Presence of lysine at aa 335 of the hemagglutinin-neuraminidase protein of mumps virus vaccine strain Urabe AM9 is not a requirement for neurovirulence

The recent global resurgence of mumps has drawn attention to the continued need for robust mumps immunization programs. Unfortunately, some vaccines derived from inadequately attenuated vaccine strains of mumps virus have caused meningitis in vaccinees, leading to withdrawal of certain vaccine strains from the market, public resistance to vaccination, or in some cases, cessation of national mumps vaccination programs. The most widely implicated mumps vaccine in cases of postvaccination meningitis is derived from the Urabe AM9 strain, which remains in use in some countries. The Urabe AM9 vaccine virus has been shown to exhibit a considerable degree of nucleotide and amino acid heterogeneity. Some studies have specifically implicated variants containing a lysine residue at amino acid position 335 in the hemagglutinin-neuraminidase (HN) protein with neurotoxicity, whereas a glutamic acid residue at this position was associated with attenuation. To test this hypothesis we generated two modified Urabe AM9 cDNA clones coding either for a lysine or a glutamic acid at position 335 in the HN gene. The two viruses were rescued by reverse genetics and characterized in vitro and in vivo. Both viruses exhibited similar growth kinetics in neuronal and non-neuronal cell lines and were of similar neurotoxicity when tested in rats, suggesting that amino acid 335 is not a crucial determinant of Urabe AM9 growth or neurovirulence.     

A CT-free, intra-operative planning and navigation system for minimally invasive anterior spinal surgery - an accuracy study.

OBJECTIVE: A comprehensive study was performed to evaluate the accuracy of a newly developed CT-free, intra-operative planning and navigation system for anterior spine surgery. MATERIALS AND METHODS: Instruments and an image intensifier were tracked using the SurgiGATE navigation system. A laboratory study was performed on 27 plastic vertebrae. Fiducial markers were implanted in the vertebrae for accuracy evaluation purposes, and a dynamic reference base was placed on the vertebrae to establish a patient coordinate system (P-COS). Two fluoroscopic images were used for intra-operative planning. The graft bed plan was recorded in P-COS, followed by surgical formation of the graft bed, which was visualized. To evaluate the accuracy, the vertebrae were scanned with CT, and the markers were used to calculate an accurate paired-point registered transformation between the CT coordinate system and P-COS. RESULTS: Using the new SPO module, accurate planning and navigation of a resection of the vertebral body is possible using two fluoroscopic images. The overall mean error between the planned resection volume and the actual resection was 0.98 mm. In addition, the module can serve as an educational tool for training spine surgeons. CONCLUSIONS: The new fluoroscopy-based system can be used safely for accurate performance of anterior resection during spondylodesis. New methods for safe and accurate registration during anterior spine surgery need to be developed.     

Obesity: determinants and therapeutic initiatives.

There are several possible determinants of obesity, including impaired thermogenesis and the differential utilization of fuels in different tissues. Whereas hypometabolism may initiate obesity in some people, once obese, individuals tend to manifest a higher resting metabolic rate because of their greater fat-free mass, exhibit an impaired thermic response to food, and expend more calories than lean individuals for equivalent amounts of activity. As a result, over a 24-h period, obese people generally expend more energy than lean people. A second determinant of obesity is related to fuel utilization and suggests that those predisposed to be obese may have an innate insulin resistance in muscle, leading to decreased uptake, oxidation, and storage of glucose in this tissue. As a result, the glucose is shunted to adipose tissue, where it is stored. With regard to treatment of obesity, emphasis on increased energy expenditure through the inclusion of reasonable amounts of activity is essential. However, this must always be combined with restraint in caloric intake.     

Revascularization of the renal artery in renovascular hypertension with progressive renal insufficiency

Sixteen patients underwent surgical treatment for severe renovascular hypertension with rapidly progressive renal failure. These patients were assessed preoperatively with the measurement of serum creatinine and blood-urea levels (means 271 +/- 204 mumol/l and 15.6 +/- 10.3 mmol/l respectively), and renal clearances. 5 patients underwent aorto-renal bypass (bilateral in one case) and 11 patients were treated by autotransplantation of the kidney. Operative mortality was 6.2%. Early results were assessed at 1 and 6 months postoperatively. Renal function was normal in 8 patients, improved in 5 (p less than 0.05), unchanged in 1 and worse in 1 by aorto-renal bypass thrombosis. At long-term with a minimum follow-up of 12 months (mean 31 +/- 12 months), the initial improvement in renal function remained steady in 12 patients whilst 1 patient has gone on to hemodialysis. At middle and long-term, 81% of the patients were normotensive without medication or had improved blood pressure (p less than 0.001). These good results confirm the reversibility of renal ischemic lesions and support an aggressive attitude towards the use of revascularization in the surgical treatment of such patients with renovascular hypertension and renal failure.     

Enhanced myocardial necrosis induced in rats by the combined administration of hydralazine and prenalterol

The cardiotoxic effects of hydralazine and prenalterol, given alone and in combination, were assessed in rats and rabbits. Acute myocardial necrosis was induced by a single administration of each drug alone in rats. However, the incidence and severity of lesions were markedly enhanced when both drugs were given in combination. Rats that received the same treatment for 10 consecutive days showed minimal or no acute necrosis, demonstrating the development of a resistance to further cardiotoxic effects of the drugs. Rabbits showed only minimal lesions when either drug was used alone and no enhancement of lesions when they were given in combination. From these data, it is concluded that the possibility of a cardiotoxic interaction exists when these drugs are used in combination and that the heavy rat (500-600 g) is a more sensitive model than the rabbit for studies of this nature.     

Comparison of morphologic and immunohistochemical features of cervical microglandular hyperplasia with low-grade mucinous adenocarcinoma of the endometrium.

Twenty cases of microglandular hyperplasia (MGH) of the uterine cervix and 14 cases of low-grade (nuclear) mucinous adenocarcinoma of the endometrium (MA) were compared morphologically and immunohistochemically. Subnuclear vacuoles were seen in 10 cases of MGH but were absent in all MA. Luminal squamous metaplasia was seen in only 10% of MGH cases versus 65% of MA cases. Stromal foam cells were present in 36% of MA but were absent in MGH cases. Both MGH and MA had minimal variation in nuclear size and inconspicuous nucleoli. As many as 8 mitoses/10 high-power fields (MF/10 HPF) were found in MA compared with 3 or fewer MF/10 HPF in MGH. Vimentin was expressed in 90% of MA but was absent in MGH. A significantly higher percentage of MA cells stained with MIB-1 than did those of MGH (mean 11% versus 0.5%). Both MA and MGH lacked CEA and p53 staining, whereas both had variable expression of ER and PR with no significant differences except that PR was absent in 40% of MGH cases. Our findings indicate that in the differential diagnosis of MGH versus MA, the presence of subnuclear vacuoles favors the former, whereas luminal squamous metaplasia, stromal foam cells, mitotic activity, vimentin expression, and MIB-1 expression favor the latter.     

Role of basal insulin in the regulation of protein kinetics and energy metabolism in septic patients.

We have investigated the role of basal insulin concentration on leucine kinetics (determined by means of 1-[13C]leucine) and energy metabolism (determined by indirect calorimetry) in eight septic patients by reducing insulin (and glucagon) secretion by somatostatin infusion. Basal glucagon concentration was elevated (744 +/- 381 pg/mL), and insulin concentration was normal (10 +/- 4 microU/mL). Basal resting energy expenditure (REE) was 151 +/- 8% that of predicted basal energy expenditure, and leucine appearance (Ra), oxidation, and nonoxidative disposal rates were all elevated above the normal ranges. Somatostatin infusion reduced insulin concentration by 52% and glucagon concentration by 64%. This resulted in a significant increase in the rate of leucine oxidation from 0.96 +/- 0.08 to 1.18 +/- 0.14 mumol/kg/min (p less than 0.01), and nonoxidative leucine disposal decreased from 2.95 +/- 0.18 to 2.67 +/- 0.17 mumol/kg/min (p less than 0.01). Somatostatin infusion also caused significant increases in REE and fat oxidation from 1310 +/- 100 to 1505 +/- 128 kcal/m2/day (p less than 0.05) and from 1.72 +/- 0.24 to 2.41 +/- 0.41 mg/kg/min, respectively, and a slight decrease of carbohydrate oxidation from 1.51 +/- 0.49 to 1.31 +/- 0.49 mg/kg/min. These metabolic responses can be attributed to the reduction in insulin concentration, because they are in the opposite direction of changes that would occur as a consequence of a reduction in glucagon concentration. We conclude that the basal insulin plays an important role in attenuating net protein loss and energy expenditure.