Measurements of CO2 reactivity and barbiturate reactivity in patients with severe head injury

Summary In nine patients with severe head injury subjected to continuous hyperventilation and barbiturate coma treatment with pentobarbitone, the regional cerebral blood flow was measured as initial slope index (ISI) with a 32 channel Cerebrograph, and cerebral metabolic rate of oxygen (CMRO₂) was calculated as the product of mean global CBF and the arterio-venous oxygen content difference.CBF was measured at strategic intervals either to follow the treatment (hyperventilation and/or pentobarbitone), or to determine whether these principles of treatment should be intensified or reduced. During the flow measurements the CO₂ reactivity and the reactivity to a bolus injection of thiopentone 5 mg/kg were calculated globally and regionally. The global CO₂ reactivity was calculated as relative (%change CBF/PaCO₂ mmHg) and absolute (CBF/ PaCO₂ mmHg), and the reactivity to barbiturate was calculated globally as CMRO₂, and regionally as %change rCBF.The absolute and relative global CO₂ reactivities correlated positively with the mean. CBF values before hyperventilation, and the global barbiturate reactivity was dependent on the CMRO₂ value obtained before hyperventilation. However, at low levels of CMRO₂ ranging between 1.0 and 1.1 ml O₂ the barbiturate reactivity was abolished. The regional studies of CBF, CMRO₂, CO₂ reactivity and barbiturate reactivity gave important information, when decisions concerning therapeutic regimes with special reference to hyperventilation and sedation with pentobarbitone were necessary.     

CO2 and indomethacin vasoreactivity in patients with head injury

Summary The purpose of this study was to compare the effect of hyper-ventilation and indomethacin on cerebral circulation, metabolism and pressures in patients with acute severe head injury in order to see if indomethacin may act supplementary to hyperventilation. Fourteen severely head injured patients entered the study. Intracranial pressure (ICP), mean arterial blood pressure (MABP) and cerebral perfusion pressure (CPP) were monitored continuously. Within the first four days after the trauma the CO₂ and indomethacin vasoreactivities were studied by measurements of cerebral blood flow (CBF) (Cerebrograph 10a, intravenous¹³³Xe technique) and arterio-venous difference of oxygen (AVdO₂). Ischaemia was evaluated from changes in CBF, saturation of oxygen in the jugular bulb (SvjO₂), lactate and lactate/oxygen index (LOI). Data are presented as medians and ranges, results are significant unless otherwise indicated. Before intervention ICP was well controlled (14.8 (9–24) mmHg) and basic CBF level was 39.1 (21.6–75.0) ml/100 g/min). The arterio-venous oxygen differences were generally decreased (AVdO₂ = 4.3 (1.8–8.1) ml/100 ml) indicating moderate luxury perfusion. Levels of CMRO₂ were decreased (1.54 (0.7–3.2) ml/100 g/min) as well.Duringhyperventilation (APaCO₂ = 0.88 (0.62–1.55) kPa) CBF decreased with 11.8 (–33.4–29.7) %/kPa and ICP decreased with 3.8 (0–10) mmHg. AVdO₂ increased 34.0 (4.0–139.2) %/kPa, MABP was unchanged, CMRO₂ and CPP increased (CPP = 3.9 (–10–20) mmHg). AVD (lactate) and LOI were unchanged. No correlations between CBF responses to hypocapnia and outcomes were observed.An i.v. bolus dose ofindomethacin (30 mg) decreased CBF 14.7 (–16.7–57.4) % and ICP decreased 4.3 (–1–17) mmHg. AVdO₂ increased 27.8 (–40.0–66.7)%, MABP (MABP = 4.9 (–2–21) mmHg) and CPP (CPP = 8.7 (3–29) mmHg) increased while CMRO₂ was unchanged. No changes in AVd (lactate) and LOI indicating cerebral ischaemia were found.Compared to hyperventilation (changes per 1 kPa, at PaCO₂ level = 4.05 kPa) the changes in MABP, CPP and CBF were significantly greater after indomethacin, while the changes in AVdO₂, ICP, SvjO₂, and LOI were of the same order of magnitude.Nocorrelation between relative reactivities to indomethacin and CO₂, evaluated from changes in CBF and AVdO₂, or between the decrease in ICP after the two procedures were found. Thus, some patients reacted to indomethacin but not to hyperventilation, and vice versa.These results suggest that indomethacin and hyperventilation might act independently, or in a complementary fashion in the treatment of patients with severe head injury.     

Correlation of continuously monitored regional cerebral blood flow and brain tissue oxygen

Summary Background. The purpose of this study was to investigate the relationship between continuously monitored regional cerebral blood flow (CBF) and brain tissue oxygen (P_tiO₂).Methods. Continuous advanced multimodal neuromonitoring including monitoring of P_tiO₂ (Licox, GMS) and CBF (QFlow, Hemedex) was performed in eight patients after severe subarachnoid haemorrhage (n=5) and traumatic brain injury (n=3) for an average of 9.6 days. Parameters were measured using a flexible polarographic P_tiO₂-probe and a thermal diffusion CBF-microprobe.Findings. Regarding the whole monitoring period in all patients, the data indicated a significant correlation between CBF and P_tiO₂ (r=0.36). In 72% of 400 analysed intervals of 30 minutes duration with P_tiO₂ changes larger than 5mmHg, a strong correlation between CBF and P_tiO₂ existed (r>0.6). In 19% of intervals a still statistically significant correlation was observed (0.3<r<0.6). During the remaining 9% no correlation was found (r<0.3). Regarding the clinical stability of the monitoring devices, the CBF monitoring system allowed monitoring of CBF in 64% of the time when P_tiO₂ monitoring was possible only. Phases of non-monitoring were mostly due to fever of the patient, when the system does not allow monitoring to avoid overheating of the cerebral tissue.Conclusions. This study suggests a correlation between CBF and P_tiO₂. The level of P_tiO₂ seems to be predominately determined by regional CBF, since changes in P_tiO₂ were correlated in 90% of episodes to simultaneous changes of CBF.     

A Prostacyclin Analogue,OP-41483α-CD,Restores the Ability of a β<Subscript>2</Subscript>-Adrenergic Agonist to Stimulate Alveolar Fluid Clearance in Rats

Purpose. It is not yet known whether a prostacyclin analogue can affect alveolar fluid clearance. According to recent studies, high-dose (10^–3M) terbutaline, a ₂-adrenergic agonist, failed to increase alveolar fluid clearance. Therefore, we examined the effects of OP-41483-CD, a prostacyclin analogue, on alveolar fluid clearance in the presence of high-dose terbutaline in rats.Methods. Albumin solution containing Evans blue dye and various drugs was instilled into the alveolar airspaces of isolated rat lungs, which were then inflated with 100% oxygen at an airway pressure of 8cmH₂O. Alveolar fluid clearance was measured by the progressive increase in dye concentrations over 1h.Results. Although 10^–5 and 10^–4M terbutaline increased alveolar fluid clearance, 10^–3M terbutaline did not. OP-41483-CD restored the ability of 10^–3M terbutaline to stimulate alveolar fluid clearance. The effect of OP-41483-CD was consistent with the effect of atenolol, a ₁-adrenergic antagonist. The effect of OP-41483-CD on alveolar fluid clearance was unchanged in lungs inflated with nitrogen. Prostaglandin E (PGE)₁ and PGE₂ analogues had similar effects to OP-41483-CD on alveolar fluid clearance.Conclusion. These results indicate that a prostacyclin analogue restores the ability of high-dose terbutaline to stimulate alveolar fluid clearance.     

Zur Bedeutung von β-hCG im serum als tumormarker fur das magenkarzinom

Zusammenfassung Einleitung: Nach neueren Untersuchungen ist davon auszugehen, daß bei des Hälfte von Patienten mit einem Magenkarzinom -hCG-positive Zellen im Tumor immunhistochemisch gefunden werden können. Ziel war daher, systematisch zu untersuchen, inwieweit -hCG-immunreaktive Magenkarzinome von einem Anstieg des Serum--hCG begleitet werden and dieses damit als Verlaufsparameter zur Verfügung steht. Methode: Bei 54 Patienten mit einem Magenkarzinom wurde zur immunhistochemischen Darstellung ein gegen -hCG gerichteter monoklonaler Antikörper (Fa. Sigma, 1:100) im APAAP-System verwendet. Die Auswertung wurde nach positiver and negatives Reaktion graduiert. Parallel wurde im Serum des Patienten -hCG präoperativ mit einem Enzymimmunoassay (MEIA, Fa. Abbot) bestimmt. Tumor-stadium, Grading and Tumor-lokalisation werden in die Auswertung mit einbezogen. Ergebnisse: Es wird bestätigt, daß 41% (22 von 54) des Karzinome, unabhängig von ihrer Lokalisation im Magen, eine positive immunhistochemische Reaktion gegen -hCG auslösen. Es zeigte sich in Abhängigkeit vom Tumorstadium eine positive -hCG-Immunreaktivität in 27% (6 von 22) des Tumoren ohne Lymphknoten- and Fernmetastasierung (T_1–4 N₀ M₀), in 54% (7 von 13) des Tumoren mit Lymphknotenaber ohne Fernmetastasen (T_1–4 N₁ M₀) und in 47% (9 von 35) des Tumoren mit Fernmetastasierung. Schlecht differenzierte Tumoren (G3–4) waren zu 42% (15 von 36) und gut differenzierte Tumoren (G_1–2) nur zu 39% (7 von 18) positiv. Aber lediglich bei einer Patientin war der -hCG-Spiegel im Serum erhöht. Zusammenfassung: Immunhistochemisch -hCG-positive Magenkarzinome werden vermehrt bei fortgeschrittenem Tumorstadium und Schlecht differenzierten Karzinomen gefunden. Diese Kar zinome scheinen aber nicht in ausreichender Menge -hCG ins Serum abzugeben, was zu serologisch meßbar erhöh-ten Werten führt. -hCG im Serum kann daher nicht als Prognosefaktor bzw. zur Verlaufskontrolle herangezogen werden. Abzuwarten bleibt, inwieweit die -hCG-Expression von Tumorzellen u. U. Einfluß auf die Propose der Patienten besitzt.

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Significance of -hCG in the serum as a tumour marker for gastric cancer

Introduction: Recent investigations indicate that in 50% of patients with gastric cancer, -hCG-posiitive cells can be found in the tumour by immunohistochemical investigations. The objective of this study was to investigate how often -hCG-immunoreactive gastric carcinomas were accompanied by an elevation in serum -hCG, that could have been used as a course control variable. Methods: In 54 patients with gastric carcinoma a monoclonal antibody directed against -hCG was used for immunohistochemical marking in the APAAP system. The evaluation was graded positive or negative. In parallel, serum -hCG was determined preoperatively using an enzyme immunoassay (MEIA). Tumour stage, grading and tumour locallization were determinants in the evaluation. Results: We found that 41% (22 of 54) of the carcinomas induced a :positive immunohistochemical response to -hCG, regardless of their location in the stomach. In relation to tumour stage, a positive -hCG immunoreactivity was apparent in 27% (6/22) of tumours without lymph node or distant metastases (TI -4N0M0), in 54% (7/13) of tumours with lymph node and without distant metastases (T1–4N1 M0) and in 47% (9/35) of tumours with distant metastases. Poorly differentiated tumours (G3–4) were positive in 42% (15/36) and well-differentiated tumors (G1–2) in 39% (7/18) of cases. In only 1 patient was the -hCG, level in serum elevated, however. Conclusions: -hCG-Positive gastric carcinomas are found more frequently in advanced tumour stages and poorly differentiated carcinomas. These carcinomas, however, seem not to excrete -hCG in sufficient amounts to produce measurable serum values. Therefore, -hCG cannot be used a prognostic factor or for course control. The relevance of -hCG expression of tumour cells to the patients' prognosis remains obscure.

     

Haematoma evacuation does not improve outcome in spontaneous supratentorial intracerebral haemorrhage: A case-control study

Summary Surgical intervention in supratentorial intracerebral haemorrhage (ICH) is still controversial. We assessed the value of haematoma evacuation with a case-control study. 145 consecutive patients with supratentorial spontaneous ICH without tumour or vascular abnormalities were analysed. Haematoma evacuation was performed in 24 patients. Age, sex, Glasgow Coma Scale (GCS), level of consciousness, pupillary reaction on admission, localisation, aetiology and volume of the haematoma, presence of ventricular blood, and Glasgow Outcome Scale (GOS) on discharge were analysed. From statistical analysis 40 patients >80 years and with haematoma volume <10ml, who were always treated conservatively, were excluded. Prognostic factors retained from a multiple regression model with the dichotomised GOS scale (GOS 1–3, 4+5) as response variable were GCS, haematoma volume and location. The only difference between all medically treated and operated patients was haematoma volume, which was larger in the operated patients. All 24 evacuated cases could be matched to a medically treated control regarding age, haematoma volume and location, GCS, and pupillary reaction. Significant differences between the two groups could not be detected. Outcome was not different between the two groups. After separating the sample into patients with and without ventricular haemorrhage, there was no different outcome between the two groups either. We conclude that haematoma evacuation did not improve outcome in supratentorial spontaneous ICH. Since haematomas were evacuated mainly in clinically deteriorating patients, our data suggest that the only effect of haematoma evacuation is to stop progressive deterioration rather than to improve overall clinical outcome.     

Haemodynamic and metabolic changes following extra-intracranial bypass surgery

Summary In order to study the haemodynamic and metabolic changes following bypass surgery, the regional cerebral blood flow (rCBF), the oxygen extraction fraction (rOEF), the cerebral metabolic rate of oxygen (rCMRO₂), and the cerebral blood volume (rCBV) were measured using a positron emission tomograph (PET) on 13 patients who had unilateral internal carotid artery and/or middle cerebral artery occlusion. The patients were divided into two subgroups according to pre-operative rOEF values from the arterial occlusion side: the misery perfusion group, which had high rOEF values (0.56), and the coupling perfusion group, which had normal rOEF values (0.38–0.48). A post-operative PET study was performed 1–2 months and/or 1–5 years following the surgery. Six of the misery perfusion cases showed a post-operative CBF increase, where an accompanying OEF decreased to its normal level, indicating an attenuated misery perfusion state. The CMRO₂ values, however, remained low. The other 7 coupling perfusion cases had an ipsilateral CBF increase in the earlier PET study. We conclude that misery perfusion is attenuated following bypass surgery, although the procedure does not consistently improve oxygen metabolism.     

FTIR microspectroscopic analysis of human osteonal bone

Fourier Transform Infrared Microspectroscopy (FTIRM) has been used to study the changes in mineral and matrix content and composition in replicate biopsies of non-osteoporotic human osteonal bone. Spectral maps in four orthogonal directions (in 10 m steps) from the centers towards the peripheries of individual osteons were obtained from iliac crest biopsies of two necropsy cases. Mineral to matrix ratios, calculated from the ratio of integrated areas of the phosphate v ₁,v ₃ band at 900–1200 cm^-1 to the amide I band at 1585–1725 cm^-1, increased from the center to the periphery of the osteon. The total carbonate (based on the v ₂ band at 850–900 cm^-1) to phosphate v ₁,v ₃ ratio decreased as the mineral to matrix ratio increased. Analysis of the v ₂ CO₃ ^2- band with a combination of second-derivative spectroscopy and curve fitting revealed a decrease in labile carbonate, a slight decrease in Type A and a slight increase in Type B carbonate from the center to the periphery of the osteon. Similar analysis of the components of the v ₁,v ₃ phosphate band with a combination of second-derivative spectroscopy and curve fitting revealed the presence of 11 major underlying moieties. These components were assigned by comparison with published frequencies for apatite and acid-phosphate containing calcium phosphates. The most consistent variations were alterations in the relative percent areas of bands at 1020 and 1030 cm^-1, which had previously been assigned to nonstoichiometric and stoichiometric apatites, respectively. This ratio was used as an index of variation in crystal perfection throughout the osteon. This ratio decreased as the mineral to matrix ratio increased. The reproducibility of these parameters at multiple sites in multiple biopsies suggests their applicability for the analysis of mineral changes in disease.     

Treatment of a patient with impaired renal function with gentamicin-PMMA-beads

Summary 150 Gentamicin-PMMA-beads were implanted (+ 160 mg gentamicin i.v. preop.) in a woman aged 73 years and with severely impaired kidney function. Frequent determination of gentamicin plasma concentrations and renal functions were possible. The plasma concentration reached a plateau at approx. 3 g/ml. No accumulation of gentamicin in plasma occurred.

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Zusammenfassung 150 Gentamycin-PMMA-Kugeln wurden implantiert (+ 160 mg Gentamicin i.v. preop.) in eine 73jährige Frau, die an einer starken Einschränkung der Nierenfunktionen litt. Relativ häufig wurden die Plasma-Konzentrationen vom Gentamycin und die renalen Funktionen bestimmt.Die Konzentration von Gentamycin im Plasma erreichte einen Plateauwert von 3 g/ml. Es trat keine Akkumulation von Gentamycin im Plasma auf.

     

Changes of local brain tissue oxygen pressure after vasopressin during spontaneous circulation

Summary. Background. Brain tissue oxygen pressure (PbtO₂) correlates to cerebral blood flow (CBF) during spontaneous circulation, with one important regulator being nitric oxide (NO). Although it is established that arginine vasopressin (AVP) improves CBF and global cerebral oxygenation during cardiopulmonary resuscitation, it is unknown whether similar beneficial effects are present during spontaneous circulation. The purpose of this study was to investigate the effects of AVP with and without pre-treatment with the NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) on local brain tissue oxygenation in a beating heart model.Methods. Following approval of the Animal Investigational Committee, nine healthy piglets underwent general anaesthesia, and were instrumented with a probe in the cerebral cortex to measure PbtO₂. Each animal was assigned to receive AVP (0.4U·kg^–1), and after a wash-out period, L-NAME (25mg·kg^–1 over 20min) followed by AVP (0.4U·kg^–1). After each AVP administration, nitroglycerine (25µg·kg^–1 over 1min) as a NO donor was infused to test the vascular reactivity independently from NOS inhibition.Findings. Three minutes after administration of AVP, PbtO₂ increased significantly (P<.05; mean±SEM, 31±11 versus 43±14mmHg, +39%), compared with baseline. After pre-treatment with L-NAME, the changes of PbtO₂ after AVP were not significant (32±11 versus 28±10, –13%) when compared with the baseline.Conclusion. In this beating heart porcine model, local brain tissue oxygenation was improved after AVP alone, but not after inhibition of NO synthesis with L-NAME.     

Expression of interferon-γ receptors on bladder cancer cells: does it correlate with biological response?

Summary Previously we have shown a differential biological response of three human bladder cancer cell lines (RT4, RT112 and MGH-U1) to gamma interferon (IFN-). The present study examines the relationship between the biological response and the expression of the interferon- receptor on the tumour cell surface. Using a competitive radioligand binding assay and Scatchard analysis, we measured the number and affinity of the IFN- receptors on each of the above cell lines. Individual cells from each line expressed large numbers (29,100–41,800) of high-affinity receptors (k _d =2.4–3.9×10¹⁰M). There was no statistically significant difference in either of these parameters between the three lines. We therfore conclude that the biological response of these bladder lines to IFN- does not relate to the number or affinity of its receptor on the plasma membrane of these tumour cells.     

The effect of ketanserin on cerebral blood flow and oxygen metabolism in healthy volunteers

Summary The effect of the anti-hypertensive agent ketanserin on average global cerebral blood flow (CBF) and average global cerebral oxygen metabolism (CMRO₂) was examined in 8 healthy volunteers. CBF and CMRO₂ were measured with the Kety-Schmidt technique before ketanserin administration (baseline) and after administration of 2 different doses of ketanserin intravenously (dose I: 10 mg bolus and an infusion of 6 mg/h; dose II: 20 mg bolus and an ifusion of 20 mg/ h). Baseline CBF and CMRO₂ were 60 and 3.6 ml/100 g/min, respectively, and were not changed by administration of ketanserin dose I. During administration of dose II, however, CBF fell to 52 ml/ 100 g/min (p=0.05) and CMRO₂ was reduced to 3.2 ml/100 g/min (p < 0.05).We conclude that when administered in a high dose, ketanserin has the ability to depress cerebral oxygen metabolism, but when administered in a clinically relevant dose ketanserin does not influence average global CBF or average global CMRO₂. Ketanserin could be a safe antihypertensive drug in neuroanaesthesia or in the neuro-intesive care unit.     

Effects of intravenous nitroglycerin combined with dopamine on intracranial pressure and cerebral arteriovenous oxygen difference in patients with acute subarachnoid haemorrhage

Summary The effects of intravenous nitroglycerin (NTG) combined with dopamine on intracranial pressure (ICP) and cerebral arteriovenous oxygen difference (AVDO₂) were studied in 11 patients with acute subarachnoid haemorrhage (SAH). The study was performed on Days 1 to 3 of SAH after aneurysmal clipping. Treatment consisted of an intravenous drip infusion of NTG in increasing incremental doses of 0.5, 1.0, 1.5, 2.0, and 2.5 g/kg/min at one-hour intervals. Dopamine (5 to 10 g/kg/min) was also given concurrently to maintain systemic blood pressure. ICP values before NTG administration ranged from 7 to 24 mmHg (mean, 11.91±5.30 mmHg). ICP began to increase immediately after the adminisration of NTG 0.5 g/kg/min and peaked at 14.64±5.93 mmHg 10 minutes after onset of infusion. Thereafter, ICP gradually returned to pretreatment levels. Increasing the dose of NTG failed to induce further significant rises in ICP. Mean AVDO₂ before NTG administration was 4.69±0.62 ml/dl. This parameter showed no significant change during NTG infusion, although cerebral perfusion pressure decreased to between 75% to 94% of the control value after NTG administration. These results indicate that continuous NTG infusion combined with dopamine does not have adverse effects on ICP (the ICP increase is minimal and transient) and may even have beneficial effects on CBF in patients with acute SAH.     

Expression of fibronectin and TGF-ß1 mRNA and protein suggest altered regulation of extracellular matrix in degenerated disc tissue

We studied the distribution of fibronectin (a marker for active reparative connective tissue processes) and TGF-1 (a cytokine controlling the connective tissue metabolism) in intervertebral disc tissue from individuals of different age and various histomorphological evidence for tissue degeneration. The protein deposition was determined by immunohistochemistry on 30 complete cross-sections of lumbar spine obtained at autopsy (0–86 years) and 12 surgically removed disc samples. The mRNA expression was detected by non-radioactive in situ hybridization in the surgical material. All control experiments (blank and isotype controls in immunohistochemistry/sense controls in in situ hybridization) were negative. Immunohistochemically, we detected enhanced staining for fibronectin in both nuclear and anular tissues in areas with histological signs of mild-to-severe tissue degeneration (e.g., cleft formation and cell clustering) beginning with 16 years of age. Anular tissue showed less fibronectin staining than did nuclear areas. Fibronectin mRNA was detected mainly in nuclear cells by in situ hybridization corresponding to the protein staining indicating de novo synthesis. In parallel, TGF-1 was expressed by nuclear and occasional anular cells spatially associated with the fibronectin synthesizing cells. This was seen by both immunohistochemistry and in situ hybridization. This preliminary study provides evidence for a significant ongoing rearrangement of the extracellular matrix during disc degeneration, as monitored by enhanced fibronectin deposition that is produced by local disc cells. These cells also synthesize TGF-1, as shown by protein and mRNA expression. Since it is known that TGF-1 induces matrix alterations (by auto and paracrine stimulation of matrix synthesis), these observations suggest that the recently described disturbance of the matrix during disc degeneration may be induced by TGF-. This may offer new approaches to interfere with disc matrix alterations.     

Do concentrations of neurotransmitters measured in lumbar cerebrospinal fluid reflect the concentrations at brain level?

Summary CSF concentrations of vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), noradrenaline (NA) and dopamine (DA) were measured in the lateral ventricles and at the lumbar level in patients with normal pressure hydrocephalus (NPH). The concentrations of VIP (n=15), NA (n=10) and DA (n=10) were significantly higher at the lumbar level than at the ventricular level, whereas the concentrations of CCK (n=9) were similar at the two sites. A signifikant positive correlation between the concentrations measured at the two levels was found for VIP (r_s=0.65; p0.01) and DA (r_s=0.94; p0.001). The results indicate that the concentrations of transmitter substances measured in CSF at the lumbar level not necessarily are indicative for concentrations measured more centrally. The negative correlations between Evans ratio and L-CSF VIP (r_s=-0.76; p 0.001), and between resistance to outflow and V-CSF as well as L-CSF CCK (r_s=-0.75); p 0.05) might be explained by a reduction in number of cortical neurons or by disturbances in CSF dynamics in patients with NPH.     

Measurement of airway resistance in anesthetized and paralyzed subjects: Proposal for evaluation of K1 values

The effects of lung volume and respiratory airflow on airway resistance were studied in five anesthetized and paralyzed patients. Airway resistance measured during the inspiratory phase with intermittent constant airflow inflatoins decreased in inverse correlationship to increases in lung volume. Airway resistance measured during the expiratory phase with an airway interruption technique, on the other hand, increased with a linear relationship to the expiratory airflow as expressed by a function of Y = K₁ + K₂X. K₁, calculated from the values of airway resistance corresponding to three different airflows, was unaffected by intentional expiratory resistance loading. Thus, simultaneously with the measurement of airway resistance by this method, expiratory gas sampling with a Douglas bag can be done if necessary. Since the K₂ value of the endotracheal tube used in this study (Portex^® I.D. 8mm, length 26cm) was quite high (5.0cmH₂O·1^–2·sec²), depending on the airflow, the presence of the endotracheal tube strongly affected the measurement of airway resistance during general anesthesia. K₁ measured by the above method, however, may be considered as the best way to evaluate the lower airway resistance independent of either lung volume or expiratory airflow.(Sakai T, Yoshida H, Yano H et al.: Measurement of airway resistance in anesthetized and paralyzed subjects: proposal for evaluation of K₁ values. J Anesth 2: 139–145, 1988)     

Comparison of deoxyribonucleic acid ploidy and nuclear expressed p62 c-myc oncogene in the prognosis of colorectal cancer

A simultaneous flow cytometric assay of the nuclear expressed protein product of the c-myc oncogene p62 and deoxyribonucleic acid (DNA) ploidy in archival paraffin-embedded tumor material was undertaken in 179 patients with colorectal cancer, followed for up to 9 years. DNA ploidy showed a survival advantage for diploid tumors ( ₁ ² =5.39,p= 0.020) and could be used to further divide patients with Dukes' A tumors ( ₁ ² =4.87,p=0.027) and Dukes' C tumors ( ₁ ² =5.33,p=0.021). By dividing patients into 2 levels of tumor expression of p62 c-myc, there was a trend for improved survival in patients with low expression ( ₁ ² =3.65,p=0.056). A combination of ploidy status and p62 c-myc expression improved upon survival prediction by ploidy alone in providing 3 groups ( ₂ ² =7.86,p=0.0197). While these results do not suggest a replacement for the Dukes' staging for prognosis ( ₃ ² =33.82,p<0.00001), they strongly support the concept that enhanced expression of c-myc oncogene is associated with the progression of colorectal cancer.

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Resumen Se realizó la determinación de la expresión nuclear del producto proteico del oncogen p62 c-myc y la ploidia de ácido deoxirri-bonucleico (DNA) por análisis de citometría de flujo en material tumoral procesado en parafina en 179 pacientes con cáncer colorrectal que fueron seguidos hasta por 9 años. El estudio de la ploidia de DNA demostró una mayor supervivencia para los tumores diploides ( ₁ ² =5.39,p=0.020) y permitió subdividir los pacientes entre aquellos con tumores Dukes A ( ₁ ² =4.87,p =0.027) y Dukes C ( ₁ ² =5.33,p=0.021). Al dividir los pacientes en 2 niveles de expresión tumoral de p62 c-myc, se halló una tendencia hacia una mayor supervivencia en los pacientes con bajos niveles de expresión ( ₁ ² =3.65,p=0.056). La combinación del estado de la ploidia y de la expresión de p62 c-myc incrementó la capacidad de predecir supervivencia sobre el uso de la ploidia solamente al definir 3 grupos ( ₂ ² =7.86,p= 0.0197). Aunque estos resultados no permiten recomendar que se reemplace el método de Dukes en la estadificación del tumor para definir pronóstico ( ₃ ² =33.82,p<0.00001) sí proveen un fuerte soporte al concepto de que una incrementada expresión del oncogen c-myc está asociado con progresión del cáncer colorrectal.

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Résumé Par la cytométrie de flux, on a étudié simultanément le produit de l'oncogène c-myc p62, et la ploïdie de l'acide désoxyribonucléique (ADN) dans du matériel tumoral inclus dans la paraffine chez 179 patients ayant un cancer colorectal, répertoriés rétrospectivement et suivis pour un maximum de 9 ans. L'étude de la ploïdie ADN a montré un avantage de survie lorsque la tumeur était diploïde ( ₁ ² =5.39,p=0.020). Ces résultats pouvaient être utilisés pour classer les patients ayant une tumeur du stade A de Dukes ( ₁ ² =4.87,p=0.027) de ceux ayant une tumeur du stade C de Dukes ( ₁ ² =5.33,p=0.021). En classant les patients selon leur niveau d'expression tumorale de l'oncogène p62 c-myc, on a constaté une tendance de meilleure survie chez les patients ayant une expression faible ( ₁ ² =3.65,p=0.056). L'association de l'étude de la ploïdie et de l'expression de p62 c-myc améliore la prédiction de survie par rapport à l'étude de la ploïdie seule. Trois groupes sont ainsi définis ( ₂ ² =7.86,p=0.0197). Alors que ces résultats ne suggèrent pas de remplacer la classification de Dukes pour le pronostic ( ₃ ² =33.82,p<0.00001), il semble que l'expression augmentée de l'oncogène c-myc est fortement associée avec l'évolutivité du cancer colorectal.

     

Analysis of oxygen transport and oxygen utilization combined

We propose a model which combines oxygen transport system from blood to tissue with oxygen utilization system at the tissue.The model consists of 3 equations; the relationship between tissue P_{O 2} (Pts_{O 2}) and O₂ utilization (Vrc_{O 2}), diffusion from vessel to tissue, and Fick equation. This model has two advantages. First, it is self-consistent. Varying Vrc_{O 2} varies the oxygen transport. Second, it enables to analyze the effects of various factors of oxygen transport/utilization on other factors.We applied this model to the brain tissue. Following values were assumed. Critical tissue P_{O 2} (Pcrit_{O 2}) 2mmHg; oxygen utilization above this level 3ml·min^–1·100g^–1; diffusion coefficient from blood vessel to tissue (D) 0.2ml·min^–1·mmHg^–1·100g^–1; cerebral blood flow (CBF) 50ml·min^–1·100g^–1; hemoglobin 15g·100ml^–1. Hill equation was used for oxygen dissociation curve with n of 2.7 and P50 of 27.0mmHg.From these, the following values were obtained; Pv_{O 2}, Pts_{O 2} and Vrc_{O 2}. The changes were analyzed for the 5 input values, Pa_{O 2}, CBF, D, P50 and Hb, changing from zero to their respective normal values. A reduction of a single parameter down to 50% of normal barely affected oxygen utilization. A further reduction resulted in significant oxygen utilization. Under conditions studied, a decrease in P50 reduced oxygen utilization faster than that in any other parameters.(Suwa K: Analysis of oxygen transport and oxygen utilization combined. J Anesth 6: 51–56, 1992)     

Diffusion theory of isotropic light dosimetry probe response

For the measurements of light energy fluence rate in tissues in vitro and in vivo we have developed an isotropic probe. The response of such a probe depends on the refractive index (n) of the medium. This has been measured in a collimated light beam with the probe in air, water (n=1.33), ehtylene glycol (n=1.43) and glycerin (n=1.46). The response as a function of n has also been calculated using diffusion theory, taking into account reflection at the boundaries. Simple formulas are proposed which very well approximate Fresnel reflection of unpolarized light, facilitating mathematical calculations. For a probe of 3.2 mm diameter with little light absorption the theoretical result depends only on n and differs from the experimental data by not more than 6 %. For a probe of 0.8 mm diameter with some light absorption excellent agreement between theory and experiment could be obtained by adjusting the (unknown) absorption and scattering coefficients ( _a, _s) of the probe material. However, a good fit was only possible within certain limits for _a, i.e. 0.35 mm^–1< _a<0.40 mm^–1, whereas _s (1-g) could be varied between at least 5 and 20 mm^–1 (g is the asymmetry parameter of the scattering function).     

Urinary thromboxane B2 as an indicator of acute rejection in human liver transplantation

Urinary thromboxane B₂ (u-TXB₂) was measured and analyzed after a human liver transplantation in 28 patients (30 transplantations) who underwent an orthotopic liver transplantation. Our results showed that the u-TXB₂ levels exceeded 3.0g/mmol creatinine in only 2 of the 13 cases that had a favorable postoperative course. In 10 of the 11 episodes of acute rejection, the u-TXB₂ levels exceeded 3.0g/mmol creatinine. In 6 episodes of acute rejection, the TXB₂ levels were more than 5.0. In 4 out of 6 episodes of infection unassociated with rejection, the u-TXB₂ values were between 3.0 and 4.9g/mmol creatinine. In 2 episodes of liver necrosis the TXB₂ value reached 5.3 in one and 0.9 in the other. In conclusion, the u-TXB₂ level was observed to be elevated in cases of acute rejection, infection, or necrosis. The diagnosis of acute rejection on the basis of u-TXB₂ showed a sensitivity of 58.8%, a specificity of 93.3%, and an accuracy of 75.0% for a threshold level of 3.0g/mmol creatinine, and a sensitivity of 85.7%, a specificity of 79.2%, and an accuracy of 80.6% for a threshold level of TXB₂ of 5.0g/mmol creatinine. These results indicate that the serial determination of u-TXB₂ is a useful diagnostic means for predicting acute rejection after liver transplantation.