Anatomical variation of cerebral venous drainage: the theoretical effect on jugular bulb blood samples

A workshop was convened to discuss safety issues for traditional-approach HIV vaccines, especially inactivated vaccines. The topics included issues pertaining to (1) cell substrates used for production and (2) vaccine virus inactivation. The use of cell substrates such as tumor-derived continuous cell lines (TCLs) or virus-transformed. CLs may be the most feasible approach to provide commercial-scale virus yields. However, especially because of concerns about tumorigenicity, TCLs have not been used to produce preventive vaccines for human trials with healthy subjects in the United States. Residual TCL material (e.g., DNA, cellular proteins, viruses) may not be removed during purification of intact HIV virions to the same extent achievable for a recombinant protein. Manufacturing processes, e.g., physicochemical methods of destroying DNA, could decrease tumorigenicity risk. Methods to assess potential for tumorigenicity may need further development. Another potential substrate for viral production that merits further study is human peripheral blood mononuclear cells (PBMCs). Regardless of the cell substrate used, extensive testing for adventitious agents (including non-HIV retroviruses) is needed. Vaccine virus inactivation can be considered in statistical terms, i.e., the probability of a surviving infectious particle. One formula to determine a "safety margin" (SM) is reduction of titer in log10 for all inactivation steps minus initial viral infectivity in log10. Calculations for appropriate SMs should include all sources of variability (e.g., lot-to-lot differences). Ensuring a specified SM, as the lower bound of the 95% confidence interval, for production lots was discussed. Sensitivity and specificity of infectivity assays may present limitations.     

Leg blood flow during slow head-down tilt with and without leg venous congestion

BACKGROUND AND STUDY AIMS: Endoscopy and biopsy from a suspicious Vater's papilla may establish an early preoperative diagnosis of a periampullary tumor. However, information regarding the diagnostic accuracy of this procedure is limited and variable. The aim of the present study was to evaluate retrospectively the accuracy of this procedure compared to that of other diagnostic methods. PATIENTS AND METHODS: Among 928 patients referred to our institute for endoscopic retrograde cholangiopancreatography (ERCP), a suspicious Vater's papilla was seen in 28. In each case comparison was made between the pre-ERCP clinical diagnosis, endoscopic appearance, histologic interpretation of endoscopic biopsies, and the final diagnosis. Two patients in whom a final diagnosis was not available were excluded from the study. RESULTS: A final diagnosis of an ampullary or periampullary carcinoma was established in 17 patients (65%), a carcinoma within an adenoma of the papilla in three patients (12%), and adenoma and a metastatic gallbladder carcinoma in one patient each. The remaining four patients (15%) were finally diagnosed as having "pseudotumors" (due to choledocholithiasis). Eight (38%) of the 21 patients with ampullary or periampullary neoplasm also had gallstones. A pre-ERCP diagnosis (by clinical evaluation and non-invasive imaging) of tumor versus choledocholithiasis was accurate in only 65% of all 26 patients. In these, the diagnostic accuracy of endoscopic appearance and endoscopic biopsy was 77% and 85%, respectively. Regarding the 21 patients with carcinomas, the diagnosis by endoscopic appearance was more accurate than that by endoscopic biopsy (90% vs 81%). Unlike the positive predictive values, the negative predictive values for malignancy were weak: 33% for the endoscopic appearance and 50% for the endoscopic biopsy. CONCLUSIONS: Because of a high incidence of concurrent cholelithiasis, many patients with a periampullary tumor seen during ERCP are misdiagnosed earlier (by clinical evaluation and non-invasive imaging) as having choledocholithiasis only. However, the accuracy of endoscopy and biopsy is also limited. This limitation must be considered when evaluating the optimal management of patients with suspected periampullary tumor.     

Exposed superior bulb of the internal jugular vein. Differential hearing loss diagnosis with pulse synchronous tinnitus

A case report is presented of a 54-year-old woman with tinnitus synchronous with her pulse and an ipsilateral conductive hearing loss. Otoscopy showed a pulsatile structure behind the right eardrum. Imaging with high-resolution computed tomography of the temporal bone showed an enlarged jugular vein bulb. Magnetic resonance imaging could not be performed because of an implanted pacemaker. Since a glomus jugulare tumor could not be excluded right diagnostic tympanoscopy was performed and revealed a high jugular bulb that filled nearly a third of the tympanum.     

Measurement of cerebral oxyhaemoglobin saturation and jugular blood flow in term healthy newborn infants by near-infrared spectroscopy and jugular venous occlusion

Data of cerebral haemodynamics and oxygenation are important for optimal treatment and prognosis in neonatal intensive care. Mostly premature and asphyxiated infants have been examined, but near-infrared spectroscopy (NIRS) allows estimations in healthy term newborns. In this study, cerebral venous saturation (CVsO2) and jugular blood flow (JBF) was estimated in 11 healthy term newborns. Mean CVsO2 was 64.12 +/- 4.6%, which conform with expectations. Mean JBF was only 6.1 ml/100 g/min, which is unacceptably low compared to earlier published data. We discuss physiological and methodological aspects and conclude that the combination of NIRS and venous occlusion appears to be a reliable method for estimation of CVsO2 in normally healthy newborns, whereas the reason for the failure of the method for estimation of JBF is unclear.     

Pulsatile ocular blood flow variations with axial length and refractive error

Benign symmetric lipomatosis (BSL), also known as Madelung's disease, is a rare condition and characterized by diffuse but painless growth of unencapsulated lipomas. A close correlation to alcohol and nicotine abuse, metabolic disturbances and malignant tumours have been observed. Surgical treatment is frequently followed by recurrence, nevertheless, it can yield satisfactory functional and cosmetic results. A case of BSL with uncommonly distributed tumors is reported.     

The high jugular bulb: report of five cases and a review of the literature

The jugular bulb varies widely in position and dimensions. A high jugular bulb is not an uncommon finding in temporal bones. Besides our five cases with different clinical manifestations, we review 52 cases diagnosed clinically and published previously in the English literature. The high jugular bulb occurs more often on the right temporal bone. Certain pathologic conditions, such as an abnormal bone formation, an aberrant sinusojugular system, or decreased pneumatization of the mastoid bone, may predispose an individual to its occurrence. Most people with this anatomical variation remain asymptomatic. However, various otologic problems and symptoms may be attributed to this condition. A high resolution computed tomography scan is the most convenient diagnostic tool at present. Law projection plain mastoid radiography may reveal a high jugular bulb in certain cases, providing a preoperative warning to an otologic surgeon. An exploratory tympanotomy is not suggested for those with a high jugular bulb with a conductive hearing loss, while jugular vein ligation has been reported to have good results in alleviating intractable pulsatile tinnitus. For most asymptomatic patients, regular long-term follow-up is recommended.     

Amplitude Doppler US: slow blood flow detection tested with a flow phantom

Unidirectional blue light directs the rhizoid-thallus axis in the apolar zygotes of Fucus and Pelvetia. Here, it is shown that blue light (but not red light) increased cyclic GMP levels of Pelvetia zygotes by about a factor of 2. When the increase in cyclic GMP was blocked by a guanylyl cyclase inhibitor, photopolarization was also blocked. Bathing the cells in a permeant cyclic GMP analog, which should tend to collapse intracellular cyclic GMP gradients, reduced the degree of photopolarization. Growing the cells in the dark in a gradient of the analog caused the rhizoids to tend to form on the low concentration side. It appears that the stimulation of the blue light photoreceptors on the side nearer the light activates guanylyl cyclase and results in a transcytoplasmic cyclic GMP gradient that is necessary for polarization.     

Pulsatile ocular blood flow in untreated diabetic retinopathy

AIMS: To study the effect of eprosartan, a nonbiphenyl tetrazole angiotensin II receptor antagonist, on digoxin pharmacokinetics in a randomized, open-label, two period, period balanced crossover study in 12 healthy men. METHODS: Each subject received a single 0.6 mg oral dose of digoxin (Lanoxicaps 0.2 mg/capsule, Glaxo Wellcome) alone or following 4 days of dosing with eprosartan 200 mg orally every 12 h. Each study period was separated by a 14 day washout interval. Serial blood samples were obtained for up to 96 h after each digoxin dose for determination of digoxin pharmacokinetics. The effect of eprosartan on digoxin pharmacokinetics was assessed through an equivalence-type approach using AUC(0, t') as the primary endpoint. RESULTS: For AUC(0, t'), the ratio of digoxin+eprosartan: digoxin alone was 0.99 with a 90% confidence interval (CI) of [0.90, 1.09]. For Cmax, the ratio was 1.00 with a 90% CI of [0.86, 1.17]. tmax was similar for both regimens. Both regimens were safe and well tolerated. CONCLUSIONS: Based on AUC and Cmax data, it can be concluded that eprosartan has no effect on the pharmacokinetics of a single oral dose of digoxin.     

Use of jugular venous blood, compared with mixed venous blood, for measurement of venous oxygenation indices in a porcine model of endotoxic shock

OBJECTIVE: To evaluate the reliability of oxygen saturation and oxygen content values measured from jugular venous blood in estimating values measured from mixed venous blood during endotoxic shock. ANIMALS: 14 random-bred 10- to 15-kg Yorkshire pigs. PROCEDURE: 60 pairs of heparinized blood samples were simultaneously collected from the pulmonary artery and right jugular vein during an independent study, using a porcine model of endotoxic shock. Endotoxic shock was induced by infusion of Escherichia coli endotoxin. Eighteen of the sample pairs were obtained from pigs prior to infusion of endotoxin or from control pigs. Oxygen saturation and venous oxygen content were measured by direct oximetry. Analysis of bias and precision was used to compare jugular venous blood values with values obtained from mixed venous blood. Samples from endotoxemic pigs were subclassified on the basis of abnormal states of global oxygen imbalance associated with septic shock. RESULTS: Indices of venous oxygenation measured from jugular venous blood were an imprecise method of estimating values measured from mixed venous blood. There was no significant difference in bias between nonendotoxemic and endotoxemic pigs, regardless of abnormal hemodynamic states. CONCLUSION: Jugular venous blood oxygen saturation and oxygen content values should not be used to assess global oxygen transport during endotoxic shock.     

Quantification of cerebral blood flow with 99mTc-ECD SPECT by a single arterial or venous blood sample

The purpose of the study is to develop a simple and less invasive method for quantifying regional cerebral blood flow (rCBF) using 99mTc-ECD and SPECT. By employing a microsphere model, a new method to measure rCBF was developed, which required a single arterial or venous sample instead of continuous withdrawal of arterial blood. Using a regression line, the integral of input function of arterial blood from 0 to 30 min was inferred by activity of arterial blood sampled at time t; A(t), by activity multiplied by its octanol extraction rate; AN(t), by activity of venous blood at time t; V(t), and by activity multiplied by its octanol extraction rate; VN(t). The optimum sampling time of arterial or venous blood was examined when mean % error for inference became minimum. Consequently, minimum error of AN(6 min) was 5.5%, A(3 min) was 8.9%, VN(6 min) was 5.9%, and V(20 min) was 10.0%. Quantitative measurement of rCBF using the value of VN(6 min) was performed on other 6 subjects with dementia etc. To validate the method, 133Xe inhalation SPECT studies were also performed on the same subjects. We found a good agreement between them (r = 0.851). The presented one-point sampling methods were simple and less invasive for quantifying rCBF.     

Jugular bulb oximetry for the monitoring of cerebral blood flow and metabolism

Jugular bulb oximetry can be used to assess the balance between oxygen supply and demand to the brain, measure metabolic byproducts, and determine cerebral blood flow. It has been useful in guiding the management of patients who are at risk of developing global ischemia. In this article, the principles upon which this monitor is based are discussed. Technical considerations such as placement techniques, factors affecting accuracy, limitations of the technique, and proper interpretation of oximetric values are reviewed. Lastly, specific clinical applications are presented.     

Diagnosis of traumatic carotid-cavernous sinus fistula by monitoring venous oxygen saturation in the jugular bulb: report of two cases

OBJECTIVE AND IMPORTANCE: A traumatic carotid-cavernous sinus fistula (CCF) is rarely diagnosed early and may sometimes be missed until clinical signs and symptoms appear. The continuous monitoring of cerebral venous oxygen saturation may reveal the presence of a CCF by means of a fiberoptic catheter that records very high oxygen saturation values when positioned in the jugular bulb. CLINICAL PRESENTATION: We report two cases of early diagnosis of CCFs unexpectedly revealed by monitoring the jugular bulb for venous oxygen saturation values that approximated arterial saturation values. One case was diagnosed on Day 3 after admission, and the other was diagnosed shortly after cannulation of the ipsilateral jugular bulb. INTERVENTION: Confirmation of the diagnosis of CCF was obtained by angiography. Intravascular treatment was performed in one case. CONCLUSION: These cases add another diagnostic role to cerebral venous oxygen saturation monitoring. When high cerebral venous oxygen saturation values rapidly or abruptly reach arterial oxygen saturation, the presence of a CCF must be considered and confirmed by arterial angiography.     

Changes of venous blood flow velocity waveforms in fetuses with supraventricular tachycardia

Studies in the fetal lamb have shown that atrial pacing beyond a rate of 300-320 beats/min may be associated with dramatic changes of venous blood velocity waveforms, an increase of venous pressure by up to 75%, hydrops, polyhydramnios and placental edema. The aim of our study was to determine the 'critical' heart rate frequency in the human fetus. In 11 fetuses (five with and six without hydrops) with supraventricular tachycardia, pulsed wave Doppler analysis of flow velocity waveforms of the inferior vena cava, the ductus venosus and the left hepatic vein were performed before and after drug treatment. In ten cases cardioversion was achieved by in utero antiarrhythmic drug therapy; in one case treated with digoxin and flecainide the supraventricular tachycardia was decreased to 160-190 beats/min with disappearance of hydrops. Before intrauterine treatment of supraventricular tachycardia, pulsatile reversal of blood flow in the inferior vena cava, ductus venosus and left hepatic vein was visible, with monophasic forward flow during systole and reversed flow during diastole in ten of 11 fetuses. One fetus with supraventricular tachycardia of 195 beats/min showed a normal biphasic forward flow pattern. During drug-induced sinus rhythm, a normal biphasic forward venous blood flow pattern was shown in all ten cases. In five cases pulsatile reversal was demonstrated during a drug-induced reduction of the heart rate from 280 to 210 beats/min and a normal biphasic forward flow velocity waveform appeared during supraventricular tachycardia below 210 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulse-spray treatment of subclavian and jugular venous thrombi with recombinant tissue plasminogen activator

PURPOSE: To evaluate the efficacy of recombinant tissue plasminogen activator (rtPA) injected by pulse-spray in lysing subclavian and jugular venous thrombi. MATERIALS AND METHODS: Twelve patients with symptomatic, venogram-confirmed, occlusive thrombi of the subclavian-axillary or jugular veins were treated with one or two daily 15-minute injections of rtPA delivered directly into the clots with pulse-spray catheters. Twenty-four hours after each treatment, repeated venograms were obtained to assess venous patency. Successful thrombolysis was defined as antegrade flow through the previously occluded segments with minimal collateral venous flow. Continued patency was assessed with repeated venograms obtained after 1 and 2 months of oral anticoagulation. RESULTS: The 15-minute rtPA injections successfully lysed thrombi in eight of the 12 patients. Hypofibrinogenemia developed in only one patient. The technique had a high success rate with thrombi less than 2 weeks old (seven of eight) regardless of the length of the clot, but had limited success with thrombi more than 2 weeks old (one of four). Continued patency over a 2-month interval was documented in four of the eight patients whose thrombi were successfully lysed. However, patency could be maintained in only one of the four patients who retained a venous access device in the treated vein. CONCLUSION: Pulse spray rtPA is an effective, safe, and practical alternative to continuous infusions of thrombolytic agents to treat upper extremity venous thrombi.     

Pulsatile versus nonpulsatile flow. No difference in cerebral blood flow or metabolism during normothermic cardiopulmonary bypass in rabbits

BACKGROUND: Although pulsatile and nonpulsatile cardiopulmonary bypass (CPB) do not differentially affect cerebral blood flow (CBF) or metabolism during hypothermia, studies suggest pulsatile CPB may result in greater CBF than nonpulsatile CPB under normothermic conditions. Consequently, nonpulsatile flow may contribute to poorer neurologic outcome observed in some studies of normothermic CPB. This study compared CBF and cerebral metabolic rate for oxygen (CMRO2) between pulsatile and nonpulsatile CPB at 37 degrees C. METHODS: In experiment A, 16 anesthetized New Zealand white rabbits were randomized to one of two pulsatile CPB groups based on pump systolic ejection period (100 and 140 ms, respectively). Each animal was perfused at 37 degrees C for 30 min at each of two pulse rates (150 and 250 pulse/min, respectively). This scheme created four different arterial pressure waveforms. At the end of each perfusion period, arterial pressure waveform, arterial and cerebral venous oxygen content, CBF (microspheres), and CMRO2 (Fick) were measured. In experiment B, 22 rabbits were randomized to pulsatile (100-ms ejection period, 250 pulse/min) or nonpulsatile CPB at 37 degrees C. At 30 and 60 min of CPB, physiologic measurements were made as before. RESULTS: In experiment A, CBF and CMRO2 were independent of ejection period and pulse rate. Thus, all four waveforms were physiologically equivalent. In experiment B, CBF did not differ between pulsatile and nonpulsatile CPB (72 +/- 6 vs. 77 +/- 9 ml.100 g-1.min-1, respectively (median +/- quartile deviation)). CMRO2 did not differ between pulsatile and nonpulsatile CPB (4.7 +/- 0.5 vs. 4.1 +/- 0.6 ml O2.100 g-1.min-1, respectively) and decreased slightly (0.4 +/- 0.4 ml O2.100 g-1.min-1) between measurements. CONCLUSIONS: During CPB in rabbits at 37 degrees C, neither CBF nor CMRO2 is affected by arterial pulsation. The absence of pulsation per se is not responsible for the small decreases in CMRO2 observed during CPB.     

Cerebral blood flow relationships associated with a difficult tone recognition task in trained normal volunteers

Tone recognition is partially subserved by neural activity in the right frontal and primary auditory cortices. First we determined the brain areas associated with tone perception and recognition. This study then examined how regional cerebral blood flow (rCBF) in these and other brain regions correlates with the behavioral characteristics of a difficult tone recognition task. rCBF changes were assessed using H2(15)O positron emission tomography. Subtraction procedures were used to localize significant change regions and correlational analyses were applied to determine how response times (RT) predicted rCBF patterns. Twelve trained normal volunteers were studied in three conditions: REST, sensory motor control (SMC) and decision (DEC). The SMC-REST contrast revealed bilateral activation of primary auditory cortices, cerebellum and bilateral inferior frontal gyri. DEC-SMC produced significant clusters in the right middle and inferior frontal gyri, insula and claustrum; the anterior cingulate gyrus and supplementary motor area; the left insula/claustrum; and the left cerebellum. Correlational analyses, RT versus rCBF from DEC scans, showed a positive correlation in right inferior and middle frontal cortex; rCBF in bilateral auditory cortices and cerebellum exhibited significant negative correlations with RT These changes suggest that neural activity in the right frontal, superior temporal and cerebellar regions shifts back and forth in magnitude depending on whether tone recognition RT is relatively fast or slow, during a difficult, accurate assessment.     

Measurement of cerebral venous oxyhemoglobin saturation in children by near-infrared spectroscopy and partial jugular venous occlusion

Surgery of the anterior cruciate ligament causes severe postoperative pain. This study aimed to compare efficacy and side effects of two postoperative analgesia methods, during 24 hours. Twenty healthy patients were assigned to two groups (n = 10): the patients of the first group were given by an epidural catheter 3 mg of morphine hydrochloride, every twelve hours. The patients of the second group received 2 mg h-1 of intravenous nalbuphine. The degree of pain was studied with a visual analogue scale. After the third postoperative hour, it was significantly higher in the second group, but the nalbuphine dose was low. The incidence of respiratory depression, nausea, pruritus was not statistically different between the groups, but 7/10 patients in the first group suffered of urinary retention (the first micturition was obtained 10.5 hours after the end of surgery in the first group and 5.3 h in the second one). Two patients needed an uretral catheter. These results might tend to show a greater efficactly of epidural morphine, with a higher incidence of urinary side effects.     

Pseudobacteriuria associated with a urine flow rate transducer

Normal wound healing in skin embraces several reparative processes, many of which directly involve components of the extracellular matrix and the cutaneous basement membrane zone. Proteoglycans are a group of extracellular matrix macromolecules that have both structural and regulatory properties. In wound healing, certain proteoglycans fulfill a mechanical function of absorbing water and preventing tissue compression. However, proteoglycans may also have other roles in wound healing including a direct influence on inflammation, cell attachment and migration, and growth factor binding. Furthermore, proteoglycans may help to determine other aspects of the long-term quality of wound healing in skin through regulation of basement membrane permeability, epidermal hyperproliferation, and dermal fibrosis.