Doxorubicin-cisplatin chemotherapy for high-grade nonosteogenic sarcoma of bone. Comparison of treatment and control groups.

OBJECTIVE: To evaluate the role of chemotherapy with a combination of doxorubicin (adriamycin) and cisplatin in high-grade, nonosteogenic, non-Ewing's sarcoma (non-OSA) of bone. DESIGN: A case series comparison with a literature-derived control group. SETTING: A university-affiliated tertiary care centre. PATIENTS: Thirty patients with a diagnosis of non-OSA. Of these, 8 had low-grade disease (grade 1 or 2) and 22 had high-grade disease (grade 3). Eleven of the 22 with high-grade disease had malignant fibrous histiocytoma. Seventeen patients with nonmetastatic high-grade non-OSA were compared with a literature cohort of 37 patients who met the eligibility criteria of nonmetastatic, high-grade non-OSA treated with surgery, with or without radiotherapy. The mean follow-up was 25.2 months. INTERVENTIONS: Eight patients with low-grade tumour underwent surgery alone; 22 patients with high-grade tumour underwent surgery and 6 courses of adriamycin (75 mg/m2 every 3 weeks) and cisplatin (100 mg/m2 every 3 weeks). MAIN OUTCOME MEASURES: Disease-free survival and overall survival in those with high-grade tumours treated with or without chemotherapy. RESULTS: Of 8 patients who had low-grade tumours and underwent surgery alone, 3 had systemic relapse. Of the 22 having high-grade tumours, 4 did not receive chemotherapy because of age and comorbid conditions. Of the other 18, 13 received 3 courses of chemotherapy preoperatively and 3 courses postoperatively, 4 received all 6 courses postoperatively and 1 received all chemotherapy preoperatively to treat metastatic disease. In the 17-patient cohort used for comparison with the literature control group, disease-free survival was 57% at a mean follow-up of 25.6 months and overall survival was 57% at a mean follow-up of 30.1 months. In the control group, disease-free survival was 16% at a mean follow-up of 20.9 months and overall survival was 26% at a mean follow-up of 29.9 months. These differences are significant: p = 0.0000, chi 2 = 41.61 for disease-free survival and p = 0.0000, chi 2 = 46.49 for overall survival. CONCLUSIONS: The findings of this study support the use of adjuvant chemotherapy in patients with high-grade non-OSA, in whom malignant fibrous histiocytoma was the predominant histologic subtype.

Presence of herpes simplex DNA in surgical tissue from human epileptic seizure foci detected by polymerase chain reaction: preliminary study.

OBJECTIVES: To determine whether herpes simplex virus causes monofocal epilepsy and to assess the presence of herpes simplex virus 1 (HSV-1) and HSV-2 in surgical specimens from patients with epilepsy by using polymerase chain reaction and Southern blot analysis. BACKGROUND: Herpes simplex virus is a common neurotropic virus capable of latency within the central nervous system; it has a predilection for the temporal lobe. Central nervous system infection with HSV has been associated with seizure activity. DESIGN AND METHODS: Surgical specimens were removed from 50 patients as part of a treatment protocol for monofocal epilepsy. Neuropathological classification was done, and adjacent sections were screened for HSV by using polymerase chain reaction. Tissues obtained post mortem from the temporal lobe cortex of persons with Alzheimer disease (n=17), Parkinson disease (n=14), or nonneurological disease (n=17) served as controls. RESULTS: Twenty (40%) of the 50 epilepsy cases and 2 (4%) of the 48 control cases had at least one sample that tested positive for HSV (P<.001). Sixty-seven percent (8/12) of the epilepsy cases with heterotopia were positive for HSV. CONCLUSIONS: There was a statistically significant difference in the frequency of HSV-positive surgical specimens from monofocal seizure epicenters compared with nonepilepsy control specimens. These data suggest an association of the virus with seizure activity. All specimens positive for HSV (surgical specimens and control specimens) should be examined to determine the activity or latency state of the virus and cellular localization.

Contractile and coronary vascular effects of pituitary adenylate cyclase activating polypeptide in neonatal pig hearts.

OBJECTIVE: The purpose was to investigate the influence of the 38-amino-acid neuropeptide, pituitary adenylate cyclase activating polypeptide (PACAP38), on contractile function and coronary vascular tone in neonatal hearts. METHODS: Isolated, paced (150 bpm), isovolumically-beating, piglet hearts (n = 19) underwent retrograde aortic perfusion at constant coronary flow (approximately 2.5 ml/min/gwet) with an erythrocyte-enriched (Hct 15-20%) solution (37 degrees C). Agonists were injected into the aortic root of hearts, and the changes in +dP/dtmax and -dP/dtmax (reflecting contractility), and coronary perfusion pressure (reflecting vascular tone) were determined. Responses to PAPCAP38 were compared to isoproterenol, and to the truncated peptide PACAP6-38. RESULTS: PACAP38 (0.1 and 0.5 nmol) increased +dP/dtmax from 1387.4 +/- 134.6 to 1619.0 +/- 118.7, and from 1296.2 +/- 93.4 to 1872.2 +/- 111.4 mmHg/s (P < 0.05); changed -dP/dtmax from -1087.6 +/- 107.5 to -1206.6 +/- 93.6, and from -1025.0 +/- 46.8 to -1375.4 +/- 80.9 mmHg/s (P < 0.05) and decreased coronary perfusion pressure from 61.8 +/- 2.5 to 51.0 +/- 3.8, and from 62.5 +/- 1.0 to 45.3 +/- 3.3 mmHg (P < 0.005), respectively. In comparison, isoproterenol (0.1 nmol) increased +dP/dtmax from 1313.6 +/- 62.8 to 1679.0 +/- 74.4 (P < 0.05), and -dP/dtmax from -1026.4 +/- 54.1 to -1222.6 +/- 57.4 mmHg/s (P < 0.05). PACAP6-38 reduced PACAP38's coronary vasodilatory, but not its contractile, effect. When compared to our previous studies of the 27-amino-acid neuropeptide PACAP27, PACAP38 had less potent contractile, but similar vasodilatory effects. CONCLUSIONS: PACAP38 enhanced contractility and produced coronary vasodilation in piglet hearts, which may make PACAP38 a promising cardiotonic agent for the treatment of neonates with heart failure.

Herpes simplex virus in postmortem multiple sclerosis brain tissue.

BACKGROUND: Herpes simplex virus (HSV) is a common neurotropic virus that is capable of long latencies. It can cause focal demyelination in animals. OBJECTIVE: To test for the presence of HSV-1 and -2 in postmortem brain samples from patients with multiple sclerosis (MS) and controls using polymerase chain reaction and Southern blot hybridization. METHODS: Dissected plaque tissue classified as active or inactive and unaffected white matter (WM) and gray matter (GM) from 37 cases of MS were screened for HSV using polymerase chain reaction and Southern blot hybridization. White matter and GM from 22 cases of Alzheimer's disease, 17 cases of Parkinson's disease, and 22 cases without neurologic disease served as controls. RESULTS: Forty-six percent (17/37) of the MS cases and 28% (17/61) of the control cases had samples that were positive for HSV (P = .11). Forty-one percent (9/22) of active plaques and 20% (6/30) of inactive plaques were positive for HSV. Twenty-four percent (9/37) and 14% (5/37) of MS cases and 23% (14/61) and 13% (8/61) of non-MS cases had HSV in WM and GM, respectively. No significant differences were found among all subgroups (P = .10). CONCLUSIONS: Herpes simplex virus was present in more MS cases than control cases and in more active plaques than inactive plaques. The presence of HSV in WM and GM in cases of MS as well as in control cases makes an etiologic association to the MS disease process uncertain, but cellular localization of HSV and its relationship to oligodendrocytes and latency may reveal such an association in future studies.

Mechanical and metabolic characterization of ischemic contracture in the neonatal pig heart.

Isolated, paced, isovolumetrically beating piglet hearts (n = 37) underwent retrograde aortic perfusion with a crystalloid solution during three periods: 1) baseline (coronary perfusion pressure 60 mm Hg), 2) ischemia (coronary flow 10% of baseline for approximately 80 min), and 3) reperfusion (perfusion pressure returned to baseline). In one group of hearts, glycolysis (using 3H2O formation from [3H]glucose) was assessed. During baseline, peak systolic pressure (PSP) was 101.1 +/- 5.0 mm Hg, end diastolic pressure (EDP) 4.4 +/- 0.5 mm Hg, glycolysis 970.5 +/- 65.3 nmol/min/gwet, and myocardial glycogen 234.8 +/- 12.0 mumol/gdry. During ischemia, PSP decreased to 23.3 +/- 2.7 mm Hg, EDP increased to 12.3 +/- 0.7 mm Hg, myocardial glycogen decreased to 181.5 +/- 30.3 mumol/gdry, and lactate (approximately 154 mumol/gwet) and glycerol (approximately 930 nmol/gwet) were released. Myocardial contracture correlated with a decrease in lactate release. Glycolysis decreased to approximately 400 nmol/min/gwet and remained stable, accounting for approximately 50% of the lactate produced. During reperfusion, PSP recovered to 79.8 +/- 3.5 mm Hg, EDP 6.6 +/- 1.7 mm Hg, and glycolysis 1103.9 +/- 81 nmol/min/gwet. In a second group of hearts, with similar mechanical responses, glucose oxidation (using 14CO2 formation from [14C]glucose) was evaluated. During baseline, glucose oxidation was 165.4 +/- 15.9 nmol/min/gwet and correlated closely (r = 0.957) with mechanical activity. With ischemia, glucose oxidation decreased to approximately 17 nmol/min/gwet, yet accounted for approximately 42% of the ATP produced. Upon reperfusion, glucose oxidation returned to baseline values, but now correlated poorly (r = 0.574) with mechanical activity.(ABSTRACT TRUNCATED AT 250 WORDS)