Elevated and absent pRb expression is associated with bladder cancer progression and has cooperative effects with p53

Rb protein (pRb) expression was evaluated in 185 cases of transitional cell carcinoma of the bladder from patients that underwent radical cystectomy. Tumors were stratified into three categories based on the percentage of nuclei expressing pRb: (a) 0, 0% of tumor cells showing nuclear reactivity; (b) 1+, 1-50% of tumor cells showing nuclear reactivity; and (c) 2+, >50% of tumor cells showing nuclear reactivity. Cases with undetectable (pRb 0) and high (pRb 2+) pRb reactivity had identical rates of recurrence. These cases had significantly higher recurrence (P = 0.0001) and lower survival rates (P = 0.0002) compared to cases with moderate (pRb 1+) pRb reactivity, indicating that high levels of pRb expression may reflect a dysfunctional (altered) Rb pathway. The tumors were also examined for alterations in p53 expression; patients with tumors altered in both p53 and pRb had significantly increased rates of recurrence (P < 0.0001) and survival (P < 0.0001) compared to patients with no alterations in either p53 or pRb; patients with alterations in only one of these proteins had intermediate rates of recurrence and survival. These results suggest that: (a) bladder cancers with high pRb expression do not show the tumor suppressor effects of the protein; and (b) alteration in both p53 and pRb may act in cooperative or synergistic ways to promote tumor progression.     

Hydrocarbon rulers in UDP-N-acetylglucosamine acyltransferases

UDP-GlcNAc acyltransferase (LpxA), the first enzyme of lipid A biosynthesis, catalyzes the transfer of an acyl chain activated on acyl carrier protein (ACP) to UDP-GlcNAc. LpxAs are very selective for the lengths of their acyl donor substrates. Escherichia coli LpxA prefers R-3-hydroxymyristoyl-ACP to R-3-hydroxydecanoyl-ACP by a factor of approximately 1000, whereas Pseudomonas aeruginosa LpxA prefers the opposite. E. coli G173M LpxA and the reciprocal P. aeruginosa M169G LpxA show reversed substrate selectivity in vitro and in vivo, demonstrating the existence of precise hydrocarbon rulers in LpxAs.     

Intraoperative magnetic resonance tomography for control of extent of neurosurgical operations

The outcome of 703 patients who underwent surgery following aneurysmal subarachnoid hemorrhage were analyzed with regards to age, associated medical conditions, vasospasm and clinical status at the time of operation. Patients with Hunt and Hess grade I, II, and III had a 96%, 90% and 93% favorable (good and fair) outcome respectively. In contrast only 58% of patients with grade IV had the same result. The outcome was unfavorable in 13% of the patients who were older than 60 years of age and only in 9% of the patients between 30-59 years of age. All the patients younger than 30 years old had a good outcome. Associated medical condition increased the incidences of poor outcome (7% vs. 12%). Patients harboring vertebro basilar aneurysms had a poorer outcome, as opposed to those with aneurysms located in the anterior circulation (20% vs. 8%). The presence of angiographic vasospasm alone did not influence outcome. A proposed point value was given for each of the adverse factors and from this the optimal surgical time was determined for each individual patient. This concept of Risk Score Estimation approach may improve the management outcome of patients with ruptured intracranial aneurysms.     

Propofol decreases ocular pressure in outpatients undergoing trabeculectomy

OBJECTIVES: The present study was conducted to compare pharmacokinetic behaviors of nicardipine enantiomers given in different doses with different formulations of racemic nicardipine in healthy volunteers. METHODS: One or two 20-mg racemic nicardipine tablets, and a 40-mg sustained-release capsule of nicardipine were administered to eight healthy volunteers in a crossover fashion and pharmacokinetic parameters were evaluated. Enantiomer concentrations were determined by GC-MS combined with chiral stationary phase HPLC. RESULTS AND CONCLUSIONS: Serum concentration of (+)-nicardipine was approximately 2-3 times higher than that of (-)-nicardipine in 20- and 40-mg doses of conventional formulations and a non-linear increase in bioavailability with dose was demonstrated. The value for AUC of (+)-nicardipine was approximately 2.3-2.8 times greater than that of the (-)-nicardipine (P < 0.05) when 20 and 40 mg racemic nicardipine were administered in a conventional preparation. Relative bioavailability of the sustained-release preparation vs the conventional preparation was 28% and 44% for (+)- and (-)-nicardipine, respectively, for the 40-mg dose.     

The effect of recombinant growth hormone on the strength of ileal anastomoses in a rat model

OBJECTIVE: In gynecologic surgery, the ileum is the primary site of bowel injury. Recombinant growth hormone (rGH) has been shown to improve the strength of colonic anastomoses in experimental models. The purpose of this study is to evaluate the effect of rGH on small bowel anastomoses, specifically in the ileum. METHODS: Twenty large female rats underwent segmental ileal resections and end-to-end ileoileostomies. The rats were randomized to be treated for 7 postoperative days with either rGH (2.0 mg/kg/day) or placebo starting on the day of surgery. On the seventh postoperative day, a segment of ileum surrounding the anastomosis was resected. The anastomoses were tested for breaking strength on a tensiometer and for tissue concentrations of hydroxyproline. RESULTS: The ileal anastomotic breaking strength in the rGH group was 163.5 +/- 6.0 g (mean +/- standard error). In the placebo group, the breaking strength of ileal anastomoses was 125.0 +/- 3.0 g (P < .001). No significant difference was demonstrated with respect to the hydroxyproline concentration between the rGH group (15.2 +/- 2.0 micrograms/mg) and the placebo group (14.6 +/- 1.0 micrograms/mg). CONCLUSION: In an animal model, a 31% increase in ileal anastomotic breaking strength was induced by rGH administration. With further research this may translate into decreases in the surgical complications that occur in ileal anastomoses. Furthermore, these serve as preliminary data to a study that evaluates the effect of rGH on ileal anastomoses in radiation-injured bowel.     

Admissions to a radiation oncology inpatient service

Lead exposure and its deleterious effects continue to be a problem in many countries. The lack of effective and safe treatments for low-level intoxication has promoted environmental interventions to control different sources of lead. In this study we evaluated the effect of milk consumption in 1849 mother-and-child pairs participating in the lead surveillance program in Mexico City. The mean lead levels were 11.2 micrograms/dL for maternal blood lead (MBL) and 10.8 micrograms/dL in umbilical cord. The correlation between blood lead and umbilical cord lead was r = 0.74. Forty-eight percent of the MBL exceeded 10 micrograms/dL and 9.5% exceeded 20 micrograms/dL. Maternal blood lead was positively related to the use of lead-glazed ceramic were and to traffic exposure and was inversely related to the consumption of milk and orange juice. Women who reported the consumption of more than 7 glasses of milk per week had a blood lead level of 8.7 micrograms/dL; in comparison, those women who reported a consumption of less than 7 glasses per week had a blood lead level of 11.1 micrograms/dL. Similar findings were observed for lead measured in umbilical cord. The association between lead levels and milk intake remained unchanged after taking in consideration other predictors of blood lead. This study suggests that a simple intervention could reduce lead burden among women and their newborns.     

Analysis of the imidazoacridinone C1311 by high-performance liquid chromatography

Natural polyphenols found in rosemary have not only potent antioxidant activities but also anticarcinogenic properties. We have studied some of the molecular mechanisms involved in their chemopreventive action using in vitro human liver and bronchial cell models. Rosemary extract, or its active components, carnosol or carnosic acid are potent inhibitors of DNA adduct formation induced by benzo(a)pyrene or aflatoxin B1. At least two mechanisms are involved in the anticarcinogenic action of rosemary extract: (i) inhibition of the metabolic activation of procarcinogens catalysed by the phase I cytochrome P450 enzymes; (ii) induction of the detoxification pathway catalysed by the phase II enzymes such as glutathione S-transferase.     

Amelanotic malignant melanoma

The purpose of this study was to investigate whether extracellular matrix proteins which influence human keratinocyte behaviour are capable of altering intracellular signalling systems in these cells. The effects of extracellular matrix proteins on two major signal transduction pathways, intracellular calcium and cyclic adenosine monophosphate (cyclic AMP), were investigated. The extracellular matrix proteins examined were the basement membrane preparation matrigel, collagens type I and IV, vitronectin and its active tripeptide component Arg-Gly-Asp (RGD). Acute additions of matrigel, vitronectin and RGD caused rapid transient increases in intracellular calcium and, together with collagen type I, also caused sustained elevations in basal calcium when cells were grown on these substrates. Cyclic AMP production was unaffected by acute exposure to these extracellular matrix proteins. Culture of cells on matrigel, collagen type I or IV, however, significantly reduced basal cyclic AMP accumulation and increased the response of the cells to the receptor-independent agonist forskolin. It is concluded that in vitro some extracellular matrix proteins can initiate both acute and sustained changes in intracellular signalling in human keratinocytes.     

Serum concentrations of luteinizing hormone, growth hormone, and cortisol in gilts treated with N-methyl-D,L-aspartate during the estrous cycle or after ovariectomy

The objective of this experiment was to determine the effects of n-methyl-d,l-aspartate (NMA), an agonist of the neurotransmitter glutamate, on circulating concentrations of LH, GH, and cortisol in gilts treated during the luteal (n = 4) or follicular (n = 4) phase of the estrous cycle, or after ovariectomy (n = 4). Blood was sampled every 15 min for 10 h on each of two consecutive days. On the 1st d, two gilts from each group received i.v. injections of NMA (10 mg/kg BW) at h 4 and 6, and the remaining gilts received .9% saline (vehicle). The following day, gilts that had received NMA on the 1st d received vehicle, and gilts that had received vehicle on d 1 received NMA. All gilts received an i.v. challenge of GnRH (.1 microg/kg BW) at h 8 on each day. The NMA treatment increased (P < .01) LH pulse frequency in luteal-phase gilts by 125%. In contrast, NMA decreased (P < .05) mean concentrations of LH by 48% and suppressed (P < .01) LH pulse frequency by 33% in ovariectomized gilts. No characteristics of LH secretion were affected (P > .05) by NMA in follicular phase gilts. Serum LH concentrations for the 2-h period following GnRH were lower (P < .05) in follicular-phase gilts than in ovariectomized gilts and were 1.15 +/- .09 (mean +/- SE), .81 +/- .05, and .51 +/- .17 ng/mL for ovariectomized, luteal-phase, and follicular-phase gilts, respectively. Treatment with NMA increased circulating concentrations of GH by 334% (P < .01) and cortisol by 77% (P < .03) in all gilts. We suggest that the effects of NMA on LH release in gilts depend on the circulating steroidal milieu. In contrast, NMA evokes secretion of GH and cortisol irrespective of the reproductive status of treated gilts.