No circulating cytomegalovirus in five patients with glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme is the most common and most aggressive type of primary brain tumor, accounting for 52% of all primary brain tumor cases and 20% of all intracranial tumors. Recently, evidence for a viral cause has been postulated, possibly SV40 or more likely cytomegalovirus (CMV). One report indicated that 80% of patients with newly diagnosed glioblastoma multiforme have detectable cytomegalovirus DNA in their peripheral blood, while sero-positive normal donors and other surgical patients did not exhibit detectable virus. PATIENTS AND METHODS: In the current study, we examined peripheral blood of 5 patients with newly diagnosed glioblastoma multiforme. Peripheral blood was collected in anticoagulated tubes from five patients with newly diagnosed glioblastoma multiforme referred for radiation therapy. We used standard methods for detecting CMV by reverse transcriptase-polymerase chain reaction (RT-PCR) and peripheral blood culture. RESULTS: None of our patients had circulating CMV. CONCLUSION: There are four subtypes of glioblastoma. We hypothesize that circulating CMV might be limited to some, but not all of these subtypes, and that our failure to detect CMV might be attributed to the fact that none of these patients had the appropriate subtype or subtypes.

Bisphosphonate-induced osteonecrosis of the jaws, bone markers, and a hypothesized candidate gene.

PURPOSE: To determine whether any abnormality in serum bone markers is related to bisphosphonate-induced osteonecrosis of the jaw. MATERIALS AND METHODS: We obtained serum bone markers and other relevant endocrine assays on 7 patients with osteonecrosis of the jaws (ONJ). The assays were C-telopeptide, N-telopeptide, bone specific alkaline phosphatase, osteocalcin, intact parathyroid hormone, T3, T4, TSH, and vitamin D 25 hydroxy. Diagnostic criteria for ONJ were those formulated by the American Association of Oral and Maxillofacial Surgeons. RESULTS: Five of our patients were women. Two had metastatic breast cancer and had been treated with zoledronic acid; 1 had also received pamidronate. Three others had osteoporosis and had been treated with daily alendronate. One man had metastatic prostate cancer treated with zoledronic acid. Another man had Gaucher's disease treated with zoledronic acid. All patients had been withdrawn from bisphosphonate for at least 6 months. None was taking or had taken corticosteroids. None of the lesions had shown any significant healing and all were still causing the patients considerable distress, yet the bone markers were within the normal range as measured in our laboratory, except for intact parathyroid hormone, which was slightly elevated in 1 case of metastatic breast cancer (177 pg/mL). CONCLUSIONS: We hypothesize that matrix metalloproteinase 2 (MMP2) is a candidate gene for bisphosphonate-induced ONJ for 3 reasons: 1) MMP2 is associated with bone abnormalities which could be related to ONJ. 2) Bisphosphonates are associated with atrial fibrillation, and MMP2 is the only gene known to be associated with both bone abnormalities and atrial fibrillation. 3) A network of disorders and disease genes linked by known disorder-gene associations indicates that cardiovascular disease and bone disease are closely related, suggesting that a single drug such as bisphosphonate, acting on a single gene, MMP2, could have both bone and cardiovascular side effects different from the osteoclast inhibition that is characteristic of bisphosphonate.

Normal serum bone markers in bisphosphonate-induced osteonecrosis of the jaws.

We obtained serum bone markers and other relevant endocrine assays on 5 patients with osteonecrosis of the jaw (ONJ). The assays were C-telopeptide, N-telopeptide, bone-specific alkaline phosphatase, osteocalcin, intact parathyroid hormone, T3, T4, TSH, and Vitamin D 25 hydroxy. Diagnostic criteria for ONJ were those formulated by the American Association of Oral and Maxillofacial Surgeons. Four of our patients were women. Two had metastatic breast cancer and had been treated with zoledronic acid; one had also received pamidronate. Two others had osteoporosis and had been treated with daily alendronate. One man had metastatic prostate cancer treated with zoledronic acid. All patients had been withdrawn from bisphosphonate for at least 6 months. None were taking or had taken corticosteroids. None of the lesions had shown any significant healing and all were still causing the patients considerable distress. Yet the bone markers were within the normal range as measured in our laboratory, except for intact parathyroid hormone, which was slightly elevated in one case of metastatic breast cancer (177 pg/mL). Because the jaws have a greater blood supply than other bones, and a high bone turnover rate, bisphosphonates are highly concentrated in the jaws. This anatomic concentration of bisphosphonates might cause bisphosphonate-osteonecrosis to be manifested exclusively in the jaws and is consistent with our finding of normal serum bone markers in ONJ patients.

Right ventricular dysfunction and organ failure in left ventricular assist device recipients: a continuing problem.

BACKGROUND: Although right ventricular assist device (RVAD) use has declined with the introduction of inhaled nitric oxide and phosphodiesterase inhibitors (type III), right ventricular dysfunction (RVD) is still a serious problem in patients receiving left ventricular assist devices (LVAD). METHODS: We retrospectively analyzed Thoratec Vented Electrical LVAD recipients between June 1996 and September 1999. RVD was defined as inotropic requirement 14 days or more or need for RVAD postoperatively, or both. RESULTS: Sixty-nine LVAD recipients were analyzed. Twenty-one patients (30.4%) had RVD, with 1 patient requiring RVAD insertion, and there were 48 non-RVD patients. There were no significant differences between both groups for age, sex, etiology of congestive heart failure, days of support, and preoperative hemodynamics. Preoperative right ventricle stroke work index (mm Hg x m(-2) x L(-1)) had a trend toward being lower in the RVD group (4.1+/-3.2 versus 6.1+/-3.7, p = 0.06). A higher preoperative total bilirubin (mg/dL) was noticed in the RVD group (4.0+/-5.2 versus 2.1+/-1.7). The RVD group had a higher postoperative creatinine (2.2+/-1.4 mg/dL versus 1.5+/-0.8 mg/dL), incidence of continuous venovenous hemofiltration dialysis (73% versus 26%), transfusion of packed red blood cells (43.2+/-28.6 units versus 24.7+/-18.9 units), platelets (58.6+/-46.1 units versus 30.2+/-20.4 units), with longer intensive care unit length of stay (33.6+/-34.7 days versus 9.1+/-6.9) and higher mortality (42.8% versus 14.5%). When deaths were excluded, both intensive care unit and postoperative length of stay were significantly longer in the RVD group. CONCLUSIONS: RVD in LVAD recipients remains poorly identified and is associated with a high transfusion rate and end organ failure that results in increased intensive care unit and hospital length of stay, and a high mortality rate. Preoperative identification of risk factors for RVD may select patients who would benefit from a biventricular assist device and prevent the subsequent end organ failure.