Characterizing prostatic adenocarcinomas in men with a serum prostate specific antigen level of < 4.0 ng/mL.

OBJECTIVE: To characterize prostate cancer in men undergoing radical prostatectomy who have a prostate-specific antigen (PSA) level of < 4.0 ng/mL, hypothesizing that a low PSA is not caused by diminished tumour production of PSA, nor does it signify clinically insignificant disease. PATIENTS AND METHODS: Seventy-nine men (mean age 59.3 years, range 43-77) with a PSA level of < 4.0 ng/mL were identified from 702 who had a radical prostatectomy between 1994 and 2000. Demographic and clinical data were analysed; pathological specimens were evaluated by routine haematoxylin and eosin staining and immunohistochemistry with anti-PSA antibody, for both pathological staging and grading, and for the presence of PSA production. Tumours were classified as 'clinically insignificant' if the tumour volume was < 0.5 mL and the Gleason score < 7. RESULTS: The mean (SD, range) preoperative PSA level was 3.04 (0.85, 0.8-3.8) ng/mL Indications for biopsy included an abnormal digital rectal examination (61%), a PSA velocity of > 0.75 ng/mL/year (12%), a strong family history of prostate cancer (3%), obstructive urinary symptoms (2%), or no obvious indication (23%). Thirty-eight (48%) tumours were clinically insignificant. Of 41 clinically significant cancers, 13 had a final Gleason score of > or = 7, 20 had extraprostatic extension and 11 had a tumour volume of > or = 10 mL Of the 79 prostate cancer specimens 78 stained strongly for PSA; the exception was a Gleason 9 tumour. With a mean (range) follow-up of 3.5 (0.18-6) years only one patient had a biochemical recurrence (PSA > or = 0.1 ng/mL). CONCLUSIONS: Most prostate cancers in men with a PSA level of < 4.0 ng/mL are clinically significant and PSA-producing. Many of these tumours are high-grade, high-volume and extraprostatic. We are currently exploring factors to explain why serum PSA is not elevated in these men, including tumour location, pattern of invasion and microvessel density.

Atypical atrial flutter originating in the right atrial free wall.

BACKGROUND: Data from experimental models of atrial flutter indicate that macro-reentrant circuits may be confined by anatomic and functional barriers remote from the tricuspid annulus-eustachian ridge atrial isthmus. Data characterizing the various forms of atypical atrial flutter in humans are limited. METHODS AND RESULTS: In 6 of 160 consecutive patients referred for ablation of counterclockwise and/or clockwise typical atrial flutter, an additional atypical atrial flutter was mapped to the right atrial free wall. Five patients had no prior cardiac surgery. Incisional atrial tachycardia was excluded in the remaining patient. High-density electroanatomic maps of the reentrant circuit were obtained in 3 patients. Radiofrequency energy application from a discrete midlateral right atrial central line of conduction block to the inferior vena cava terminated and prevented the reinduction of atypical atrial flutter in each patient. Atrial flutter has not recurred in any patient (follow-up, 18+/-17 months; range, 3 to 40 months). CONCLUSIONS: Atrial flutter can arise in the right atrial free wall. This form of atypical atrial flutter could account for spontaneous or inducible atrial flutter observed in patients referred for ablation and is eliminated with linear ablation directed at the inferolateral right atrium.

[Primary intestinal tuberculosis]. / La tubercolosi intestinale primitiva.

Tuberculosis, with its pulmonary and extrapulmonary localizations, is rapidly increasing in Italy. The authors describe a case of a primary colonic tuberculosis in a 52-year-old Caucasian man. At admission the patient reported a 6-month history of constipation, weight loss and abdominal pain. He had rectal bleeding in the last two weeks. Haematological tests and chest X-ray were negative. Colonoscopy showed a stricture in the proximal transverse colon and multiple ulcers in the ileocecal tract. Multiple biopsies and culture demonstrated tuberculosis. The patient underwent a right hemicolectomy after an episode of acute intestinal hemorrhage and received pharmacological treatment for nine months. After four years he is still free of disease.

[Sacrococcygeal chordoma: clinico-radiologic and histologic characteristics]. / Cordoma sacrococcigeo: aspetti clinico-radiologici e istologici.

Chordoma is a rare, slow-growing, malignant tumor which usually localizes in the sacrococcygeal area. The authors report the case of a 36-year-old woman treated by sacral resection by a posterior approach. At admission, the patient reported a 5-month history of sacral pain. Digital rectal examination revealed a presacral mass. CT and above all MR revealed the presence and the precise extent of the mass which involved the last sacral vertebra and the coccyx. Diagnosis was confirmed histologically. Bilateral S-3 nerve roots were preserved. No radiotherapy was given. After 4 years the patients is free of disease.

Ethnic differences in circadian hemodynamic profile.

Since the introduction of 24-h ambulatory blood pressure monitoring (ABPM), some studies, although not all, have suggested the presence of a blunted nocturnal blood pressure decline in black versus white subjects, a difference that may help explain the higher incidence of target organ damage in blacks. To better define ethnic differences in diurnal hemodynamic profiles, we studied ABPM recordings from 275 black (55.6% women) and 246 white (43.1% women) previously untreated subjects, with a similar age distribution (from 20 to 79 years) and a wide range of systolic (100-230 mm Hg) and diastolic (50-130 mm Hg) blood pressures. Average clinic systolic (diastolic) blood pressures were higher in black v white men by 10.2 (7.3) mm Hg; P = .04 (P = .004), with a similar trend in women (P = NS). On ABPM, blacks had higher average values, a difference that was greater during sleep (9.4 mm Hg for systolic blood pressure) than while awake (4.7 mm Hg; P = .003). Average diurnal change in systolic blood pressure (awake minus sleep values) was 13.1 +/- 0.7 v 18.0 +/- 0.6 mm Hg for blacks v whites (P < .001). There was a strong negative correlation between baseline (ie, sleep) blood pressure and the diurnal change (r = -0.58; P < .001), but at each given level, blacks had a lower daytime increment/nocturnal fall (P = .02). Results for diastolic blood pressure and heart rate were similar. The data suggest that the smaller diurnal change in blacks may be related in part to their higher blood pressure levels, but that there is an additional, independent effect of race. This results in a greater 24-h blood pressure load in blacks than whites for each given clinic (daytime) value, and may help explain differences in target organ damage. Future studies investigating the effects of blood pressure on target organs in different populations should consider diurnal profiles in addition to clinic blood pressure.

Diurnal blood pressure variation and cardiac mass in American blacks and whites and South African blacks.

American blacks exhibit higher nocturnal blood pressure than American whites with similar daytime pressure. To determine whether this represents a true racial difference, as opposed to a consequence of different environmental factors, we measured ambulatory blood pressure, cardiac left ventricular mass, and urinary electrolyte excretion in 22 South African blacks (15 women, aged 36 +/- 12 years) and age, sex, and daytime mean pressure-matched American blacks and whites. While all three groups exhibited similar daytime blood pressure, American blacks displayed significantly higher nighttime mean blood pressure. Both African blacks and American whites experienced the same fall in nighttime blood pressure. Left ventricular mass index was highest in American blacks and lowest in South African blacks. Urine sodium excretion was similar in all groups, but both black populations excreted significantly less potassium than American whites. The data suggest that the differences in diurnal blood pressure rhythm between American blacks and whites do not represent a true racial difference, but more likely are environmental in origin. Furthermore, since both black populations had similar cation excretion rates, yet differed in blood pressure pattern and cardiac mass, divergence in dietary sodium or potassium intake cannot explain the ethnic group differences in the United States.

Diurnal blood pressure variation: differences among disparate ethnic groups.

We examined the possibility that excess cardiovascular morbidity in American blacks compared with whites might be partly the result of differences in diurnal blood pressure variation. Urban American blacks have higher night-time blood pressures and show a smaller increase in blood pressure during the waking day than whites. This difference is associated with a higher cardiac mass in the blacks and occurs despite similar duration and quality of sleep in blacks and whites. Both groups show similar levels of sympatho-adrenal activity at night, but the diurnal increase is smaller in blacks, paralleling the smaller increase in blood pressure. In Africa blacks show a diurnal pressure pattern similar to American whites. Disparities in cation consumption do not explain the differences in blood pressure variation between these groups.

Influence of diuretic therapy on the clonidine suppression test.

Moduretic has been reported to inhibit the suppression of plasma norepinephrine (NE) levels by the alpha 2 adrenoceptor agonist, clonidine. To determine whether plasma volume reduction by hydrochlorothiazide (HCTZ) or antagonism of Na+/H+ exchange by amiloride (the constituents of Moduretic) is responsible, the authors performed a modified clonidine suppression test (CST) in nine normal volunteers (aged 25 +/- 2 years), pretreated for 1 week with HCTZ 50 mg daily, amiloride 10 mg daily, or placebo, in a randomized, double-blind, crossover study. Baseline characteristics were identical on all study days, except serum [K+] and weight, which were lowest on HCTZ (3.6 +/- 0.2 mEq/L and 78.7 +/- 2.5 kg), compared with amiloride (4.2 +/- 0.1 mEq/L and 79.9 +/- 2.4 kg) and placebo (4.0 +/- 0.1 mEq/L and 80.2 +/- 2.7 kg, P less than .05). Oral clonidine (0.3 mg) produced a reduction in mean blood pressure by about 20%. Plasma norepinephrine levels were similar in patients receiving placebo, HCTZ, and amiloride (205 +/- 18, 272 +/- 40 and 277 +/- 44 pg/mL, P greater than .20), and decreased significantly during CST. The maximal reduction for each subject averaged 72.7 +/- 12.4%, 87.9 +/- 3.8%, and 82.9 +/- 5.7% for placebo, HCTZ, and amiloride. Clonidine also produced a four to seven-fold increase in plasma growth hormone levels, reduced salivary flow by about 75%, and increased the level of sedation. There were no differences among the three pretreatment regimens in the effects of clonidine, indicating that diuretic therapy does not need to be systematically discontinued in patients undergoing CST.

Renal and hemodynamic effects of intravenous fenoldopam versus nitroprusside in severe hypertension.

The renal and hemodynamic effects of intravenously administered fenoldopam mesylate, a novel dopamine-1 receptor agonist, were compared with those of sodium nitroprusside in 28 patients (18 male; 26 black, two white; average age, 49 +/- 3 years) with an average blood pressure of 219/137 mm Hg, most of whom presented with acute target organ damage. Fenoldopam and nitroprusside lowered blood pressure safely to an average pressure of 176/105 mm Hg; highly significant dose-response relations were found for the 13 patients receiving fenoldopam and the 15 receiving nitroprusside. Volume and sodium, potassium, and creatinine concentrations were measured in freely voided urine specimens both before and during intravenous therapy. In the fenoldopam-treated patients, there were significant increases in urinary flow (92 +/- 21 to 168 +/- 37 ml/hr, p less than 0.003), sodium excretion (227 +/- 73 to 335 +/- 90 mu eq/min, p less than 0.001), and creatinine clearance (70 +/- 11 to 93 +/- 13 ml/hr, p less than 0.003). In the nitroprusside-treated group, however, all these parameters decreased, but not significantly. For direct comparison of the two agents, the increments in urinary flow rate (+76 +/- 20 vs. -16 +/- 15 ml/hr, fenoldopam vs. nitroprusside), sodium excretion (+109 +/- 28 vs. -39 +/- 28 mu eq/min), and creatinine clearance (+23 +/- 6 vs. -11 +/- 7 ml/min) were significantly greater (p less than 0.001 for each) in the fenoldopam-treated group. Significant differences were also obtained when these parameters were calculated as percentage increase over baseline. Fenoldopam and nitroprusside are effective therapies for severe, accelerated, or malignant hypertension, but fenoldopam had additional salutary renal effects in these patients.

Inhibition of Chinese hamster ovary cell DNA synthesis by hydrogen peroxide.

The DNA synthesis inhibitory effect of hydrogen peroxide has been examined under a number of experimental conditions. Results have indicated that the effect of the oxidant is more pronounced when the treatment is performed at 37 degrees C than at 4 degrees C and in low density as compared to high density cultures. In addition, similar levels of inhibition were achieved by measuring the incorporation of radiolabelled thymidine in the presence of, or following treatment with, the oxidant. Although early events seem to be responsible for the decreased rate of DNA synthesis, it would appear that hydrogen peroxide does not alter thymidine extracellularly and/or decrease the transport of the nucleoside across the plasma membrane, which may actually be slightly augmented. Thus, the previously illustrated results may represent an underestimate of the actual capacity of the oxidant to reduce DNA synthesis. This inference is further supported by the fact that the effect of hydrogen peroxide appears markedly enhanced in cells preloaded with the radiolabelled precursor. A temporal relationship seems to exist between the steady state level of DNA single strand breaks and the extent of DNA synthesis inhibition by hydrogen peroxide. The oxidant has no effect on DNA chain elongation. In conclusion, data presented in this paper suggest that early events, involving selective effects on replicon initiation, mediate the DNA synthesis inhibitory effect of hydrogen peroxide.

Role of metal ions in oxidant cell injury.

This paper represents a short review of recent data on the molecular mechanism(s) of H2O2 cytotoxicity. The role of metal ions has been discussed in light of their ability to drive a reaction of the Fenton type. Hydroxyl radicals play a key role in mediating the deleterious effects of the oxidant, although these species do not seem to directly produce the lethal lesions. It still remains unclear whether or not DNA represents a critical target for H2O2-induced cytotoxicity.