Propylene glycol toxicity from compulsive corn starch ingestion.

INTRODUCTION: Propylene glycol (PG) is usually considered safe, however, toxicity can develop with high doses or when used for prolonged periods of time. PG can be found in some medications as well as some food products. We report a case of likely PG toxicity that occurred after compulsive daily ingestion of large amounts of corn starch. CASE REPORT: Our patient initially presented to an outside hospital (OSH) via ambulance for altered mental status. Her mental status improved after her blood sugar of 25 was corrected. On admission to OSH Emergency Department her initial vital signs included a heart rate of 115 bpm, blood pressure 113/59 mm/hg, temperature 35.8C. Pertinent labs included: sodium 119 mEq/L, bicarbonate 9 mEq/L, anion gap 29 mEq/L, creatinine 2.5 mg/dL and lactic acid 20 mEq/L. On transfer to our hospital her repeat lactic acid was 20 mEq/L, osmolar gap was 20. Her PG level, which was drawn several hours after her initial presentation, was 11 mg/dL. Our patient noted that she ingested a 16 oz. package of corn starch mixed with baking soda approximately every 2 days. Given the concerns for PG she was underwent intermittent hemodialysis. PG and lactic acid levels improved, however, she ultimately died due to complications from her hospitalization. DISCUSSION: PG causes toxicity through metabolism to lactic acid. While there are small amounts in food products and medications, under the right circumstances, PG can accumulate and lead to significant toxicity.

Efficacy of BRAF/MEK-inhibitor therapy for epithelioid glioblastoma with a novel BRAFV600 mutation.

Epithelioid glioblastoma (eGB), a very aggressive and rare brain tumour, is associated with a dismal median overall survival. Effective therapies for patients with eGB, particularly with leptomeningeal dissemination, are still lacking. Here, we describe a case of a 25-year-old male diagnosed with an intramedullary cervical tumour with subsequent leptomeningeal disease. Histopathology identified a highly necrotising, epithelioid-type tumour with high cell density, most compatible with the diagnosis of an eGB. DNA analysis revealed an unprecedented B-Raf protooncogene, serine/threonine kinase (BRAF) gene variant in exon 15 (ENST00000288602.6, c.1799_1810delinsATG, p.(V600_W604delinsDG)), triggering activation of the mitogen-activated protein kinase (MAPK) pathway. Consequently, we initiated MAPK inhibitor (MAPKi) therapy, utilizing a combination of BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors. Liquid chromatography-tandem mass spectrometry analysis confirmed the drugs' presence in the patient's cerebrospinal fluid, indicating their capacity to cross the blood-brain barrier. Remarkably, the patient responded very well to therapy and transitioned from a near-comatose state to significantly improved health, sustained for over three months. This study highlights that MAPKi, particularly targeted towards novel BRAFV600 mutations, might offer promising advancements in eGB treatment strategies.

[Carboxyhemoglobin concentration in carbon monoxide poisoning. Critical appraisal of the predictive value]. / Carboxyhämoglobinkonzentration bei Kohlenmonoxidvergiftung. Kritische Betrachtung der prädiktiven Aussagekraft.

In cases of unclear depression of conciousness, arrhythmia and symptoms of cardiac insufficiency inadvertent carbon monoxide intoxication should always be taken into consideration. Rapid diagnosis of acute carbon monoxide intoxication with mostly unspecific symptoms requires an immediate supply of high dose oxygen which enables a distinct reduction of mortality and long-term morbidity. Levels of carboxyhemoglobin, however, should not be used as a parameter to decide whether to supply normobaric or the more efficient hyperbaric oxygen. There is no sufficient coherence between carboxyhemoglobin blood levels and clinical symptoms. Increased carboxyhemoglobin concentrations help to diagnose acute carbon monoxide intoxication but do not allow conclusions to be drawn about possible long-term neuropsychiatric or cardiac consequences.

[A rare coagulation disorder. Diagnostics and management in cases of hereditary dysfibrinogenemia]. / Seltene Ursache einer hämorrhagischen Diathese. Diagnostik und perioperatives Management bei hereditärer Dysfibrinogenämie.

Before elective surgery, it is mandatory that a precise history be taken to detect increased hemorrhagic diathesis and that thrombocytes, Quick/INR, and aPTT be determined. If pathological levels are found, further laboratory tests are necessary after frequent causes (e.g., liver cirrhosis) have been excluded. Single-factor analysis for the von Willebrand's factor antigen and if necessary further tests to check for von Willebrand's syndrome (multimeric analysis) as well as platelet function tests should be performed.Dysfibrinogenemia is a rare coagulation disorder, which causes elevated INR. It shows a wide spectrum of clinical manifestations including thrombophilia, excessive bleeding, and even asymptomatic cases. We present a 72-year-old patient with asymptomatic dysfibrinogenemia who needed hip replacement due to arthrosis. Lowered fibrinogen levels were substituted prior to operation and the clinical course afterwards was uneventful under additional prophylactic anticoagulation in order to prevent thrombosis. The case report illustrates the interdisciplinary teamwork which is very important in the management of patients with coagulation disorders.

Cardiac muscarinic receptors decrease with age. In vitro and in vivo studies.

The M1 muscarinic receptor antagonist pirenzepine in low doses decreases resting heart rate; this effect declines with age (Poller, U., G. Nedelka, J. Radke, K. Pönicke, and O.-E. Brodde. 1997. J. Am. Coll. Cardiol. 29:187-193). To study possible mechanisms underlying this effect, we assessed (a) in six young (26 yr old) and six older volunteers (61 yr old), pirenzepine effects (0.32 and 0.64 mg intravenous [i.v.] bolus) on isoprenaline-induced heart rate increases; (b) in five heart transplant recipients, pirenzepine effects (0.05-10 mg i.v. bolus) on resting heart rate in the recipient's native and transplanted sinus nodes; and (c) in right atria from 39 patients of different ages (5 d-76 yr) undergoing open heart surgery, M2 muscarinic receptor density (by [3H]N-methyl-scopolamine binding) and adenylyl cyclase activity. (a) Pirenzepine at both doses decreased heart rate in young volunteers significantly more than in older volunteers; (b) pirenzepine (< 1 mg) decreased resting heart rate in the recipient's native but not transplanted sinus node; and (c) M2 receptor density and carbachol-induced inhibition of forskolin-stimulated adenylyl cyclase activity decreased significantly with the age of the patients. We conclude that pirenzepine decreases heart rate via inhibition of presynaptic M1 autoreceptors, thereby releasing endogenous acetylcholine, and that the heart rate-decreasing effect of acetylcholine declines with age because right atrial M2 receptor density and function decrease.

Revision surgery for cervical artificial disc: Surgical technique and clinical results.

OBJECTIVE: Cervical artificial disc replacement (C-ADR) was developed with the goal of preserving mobility of the cervical segment in patients with degenerative disc disease. So far, little is known about experiences with revision surgery and explantation of C-ADRs. Here, we report our experience with revision the third generation, Galileo-type disc prosthesis from a retrospective study of two institutions. PATIENTS AND METHODS: Between November 2008 and July 2016, 16 patients with prior implantation of C-ADR underwent removal of the Galileo-type disc prosthesis (Signus, Medizintechnik, Germany) due to a call back by industry. In 10 patients C-ADR was replaced with an alternative prosthesis, 6 patients received an ACDF. Duration of surgery, time to revision, surgical procedure, complication rate, neurological status, histological findings and outcome were examined in two institutions. RESULTS: The C-ADR was successfully revised in all patients. Surgery was performed through the same anterior approach as the initial access. Duration of the procedure varied between 43 and 80min. Access-related complications included irritation of the recurrent nerve in one patient and mal-positioning of the C-ADR in another patient. Follow up revealed two patients with permanent mild/moderate neurologic deficits, NDI (neck disability index) ranged between 10 and 42%. CONCLUSIONS: Anterior exposure of the cervical spine for explantation and revision of C-ADR performed through the initial approach has an overall complication rate of 18.75%. Replacements of the Galileo-type disc prosthesis with an alternative prosthesis or conversion to ACDF are both suitable surgical options without significant difference in outcome.

Blunted cardiac responses to receptor activation in subjects with Thr164Ile beta(2)-adrenoceptors.

BACKGROUND: Recent evidence indicates that certain genotypes of beta(2)-adrenoceptors (AR) may indicate an increased risk of cardiovascular disease or an increased rate of disease progression. Of particular importance, the Thr164Ile polymorphism, which is found in approximately 4% of humans, shows decreased receptor signaling, blunted cardiac response when expressed in transgenic mice, and is associated with a decreased survival rate in patients with congestive heart failure. METHODS AND RESULTS: In this study, we compared functional activity, ie, chronotropic (heart rate increases) and inotropic (duration of the electromechanical systole) responses to intravenously administered terbutaline, in 6 subjects (4 women and 2 men) who were heterozygous for Thr164Ile with the responses in 12 volunteers (6 women and 6 men) who were homozygous for wild-type (WT) beta(2)-AR (ie, Arg16, Gln27, and Thr164). The beta(2)AR polymorphism significantly affected the dose-response curves for terbutaline-induced inotropic and chronotropic responses: compared with WT individuals, subjects with the Thr164Ile receptor had substantial blunting in maximal increases in heart rate (WT, 29.7+/-3.9 beats/min; Ile164, 20.7+/-1.9 beats/min; P:=0.016) and a shortening of the duration of electromechanical systole (WT, 51.9+/-4.5 ms; Ile164, 37.9+/-4.6 ms; P:=0.02). CONCLUSIONS: These data show that humans with the Ile164 genotype show blunted cardiac beta(2)-AR responsiveness, which may help explain the decreased survival of patients with this genotype in the setting of congestive heart failure.

Age-dependent changes in cardiac muscarinic receptor function in healthy volunteers.

OBJECTIVES: This study was conducted to determine possible age-dependent changes in the responsiveness of human cardiac muscarinic receptors. BACKGROUND: It is well known that the baroreflex activity decreases with aging. However, the mechanisms underlying this phenomenon are not completely understood at present. METHODS: In six healthy young (mean [+/-SEM] age 26 +/- 2 years) and six healthy older volunteers (mean age 60 +/- 2 years), we determined 1) the effects of graded doses of atropine (bolus application, six doses, each for 20 min, range 0.03 to 0.96 mg) and the M1-cholinoceptor selective antagonist pirenzepine (bolus application, eight doses, each for 20 min, range 0.04 to 10 mg) on heart rate, blood pressure and systolic time intervals (as measure of inotropism); and 2) the baroreflex activity by assessing the bradycardic response to phenylephrine. RESULTS: Atropine and pirenzepine caused biphasic effects on heart rate: At lower doses (< 0.12 mg for atropine, < 5 mg for pirenzepine) they decreased heart rate, whereas at higher doses they increased heart rate. Heart rate decreases induced by both antimuscarinic drugs were significantly larger in the young volunteers than in the older volunteers, whereas heart rate increases were not significantly different for both drugs. Atropine and pirenzepine did not significantly affect blood pressure and systolic time intervals. Infusion of graded doses of phenylephrine (four doses ranging from 0.1 to 1.0 microgram/kg body weight per min for 15 min each) caused a higher increase in systolic blood pressure and a smaller decrease in heart rate at each dose in the older volunteers than in the young volunteers. The slopes of the regression lines were 16 +/- 2.3 ms/mm Hg for the young and 6 +/- 0.5 ms/mm Hg for the older volunteers (p < 0.01). CONCLUSIONS: Human cardiac muscarinic receptor activity is diminished with increasing age; such decreased cardiac muscarinic receptor activity could contribute to the decrease in baroreflex activity with aging. In contrast, antimuscarinic drugs seem to have no effect on human cardiac contractility.

Terbutaline-induced desensitization of human cardiac beta 2-adrenoceptor-mediated positive inotropic effects: attenuation by ketotifen.

BACKGROUND: In patients with chronic heart failure cardiac beta 1-adrenoceptors are desensitized whereas beta 2-adrenoceptors are only marginally affected. The mechanism underlying this differential regulation is not known. OBJECTIVES: To find out whether or not human cardiac beta 2-adrenoceptors might be 'resistant' to agonist-induced desensitization and whether or not the antiallergic drug ketotifen might attenuate possible desensitization. METHODS: We investigated, in a single blinded, randomised, placebo-controlled, cross-over study of ten healthy male volunteers (mean age, 25.3 +/- 0.7 years), the effects of two weeks treatment with the beta 2-adrenoceptor agonist terbutaline (3x5 mg/day p.o.) with and without simultaneous treatment with ketotifen (2x1 mg/day p.o. for three weeks) or placebo on beta-adrenoceptor-mediated cardiovascular effects. Cardiovascular effects were assessed as isoprenaline (3.5-35 ng/kg/min)- and terbutaline (25-150 ng/kg/min)-infusion-induced increases in heart rate and systolic blood pressure, decreases in diastolic blood pressure and shortening of the systolic time intervals (STIs), heart rate corrected duration of electromechanical systole (QS2c) and pre-ejection period (PEP; as a measure of inotropism). RESULTS: Ketotifen did not significantly affect basal haemodynamics in the volunteers. Isoprenaline- and terbutaline-infusion caused dose-dependent increases in systolic blood pressure and heart rate, decreases in diastolic blood pressure and shortening of QS2c and PEP, whereby isoprenaline effects were more pronounced. After two weeks of treatment with terbutaline p.o., isoprenaline- and terbutaline-infusion-induced increases in heart rate, shortening of QS2c and PEP were significantly reduced whereby terbutaline-infusion effects were markedly more attenuated than isoprenaline-infusion effects. Ketotifen significantly reduced terbutaline p.o. treatment-induced attenuation of all terbutaline-infusion effects (largely beta 2-adrenoceptor-mediated) and the isoprenaline-infusion-induced increase in heart rate (beta 1- and beta 2-adrenoceptor-mediated), but did not (or only marginally) affect reduction in isoprenaline-induced shortening of QS2c and PEP (largely beta 1-adrenoceptor-mediated). CONCLUSION: Human cardiac beta 2-adrenoceptors are not 'resistant' to agonist-induced desensitization: Ketotifen might prevent such beta 2-adrenoceptor-agonist-evoked desensitization.

In-vivo studies do not support a major functional role for the Gly389Arg beta 1-adrenoceptor polymorphism in humans.

beta 1-adrenoceptors play a pivotal role in regulating contractility and heart rate in the human heart. Recently, a polymorphism of the beta 1-adrenoceptor has been detected: at amino acid position 389 either Gly or Arg has been found with the Gly389 exhibiting reduced responsiveness upon agonist-induced stimulation in vitro. In order to find out whether the Gly389 polymorphism exhibits blunted responsiveness also in vivo we studied, in healthy volunteers, the effects of exercise on heart rate and heart rate-corrected duration of electromechanical systole (QS2c as a measure of inotropism) which, in humans, is mediated by beta 1-adrenoceptors stimulation. Twenty-four healthy volunteers (12 female, 12 male) homozygous for the Gly389 or Arg389 exercised on a bicycle in supine position (25, 50, 75 and 100 W for 5 min each), and heart rate and QS2c were assessed; in addition, plasma renin activity (PRA) was determined which is also regulated by beta 1-adrenoceptors in humans. Exercise caused work-load dependent increases in heart rate and PRA, and shortening of QS2c; however, these changes were not significantly different between the Gly389 and Arg389 polymorphism. Thus, these three beta 1-adrenoceptor responses did not differ between volunteers with the Arg389 versus the Gly389 polymorphism. Intragroup analysis, however, revealed that exercise induced increase in heart rate and shortening of QS2c were higher in female than in male volunteers. In conclusion, our data do not support the idea that the reduced responsiveness of Gly389 against agonist-induced stimulation observed in vitro is of major functional importance in vivo.

Human cardiac beta1- or beta2-adrenergic receptor stimulation and the negative chronotropic effect of low-dose pirenzepine.

OBJECTIVES: The M1-muscarinic receptor antagonist pirenzepine in low doses (<1 mg intravenously) decreases heart rate. We investigated whether these effects of pirenzepine differ in volunteers with activated cardiac beta1-adrenergic receptors versus activated cardiac beta2-adrenergic receptors. METHODS: In 17 male volunteers (25 +/- 1 years) we studied effects of pirenzepine infusion (0.5 mg intravenous bolus followed by continuous infusion of 0.15 microg/kg/min) on heart rate and heart rate-corrected duration of electromechanical systole (QS2c, as a measure of inotropism) that had been stimulated by activation of cardiac beta1-adrenergic receptors (bicycle exercise in the supine position for 60 minutes at 25 W) or cardiac beta2-adrenergic receptors (continuous intravenous infusion of 100 ng/kg/min terbutaline). RESULTS: Bicycle exercise and terbutaline infusion significantly increased heart rate and shortened QS2c. When pirenzepine was infused 20 minutes after the beginning of the exercise or terbutaline infusion, heart rate decreased in both settings by approximately the same extent (approximately -10 to -14 beats/min), although exercise and terbutaline infusion continued; however, QS2c was not affected. Pirenzepine (0.05 to 1 mg intravenous bolus)-induced decrease in heart rate was abolished after 6 days of transdermal scopolamine treatment of volunteers. CONCLUSIONS: Low-dose pirenzepine decreased heart rate by muscarinic receptor stimulation, because this was blocked by scopolamine. Moreover, low-dose pirenzepine did not differentiate between cardiac beta1- or beta2-adrenergic receptor stimulation; however, low-dose pirenzepine did not affect cardiac contractility as measured by QS2c. Low-dose pirenzepine therefore exerted a unique pattern of action in the human heart: it decreased heart rate (basal and beta1- and/or beta2-adrenergic receptor-stimulated) without affecting contractility.

A cell cycle model for the tachyzoite of Toxoplasma gondii using the Herpes simplex virus thymidine kinase.

Toxoplasma gondii (RH strain) tachyzoites were transfected with a plasmid containing a fusion of the chloramphenicol acetyl transferase and the Herpes simplex virus-2 thymidine kinase coding regions and transgenic parasites obtained by chloramphenicol selection. CTK11, a single high expressing clone was isolated based on immunofluorescence and contained approximately five integrated copies of the fusion sequence. Lysates prepared from this clone displayed thymidine kinase activity of 2.9 pmol min(-1) microg(-1) protein, whereas thymidine kinase activity was not detected in lysates from the parental RH strain. Growth of CTK11 tachyzoites was fully inhibited in 5 microM ganciclovir and thymidine and in 2.5 microM 5-bromo-2'-deoxyuridine. While the inhibitory effects of ganciclovir were lethal, low concentrations of thymidine (10 microM) were largely reversible. Asynchronously growing CTK11 tachyzoites were found to contain major G1 (1 N) and S phase (1 N+) distributions as determined by relative propidium iodide fluorescence and with reference to the haploid (1 N) DNA content of a T. gondii sporozoite population. CTK11 tachyzoites blocked 4 h in 10 microM thymidine exhibited mean fluorescence consistent with a 1 N complement of DNA indicating growth was arrested in G1. Following the removal of excess thymidine, parasites immediately entered S phase, thus confirming the late G1 block. Parasites with a 2 N complement of DNA (G2 + M) first appear at 2 h post-release, while 1 N (G1) parasites re-appear at 3 h suggesting the length of S phase is < or = 2 h and that of G2 + M is < or = 1 h. Within 7 h, parasites had transited G2 + M and much of G1 and re-entered S of the subsequent cell cycle--a time consistent with the doubling of these parasites in culture. Thus, the CTK11 tachyzoite cell cycle is similar to those of higher eukaryotic cells and is characterized by major G1 and S phases and a relatively short G2 + M.

Defining the cell cycle for the tachyzoite stage of Toxoplasma gondii.

Tachyzoite endodyogeny is characterized by a three phase cell cycle comprised of major G1 and S phases with mitosis following immediately upon the conclusion of DNA replication. Cytokinesis, which begins with the formation of daughter apical complexes, initiates in late S phase and overlaps mitosis. There is no evidence to support an extended G2 period in these parasites. In all strains, parasites with a 2 N DNA content are a relatively small subpopulation and when tachyzoites expressing a fluorescent nuclear marker (green-fluorescent-protein fused to proliferating-cell-nuclear-antigen) were observed by time-lapse microscopy, there appeared to be little delay between S phase and mitosis. Measurements of the DNA content of RH parasites by flow cytometry demonstrated that the G1 and S periods were approximately 60 and approximately 30% of a single division cycle, although these phases were longer in strains that display a slower growth rate. The overall length of S phase was determined by [3H]-thymidine autoradiography using transgenic parasites expressing herpes simplex thymidine kinase and validated by Northern analysis of S phase specific genes during synchronous growth. The fraction of S phase parasites by flow cytometry paralleled autoradiography, however, within S phase, the distribution of parasites was bimodal in all strains examined. Parasites containing a 1-1.7 N DNA complement were a small fraction when compared to the major S phase population which contained a near-diploid ( approximately 1.8 N) complement, suggesting parasites in late S phase have a slower rate of DNA replication. In lieu of a short or missing G2, where checkpoints are thought to operate in other eukaryotes, the bimodal replication of tachyzoite chromosomes may represent a distinct premitotic checkpoint associated with endodyogeny.

Neuronal release of somatostatin in the rat striatum: an in vivo microdialysis study.

Extracellular levels of somatostatin in the rat striatum were studied using in vivo microdialysis and radioimmunoassay. In vitro studies were performed using three different dialysis membranes at various flow rates and temperatures to assess the optimal recovery of somatostatin. The best results were obtained when a cellulose fibre membrane was utilized at 37 degrees C with a flow rate of 0.5 microliters/min. For the in vivo studies, transcerebral cellulose probes were implanted in the striatum of chloryl hydrate-anaesthetized rats. Basal levels of somatostatin were detected in the striatum of the freely moving animals and found to be 5-15 fmol. Stimulation with 100 mM KCl increased the recovered somatostatin by 138% (P < 0.05). A second stimulation following a 3-h interval increased the somatostatin levels by approximately 60%. The addition of veratridine (100 microM) in the perfusion medium increased the somatostatin levels recovered from the striatum by 85% (P < 0.01). Following a 3-h interval, a second stimulation by veratridine also increased somatostatin levels (43%). The increases observed after the second depolarizing stimulus (KCl and veratridine) were not found to be significantly different from basal levels. Both EGTA and the sodium channel blocker tetrodotoxin attenuated the effect of KCl and veratridine, respectively. However, neither EGTA nor tetrodotoxin had an effect on the basal levels of somatostatin recovered. These results indicate that (i) the somatostatin measured is neuronally released in the striatum and (ii) microdialysis is a useful tool for examining the regulation of somatostatin release in the brain.

YAG laser photoresection of lesions obstructing the central airways.

Some patients with cancer and others with benign lesions which obstruct the central airways (larynx, trachea, major bronchi) can be treated with a laser. Ninety-nine patients were considered for treatment during the first 18 months of experience with a YAG (yttrium aluminum garnet) laser at Henry Ford Hospital; 55 patients were treated 82 times. Results were satisfactory (surgery was avoided) in eight of ten patients with benign lesions. Satisfactory results (doubling of airway size with relief of dyspnea/drainage of obstructive pneumonia) were obtained in 12 of 13 patients with bronchogenic carcinoma managed initially with the laser, and in 22 of 32 (69 percent) patients with recurrent malignancies. There were five minor and seven major complications, including two deaths. We conclude that laser treatment can relieve central airways obstruction with its associated symptoms of dyspnea and infection. Avoidance of complications requires a skillful approach, careful anesthetic management, and availability of back-up posttreatment intensive care.

Diagnostic accuracy in peripheral lung lesions. Factors predicting success with flexible fiberoptic bronchoscopy.

Ninety-seven consecutive peripheral lung lesions were evaluated by biplane fluoroscopically guided flexible fiberoptic bronchoscopy and analyzed to define features that predict diagnostic yield. The overall diagnostic accuracy was 56 percent (63 percent for malignant and 38 percent for benign lesions). The most important characteristic associated with a positive cyto- or histopathologic diagnosis was size of the lesion; the yield was 28 percent when the diameter was less than 2.0 cm compared to 64 percent if the diameter was greater than or equal to 2.0 cm (P = 0.0035). The diagnostic yield was similar for lesions located in the outer and middle third of the lung if the diameter was greater than 2.0 cm; inner one-third lesions were correctly diagnosed more frequently, related in part to the larger size of these lesions. There was no significant difference in diagnostic yield for the following: segmental location, greatest distance from carcina on either the posteroanterior or lateral radiograph, or radiographic characteristics of the lesion. We conclude that biplane fluoroscopically guided flexible fiberoptic bronchoscopy is a reasonable diagnostic procedure for peripheral lesions greater than or equal to 2.0 cm in diameter, but that alternative procedures should be used for lesions under 2.0 cm in diameter.

Initial combination therapy with YAG laser photoresection and irradiation for inoperable non-small cell carcinoma of the lung. A preliminary report.

Patients presenting with inoperable non-small cell carcinoma of the lung and major symptomatic bronchial obstruction were treated initially with debulking of the airways by YAG laser, followed by conventional external-beam radiotherapy. The former method was used to minimize postobstructive pneumonitis or respiratory failure (or both) that often complicates major brochial obstruction and also to lessen the burden of tumor to be treated by radiotherapy. The preliminary results of 19 patients treated in this manner are reported, emphasizing the impact of this combined method on morbidity and mortality.

Comparison between continuous brain tissue pO2, pCO2, pH, and temperature and simultaneous cerebrovenous measurement using a multisensor probe in a porcine intracranial pressure model.

Local brain tissue oxygenation (p(ti)O2) and global cerebrovenous hemoglobin saturation (SjO2) are increasingly used to continuously monitor patients after severe head injury (SHI). In patients, simultaneous local and global oxygen measurements of these types have shown different results regarding the comparability of the findings during changes in CPP and ICP. This is in contrast to theoretical expectations. The aim of this study was to compare p(ti)O2 measurement with cerebrovenous oxygen partial pressure measurement (p(cv)O2) in an animal intracranial pressure model. To this end, a multisensor probe was placed in the left frontoparietal white matter to measure p(ti)O2, pCO2 (p(ti)CO2), pH (pH[ti]), and temperature (t[ti]) while simultaneously measuring these same parameters (p(cv)O2, p(cv)CO2 pH(cv), t[cv]) in the sagittal sinus of 9 pigs under general anesthesia. By stepwise inflating a balloon catheter, placed in supracerebellar infratentorial compartment, ICP was increased and CPP was decreased. The baseline levels of p(ti)O2, p(ti)CO2, and pH(ti) in the noninjured brain tissue showed more heterogeneity compared to the findings in cerebrovenous blood. Both, p(ti)O2 and p(cv)O2 were significantly correlated to the induced CPP decrease. PCO2 was inversely correlated to the course of CPP in both measurement compartments. Temperature measurement showed a positive correlation with CPP in both compartments. These findings demonstrate that brain tissue oximetry and cerebrovenous PO2 measurement are sensitive to CPP changes. The newly available continuous parameters in multisensor probes could be helpful in interpreting findings of cerebral oxygen measurement in man by analyzing the interrelationship of these parameters.

High-dose intravenous magnesium sulfate in the management of life-threatening status asthmaticus.

In severe status asthmaticus basic medical treatment often fails to improve the patient's condition. Mechanical ventilation in this situation is associated with a high incidence of serious complications. After the bronchodilating effect of moderate-dose magnesium sulfate in asthmatic patients had been demonstrated in previous studies we treated five mechanically ventilated patients with refractory status asthmaticus successfully with high dosages of MgSO4 IV (10-20 g within 1 h depending on the bronchodilating effect). MgSO4 resulted in a significant decrease of peak airway pressure (43.0 +/- 6.8 to 32.0 +/- 8.0 cmH2O) and inspiratory flow resistance (22.7 +/- 7.0 to 11.9 +/- 6.0 cmH2O.l-1.s-1) within 1 h. The resulting serum magnesium levels after one hour were up to threefold of the normal serum levels. Although a maintainance dose of 0.4 g/h had been administered continuously during the following 24 h serum magnesium decreased towards normal values within this time. The only relevant side-effect was a mild to moderate arterial hypotension in two of the five patients during the high dose administration period of MgSO4 which responded readily to dopamine treatment.

Intra-cerebral cysteamine infusions attenuate the motor response to dopaminergic agonists.

Previous studies have suggested that somatostatin neurons in the basal ganglia may be involved in motor activity. In the present experiments, the effects of cysteamine, a drug which reduces somatostatin levels, on the basal and dopamine-mediated motor activities were examined in the rat. Neither intra-striatal nor intra-accumbens infusions of cysteamine had any effect on motor activity prior to the administration of dopamine agonists. However, intra-striatal cysteamine infusions reduced the duration of the stereotypic behavior induced by systemic apomorphine. In addition, intra-accumbens infusions of cysteamine produced a slight reduction in the locomotor response induced by amphetamine. The direct intra-cerebral infusion of cysteamine produced a significant depletion in the levels of somatostatin at the site of injections as measured by radioimmunoassay. These results indicate that somatostatin neurons in the basal ganglia may modulate the motor responses following dopaminergic activation, and further support the presence of a dopamine-somatostatin interaction in this region.