Post-obstructive pulmonary edema as a complication of endotracheal tube obstruction

Pulmonary edema following acute or chronic upper airway obstruction is a threatening complication. A case is presented in which a 15 year old boy developed a massive pulmonary edema after a acute endotracheal tube obstruction during emergence from anesthesia. Leading pathophysiologic cause for the formation of the edema is a markedly negative intrapleural pressure due to the forceful inspiration against the obstructed airway. Treatment modalities include the instantaneous solution of the obstruction, a rapid reoxigenation and the ventilation with PEEP or CPAP. Sound knowledge of the disease increases the vigilance of the caring anaesthesiologist and helps to identify patients at risk. Preventing measures may further reduce the risk of occurrence of the postobstructive pulmonary edema.     

Whole blood cryopreservation in epidemiological studies.

Standardized and cost-effective biological sample collection, processing, and storage procedures are needed in large-scale epidemiological studies to provide material for testing a broad range of etiological hypotheses. One component of sample collection in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial involves shipment of blood in acid-citrate-dextrose anticoagulant to a central processing laboratory, where 10% DMSO is added, and whole blood aliquots are cryopreserved. A single technician is able to routinely process 50-60 samples/day. Tests conducted to evaluate potential uses of cryopreserved whole blood showed successful EBV transformation (>90%, up to 20 months of storage). In addition, lymphocytes maintained good viability and stable T-cell:B-cell ratios, and T cells maintained the capacity to proliferate in response to solid phase anti-CD3/CD28 plus interleukin 2. Whole blood cryopreservation is a cost-effective approach to large-scale storage of viable cells in epidemiological studies.     

Regional distribution of benzodiazepine binding sites in the human newborn and infant hypothalamus. A quantitative autoradiographic study

Using in vitro quantitative autoradiography and [3H]flunitrazepam we examined the rostrocaudal distribution of benzodiazepine binding sites in the human neonate/infant hypothalamus. The autoradiographic analysis shows the presence of a heterogeneous distribution throughout the rostrocaudal extent of this brain structure. High [3H]flunitrazepam binding corresponds primarily to the diagonal band of Broca and the preoptic region. The labelling in the preoptic region showed a rostrocaudal increase, contrasting in that with the other hypothalamic structures. Intermediate densities were present in the septohypothalamic, suprachiasmatic, periventricular and paraventricular nuclei as well as in the mammillary complex. Low binding was observed in the other hypothalamic structures. The benzodiazepine binding sites analyzed belong mostly to type II receptors. In an attempt to unravel possible differences related to age, we compared the autoradiographic distribution in three postnatal age ranges. The topographical distribution of these binding sites was almost identical in each period analyzed. We found, however, that benzodiazepine binding is generally low in the neonatal period and a tendency in increasing densities is observed during development. Taken together, these results provide evidence for a large distribution of benzodiazepine binding sites in neonate/infant hypothalamus, suggesting their implication in the development of this brain structure and the maintenance of its various functions.     

The financial impact of maintenance treatment in heroin addictive behavior: the case of Subutex

BACKGROUND: The development of maintenance treatment for subjects with addictive behavior is an important public health issue. As such, the social effectiveness of maintenance products must be examined from an economical and social point of view. This paper aims at presenting the financial costs involved in the use of Subutex, a product commercialized since 1996. METHODS: A complete typology of costs related to drug addiction and its consequences was set up. Some of these costs were estimated on the basis of data drawn from the literature. The cost of Subutex use for maintenance treatment was assessed and compared with the financial stakes including the potential reduction of the economic and social cost of drug addiction. RESULTS: Monthly treatment cost of Subutex was 1252 FrF per drug abuser on maintenance treatment. By extrapolation, for a population of 40,000 drug abusers, the direct medical cost of Subutex during a course of maintenance treatment with general practitioner follow-up was estimated at 600 millions FrF. US data sources were applied to France to assess the cost of illnesses attributable to drug addiction. The cost reached 4.8 billions FrF. The cost of delinquency associated with drug addiction, which mostly concerns money laundered to purchase substances was an estimated 6.4 billions FrF. Finally, the cost of public anti-drug abuse programs was nearly 4.7 billions FrF. Thus, the direct cost of drug addiction consequences reached 15.6 billions FrF. This cost should be compared with the annual cost of Subutex for public organizations which was an estimated 600 millions FrF. CONCLUSIONS: The "profit" threshold of maintenance treatment with Subutex in terms of direct costs is very low. A decrease of only 4% of the costs associated with drug addiction would make it possible to balance the financial budget for the community. Our analysis does not take into acount absolutely all the public health and safety aspects involved in the use of Subutex. It does however provide a useful assessment of the financial aspects of the question and justification for this therapeutic strategy from a budgetary point of view.     

Reduced hematopoietic function and enhanced radiosensitivity of transforming growth factor-beta1 transgenic mice

The cytokine transforming growth factor-beta1 (TGF-beta1) has been implicated in some tissue responses to radiation. Previous studies have demonstrated that exogenous TGF-beta1 increased the lethality of radiation in mice, but the effects of endogenous TGF-beta1 have not been investigated. To this end, we examined mice that are transgenic for active TGF-beta1 (Alb/TGF-beta1), over-expressed via an albumin promoter in the liver with resultant elevation of circulating levels of this cytokine. Alb/TGF-beta1 mice subjected to 8 Gy of total body irradiation at 3 or 5 weeks of age experienced significantly higher mortality than wild type age- and sex-matched controls by 1 to 2 weeks after irradiation. Alb/TGF-beta1 3 weeks of age also succumbed to 2 and 4 Gy of whole-body irradiation, while no mortality was observed in wild type mice. Four-week-old Alb/TGF-beta1 mice exhibited mild anemia and mild uremia. At one week after whole body irradiation with 2 Gy, 4-week-old Alb/TGF-beta1 mice had significantly reduced white blood cell counts, hematocrit, and platelet counts. Histopathologically, irradiated Alb/TGF-beta1 mice exhibited decreased bone marrow cellularity and decreased splenic extramedullary hematopoiesis. These results suggest that chronic over-expression of active TGF-beta1 is associated with increased radiosensitivity and that this effect may be mediated by increased sensitivity of bone marrow to the suppressive effects of radiation. Since TGF-beta1 levels can be greatly elevated in patients with certain tumors, these findings may be significant for radiotherapy. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 13-21 (2000). Published 2000 Wiley-Liss, Inc.     

Changes in energy during treatment of depression: an analysis of fluoxetine in double-blind, placebo-controlled trials

More than two thirds of patients with depression present with symptoms of fatigue, low energy, and listlessness. Because daytime sedation may be a concern in such patients, a "nonsedating" antidepressant should be considered. The authors examined the effects of fluoxetine on depression-related disturbances in energy. Data from seven double-blind, placebo-controlled clinical trials in 2,075 patients with major depression were retrospectively analyzed. The Hamilton Rating Scale for Depression (HAM-D) Retardation factor score (total of items 1, 7, 8, and 14) was used as the primary measure of energy improvement, whereas the HAM-D-17 total score was used to assess changes in overall depression. Elderly patients (aged 60 years and older) were included in the overall group and were also analyzed separately. In addition, a subgroup analysis was performed using the HAM-D Retardation factor score to categorize patients as having low (score < 8) or high (score > or = 8) levels of retardation at baseline. Beginning at week 3, fluoxetine-treated patients experienced statistically significant reductions in their HAM-D Retardation factor score compared with placebo-treated patients. The reductions for the elderly subgroup were less than those for the overall population, but they were still statistically significant beginning at week 4. Patients in both the low and high baseline retardation groups improved significantly. HAM-D-17 total scores for fluoxetine-treated patients in all groups (total, elderly, high retardation, and low retardation) improved significantly compared with placebo-treated patients. These findings demonstrate that fluoxetine-treated patients experience an improvement in energy symptoms as their overall depression improves.     

Polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose in combination with interleukin 2 in patients with cancer: clinical and immunological effects.

We have performed a phase IB study of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose (poly-ICLC) in combination with interleukin 2 (IL-2) in 25 patients with a variety of cancers. Patients received weekly or biweekly poly-ICLC by i.m. injection, at doses ranging from 0.01 to 1.0 mg/m2, for 1 month. This was followed by 2 months of outpatient therapy with biweekly i.m. poly-ICLC in combination with IL-2 (3 x 10(6) units/m2) given i.v. by 24-h continuous infusion twice weekly, using a portable infusion pump. No objective tumor responses were observed. Toxicity was moderate at all poly-ICLC doses tested and increased only slightly following the addition of IL-2. No increases in peripheral blood natural killer (NK) activity were observed after treatment with poly-ICLC alone. However, high dose poly-ICLC (greater than or equal to 0.3 mg/m2) in combination with IL-2 resulted in NK activity greater than that seen using the same dose of IL-2 in combination with lower poly-ICLC doses. Increases in the number and percentage of CD56+ cells were evident only after initiation of IL-2 therapy and were unaffected by the poly-ICLC dose. In the majority of patients, these increases were preferentially associated with the subset of CD56+ cells coexpressing CD8, while the CD56+/CD16+ population was elevated to a lesser extent. Moderate increases in serum neopterin levels and 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells were noted at 72 h following initial treatment with 1.0 mg/m2 poly-ICLC. No induction of alpha or gamma interferon was detected. This study shows that the addition of poly-ICLC to a well tolerated IL-2 regimen can significantly enhance NK activity. Poly-ICLC can be used to enhance IL-2-induced NK lytic activity without increases in the dose and, therefore, the toxicity of IL-2 treatment.     

Blood choline and response to clonazepam and haloperidol in Tourette's syndrome

This paper reports the results of a single blind clinical study of drug treatment response of 20 patients with Tourette's syndrome to haloperidol and clonazepam. Because patients with Tourette's syndrome have been reported to have increased red blood cell choline levels, choline levels were examined in relation to treatment response. Differential drug treatment response was found among patients with high versus low red blood cell-to-plasma choline ratios. Patients with high red blood cell-to-plasma choline ratios responded better to clonazepam than to haloperidol. This suggests that there may be two distinct subtypes of patients with Tourette's syndrome.