselines in the two co-ordinate systems were a modification of the canthomeatal (inCM) line and the anterior-posterior commissural )AC-PC) line. Axial spin-echo MR images of four subjects at 1.5T were used. Operator error was computed from the replicate analyses of two operators. The mCM line was determined by the lens of the eye and the internal auditory canal, and the AC-PC line was determined by the intersection of the AC and PC with the interhemispheric fissure. Reproducibility of the mCM markers (SD=0.59 mm) did not differ significantly from that of the AC-PC line (SD=0.68 mm). The measurement error of the angle of the baseline (), however, was more than 7 times as large for the AC-PC line as for the mCM line. An additional error affecting the rostrocaudal rotation of the co-ordinate systems, attributable to the distance between the anatomic markers, was 2.1 and 3.6° (3 mm and 5 mm slice thickness) for the mCM co-ordinate system and 8.2 and 11.0° (3 mm and 5 mm slice thickness) for the AC-PC system. The AC-PC line based co-ordinate system is therefore, less reproducible than the mCM line based system. this could be improved if a combination of axial and sagittal images were used for the definition of the AC-PC line.     

A technique for accurate use of CD4+ cell counts

Despite uncertainty over their reliability, CD4+ cell counts are used extensively in both clinical and research settings to document progression in HIV infection. We examined, therefore, whether the performance of a simple statistical test would facilitate greater accuracy in the use of this marker. CD4+ cell count data were collected from a cohort of deceased (N = 60) and living HIV-positive gay men (N = 100). Pearson's product moment correlation coefficients were calculated for each individual in order to examine the association between CD4+ counts and time since diagnosis. Correlations of 0.7 or greater were obtained in approximately 50 percent of cases in each cohort. For these individuals, CD4+ cell counts were deemed to be a reliable indicator of rate of progression. The results suggest that the proposed technique ensures greater precision in the use of CD4+ cell counts and that the technique cna be used in individuals with either complete (deceased patients) or partial (living patients) CD4+ data.     

K-ras mutation in colorectal carcinomas from singapore

54 sporadic colorectal cancers were analyzed for aberrations in the K-ras oncogene. DNA was extracted from frozen tissues obtained from surgical resection and analyzed for mutations in codons 12, 13 and 61 of the K-ras oncogene using single strand conformation polymorphism analysis (SSCP) and direct sequencing. Point mutations in the K-ras oncogene were found in 26/54 (48%) cases, all of which resulted in amino acid substitutions. No other types of mutations (e.g. insertions or deletions) were found. 4 of the mutations were at codon 12, 22 in codon 13 and only 1 was a codon 61 mutant. G-->A transitions were found to be predominant. A remarkable finding was the high preponderance of (13)Gly-(13)Ser mutations (54%). No correlation was observed between K-ras mutations and tumor location, Dukes' stage, differentiation levels, age or sex of the patient.     

Vitamin A-sensitive tissues in transgenic mice expressing high levels of human cellular retinol-binding protein type I are not altered phenotypically.

The suggested function of cellular retinol-binding protein type I [CRBP(I)] is to carry retinol to esterifying or oxidizing enzymes. The retinyl esters are used in storage or transport, whereas oxidized forms such as all-trans or 9-cis retinoic acid are metabolites used in the mechanism of action of vitamin A. Thus, high expression of human CRBP(I) [hCRBP(I)] in transgenic mice might be expected to increase the production of retinoic acid in tissues, thereby inducing a phenotype resembling vitamin A toxicity. Alternatively, a vitamin A-deficient phenotype could also be envisioned as a result of an increased accumulation of vitamin A in storage cells induced by a high hCRBP(I) level. Signs of vitamin A toxicity or deficiency were therefore examined in tissues from transgenic mice with ectopic expression of hCRBP(I). Testis and intestine, the tissues with the highest expression of the transgene, showed normal gross morphology. Similarly, no abnormalities were observed in other tissues known to be sensitive to vitamin A status such as cornea and retina, and the epithelia in the cervix, trachea and skin. Furthermore, hematologic variables known to be influenced by vitamin A status such as the hemoglobin concentration, hematocrits and the number of red blood cells were within normal ranges in the transgenic mice. In conclusion, these transgenic mice have normal function of vitamin A despite high expression of hCRBP(I) in several tissues.     

An improved model of galactosamine-induced fulminant hepatic failure in the pig

Fulminant hepatic failure is a serious condition with very high mortality. Development of new therapies designed to bridge the patient through the acute period of their disease has been hampered by the lack of a large animal model that closely reproduces the changes in humans. We have established an improved model of fulminant hepatic failure in the pig by administration of an aminosugar d-galactosamine hydrochloride. Galactosamine in a dose of 1.0 g/kg was dissolved in 5% dextrose in water (D5W) and given intravenously to seven young pigs weighing 8 to 15 kg. Seven control pigs received an equal volume of D5W alone. Two days prior to injection, a baseline ultrasound-guided liver biopsy was done in each pig under general anesthesia using isofluorane. Clinical data were recorded and blood for laboratory determinations was drawn at 0 h (baseline), 24 h, 48 h, and 72 h after infusion of galactosamine or D5W alone, under general anesthesia. Neurological data were recorded at the same intervals before inducing anesthesia. Galactosamine-treated animals showed 100% mortality. All of them died by 86 h after injection of galactosamine, with death resulting from fulminant hepatic failure characterized by marked increases in total bilirubin, liver enzymes, ammonia, and lactate; associated coagulopathy; hypoglycemia; and coma. Liver histology showed massive hepatocellular necrosis in all seven galactosamine-treated animals. This large and highly reproducible animal model appears promising for future evaluation of bioartificial liver support systems designed to treat fulminant hepatic failure in humans.     

Evaluation of oxidative DNA damage in human sperm and its association with male infertility

Recently, there is increasing evidence suggesting that oxidative sperm DNA damage is closely associated with impaired sperm function and male infertility. 8-Hydroxydeoxyguanosine (8-OHdG) is considered to be a precise and sensitive biomarker of oxidative DNA damage. The present study was thus designed to evaluate the extent of oxidative DNA damage in sperm and its association with male infertility by assaying the 8-OHdG levels in human sperm samples. A total of 114 subjects (60 infertile patients and 54 age-matched healthy workers) participated in this study. The level of 8-OHdG in sperm DNA was determined by high-performance liquid chromatography with electrochemical detection, and the conventional seminal parameters were also measured according to World Health Organization guidelines. It was found that the level of sperm 8-OHdG in infertile patients was significantly higher than that in healthy subjects (10.03 vs. 4.79 8-OHdG/10(5) dG; geometric mean, P < 0.001). The correlation between sperm 8-OHdG levels and conventional seminal parameters were also analyzed. There is a significant positive correlation between 8-OHdG and sperm head defects (r = 0.38, P < 0.001), whereas significant inverse correlations were noted for 8-OHdG with sperm density (r = -0.42, P < 0.001), total sperm number (r = -0.42, P < 0.001), sperm motility (r = -0.24, P < 0.01), and normal sperm morphology (r = -0.39, P < 0.001). Data from this study thus indicate that oxidative damage to sperm DNA may be important in the etiology of male infertility and that the assay of sperm 8-OHdG may have potential diagnostic value in the evaluation of sperm function and male fertility.     

First report of byssinosis in Hong Kong.

There has been no report of byssinosis in Hong Kong although the textile industry has been one of the leading industries for many years. Three workers with a long history of exposure to cotton dust had chronic obstructive airways disease precipitated by their work environment. One had irreversible airways obstruction but none had chronic bronchitis, emphysema, or asthma. Only one gave a history of "Monday morning tightness," and this was attributed to the fact that most of the textile workers in Hong Kong work seven days a week. It was suggested that a survey be carried out to ascertain the importance of byssinosis in the textile workers of Hong Kong and tha byssinosis should there be added to the list of notifiable occupational diseases.     

Salbutamol disposition and dynamics in conscious rabbits: Influence of the route of administration and of the dose

This study assessed the influence of dose and route of administration on salbutamol kinetics and hypokaliemic effect. Salbutamol plasma kinetics were studied in a first group of 6 rabbits who received 60, 800, and 60 g/kg by the intravenous (iv), oral (po), and intratracheal (it) routes, respectively, at 1-week intervals. A second group of 6 rabbits received 120, 2400, and 120 g/kg of salbutamol by the same three routes. Multiple blood samples were withdrawn to assay salbutamol and potassium. Following iv salbutamol (60 g/kg), total plasma clearance was 82±5 ml/min per kg, apparent volume of distribution was 5.0±0.5 l/kg, and terminal half- life was 41±2 min. Similar values were estimated when 120 g/kg of salbutamol was administered iv or was given po or it. The bioavailability of po and it salbutamol was approximately 1 and 20%, respectively. For the first group, the maximal decrease in plasma potassium elicited by salbutamol was 0.80±0.19, 0.48±0.22, and 0.78±0.46 mmol/l, and for the second group, maximal decrement was 1.31±0.37, 0.70±0.24, and 0.84±0.17 mmol/l for the iv, po, and it routes, respectively. Compared to salbutamol peak plasma concentrations, maximal decrease in plasma potassium appeared between 60 and 108 min later for the iv route, 90 and 25 min later for po and it routes, and for this reason, the hypokaliemic effect was not associated to salbutamol plasma concentrations. The hypokaliemic effect was dependent upon the route, e.g., po>it>iv. It is concluded that (i) salbutamol plasma kinetics are first-order independently of the route of administration, and (ii) salbutamol hypokaliemic effect is modulated by the dose and the route of administration.List of abbreviations AUC Area under salbutamol plasma concentration-time curve - cl_INT Salbutamol intrinsic clearance - cl_T Salbutamol total plasma clearance - c_MAX Salbutamol maximal plasma concentration - F Fraction of the dose of salbutamol reaching the systemic circulation - iv Intravenous route of administration - it Intratracheal route of administration - po Oral route of administration - V_area Salbutamol apparent volume of distribution - T ₂ ¹ Salbutamol half-life of the terminal phase - t_MAX Time to observe the maximal decrease in plasma potassium - e_MAX Predicted maximal effect of salbutamol - EC₅₀ Concentration of salbutamol eliciting 50% of e_MAX Supported by the Medical Research Council of Canada (MT-10874). Sylvie Perreault is recipient of a Bourse Formation de troisième cycle des Fonds de la Recherche en Santé du Québec.     

Efficacy of "high-intensity" blue-light and "standard" daylight phototherapy for non-haemolytic hyperbilirubinaemia

We report our clinical experience with phototherapy in 3802 infants; 3629 were exposed to "standard" daylight phototherapy and 173 to "high-intensity" blue-light phototherapy. High-intensity blue-light phototherapy was twice as effective as standard daylight phototherapy in decreasing bilirubin concentrations. No failures occurred with high-intensity phototherapy compared with an overall failure rate of 1.84/1000 with daylight lamps; these cases were transferred to high-intensity phototherapy with prompt response. Rebound after cessation of phototherapy was greater in those exposed to high-intensity blue light with a significantly greater number requiring a second exposure. However, the incidence was still low. No third exposure was required in any infant. Nursing of infants under high-intensity blue light was more difficult and inconvenient as was clinical monitoring. The light also caused more stress on the nursing and medical personnel. However, the infants tolerated both types of phototherapy equally well. High-intensity blue-light phototherapy would seem to be the treatment of choice for infants with rapidly increasing or very high bilirubin levels, as well as in those not responding adequately to daylight phototherapy.     

The ONG capsular lens,report of 100 implantations

This Capsular Lens (ONG, type IV, to be called O.C.L.) has been developed for routinely performed extracapsular cataract extraction with lens implantation. The fundamental surgical procedure was based on continuing experience with the bimanual aspiration-irrigation technique and system developed by the author in 1971. The biomechanical properties of the asymmetric partly flexible, haptic loops are designed to give tensionfree fixation in two capsular pockets. The plano-anterior position of the lens ensures well-defined irido-lenticular clearance and proper alignment of the convex side with the posterior capsule. Consequently no iridectomy or iridotomy is needed for proper aqueous flow.