How pediatricians can respond to the psychosocial implications of disasters. American Academy of Pediatrics. Committee on Psychosocial Aspects of Child and Family Health, 1998-1999

Natural and human-caused disasters, violence with weapons, and terrorist acts have touched directly the lives of thousands of families with children in the United States.1 Media coverage of disasters has brought images of floods, hurricanes, and airplane crashes into the living rooms of most American families, with limited censorship for vulnerable young children. Therefore, children may be exposed to disastrous events in ways that previous generations never or rarely experienced. Pediatricians should serve as important resources to the community in preparing for disasters, as well as acting in its behalf during and after such events.     

Effects of systemic resiniferatoxin treatment on substance P mRNA in rat dorsal root ganglia and substance P receptor mRNA in the spinal dorsal horn

Capsaicin depletes the sensory neuropeptide substance P (SP) in the rat due to a combination of neuron loss and decreased synthesis in the surviving cells. Resiniferatoxin (RTX) mimics most, but not all, capsaicin actions. In the present study, the effects of RTX (300 μg/kg, s.c.) were examined on mRNA levels for SP and its receptor in the adult rat. The percentage of dorsal root ganglia (DRG) neuronal profiles showing an in situ hybridization signal for preprotachykinin mRNAs encoding SP was not altered following RTX treatment (up to 8 weeks), though the signal became perceptibly weaker. In accord, 2 weeks after RTX administration a 60% decrease was observed in the steady-state levels of SP-encoding mRNAs using Northern blot analysis, leaving the ratio of β- and γ-preprotachykinin mRNAs unchanged. No change was, however, observed in mRNA levels encoding tachykinins NK-1 receptors in the dorsal horn, the spinal targets for SP. The present findings suggest that RTX does not kill SP-positive DRG neurons, though it suppresses the synthesis of SP. Since RTX treatment does not alter NK-1 receptor expression, this reduced SP synthesis is likely to play a central role in the analgesic actions of RTX.     

Event-related alpha synchronization/desynchronization in a memory-search task in adolescent survivors of childhood cancer.

OBJECTIVES: Event-related desynchronization (ERD) and synchronization (ERS) of the 8-10 and 10-12 Hz frequency bands of the background EEG were studied in 19 adolescent survivors of childhood cancer (11 leukemias, 8 solid tumors) and in 10 healthy control subjects performing an auditory memory task. METHODS: The stimuli were auditory Finnish words presented as a Sternberg-type memory-scanning paradigm. Each trial started with the presentation of a 4 word set for memorization whereafter a probe word was presented to be identified by the subject as belonging or not belonging to the memorized set. RESULTS: Encoding of the memory set elicited ERS and retrieval ERD at both frequency bands. However, in the survivors of leukemia, ERS was turned to ERD during encoding at the lower alpha frequency band. ERD was lasting longer at the lower frequency band than at the higher frequency band, in each study group. At both frequency bands, the maximum of ERD was achieved later in the cancer survivors than in the control group. CONCLUSION: The previously reported type of ERD/ERS during an auditory memory task was reproducible also in the survivors of childhood cancer, at different alpha frequency bands. However, the temporal deviance in ERD/ERS magnitudes, in the cancer survivors, was interpreted to indicate that both survivor groups had prolonged information processing time and/or they used ineffective cognitive strategies. This finding was more pronounced in the group of leukemia survivors, at the lower alpha frequency band, suggesting that the main problem of this patient group might be in the field of attention.     

Effects of adjuvant tamoxifen on the endometrium in postmenopausal women with breast cancer: a prospective long-term study using transvaginal ultrasound.

PURPOSE: To study the value of transvaginal ultrasound (TVS) in endometrial screening of postmenopausal breast cancer patients treated with tamoxifen. PATIENTS AND METHODS: In 247 tamoxifen-treated (20 to 30 mg/d for >/= 2 years) women and 98 controls, the endometrium was prospectively followed-up by means of TVS every 6 months for up to 5 years. Patients with homogeneous endometrium of more than 10-mm thickness were then scanned repeatedly every 3 months. RESULTS: The mean endometrial thickness was 3.5 +/- 1.1 mm before treatment and increased to a maximum of 9. 2 +/- 5.1 mm after 3 years of tamoxifen application (P: <.0001), which was significantly (P: <.0001) thicker compared with controls. Fifty-two asymptomatic patients with thickened or morphologically suspect endometrium underwent hysteroscopy and dilatation and curettage (D&C), resulting in four uterine perforations. Histopathologically, atrophy was found in 38 patients (73.1%), polyps in nine, hyperplasia in four, and endometrial cancer in one case. In 20 screened patients who reported vaginal bleeding, five atrophies (25%), five polyps, four hyperplasias, and two endometrial cancers were found. Before hysteroscopy and D&C were performed, 36 (69.2%) of 52 asymptomatic and four (20%) of 20 symptomatic patients were scanned by repeated TVS over 2 to 30 months. Invasive diagnostic procedures were significantly (P: <.05) more frequent in younger and obese patients. In the controls, one asymptomatic polyp and one symptomatic hyperplasia were found. CONCLUSION: In tamoxifen-treated patients, TVS offered a high false-positive rate, even with a cutoff value of 10 mm for endometrial thickness and repeated TVS scans. Increased iatrogenic morbidity and only one asymptomatic endometrial carcinoma do not warrant endometrial screening by TVS in tamoxifen-treated patients.     

Imaging and neural modelling in episodic and working memory processes.

Neuroimaging studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have revealed the involvement of distributed brain regions in memory processes mainly by the use of subtraction strategy based data analyses. Covariance analysis based data analysis strategies have been introduced more recently which allow functional interactions between brain regions of a neuronal network to be assessed. This contribution focuses on studies aiming to (1) establish the functional topography of episodic and working memory processes in young and old normal volunteers, (2) to assess functional interactions between modules of networks of brain regions by means of covariance based analyses and systems level modelling, (3) to characterise the temporal dynamics by the use of magnetoencephalography (MEG) and (4) to relate neuroimaging data to the underpinning neural networks. Male normal young and old volunteers without neurological or psychiatric illness participated in neuroimaging studies (PET, fMRI, MEG). Studies were approved by the ethical committee and federal authorities. Our results in young volunteers show distributed brain areas that are involved in memory processes (episodic and working memory) and show much of an overlap with respect to the network components. Systems level modelling analyses support the hypothesis of bihemispheric, asymmetric networks subserving memory processes and revealed both similarities in general and differences in the interactions between brain regions during episodic encoding and retrieval as well as working memory. Changes in memory function with ageing are evident from functional topographic studies in old volunteers activating more brain regions as compared to young volunteers. There are more and stronger influences of prefrontal regions in elderly volunteers comparing the functional models between old and young subjects. We discuss the way that the systems level models of the PET and fMRI results have implications for the underlying neural network functioning of the brain. This is done by developing simplifying assumptions, which lead from the equations describing the activities of the coupled neural modules to the systems level model equations. The resulting implications for the neural interactions are then discussed, in terms of a set of synaptically coupled neural modules. Finally, we consider how a similar analysis could be extended from the spatial to the temporal domain thus including the EEG and MEG results. The implication of preliminary MEG results presented here for the temporality arising in the interaction between the coupled neural modules in a working memory paradigm is discussed in terms of the previously developed neural network models arising from the PET and fMRI data.     

Zur Frage der Transformation von Atem- in Blutalkoholkonzentrationen Experimentelle Untersuchungen mit einem geeichten Atemalkoholtestger?t Alcotest 7110 Evidential MK III Experimentelle Untersuchungen mit einem geeichten Atemalkoholtestger?t Alcotest 7110 Evidential MK III

Mit dem Alcotest 7110 Evidential MK III, durch die PTB in Braunschweig zugelassen und geeicht, steht ein hochwertiges Ger?tesystem zur Messung der Alkoholkonzentration in der Ausatemluft zur Verfügung. Der Umrechnungsfaktor von Atem- in Blutalkoholkonzentrationen wurde von Schoknecht [17] im Gutachten des Bundesgesundheitsamtes 1992 experimentell als BAK/AAK-Quotient mit 2,098 ±0,11 bestimmt und auf 2,1 gerundet. Der Mittelwert von 455 zeitgleichen Wertepaaren der vorliegenden Arbeit lag bei 2,2. Der Maximalwert betrug 3,29, der Minimalwert 0,74. Die Streubreite stimmte im Wesentlichen mit den theoretischen Berechnungen von Wehner et al. [19] überein. Die gefundenen Quotienten w?ren theoretisch als Umrechnungsfaktoren von AAK in BAK denkbar. Aufgrund der sehr gro?en Variabilit?t sollte aber grunds?tzlich in forensischen Gutachten eine Transformation von AAK in BAK und umgekehrt nicht erfolgen. Demzufolge erscheint auch eine Rückrechnung mit „transformierten” BAK-Werten oder die Berücksichtigung von angegebenem Nachtrunk nicht m?glich. Insbesondere ist ein strafrechtsrelevanter AAK-Grenzwert auch nicht durch einfache Multiplikation zu errechnen, sondern bedarf einer breiten experimentellen psycho-physiologischen und verkehrsmedizinischen Grundlagenforschung.     

Endemic melioidosis in tropical northern Australia: a 10-year prospective study and review of the literature.

In a prospective study of melioidosis in northern Australia, 252 cases were found over 10 years. Of these, 46% were bacteremic, and 49 (19%) patients died. Despite administration of ceftazidime or carbapenems, mortality was 86% (43 of 50 patients) among those with septic shock. Pneumonia accounted for 127 presentations (50%) and genitourinary infections for 37 (15%), with 35 men (18%) having prostatic abscesses. Other presentations included skin abscesses (32 patients; 13%), osteomyelitis and/or septic arthritis (9; 4%), soft tissue abscesses (10; 4%), and encephalomyelitis (10; 4%). Risk factors included diabetes (37%), excessive alcohol intake (39%), chronic lung disease (27%), chronic renal disease (10%), and consumption of kava (8%). Only 1 death occurred among the 51 patients (20%) with no risk factors (relative risk, 0.08; 95% confidence interval, 0.01-0.58). Intensive therapy with ceftazidime or carbapenems, followed by at least 3 months of eradication therapy with trimethoprim-sulfamethoxazole, was associated with decreased mortality. Strategies are needed to decrease the high mortality with melioidosis septic shock. Preliminary data on granulocyte colony-stimulating factor therapy are very encouraging.     

Spinal epidural abscess following blunt pelvic trauma

A 17-year-old patient with pre-existing grade II spondylolisthesis of L5/S1 sustained a partial disruption of the left sacroiliac joint with haematoma of the iliac muscle after a fall. The haematoma probably led to occlusion of the left ureter, resulting in a urinary tract infection. After initial conservative treatment the patient developed fever and radicular pain of the left leg. Magnetic resonance imaging (MRI) revealed a left-sided epidural abscess at L5/S1, which had probably spread from the infected iliac haematoma along the injured sacroiliac joint. Prompt surgical drainage and antibiotic coverage with cefuroxime and flucloxacillin led to rapid clinical improvement. Staphylococcus aureus was identified as the pathogen. At follow-up 6 months postoperatively all symptoms had resolved, while MRI still revealed residual osseous oedema of the sacroiliac joint. The haematoma of the iliac muscle resolved without surgical intervention. Received: 1 June 1999/Revised: 11 October 1999/Accepted: 22 October 1999     

The biosynthesis of thymol,carvacrol, and thymohydroquinone in Lamiaceae proceeds via cytochrome P450s and a short-chain dehydrogenase

Thymol and carvacrol are phenolic monoterpenes found in thyme, oregano, and several other species of the Lamiaceae. Long valued for their smell and taste, these substances also have antibacterial and anti-spasmolytic properties. They are also suggested to be precursors of thymohydroquinone and thymoquinone, monoterpenes with anti-inflammatory, antioxidant, and antitumor activities. Thymol and carvacrol biosynthesis has been proposed to proceed by the cyclization of geranyl diphosphate to γ-terpinene, followed by a series of oxidations via p-cymene. Here, we show that γ-terpinene is oxidized by cytochrome P450 monooxygenases (P450s) of the CYP71D subfamily to produce unstable cyclohexadienol intermediates, which are then dehydrogenated by a short-chain dehydrogenase/reductase (SDR) to the corresponding ketones. The subsequent formation of the aromatic compounds occurs via keto–enol tautomerisms. Combining these enzymes with γ-terpinene in in vitro assays or in vivo in Nicotiana benthamiana yielded thymol and carvacrol as products. In the absence of the SDRs, only p-cymene was formed by rearrangement of the cyclohexadienol intermediates. The nature of these unstable intermediates was inferred from reactions with the γ-terpinene isomer limonene and by analogy to reactions catalyzed by related enzymes. We also identified and characterized two P450s of the CYP76S and CYP736A subfamilies that catalyze the hydroxylation of thymol and carvacrol to thymohydroquinone when heterologously expressed in yeast and N. benthamiana. Our findings alter previous views of thymol and carvacrol formation, identify the enzymes involved in the biosynthesis of these phenolic monoterpenes and thymohydroquinone in the Lamiaceae, and provide targets for metabolic engineering of high-value terpenes in plants.

The phenolic monoterpenes of the Lamiaceae are widely used constituents of pharmaceuticals, cosmetics, and food products (1). Extracts of plants containing thymol or carvacrol are employed in medicine for their antibacterial, anti-spasmodic, antioxidant, and anti-cancer properties. Because of their pungent, warm, and aromatic odors, they also serve as additives to cosmetics and are used in aromatherapy. Thymol and carvacrol are best known as the aroma compounds of oregano and thyme, in which they provide the herbal, pizza-like tastes that are traditionally used in Mediterranean cuisine and food preservation (2). The occurrence of phenolic monoterpenes is restricted to a few genera in the Lamiaceae (Thymus, Origanum, Satureja, and Thymbra), Apiaceae (Trachyspermum), and Verbenaceae (Lippia). Of these, the essential oils of Thymus are the most important commercial source of phenolic monoterpenes (3). Thymus vulgaris L. and Origanum species also produce the structurally related monoterpenes thymohydroquinone and thymoquinone, which were first described in the essential oil of Nigella sativa L. black seed (4). Thymohydroquinone was shown to exhibit anti-cancer activity (5), and thymoquinone displays anti-inflammatory, hepatoprotective, antioxidant, cytotoxic, and anti-cancer activities (6).To date, only a few biosynthetic pathways to pharmaceutically valuable, oxidized terpenes have been completely elucidated, such as those leading to artemisinin, paclitaxel, and the phenolic, labdane-type diterpenes of sage and rosemary (7–9). For monoterpenes, a complex biosynthetic pathway has only been described for menthol and its derivatives in Mentha (10). However, the biosynthetic pathways for phenolic monoterpenes like thymol or carvacrol remain uncharacterized. Most monoterpenes are biosynthesized by fusion of the ubiquitous C₅ intermediates, isopentenyl diphosphate, and its isomer dimethylallyl diphosphate, resulting in the formation of a C₁₀ compound, geranyl diphosphate (GDP). This acyclic intermediate is the substrate for the large enzyme family of monoterpene synthases that form cyclic or acyclic products with an enormous variety of carbon skeletons (11, 12). In previous studies in thyme and oregano, the cyclic monoterpene olefin γ-terpinene was proposed as a precursor of thymol and carvacrol (Fig. 1A). Studies with ³H-labeled γ-terpinene showed that this compound was converted into thymol and carvacrol after incubation with young thyme leaves (13). Furthermore, the essential oils of plant species rich in either thymol or carvacrol have always been reported to contain substantial amounts of γ-terpinene (3). Terpene synthases forming γ-terpinene have been identified and characterized from various Lamiaceae species (14–19). In oregano, the expression of the γ-terpinene synthase OvTPS2 was found to correlate with thymol and carvacrol content in leaves (14). Beyond γ-terpinene, however, no further precursors of phenolic monoterpenes have been identified. The aromatic hydrocarbon p-cymene was suggested to be an intermediate in thymol and carvacrol formation from γ-terpinene (20), but its participation in the phenolic monoterpene pathway and the nature of the enzymes involved in formation of the aromatic ring still remain unknown. Moreover, there is little information about the conversion of the thymol and carvacrol to thymohydroquinone.Open in a separate windowFig. 1.T. vulgaris is composed of different monoterpene chemotypes. (A) Proposed biosynthetic pathway to the phenolic monoterpenes thymol and carvacrol as well as thymohydroquinone and thymoquinone. γ-terpinene and p-cymene were suggested as intermediates in the formation of thymol and carvacrol (17). (B) Essential oil composition of the T. vulgaris chemotypes dominated by carvacrol (C type), thymol (T type), and geraniol (G type). Terpenes were extracted with hexane and analyzed by GC-MS. The following terpenes were identified: 1, α-thujene; 2, α-pinene; 3, myrcene; 4, α-terpinene; 5, p-cymene; 6, γ-terpinene; 7, cis-sabinene hydrate; 8, linalool; 9, nerol; 10, neral; 11, thymoquinone; 12, geraniol; 13, geranial; 14, thymol; 15, carvacrol; 16, geranyl acetate; 17, (E)-β-caryophyllene; 18, thymohydroquinone; and 19, germacrene D. Nonyl acetate (10 µl/mL) was added as internal standard (IS) for quantification.In this study, we investigated the biosynthetic pathway leading to the formation of thymol, carvacrol, and thymohydroquinone in thyme and oregano. We isolated and characterized six cytochrome P450 monooxygenases (P450s) of the CYP71D subfamily from thyme and oregano accessions producing high levels of thymol and carvacrol. When these CYP genes were heterologously expressed and combined with a short-chain dehydrogenase from thyme in vitro or coexpressed in vivo in Nicotiana benthamiana, thymol or carvacrol were formed. Based on the characteristics of the expressed enzymes and their reaction with other substrates, we constructed the biosynthetic pathway leading to thymol and inferred the nature of unstable intermediates. Furthermore, we identified and characterized two P450s of the CYP76S and CYP736A subfamilies that hydroxylate thymol and carvacrol to thymohydroquinone when expressed in vivo in yeast and in N. benthamiana.     

Combined thallium 201/technetium 99m-labeled pyrophosphate tomography for identification of the “culprit” vessel in acute myocardial infarction

Background

Many previous investigations have used the presence of transient ischemic ²⁰¹Tl perfusion defect to localize coronary artery stenosis. This study reports the results of ²⁰¹Tl tomography alone and combined ²⁰¹Tl/^99mTc-labeled pyrophosphate (^99mTc PYP) tomography employed to identify the infarct-related vessel in patients with acute myocardial infarction (AMI).

Methods and Results

All short-axis images were evaluated by dividing each left ventricular slice into eight equal sectors. In addition, for combined ²⁰¹Tl/^99mTc PYP tomography, two sectors were added to evaluate involvement of the right ventricle. In a preevaluation phase of the study, the sectors were assigned to the supplying coronary arteries in 75 patients with single chronic myocardial infarction related to the left anterior descending coronary artery (LAD), left circumflex artery (LCX), or right coronary artery (RCA). In this pilot phase, ²⁰¹Tl tomograms were reviewed in conjunction with the angiographic data. This assignment was then tested prospectively in 117 patients with AMI. As confirmed by angiography, the AMI was related to the LAC, LCX, and RCA in 54, 17, and 46 patients, respectively. Sensitivity and specificity for ^99mTc PYP accumulation on combined ²⁰¹Tl/^99mTc PYP tomography were 98% a nd 100% for the LAD, 88% and 99% for the LCX, and 98% and 96% for the RCA, respectively. For ²⁰¹Tl tomography, sensitivity and specificity for identification of the culprit vessel were 94% and 89% for the LAD, 82% and 91% for the LCX, and 72% and 96% for the RCA, respectively.

Conclusion

This prospective study demonstrates that combined ²⁰¹Tl/^99mTc PYP tomography is highly accurate for identification of the infarct-related artery in AMI, even in patients with multivessel disease. Positive contrast visualization of myocardial necrosis in both the left and right ventricle allows for reliable differentiation between AMI related to the LCX or RCA territory. In comparison, for ²⁰¹Tl tomography the sensitivity to detect the culprit vessel, particularly the LCX and RCA, appears to be lower than for ²⁰¹Tl/^99mTc PYP imaging, particularly in patients with prior infarction or right dominant coronary artery.