Positive and negative network correlations in temporal lobe epilepsy

Temporal lobe seizures are accompanied by complex behavioral phenomena including loss of consciousness, dystonic movements and neuroendocrine changes. These phenomena may arise from extended neural networks beyond the temporal lobe. To investigate this, we imaged cerebral blood flow (CBF) changes during human temporal lobe seizures with single photon emission computed tomography (SPECT) while performing continuous video/EEG monitoring. We found that temporal lobe seizures associated with loss of consciousness produced CBF increases in the temporal lobe, followed by increases in bilateral midline subcortical structures. These changes were accompanied by marked bilateral CBF decreases in the frontal and parietal association cortex. In contrast, temporal lobe seizures in which consciousness was spared were not accompanied by these widespread CBF changes. The CBF decreases in frontal and parietal association cortex were strongly correlated with increases in midline structures such as the mediodorsal thalamus. These results suggest that impaired consciousness in temporal lobe seizures may result from focal abnormal activity in temporal and subcortical networks linked to widespread impaired function of the association cortex.     

Inguinal hernia: Challenging the traditional indication for surgery in asymptomatic patients

Background: It is generally accepted that most inguinal hernias should be operated on electively in order to avoid the high morbidity and mortality associated with incarceration and small bowel obstruction. The present study reassesses the indication for surgery in asymptomatic inguinal hernia patients. Methods: We analyzed profiles, separately, for elective and emergency inguinal herniorrhaphies and compared the morbidity and mortality rates. Results: Two hundred randomly selected elective hernia repairs were compared with 67 incarcerated cases. Postoperative complications were more common following emergency (23.9%) than elective repair (10.5%); however, in both groups, minor complications predominated. The mortality rate in the incarcerated group (6%) was clearly linked with a high preoperative American Society of Anesthesiologists (ASA) score. A bowel resection rate of 4.5% was found in the incarcerated cases, which was not correlated with mortality. Conclusions: Patients with asymptomatic inguinal hernia and unfavorable medical conditions should be recommended an elective repair, preferably under local anesthesia, to avoid the high mortality associated with an emergency operation.     

Recognition strategies in the innate immune system of ancestral chordates

Many components of the innate immune system in vertebrates can be reliably traced to urochordates and successful strategies for the detection and elimination of pathogens are present at that level of animal evolution, but the issue of where and how the adaptive immune system emerged is still obscure. There is a paucity of evidence for a gradual transition from the innate immune system of invertebrates to the recombinatorial immune system of higher vertebrates. None of the classical elements of MHC based transplantation immunity (MHC, TCR) or humoral immunity (Ig) have been found in urochordates or Agnathans. Nevertheless there is abundant evidence for adaptive immune responses in the agnathans. This remarkable paradox raises a number of questions. How do these ancestral chordates discriminate between the constituents of the external world and the constituents of "self"? Are these strategies universal within the animal kingdom and among chordates, or are different strategies used by representatives of the different taxonomic groups? The current state of our knowledge indicates that the immune system of lower chordates is very different from that of cartilaginous fishes. Pure homology hunting for vertebrate-specific immuno-relevant molecules in invertebrates is therefore of limited value. A more promising approach may involve unbiased functional screening methods. To understand better the evolution of adaptive immune systems, more comparative data from jawless vertebrates (lamprey or hagfish) and a representative of Acrania (e.g. Amphioxus) are clearly needed.     

Homocysteine effect on protein degradation rates

OBJECTIVES: To show the effect of homocysteine (Hcy) on the degradation rates of proteins. DESIGN AND METHODS: Degradation rates of short-lived proteins in neutrophils were measured in in vivo human model of elevated plasma Hcy and lower vitamin status and in animal model of Hcy added in vitro to rat neutrophils. RESULTS: In the human study, we found significant coefficients of correlation between plasma total homocysteine (tHcy) and the degradation rates of 21 protein fractions. In the animal model, Hcy significantly increased degradation rates of 57 protein fractions. CONCLUSIONS: The increase in protein degradation rates, induced by Hcy, may provide a clue to our understanding of the mechanism of Hcy detrimental effects. Hcy may amplify the specific effect of cellular solutes on protein conformation, thereby monitor protein degradation rates to control enzyme activity. Consequently, the cell may lose its ability to maintain an efficient control of some crucial metabolic pathways, possibly leading to atherogenesis.     

Hydrochlorothiazide induced hepato-cholestatic liver injury

Hydrochlorothiazide and other thiazide-like diuretics are considered as a first-line drug for initial therapy in uncomplicated arterial hypertension [1]. There are several reports [2-6] of thiazide-induced cholecystitis, but here we report a case of serious hepatotoxicity associated with hydrochlorothiazide treatment.     

Different pathways mediated by CCK1 and CCK2 receptors: effect of intraperitonal mrna antisense oligodeoxynucleotides to cholecystokinin on anxiety-like and learning behaviors in rats

Cholecystokinin (CCK) and its analogs generate anxiety in humans and measurable anxiety-like behaviors in rats. CCK receptor blockers have been reported to have variable effects in the treatment of anxiety disorders. In a prior study, intracerebroventricular administration of CCK-antisense oligodeoxynucleotides (ASODN) for 3 days significantly diminished anxiety-like behavior in rats. Counter to our expectations, intraperitoneal (i.p.) administration of CCK-ASODN significantly increased anxiety-like behavior and impaired retention performance in the Morris water maze. The aim of the present study was to manipulate CCK-mediated anxiety-like behavior and spatial memory in rats by peripheral (i.p.) administration of ASODN to preproCCK in the presence of antagonists to CCK1 and CCK2 receptor subtypes to further elucidate the roles of these two receptors and better understand the effects of i.p. CCK-ASODN. CCK-ASODN was injected i.p. to rats five times at 24-hr intervals with and without administration of CCK1R antagonist PD135158 or CCK2 antagonist benzotrip. Control groups received injections of either a scrambled oligodeoxynucleotide (ScrODN) or vehicle. On Day 6, the rats were assessed in the elevated plus maze paradigm and in the Morris water maze. The rats were sacrificed and their blood was assessed for corticosterone, ACTH, and prolactin levels. The results show that i.p. CCK-ASODN significantly increased anxiety-like behavior and impaired retention performance in the Morris water maze, compared to both control groups, accompanied by increased plasma corticosterone and plasma ACTH concentrations. In contrast, administration of CCK-ASODN together with CCK2R antagonist, but not with CCK1R antagonist, significantly decreased anxiety-like behavior in rats, but still impaired retention performance in the Morris water maze paradigm. Lower levels of plasma corticosterone and ACTH in CCK-ASODN+CCK2R antagonist-treated rats accompanied the reduced anxiety-like behavior. The present study showed an anxiolytic effect of i.p. CCK-ASODN in the presence of CCK2R, but not CCK1R.     

Bone strength in multiple sclerosis: cortical midtibial speed-of-sound assessment

It has been previously suggested that multiple sclerosis (MS) patients are at increased risk for osteoporosis due to reduced mobility, decreased exposure to sunlight and recurrent steroid treatment. In order to systematically evaluate bone strength we assessed 256 MS patients (171 females, 75 males) through quantitative ultrasound measurement of cortical bone. Tibial speed of sound (SOS, m/sec) was measured at midpoint of the tibial shaft using a Soundscan 2000 (Myriad Ultrasound Systems, Rehovot, Israel) and results were compared to age- and gender-matched population norms. T-score distribution in male MS patients was similar to normal population. In contrast, for female MS patients T-score distribution was significantly different from population norms, reflected by increased SOS in 30.4% (T-score intervals 1-2 and >2 above normal values; P=0.001), compared with 7.4% in controls. These findings held true for both female patients younger and older than 45 years of age. Increased neurological disability and specifically motor involvement were more frequent in female patients with increased SOS (P<0.05). Bone strength was preserved in MS patients. In a subgroup of female patients increased SOS was conceivably related to spasticity.     

Clinical and ultrasonographic weight estimation in large for gestational age fetus

OBJECTIVE: To examine prospectively the effect on pregnancy outcome of a management protocol, that adds ultrasonographic weight estimation in fetuses suspected clinically as large. STUDY DESIGN: Prospective follow up study of all singleton deliveries during a 1 year period. All patients underwent routine clinical estimation of fetal weight. When clinical estimation of fetal weight was > or = 3700 g, patients were referred for ultrasonographic estimation of fetal weight. When the latter was > or = 4000 g the patient was informed about the risks of birth trauma. Cesarean section was recommended only when > or = 4500 g. Ultrasonography was repeated every 4 days when possible. Predictive values of clinical and ultrasonographic estimations of fetal weight for diagnosing macrosomia, defined for the purpose of this study as 4000 g or more, and their effect on the rate of cesarean sections. RESULTS: Five hundred fifty-five (14.4%) out of 3844 singletons were estimated as 3700 g or more. Only 315 fetuses had ultrasonographic estimation of weight within 3 days of delivery. The sensitivity of clinical and ultrasonographic prediction of macrosomia was 68 and 58%, respectively. Cesarean section rate in newborns weighing 4000 g or more was 22% when macrosomia was clinically suspected compared to 11% when it was not (P<0.05). In fetuses estimated ultrasonographically as 4000 g or larger the cesarean section rate was doubled (50.7% versus 24.9%, P<0.05) compared to those estimated as smaller than 4000 g, although actual weight of 4500 g or more was recorded in 10.6 and 8.5% of these groups, respectively. There were no cases of shoulder dystocia in macrosomic babies when macrosomia was not detected by ultrasound compared to two cases of shoulder dystocia (2.7%) when macrosomia was detected by ultrasound. CONCLUSION: Antenatal suspicion of macrosomia increased the cesarean section rate while the associated improvement in pregnancy outcome remains questionable. The contribution of ultrasound, added to routine clinical estimation of fetal weight, was clinically insignificant apart from a further increase in cesarean section rate.     

The clinical therapeutic window for luteinizing hormone in controlled ovarian stimulation

Objective: To discuss the clinical therapeutic window for LH during the follicular phase.

Design: Review of selected papers that were retrieved through a Medline search and a review of clinical trials, the results of which are in the process of publication.

Patient(s): Women undergoing infertility treatment.

Intervention(s): Recombinant human LH (r-hLH) was administered SC as a supplement to FSH during controlled ovarian hyperstimulation.

Main Outcome Measure(s): Follicular development, E₂ production, and endometrial thickness.

Result(s): Optimal follicular maturation is the result of both FSH and LH stimulation. In patients with hypogonadotropic hypogonadism, 75 IU of r-hLH and 150 IU of FSH per day resulted in more follicles and provided sufficient E₂ for optimal endometrial proliferation. Additional r-hLH (>250 IU/day), in patients with either hypogonadotropic hypogonadism or polycystic ovary disease, may precipitate a series of deleterious physiological actions leading to atresia of developing follicles. Adding r-hLH to FSH in women treated with GnRH agonist showed no benefits in terms of number of mature oocytes, fertilization, and cleavage. However, those who experience profound pituitary desensitization may benefit from adding LH to the stimulation protocol. No obvious clinical criteria have been established to define this group of patients.

Conclusion(s): A “threshold” and “ceiling” level for LH (therapeutic window) is proposed, below which E₂ production is not adequate and above which LH may be detrimental to follicular development.     

Simple technique to ensure coaxial guidewire positioning for placement of iliac limb of modular aortic endograft

Endovascular abdominal aortic aneurysm repair using a modular bifurcated stent-graft requires the initial placement of the main component in the infrarenal aorta, followed by insertion of additional iliac stent-graft(s) to exclude aneurysm and to securely affix the device. Placement of the contralateral iliac component within the main bifurcated device is critical in this endovascular procedure, as malpositioning of the contralateral iliac limb can require conversion to open aneurysm repair. A simple adjunctive technique utilizing a rotational maneuver of a pigtail catheter is described. This maneuver reliably confirms the proper placement of the contralateral iliac stent-graft within the main bifurcated device.