Cerebral Critical Closing Pressure: Is the Multiparameter Model Better Suited to Estimate Physiology of Cerebral Hemodynamics?

BACKGROUND: Cerebral critical closing pressure (CrCP) is the level of arterial blood pressure (ABP) at which small brain vessels close and blood flow stops. This value is always greater than intracranial pressure (ICP). The difference between CrCP and ICP is explained by the tone of the small cerebral vessels (wall tension). CrCP value is used in several dynamic cerebral autoregulation models. However, the different methods for calculation of CrCP show frequent negative values. These findings are viewed as a methodological limitation. We intended to evaluate CrCP in patients with severe traumatic brain injury (TBI) with a new multiparameter impedance-based model and compare it with results found earlier using a transcranial Doppler (TCD)-ABP pulse waveform-based method. METHODS: Twelve severe TBI patients hospitalized during September 2005-May 2007. Ten men, mean age 32 years (16-61). Four had decompressive craniectomies (DC); three presented anisocoria. Patients were monitored with TCD cerebral blood flow velocity (FV), invasive ABP, and ICP. Data were acquired at 50 Hz with an in-house developed data acquisition system. We compared the earlier studied "first harmonic" method (M1) results with results from a new recently developed (M2) "multiparameter method." RESULTS: M1: In seven patients CrCP values were negative, reaching -150 mmHg. M2: All positive values; only one lower than ICP (ICP 60 mmHg/ CrCP 57 mmHg). There was a significant difference between M1 and M2 values (M1 < M2) and between ICP and M2 (M2 > ICP). CONCLUSION: M2 results in positive values of CrCP, higher than ICP, and are physiologically interpretable.

The ontogeny of cerebrovascular pressure autoregulation in premature infants.

OBJECTIVE: To quantify cerebrovascular autoregulation as a function of gestational age (GA) and across the phases of the cardiac cycle. STUDY DESIGN: The present study is a hypothesis-generating re-analysis of previously published data. Premature infants (n=179) with a GA range of 23 to 33 weeks were monitored with umbilical artery catheters and transcranial Doppler insonation of the middle cerebral artery for 1-h sessions over the first week of life. Autoregulation was quantified by three methods, as a moving correlation coefficient between: (1) systolic arterial blood pressure (ABP) and systolic cerebral blood flow (CBF) velocity (Sx); (2) mean ABP and mean CBF velocity (Mx); and (3) diastolic ABP and diastolic CBF velocity (Dx). Comparisons of individual and cohort cerebrovascular pressure autoregulation were made across GA for each aspect of the cardiac cycle. RESULTS: Systolic, mean and diastolic ABP increased with GA (r=0.3, 0.4 and 0.4; P<0.0001). Systolic CBF velocity was pressure-passive in infants with the lowest GA, and Sx decreased with advancing GA (r=-0.3; P<0.001), indicating increased capacity for cerebral autoregulation during systole during development. By contrast, Dx was elevated, indicating dysautoregulation, in all subjects and showed minimal change with advancing GA (r=-0.06; P=0.05). Multivariate analysis confirmed that both GA (P<0.001) and 'effective cerebral perfusion pressure' (ABP minus critical closing pressure (CrCP); P<0.01) were associated with Sx. CONCLUSION: Premature infants have low and usually pressure-passive diastolic CBF velocity. By contrast, the regulation of systolic CBF velocity by pressure autoregulation developed in this cohort between 23 and 33 weeks GA. Elevated effective cerebral perfusion pressure derived from the CrCP was associated with dysautoregulation.

Repeatability of cerebrospinal fluid constant rate infusion study.

OBJECTIVE: Infusion tests are important tools to assess cerebrospinal fluid (CSF)dynamics used in the preoperative selection of patients for shunt surgery, or to predict the scope of improvement from shunt revision. The aim of this study was to assess the repeatability of the key quantitative parameters describing CSF dynamics that are determined with infusion testing. MATERIALS AND METHODS: Eighteen patients in whom a constant infusion test was repeated within 102 days, without any intermediate surgical intervention, were studied. From each test baseline ICP, baseline pulse amplitude, outflow resistance, elastance coefficient and slope of the amplitude-pressure line were calculated and investigated with a regression and Bland-Altman analysis. RESULTS: Significant correlations (P < 0.01) were found for the outflow resistance (R = 0.96), the elastance coefficient (R = 0.778) and the slope of the amplitude-pressure line (R = 0.876). The estimated 95% confidence level for outflow resistance was 3 mmHg/ml min. Likewise, the elastance coefficient lay within a range of 0.16/ml and the slope of the amplitude-pressure line within 0.25. The most inconsistent parameter found were baseline ICP (R = 0.272) and baseline pulse amplitude (R = 0.171). CONCLUSION: The results of this study imply that the parameters resulting from an infusion study have to be considered within a range rather than as an absolute value.

Adjuvant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non-Hodgkin lymphoma. Results of a prospective randomized study.

BACKGROUND: In a prospective randomized manner, this study evaluated the effect of adjuvant chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone; CHOP) in patients with Stage I non-Hodgkin lymphoma (NHL) who have achieved a complete response (CR) after radiation therapy (RT). METHODS: Forty-four patients with clinical or pathologic Stage I intermediate-grade or low-grade NHL were randomized to receive regional RT alone (median dose, 40 Gy) or regional RT followed by six cycles of CHOP chemotherapy. There were no differences in clinical and pathologic characteristics between the two treatment groups. RESULTS: The median follow-up was 7 years (range, 2-10 years). The actuarial relapse-free survival (RFS) rate for the RT plus CHOP group at 7 years was 83% compared with 47% (P < 0.03) for the RT-alone group. The overall survival (OS) for the two groups was 88% and 66%, respectively (P = 0.2). In patients with intermediate-grade NHL, the 7-year actuarial RFS for RT and CHOP was 86% compared with 20% for RT alone (P = 0.004). The corresponding actuarial survival rates were 92% and 47%, respectively (P = 0.08). In patients with low-grade histologic findings, the addition of adjuvant CHOP did not improve RFS (P = 0.6) or OS. All relapses in this study were at sites remote from the initially involved areas, and in 5 of 11 patients (45%), there were recurrences 5 years or longer after initial treatment. CONCLUSIONS: This study showed that adjuvant CHOP chemotherapy significantly improves RFS in patients with Stage I intermediate-grade NHL who achieve a CR after regional-field RT. The chemotherapeutic regimen favorably affected their probability of survival.

Lactation following conservation surgery and radiotherapy for breast cancer.

A 38-year-old woman with early stage invasive breast cancer was treated with wide excision of the tumor, axillary lymph node dissection, and breast irradiation. Three years later, she gave birth to a normal baby. She attempted breast feeding and had full lactation from the untreated breast. The irradiated breast underwent only minor changes during pregnancy and postpartum but produced small amounts of colostrum and milk for 2 weeks postpartum. There are only a few reports of lactation after breast irradiation. These cases are reviewed, and possible factors affecting breast function after radiotherapy are discussed. Because of scant information available regarding its safety for the infant, nursing from the irradiated breast is not recommended.

Diffuse large cell lymphoma. Prognostic factors with treatment.

Five successive chemotherapy protocols for stages II, III and IV diffuse large cell lymphoma (DLCL) have resulted in identical overall survivals. Between 35% to 45% of patients survived. In a multivariate analysis employing the Weibull model 3 factors were associated with shortened survival: bulky mediastinal and/or retroperitoneal disease, elevated serum LDH and advanced age. In young patients with bulky mediastinal and/or retroperitoneal disease and high serum LDH, autologous bone marrow transplantation following high dose chemotherapy and radiation therapy (RT) as part of the initial treatment have produced more promising results. In a randomized trial, a significantly longer disease-free survival was found for patients with stages I or IE diffuse lymphomas with RT followed by adjuvant chemotherapy than with RT alone.

Alternatives in the Management of Gastric Lymphoma.

Advances in endoscopic technology now enable non-surgical diagnosis of gastric lymphoma, while combination chemotherapy and modern radiotherapy techniques offer an alternative to gastrectomy as the primary treatment of gastric lymphoma. Cumulative data challenge the traditional concept that non-operative treatment of gastric lymphoma often leads to fatal complications, such as perforation and hemorrhage. The reported risk of major side effects is reviewed and the alternative approaches to the management of gastric lymphoma are analyzed. In addition, pathologic considerations unique to lymphomatous involvement of the stomach are discussed.