Concurrent CBF and CMRGlc changes during human brain activation by combined fMRI-PET scanning

A novel approach for concurrent measurement of regional cerebral blood flow (CBF) and regional cerebral metabolic rate for glucose consumption (CMRGlc) in humans is proposed and validated in normal subjects during visual stimulation. 18F-labeled fluorodeoxyglucose was administered during the measurement of CBF by continuous arterial spin labeled magnetic resonance imaging (MRI). Subsequent positron emission tomographic (PET) scanning demonstrated the distribution of labeled deoxyglucose during the MRI acquisition. An excellent concordance between regional CBF and regional CMRGlc during visual stimulation was found, consistent with previously published PET findings. Although initially validated using a brief, non-quantitative protocol, this approach can provide quantitative CBF and CMRGlc, with a broad range of potential applications in functional physiology and pathophysiology.     

Association between transient pulmonary congestion during acute myocardial infarction and high incidence of death in six months

In a prospective multicenter study of 866 patients after acute myocardial infarction (AMI), an increased or excessive mortality rate (13%) was confined to the first 6 months after AMI. In the subsequent 18 months of follow-up, the mortality rate (4%) was similar to that in coronary patients in chronic stable condition. Analysis of patients who died in the first 6 months revealed that 55% had had pulmonary congestion at the time of the index AMI. Neither these patients nor the others who died in the early period were found to have more severe ventricular dysfunction, more malignant arrhythmias or more severe ischemia than patients who died after 6 months. The reason for the high and early mortality in patients with pulmonary congestion is not clear, particularly because 30% had reasonable ventricular function, with an ejection fraction of more than 40%. However, given the poor prognosis of these patients, early and aggressive diagnostic efforts should be undertaken to exclude jeopardized regions remote from the initial AMI.     

Heparin-associated thrombocytopenia and thrombosis: a serious clinical problem and potential solution

Heparin-associated thrombocytopenia and thrombosis (HATT) is an unusual but serious complication of heparin therapy. Twenty-five patients (13 men and 12 women) had thrombocytopenia and arterial or venous thrombosis 1 to 10 days (mean, 6.3 days) after the start of heparin administration. The vessels in the affected extremity had been entered for catheterization, arteriography, or passage of a balloon counterpulsation device in 19 of the 25 patients. In vitro platelet aggregation with heparin was seen in all patients. Additional studies were performed to see whether other lots or sources of heparin also produced in vitro aggregation. Four separate lots of beef lung heparin, commercial heparin from porcine intestinal mucosa, and two types of low molecular weight heparin were all highly stimulatory in this system. However, Org 10172, a heparinoid, did not induce aggregation in any of 13 patient plasmas tested. Inhibition of platelet aggregation by aspirin was also examined. Aspirin abolished in vitro aggregation in 9 of 16 cases and decreased the degree of aggregation from 85% to 55% (p = 0.02) in the remaining seven cases. We conclude that in patients with HATT platelet aggregation is equally induced by beef lung, porcine intestinal, and some forms of low molecular weight heparin. Org 10172 does not stimulate platelet aggregation in plasma from these patients in vitro. Finally, there may be a role for aspirin in treating patients with HATT.     

Solid and papillary epithelial tumour of the pancreas: Cytological case study with ultrastructural and flow cytometric evaluation

An intraoperative cytological diagnosis of a rare solid and papillary epithelial tumor of the pancreas was made at laparotomy in a 15-year-old Indian female. The characteristic cytological features were the presence of numerous large branching papillary clusters with central vascular stalks lined by multiple layers of uniform bland cells. Perivascular metachromatic material was prominent on Romanovsky stain. Ultrastructural identification of endocrine and exocrine features supports a multipotential cell origin in small pancreatic ductules. DNA analysis, not previously reported for this tumour, demonstrated a diploid population of tumour cells with a low S-phase fraction (0.4%). This would explain the bland nuclear morphology and favourable prognosis with a high rate of surgical cure for this neoplasm.     

Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2

Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.     

An assessment of a urinary biomarker for total human environmental exposure to benzo[a]pyrene

Urinary banzo[a]pyrene (BaP) metabolite levels were compared to human environmental exposure to BaP through inhalation and dietary ingestion to assess the predictive validity of the exposure biomarker. These measurements were made for 14 adult volunteers over 14 consecutive days, once during summer/fall, again during winter periods. Based on personal air monitoring, median potential inhalation doses of 11.0 and 2.3 ng/day were estimated for the winter and summer/fall studies, respectively. A median potential ingested dose of 176 ng/day, estimated from duplicate plate sampling, exceeded inhalation by 6-and 122-fold for the winter and summer/fall studies, respectively. Total urinary BaP metabolites were measured using a published reverse metabolism (BaP) method of analysis. Median rates of urinary BaP metabolite elimination for the winter and summer/fall studies were 121 and 129 ng/day, respectively. The changes in inhaled and ingested potential doses were regressed on the change in urinary metabolite elimination from week 1 to week 2 to test the predictive validity of the biomarker measurement. The regression was statistically significant (r = 0.620, p = 0.015, n = 25) when body weight was included and two extreme values were removed. Consistent with the exposure measurements showing diet as the dominant route of exposure, most of the variation in urinary metabolite elimination was explained by the ingested dose. It is concluded that the measurement of urinary BaP by reverse metabolism is qualitative and of marginal predictive validity as an exposure biomarker due to the method's low recoveries and the large unexplained variance.     

Use of systemic therapy and factors affecting survival for patients undergoing cytoreductive nephrectomy

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To present a multi‐institutional experience evaluating the use of systemic therapy in patients undergoing cytoreductive nephrectomy (CN), as prospective randomized trials showed a survival benefit for CN in patients with metastatic renal cell carcinoma treated with immunotherapy, and these data have been extrapolated to support CN in the era of targeted therapy, but the likelihood that patients with metastatic kidney cancer who undergo CN will receive systemic treatment afterward remains poorly defined.

PATIENTS AND METHODS

In all, 141 patients who underwent CN between 1990 and 2008 were identified from our Institutional Kidney Cancer Registries. Kaplan‐Meier analyses and Cox regression models were used to assess the effect of clinicopathological and perioperative variables on patients’ subsequent receipt of systemic therapy, and survival after CN.

RESULTS

Overall, 98 of the 141 patients (69.5%) received postoperative systemic treatment, at a median (range) of 2.5 (0.1–61.5) months after CN. In this group, 52 (53%) patients received immunotherapy, 34 (35%) targeted agents, and 12 (12%) other regimens. By contrast, 43 patients (31%) did not receive systemic therapy, because of rapid disease progression (13, 30%), decision for surveillance by medical oncology (nine, 21%), patient refusal (10, 23%), perioperative death (eight, 19%), and unknown reasons in three (7%). The median (range) survival after CN was 16.7 (0–120) months. The risk of death after surgery correlated with the number of metastatic sites (P = 0.012) and symptoms (P = 0.001) at presentation, poor performance status (P = 0.001), high tumour grade (P = 0.006), and presence of sarcomatoid features (P < 0.024).

CONCLUSION

Nearly a third of patients undergoing CN did not receive systemic treatment. While some were electively observed or declined therapy, others did not receive treatment due to rapidly progressive disease. Further investigation is warranted to identify those patients at highest risk of rapid postoperative disease progression who might benefit instead from an initial approach to treatment with systemic therapy.