Use of a monoclonal antibody for the therapeutic monitoring of cyclosporine in plasma and whole blood

The evaluation of a radioimmunoassay (RIA) for the monitoring of cyclosporine (CSA) that utilizes a monoclonal antibody specific for the parent compound is described. The assay exhibited good analytical recovery (greater than 95%), precision (coefficient of variation less than 10%), and linearity in plasma and whole blood specimens. The percentage cross reactivity of the major CSA metabolites M-17, M-1, and M-21 was less than 2%. The RIA gave values that were on average indistinguishable from those obtained by high-pressure liquid chromatography in plasma and whole blood specimens obtained from 49 renal transplant recipients.     

Blood lactate and catecholamine levels in the carbon monoxide-exposed rat: the response to elevated glucose.

Previous studies have shown that elevated blood glucose is detrimental to the outcome in acute carbon monoxide (CO) poisoning. The present goals were to characterize the blood lactate and catecholamine changes and to determine whether elevated blood glucose results in increases in the levels of these substances. Two groups of adult Sprague-Dawley, Levine-prepared, female rats (n = 22 each) were exposed to 2400 ppm CO for 90 min: one group received nothing (CO alone), while the other group was infused with a 50% glucose solution (4 ml/kg) (CO + glucose). The usual hypothermia, hypotension, bradycardia and hemoconcentration associated with acute severe CO poisoning were observed. Survival rates were 68% and 54% in the CO alone and CO + glucose groups, respectively. Arterial blood pressure tended to decline more in rats that died; the difference was significant in the CO + glucose group. In the CO alone group, plasma glucose concentration was significantly lower after CO exposure in rats that died than in survivors (35 +/- 15 vs. 99 +/- 16 mg/dl). In the CO + glucose group, glucose concentration was significantly higher after 45 min in rats that died (d) than in survivors (s) (447 +/- 29 vs. 324 +/- 31 mg/dl). Elevated blood glucose in the CO + glucose group failed to significantly increase blood lactate; however, lactate tended to be higher in rats that died in both groups [CO alone group: 175 +/- 17 (d) vs. 138 +/- 9 (s); CO + glucose group: 154 +/- 10 (d) vs. 143 +/- 8 (s)]. Plasma epinephrine and norepinephrine increased significantly 6-10-fold and 2-6-fold in each of the two groups, respectively; however, catecholamine levels were not related to either the administration of glucose or survival. With regard to CO poisoning in this animal model, the results do not support the hypotheses that elevated blood glucose exacerbates the increase in blood lactate, that increased catecholamine increases glucose, or that greater CO-induced hypoglycemia results from increased lactate production. The results do show that death is related to abnormally high or low blood glucose, but that it is not due to higher blood lactate or catecholamine levels.     

Vitreous humor in the evaluation of postmortem blood ethanol concentrations

Many studies have been published comparing blood (B) ethanol (EtOH) and vitreous humor (VH) EtOH concentrations. We conducted a similar study of routinely collected specimens to determine (1) whether the reported average VH/B ratios are consistent, (2) the percentage of cases with VH/B ratios outside of the expected range, and (3) the magnitude of B EtOH that can be associated with negative VH EtOH (less than 0.01 g/dL). VH EtOH less than 0.01 g/dL was associated with 41 specimens; 34 specimens had B EtOH less than 0.03 g/dL while a B EtOH as high as 0.12 g/dL was measured. For B EtOH less than 0.10 g/dL, 67% had VH EtOH within 0.02 g/dL of B EtOH (N = 101). For B EtOH greater than or equal to 0.10 g/dL, the VH/B EtOH ratio ranged from 0.10 to 1.91; the mean ratio was 1.17 and the median ratio was 1.18 (N = 205); and 64% had a ratio between 1.00 and 1.39. Vitreous humor can be used to facilitate understanding the significance of postmortem blood EtOH concentrations.     

Case studies of postmortem quetiapine: therapeutic or toxic concentrations?

The focus of this study was to determine if the analysis of a variety of postmortem biological specimens would aid in the toxicological interpretation of quetiapine in the cause and manner of death determinations. Postmortem quetiapine concentrations were examined in 21 medical examiner cases using liquid-liquid extraction and high-performance liquid chromatography analysis. Specimens analyzed were peripheral blood, central blood, liver, vitreous humor, and gastric contents, when available. Findings from this study suggest that therapeutic postmortem quetiapine concentrations may be less than 1 mg/L in both peripheral and central blood, less than 0.5 mg/L in vitreous, and less than 5 mg/kg in liver. Quetiapine concentrations indicative of toxicity were estimated at greater than 1 mg/L in peripheral and central blood, greater than 0.5 mg/L in vitreous, and greater than 5 mg/kg in the liver. Liver concentrations appeared to be particularly helpful in determining the potential for toxicity when compared with blood concentrations. Cases in which quetiapine was determined to play a significant role in the death indicated postmortem liver concentrations greater than 5 mg/kg. Cases in which quetiapine concentrations were considered incidental or noncontributory in the death had liver concentrations 2 mg/kg or less.     

Tissue distribution and in vivo immunosuppressive activity of liposomal cyclosporine.

The distribution and immunosuppressive activity of liposomal cyclosporine (L-CSA) when administered iv as single- and multiple-doses were compared with the commercially available cyclosporine (C-CSA) in rats. CSA concentrations in the spleen and liver were significantly greater 1 hr after dosing in rats given L-CSA compared with C-CSA. The apparent tissue to blood partition coefficient at 1 hr after dosing was significantly greater for the liver and spleen of rats treated with L-CSA compared with C-CSA. Drug concentrations 24 hr after single doses of L-CSA were significantly lower in the kidney, heart, lung, and adipose tissues compared with animals given C-CSA. Lymphocyte-blastogenic response was studied in a separate group of rats given 10 mg/kg/day of L-CSA or C-CSA for 10 days compared with drug-free control groups. A 3-fold decrease in blastogenic response was observed in rats given L-CSA compared with C-CSA-treated rats (12.7 +/- 11.8 vs. 34.9 +/- 11.3 x 10(3) dpm/10(6) cells; p less than 0.05). These data suggest that the liposomal formulation of CSA leads to enhanced tissue levels of CSA in the spleen coupled with augmentation in immunosuppressive activity.     

Metabolic predictors of carbon monoxide poisoning

In a retrospective study of 54 carbon monoxide (CO) levels greater than 10%, we looked for correlations with glucose, electrolytes and anion gap. Electrolytes and anion gap were not found to be significant. We did find, however, that 8 out of the 12 CO levels greater than 25 had glucose values greater than 110. We, therefore, conclude that if a patient presents with the appropriate history or signs of vague CNS symptoms and an increased blood glucose, a measurement of CO should be considered.     

Effect of epinine on systemic hemodynamics and regional blood flow in conscious pigs.

Intravenous (i.v.) infusions (1, 2.5, 5, and 10 micrograms/kg/min for 10 min) were used to evaluate the cardiovascular effects of epinine (N-methyl-dopamine) in 8 conscious pigs. Epinine is a nonselective and nonspecific dopamine (DA) agonist, that also stimulates alpha- and beta-adrenoceptors. Epinine (1-5 microgram/kg/min) increased cardiac output (CO) by up to 15 +/- 5% (p less than 0.05), owing to an increase in heart rate (HR, 24 +/- 6%), but an increase in stroke volume (SV, 16 +/- 4%) caused the further increase in CO at 10 micrograms/kg/min. Mean arterial blood pressure decreased gradually from 100 +/- 5 mm Hg to 84 +/- 4 mm Hg during infusions up to 5 microgram/kg/min, but increased to 89 +/- 4 mm Hg during infusion of 10 micrograms/kg/min (p less than 0.05). Systemic vascular resistance had decreased from 36.5 +/- 2.8 to 27.5 +/- 3.0 mm Hg/L/min after infusion of 5 micrograms/kg/min but did not change further during infusion of 10 micrograms/kg/min. LV dP/dtmax increased only at 10 micrograms/kg/min. Myocardial blood flow did not change at any dose, owing to metabolically regulated coronary vasodilatation (myocardial work did not change). Flow to the adrenals (up to 110 +/- 37%) and the spleen (up to 95 +/- 13%) increased dose dependently. Cerebral blood flow increased only at the highest dose (15 +/- 5%, p less than 0.05); flow to the kidneys, liver, small intestine, and skeletal muscle did not change. Flow decreased to the stomach (21 +/- 5%) and skin (for doses less than 2.5 micrograms/kg/min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Drug concentrations in post‐mortem specimens

A meta‐analysis of drug concentrations in post‐mortem specimens is presented. The analysis involved 50 commonly used drugs and their concentrations in femoral blood, other blood (such as cardiac blood), vitreous humor, muscle, liver, kidney, brain, heart, lung, spleen, and bile. A total of 10 993 analytical results from 5375 post‐mortem cases in 388 studies were gathered and the ratios of drug concentrations in tissue material to median femoral blood concentrations were calculated. Analytical results from the laboratory's own database (years 2000–2018) were also included. The results show that the variation of ratios between post‐mortem specimens and femoral blood is highly compound dependent. This database can be utilized in interpretation of toxicological results in cases where femoral blood is not available. The specimens with similar concentrations as in femoral blood were vitreous humor, muscle, and other blood, such as cardiac blood, and the highest concentrations were generally measured from liver and bile. For these reasons we suggest the following order for biological specimens to be used for a quantitative toxicological analysis in cases where femoral blood is not available: 1. other blood, 2. muscle, 3. vitreous humor, 4. brain, 5. heart, 6. spleen, 7. kidney, 8. liver, and 9. bile.     

Effect of ligation of spleen vessels on left ventricular function and coronary blood flow in dogs injected with scorpion venom

Scorpion sting may cause myocardial dysfunction in human victims, probably by increased O2 demand and decreased O2 supply. In dog, scorpion venom (SV) causes no myocardial dysfunction. Myocardium is probably protected by "autotransfusion" of blood from the spleen to the circulation, increasing coronary blood flow (CBF) and O2 delivery. We hypothesized that ligation of spleen vessels prior to injection of SV in dogs would prevent the autotransfusion of blood, thereby causing myocardial ischemia due to decreased CBF, simulating the hemodynamic pattern of human envenomation. We studied cardiac output (CO), CBF, left ventricular (LV) O2 delivery and contractility in 11 dogs injected with 0.07 mg/kg of SV (Leiurus quinquestriatus). Ligation of spleen vessels was performed on 6 of the 11 dogs prior to SV injection. 15 min after SV injection CO had increased by 186% in control dogs, while ligation of spleen vessels completely prevented CO elevation (p<0.001). In both groups, however, LV dp/dt increased by 400% and dp/dt/p by 170% (p<0.001). CBF increased by 350% and 550% in the spleen and control groups (p<0.001) respectively. This was associated with elevation of diastolic blood pressure and a decrease in coronary vascular resistance. LV O2 delivery increased (p<0.05) in both groups. At 60 minutes there was a decrease in CO, stroke work, and LV end systolic pressure in both groups, while LV contractility remained above baseline. Scorpion venom injection in dogs causes an initial increase in CO by auto-transfusion of blood from the spleen. Prevention of the autotransfusion does not preclude increases in CBF, O2 delivery and LV contractility.     

The effects of 7.5% carbon dioxide inhalation on task performance in healthy volunteers

Studies have shown that anxiety can positively or negatively affect performance with respect to focusing of attention or distractibility, subjective workload and effort (Humphreys and Revelle, 1984). The inhalation of carbon dioxide (CO(2)) is associated with physiological and psychological effects of anxiety (Bailey et al., 2005) but its effects on performance have rarely been reported. The studies reported here looked at the effects of CO(2) inhalation on physiological and subjective measures and performance on two tasks. Eight healthy male participants completed a tracking task with a reaction time component, and 12 healthy participants (six male) completed a complex target identification task. Tasks were performed during 20-min inhalations of 7.5% CO(2)/21% O(2)/71.5% N(2) mixture or medical air. Continuous heart rate and blood pressure measures were taken, in addition to subjective measures of mood and workload. In comparison with air, CO(2) increased heart rate and blood pressure, increased subjective scores of panic, anxiety, fear, and tension, and reduced subjective scores of relaxation and happiness. Attention was focussed when inhaling CO(2) during the simple task, and central demand was greater when inhaling CO(2) during the complex task. Therefore, inhalation of 7.5% CO(2) produces effects on task performance which are consistent with anxiety.     

Determination of tin in biological materials by atomic-absorption spectrometry with a graphite furnace

The determination of tin in the blood, liver, kidney, and spleen by atomic-absorption measurement using a graphite furnace was investigated. The presence of 20 micrograms/mL Fe(III) reduced absorbance of 0.2 microgram/mL Sn to 50%. To remove the interference of Fe(III), it was reduced to Fe(II) by 10% ascorbic acid, and Sn(IV) was extracted by methylisobutylketone (MIBK) without a chelating agent. This technique can be applied when 100 micrograms/mL Fe coexists with 0.2 microgram/mL Sn. Four methods for determination of tin in the blood were examined: (a) standard addition, (b) low-temperature ashing/MIBK extraction, (c) wet ashing/MIBK extraction, and (d) direct determination. The results of (a), (b), and (c) showed a high correlation (r greater than 0.86, n = 12), while the values obtained by (d) were scattered widely and showed little correlation with those determined by the other three methods. In methods (b) and (c), the detection limit was 10 ng/mL (0.2 ng Sn) without expansion mode, 2 ng/mL (0.04 ng Sn) with X 5 expansion mode, the recovery more than 90%, and the coefficient of variation 6.6% (n = 8). Method (c) was recommended for large sample sizes, and was also suitable for determination of tin in liver, kidney, and spleen, using 0.5%, instead of 10%, ascorbic acid.     

A RANDOMIZED CONTROLLED TRIAL OF WEIGHT REDUCTION AND METOPROLOL IN THE TREATMENT OF HYPERTENSION IN YOUNG OVERWEIGHT PATIENTS

The effects of weight reduction and metoprolol (100 mg, b.d.) in the treatment of hypertension (diastolic blood pressure 90-109 mmHg) in 56 young, overweight patients were investigated in a randomized placebo controlled trial. After a 4-week baseline, subjects were followed up for 21 weeks. In the weight reduction group, the fall in systolic and diastolic blood pressure (13/10 mmHg), associated with a mean group weight loss of 7.4 kg, was greater (P less than 0.001) than that in the placebo group (7/3 mmHg); the fall in diastolic pressure but not systolic pressure was also greater than that in the metoprolol group (10/6 mmHg). At the end of follow-up, 50% of the weight reduction group, 39% of the metoprolol group and 17% of the placebo group had a diastolic blood pressure of less than 90 mmHg. In the weight reduction group there was a fall in total cholesterol and the ratio of total to HDL-cholesterol (P less than 0.001); in the metoprolol group there was a fall in HDL-cholesterol and an increase in the ratio of total to HDL-cholesterol (P less than 0.001). The results suggest that in the first step of treatment for hypertension in overweight patients, modest weight reduction produces significant and clinically important reductions in blood pressure, without incurring the adverse effects on plasma lipids and lipoproteins often associated with the first step of drug therapy.     

Time required for blood lead levels to decline in nonchelated children.

OBJECTIVE: To determine the time for a decline in blood lead to less than 10 microg/dL in nonchelated children who are enrolled in case management. STUDY DESIGN: Retrospective analysis of venous blood lead data of lead-poisoned children followed in a case management program designed to decrease lead exposure. Children were excluded if their blood lead had not yet declined to less than 10 microg/dL, if they received chelation therapy, or if they had not received follow-up for more than 15 months. We calculated the time between peak elevation of lead and decline to less than 10 microg/dL. Data were categorized based on the child's peak blood lead and season in which their peak blood lead occurred. Data were analyzed using ANOVA and linear regression. Kaplan-Meier survival analysis was used to describe data in population form. RESULTS: 579 patients were included in the analysis. Blood leads of 25-29, 20-24, 15-19, and 10-14 microg/dL required 24.0, 20.9, 14.3, and 9.2 months, respectively, to decline to less than 10 microg/dL. For continuous data, a linear relationship was described by the following equation: Time (# of months required to achieve a blood lead less than 10 microg/dL) = 0.845 x peak lead; p < 0.0001. Kaplan-Meier curves complement the findings in a population-based fashion. CONCLUSIONS: The mean time for blood lead to decline was linearly related to the peak in blood lead. The time for 50% of the blood lead to decline to less than 10 microg/dL was not linear and varied with peak lead.     

Quantitative analysis of the aminosteroidal non-depolarizing neuromuscular blocking agent vecuronium by LC-ESI-MS: A Postmortem Investigation

The apparent recreational use of an aminosteroidal non-depolarizing neuromuscular blocking agent, vecuronium, is reported in this postmortem investigation. A quantitative method for the analysis of vecuronium and its active metabolite, 3-desacetylvecuronium, in blood and tissue samples was developed using liquid chromatography-electrospray ionization mass spectrometry operated in positive selected ion monitoring mode. Chromatographic separation was performed on a Gemini 5-microm C18 column using a mobile phase of 0.1% formic acid/acetonitrile at 0.700 mL/min. The method was linear from 0.01 to 1.00 mg/L with correlation coefficients of 0.999 and greater for both compounds. The limits of detection and quantitation were determined in blood to be 0.005 and 0.010 mg/L, respectively. The coefficients of variation were less than 10% for both intra- and interday assays. Vecuronium was quantitated in blood at 0.070 mg/L and in the kidney, liver, and spleen at 0.224, 0.045, and 0.080 mg/kg, respectively. The active metabolite 3-desacetylvecuronium was quantitated in blood at 0.100 mg/L, in the urine at 0.040 mg/L and in the kidney, liver, spleen, and lung at 0.271, 0.100, 0.082, and 0.164 mg/kg, respectively.     

Role of blood pressure in the natriuretic response to acute calcium channel blockade in humans.

Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and renal excretion of sodium and lithium were measured before and after acute oral administration of 20 mg nifedipine in 19 essential hypertensive patients. In 10 of them, with a diastolic pressure less than 105 mm Hg, nifedipine resulted in a decrease in mean blood pressure toward normal (109 +/- 2 to 97 +/- 2, p less than 0.001), a 27% increase in ERPF (p less than 0.001), no change in GFR, and an increase in fractional sodium excretion (28%, p less than 0.001). In nine subjects with a diastolic pressure greater than or equal to 105 mm Hg, nifedipine produced a decrease in mean blood pressure (133 +/- 6 to 117 +/- 4, p less than 0.001), which however remained higher than in mild hypertensives (p less than 0.001). ERPF rose by 29% (p less than 0.001), GFR remained unchanged, and fractional sodium excretion definitely increased more than in mild hypertensives (126%, p less than 0.001), as did fractional lithium excretion, used as an estimate of proximal tubular sodium handling. Acute nifedipine produces renal vasodilation in hypertensives, but with a greater natriuretic response in those subjects whose blood pressure remains elevated. Thus, acute natriuresis following nifedipine administration is largely dependent on the interaction between changes in arterial pressure and renal hemodynamics.     

Gamma-hydroxybutyrate and ethanol effects and interactions in humans

BACKGROUND: Gamma-hydroxybutyrate (GHB) is a common drug of abuse that can produce serious toxicity, particularly when used with other sedatives. We examined the individual and combined effects of GHB and ethanol in human volunteers. METHODS: Sixteen healthy adults (7 men) were given 50 mg/kg GHB (Xyrem), 0.6 g/kg ethanol in 2 doses, alone and combined in a double-blind, placebo-controlled, crossover study. Plasma concentrations, heart rate (HR), blood pressure (BP), and oxygen saturation (O2sat) were serially monitored for 24 hours. RESULTS: Adverse events included 2 instances of hypotension and 6 episodes of vomiting with GHB-plus-ethanol ingestion. Oxygen saturation was decreased by GHB and ethanol individually, and maximally decreased by the drugs combined (max -2.1% +/- 0.3%, P < 0.0001 vs placebo). Compared with baseline, systolic and diastolic BP were significantly decreased, and HR was increased by ethanol but not affected by GHB alone (maximum systolic BP change -15.7 +/- 3.0 mm Hg, P = 0.0006; maximum HR change 13.5 +/- 2.3 beats per minute, P = 0.006). Ethanol coingestion resulted in 16% higher GHB maximal plasma concentration and 29% longer elimination half-life, indicating possible enhanced bioavailability or reduced clearance of GHB caused by ethanol, however, these effects were not statistically significant. CONCLUSIONS: Modest doses of GHB do not affect hemodynamic function, but O2sat was decreased. Gamma-hydroxybutyrate-plus-ethanol resulted in more adverse effects, including gastrointestinal disturbances, hypotension, and decreased O2sat, but only minimal pharmacokinetic interactions were observed.     

EFFECTS OF ONE-CLIP, ONE-KIDNEY HYPERTENSION IN CHRONICALLY CATHETERIZED PREGNANT EWES

1. Hypertension secondary to renal disease was studied in non-pregnant and pregnant ewes to determine whether there were any changes in arterial pressure and the distribution of cardiac output and, in particular, whether uteroplacental blood flow was affected. 2. In six non-pregnant, chronically catheterized, uninephrec-tomized ewes, a reduction in renal blood flow (RBF) to 40–50% of control caused hypertension within 3 h. This was maintained for as long as RBF was reduced (72 h) and returned to control 24 h after the occluder around the renal artery was released. When this experiment was repeated in 16 uninephrectomized pregnant ewes (118–134 days gestation) hypertension occurred within 3 h and was sustained for as long as RBF was reduced (between 24 and 72 h). Arterial pressure returned to control within 24–72 h of restoring RBF. 3. Compared with non-pregnant ewes, pregnant ewes had similar arterial pressures, higher cardiac outputs (CO; P < 0.001) and heart rates (HR; P < 0.001), lower total peripheral resistances (TPR; P < 0.001) and similar blood flows to brain, ovary, pancreas, kidney and spleen. Splenic vascular resistance (VR) was greater (P= 0.006), gut blood flow was greater (P < 0.05) and gut VR was less (P < 0.05). Myoendometrial blood flow/g was greater (P < 0.005) and myoendometrial VR was less (P= 0.006). 4. In pregnant sheep with renal clip hypertension, there was no change in CO and HR, but TPR increased (P < 0.01), as did plasma renin activity. Gut, brain, pancreatic and myoendometrial VR were increased as long as RBF was reduced; in addition, myoendometrial VR remained high for the rest of the experiment. Placental blood flow was unchanged at 3h; 24–72 h later it was reduced (P < 0.05) and remained low. Placental VR was increased 24–72 h after RBF was restored when ewes were again normotensive. 5. Thus, one-clip, one-kidney renal hypertension in the pregnant ewe was due to increased TPR associated with a fall in uteroplacental blood flow that persisted even when RBF was restored and ewes were normotensive. This reduction in uteroplacental blood flow could account for the high foetal morbidity and mortality that occurs in pregnant women with renovascular hypertension.     

Comparative effects of a new cardioselective beta-blocker nebivolol and nifedipine sustained-release on 24-hour ambulatory blood pressure and plasma lipoproteins.

This double-blind, parallel-group study compared the effects of nebivolol, a novel cardioselective beta-blocker, with those of nifedipine sustained-release on 24-hour ambulatory blood pressure and plasma lipoprotein levels. After a washout period of 8 weeks, 51 patients with mild to moderate essential hypertension were randomized to double-blind treatment with either nebivolol 5 mg once a day (n = 26) or nifedipine sustained-release 20 mg bid (n = 25) over a period of 12 weeks. Both treatments produced similar and significant (P = .0001) reduction in office blood pressure as well as in 24-hour, work, awake, and sleep ambulatory blood pressure. The clinical response (diastolic blood pressure less than 90 mmHg or decreased by greater than or equal to 10 mmHg) rate was 69% for nebivolol and 59% for nifedipine, respectively. Moreover, the nebivolol and nifedipine treatment-induced decreases in mean 24-hour ambulatory blood pressure were similar to the decreases in clinic blood pressure. Furthermore, the percentages of "blood pressure loads" (awake greater than 140/90 mmHg and asleep greater than 120/80 mmHg) were lowered significantly (P = .0001), from 60% to 29% with nebivolol and from 60% to 39% with nifedipine. Mean ambulatory heart rate was reduced (P = .0001) from 79 +/- 7 to 68 +/- 7 beats/minute during nebivolol therapy and from 80 +/- 9 to 79 +/- 7 (not significant) with nifedipine. Total plasma cholesterol and low-density lipoprotein levels decreased significantly (P less than .05) by 5 and 8%, respectively, after nebivolol treatment, and each decreased by 3% after nifedipine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuroendocrine immunophenotype as predictor of clinical recurrence in 110 patients with prostate cancer

We evaluated the relationship between NE expression and well-known prognostic factors and assessed whether tumor relapse after radical surgery correlates with the extent of NE differentiation. Radical prostatectomy specimens from 110 patients with clinically localized prostate cancer were assessed. Patients were followed up every three months for the first two years after surgery and six monthly for 5 additional years until failure, or for a mean of 48 months from the time of surgery for those who did not experience failure. The percentage of cells showing CgA immunoreactivity was evaluated using a visual quantitative method. Tumor staining was categorized as positive if greater than 10 percent and negative if less than 10 percent of tumor cells were stained, to ensure that only cases with significant positivity were included in the positive group. The median follow-up was 5.4 years (range 1.8 to 7.2). The median time to clinical recurrence was 7.5 years and the median time to biochemical recurrence was 2.8 years. Of 31 patients (28 percent) who experienced a PSA recurrence, 15 developed a clinical recurrence. The mean preoperative PSA level was 9 ng/ml (range 2.7 to 25). Most cases were well differentiated (Gleason score less than 7), intraprostatic (less than pT2) tumors. Immunoreactivity in >or= 10 percent of the cells was seen in 17.2 percent (n=19) of the tumor specimens. The preoperative PSA level, Gleason score, use of neoadjuvant or adjuvant therapy, lymphnode positivity were not statistically associated with NE expression. Only the primary pathologic stage appeared to be associated with CgA staining in the primary tumor (p=0.001). On the univariate analysis NE expression did not predict biochemical recurrence free survival, whereas it was associated with clinical recurrence. NE differentiation in clinically localized prostate cancer can be associated with failure after definitive surgical treatment, even if no conclusions can be drawn regarding its value as an independent prognostic factor.     

A new tool for the early diagnosis of carbon monoxide intoxication

Invasive measurement of carboxyhemoglobin (COHb) by blood gas analysis (BGA) is accepted as the standard diagnostic procedure in diagnosis of inhalation injury and carbon monoxide (CO) intoxications. The main disadvantage of BGA with COHb testing is the unavailability in pre-hospital rescue conditions. The non-invasive SpCO analysis using pulse CO oximetry (Rad57, Masimo Corp., USA) represents an easy-to-handle device to facilitate the diagnosis of CO intoxication. Between January 2006 and August 2008, 20 patients who were admitted with CO intoxication to our burn centre were included in this study. Blood gas analysis including COHb testing was performed on the first day, hourly. At the same time, SpCO was determined using the Rad57 pulse CO oximeter. Patients received inhalative oxygen according to the parameters of blood gas analysis or hyperbaric oxygenation if COHb?>?10%. Five young healthy volunteers served as control group. The SpCO of the volunteers was cross-checked against their COHb levels, which were measured by blood gas analysis. Results of pulse CO oximetry revealed a mean error of approximately 3.15% from the results achieved by blood gas analysis. If COHb resulted in values higher than 10%, the bias remained approximately the same (3.43%/precision 2.362%). When different blood gas analyzers in our department were tested with the same patient sample, a mean error of 2.4% was found. This is only 1% lower compared to the mean error of pulse CO oximetry. Therefore, pulse CO oximetry represents a reliable measurement technique that is easy to handle and could facilitate the early diagnosis of CO intoxication in pre-hospital rescue conditions.