Nicotine and ethanol activate protein kinase A synergistically via G(i) betagamma subunits in nucleus accumbens/ventral tegmental cocultures: the role of dopamine D(1)/D(2) and adenosine A(2A) receptors

Tobacco and alcohol are the most commonly used drugs of abuse and show the most serious comorbidity. The mesolimbic dopamine system contributes significantly to nicotine and ethanol reinforcement, but the underlying cellular signaling mechanisms are poorly understood. Nicotinic acetylcholine (nACh) receptors are highly expressed on ventral tegmental area (VTA) dopamine neurons, with relatively low expression in nucleus accumbens (NAcb) neurons. Because dopamine receptors D(1) and D(2) are highly expressed on NAcb neurons, nicotine could influence NAcb neurons indirectly by activating VTA neurons to release dopamine in the NAcb. To investigate this possibility in vitro, we established primary cultures containing neurons from VTA or NAcb separately or in cocultures. Nicotine increased cAMP response element-mediated gene expression only in cocultures; this increase was blocked by nACh or dopamine D(1) or D(2) receptor antagonists. Furthermore, subthreshold concentrations of nicotine with ethanol increased gene expression in cocultures, and this increase was blocked by nACh, D(2) or adenosine A(2A) receptor antagonists, Gbetagamma or protein kinase A (PKA) inhibitors, and adenosine deaminase. These results suggest that nicotine activated VTA neurons, causing the release of dopamine, which in turn stimulated both D(1) and D(2) receptors on NAcb neurons. In addition, subthreshold concentrations of nicotine and ethanol in combination also activated NAcb neurons through synergy between D(2) and A(2A) receptors. These data provide a novel cellular mechanism, involving Gbetagamma subunits, A(2A) receptors, and PKA, whereby combined use of tobacco and alcohol could enhance the reinforcing effect in humans as well as facilitate long-term neuroadaptations, increasing the risk for developing coaddiction.     

HBO and gas embolism

Gas embolism, which occurs with the entry of gas into the circulatory system from the vein, artery or both, is a potentially serious even fatal condition. The two main causes of gas embolism are iatrogenic and diving. The site of entry and the signs and symptoms distinguish between arterial and venous embolism. The entering gas may be air, but may also be CO(2) or other gases, especially in iatrogenic embolism. Supportive care is the primary therapy for venous gas embolism, while hyperbaric oxygen therapy in addition to supportive care is the first line of treatment for arterial gas embolism. In this article, we will review the pathophysiology, etiology, diagnosis and treatment of gas embolism.     

Probably benign breast masses at US: is follow-up an acceptable alternative to biopsy?

PURPOSE: To retrospectively determine whether nonpalpable solid breast masses that were partially or completely obscured at mammography and diagnosed as probably benign only at ultrasonography (US) can be safely managed with follow-up. MATERIALS AND METHODS: The local ethics committee approved this study; informed consent was not required. In 409 women, 448 nonpalpable solid masses were identified and classified as probably benign at US; at mammography these masses were either partially or completely obscured by dense fibroglandular tissue. Of the 448 masses, 445 were followed up, while biopsy was performed after initial imaging in the remaining three. False-negative rates, negative predictive values (NPVs), and exact 95% confidence intervals (CIs) were calculated. RESULTS: Of the 445 masses, 442 remained stable at follow-up (range, 2-5 years; mean, 3.3 years). Two masses increased (fibroadenomas at biopsy). One mass became palpable, and cancer was diagnosed at biopsy. The three masses in which initial biopsy was performed were fibroadenomas. The false-negative rate was 0.2% (one of 448; NPV, 99.8%; 95%CI: 0.0%, 1.23%). CONCLUSION: Follow-up US appears to be an acceptable alternative to biopsy for solid masses with benign morphologic features seen at US owing to the extremely high NPV (99.8%).     

Mobiles Single-pass-batch-Hämodialyse-System in der Intensivmedizin

This paper describes the introduction of a single-pass batch hemodialysis system for renal replacement therapy in a 14 bed intensive care unit. The goals were to reduce the workload of intensive care unit physicians using an alternative and simpler method compared to continuous veno-venous hemodiafiltration (CVVHDF) and to reduce the costs of hemofiltrate solutions (80,650 EUR per year in our clinic in 2005). We describe and evaluate the process of implementation of the system as well as the achieved and prospective savings. We conclude that a close cooperation of all participants (physicians, nurses, economists, technicians) of a hospital can achieve substantial benefits for patients and employees as well as reduce the economic burden of a hospital.     

The chemiluminescence activity of peripheral blood mononuclear cells during acute experimental allergic encephalomyelitis

The spontaneous chemiluminescence activity (CL-A) of peripheral mononuclear cells (MNC) was examined in Lewis rats with acute experimental allergic encephalomyelitis (EAE), compared to rats immunized with complete adjuvant (n = 11) and healthy animals (n = 16). In rats with EAE, CL-A increased sharply 8-9 days after immunization (3420 +/- 3124 counts/10 s, n = 16) at the time of flattening of the weight curve. This CL-A peak was compared to that of animals immunized with complete adjuvant: 765 +/- 441 counts/10 s (P = 0.01) and healthy rats: 450 +/- 172 counts/10 s (P = 0.0001). After this initial peak in EAE rats, CL-A decreased almost to normal values when animals lost weight (746 +/- 251 counts, n = 19) and tail paralysis developed (557 +/- 251 counts/10 s, n = 15). CL-A increased again with the onset of paralysis of the extremities (1527 +/- 990 counts/10 s, n = 11), followed by a decrease as the clinical course deteriorated. Finally, CL-A approached normal values as the animals improved. A significant increase in the number of meningeal (P less than 0.01) and perivascular (P less than 0.01) cells in the CNS coincided with the initial CL-A peak. Gel filtration of the serum of rats with increased CL-A revealed at least one substance, with a molecular weight between 13,700 and 43,000 Da, which stimulated the CL-A of normal mononuclear cells.     

Abolished laser-evoked potentials and normal blink reflex in midlateral medullary infarction

We investigated two patients presenting with the rare finding of almost isolated hemianalgesia with a sensory level on the contralateral side sparing the face. Clinical findings, electrophysiological studies (absent laser-evoked pain-related somatosensory potentials, normal electrically evoked somatosensory potentials, magnetically evoked potentials, and blink reflexes), and magnetic resonance imaging showed the ventrolateral medullar tegmentum containing the spinothalamic tract to be affected by lacunar infarction. The blink reflex R2 component was unimpaired in both patients. Received: 7 May 1998 Received in revised form: 21 July 1998 Accepted: 26 August 1998     

Increased risk of sensory neuropathy in workers with chloracne after exposure to 2,3,7,8-polychlorinated dioxins and furans

OBJECTIVE: The existence of a peripheral neuropathy after exposure to polychlorinated dioxins (PCDD) is still discussed, as studies concerning dioxin effects on the peripheral nervous system are rare and contradictory. MATERIAL AND METHODS: Clinical and neurophysiological examinations (motor conduction velocity of the peroneal nerve, sensory conduction velocities of the sural and ulnar nerves) were made in 156 dioxin exposed workers (42 with, 114 without cloracne) from one pesticide producing plant. Because of known risk factors for peripheral neuropathy, 7 workers with and 28 without cloracne were excluded from further analysis. RESULTS: Workers with chloracne had a significantly higher exposure against PCDD as documented by back calculated lipid levels. They complained significantly more often of sexual impotence (28.6% compared to 5.8% of workers without chloracne, P<0.001), had significantly more frequent clinical signs of a sensory neuropathy (= abnormal sensory findings plus deep tendon reflex abnormalities) restricted to the legs (17.1% compared to 1.2%, P<0.001), had significantly more frequent > or =2 neurophysiologic abnormalities (34.3% compared to 14.0%, P<0.025), and had significantly lower mean amplitudes of the motor compound muscle potential of the peroneal nerve. CONCLUSION: PCDD has a mild toxic effect on the peripheral nervous system manifesting as mild sensory neuropathy of the legs in a minority of the most severely exposed persons.     

Visual discrimination and short-term memory for random patterns in patients with a focal cortical lesion

Visual discrimination and short-term recognition memory for computer- generated random patterns were explored in 23 patients with a postsurgical lesion in one of the cortical hemispheres. Their results are compared with those of 23 age-matched volunteers. In a same- different forced-choice discrimination task, d' and log beta (measures of sensitivity and bias), as well as reaction time (RT) were determined. All participants viewed patterns defined either by luminance contrast or isoluminant red-green color contrast, the amplitude of which was adjusted to be 10 times the respective detection threshold level. Block patterns consisting of a 6 x 6 matrix of light and dark (red and green) checks were randomly configured on each presentation. They were presented in pairs, randomly in two visual quadrants for a duration of 200 msec. Three presentation conditions were used: simultaneous presentation of reference and test stimulus, sequential presentation with a short delay (interstimulus interval, ISI = 3 s), and sequential presentation with a long delay (ISI = 6 s). The results indicate that patients with a lesion in the occipitotemporal cortex, the superior temporal cortex and the frontal cortex were significantly impaired on both luminance-contrast and color-contrast pattern discrimination. Patients with damage in the anterior inferotemporal cortex showed no overall impairment. The results suggest that performance in visual discrimination and recognition memory tasks rely on distributed neural processes with more than one neocortical location.