Transforming growth factor alpha treatment alters intracellular calcium levels in hair cells and protects them from ototoxic damage in vitro

To determine if transforming growth factor alpha (TGFα) pretreatment protects hair cells from aminoglycoside induced injury by modifying their intracellular calcium concentration, we assayed hair cell calcium levels in organ of Corti explants both before and after aminoglycoside (i.e. neomycin, 10⁻³M) exposure either with or without growth factor pretreatment. After TGFα (500ng/ml) treatment, the intracellular calcium level of hair cells showed a five-fold increase as compared to the levels observed in the hair cells of control cultures. After ototoxin exposure, calcium levels in hair cells of control explants showed an increase relative to their baseline levels, while in the presence of growth factors pretreatment, hair cells showed a relative reduction in calcium levels. Pretreatment of organ of Corti explants afforded significant protection of hair cell stereocilia bundle morphology from ototoxic damage when compared to explants exposed to ototoxin alone. This study correlates a rise in hair cell calcium levels with the otoprotection of hair cells by TGFα in organ of Corti explants.     

RELATIONSHIP BETWEEN PLATELET CYTOSOLIC FREE CALCIUM CONCENTRATION AND PLASMA RENIN ACTIVITY

1. Plasma renin activity (PRA) and platelet cytosolic free calcium concentration ([Ca2+]i) were simultaneously determined in 18 untreated essential hypertensive subjects and 17 normotensive controls. A significant positive correlation was found between [Ca2+]i and PRA (slope = 42 nmol/l/ng/ml/h) in these 35 subjects. 2. Two determinations more than one week apart in nine subjects confirmed the parallel fluctuations of [Ca2+]i and PRA. A strict sodium restriction produced a progressive PRA elevation associated with a parallel rise in [Ca2+]i in one subject. 3. These results are consistent with the hypothesis that angiotensin II causes a concentration-dependent calcium mobilization.     

Lhermitte-Duclos disease

Lhermitte-Duclos disease (dysplastic gangliocytoma of the cerebellum) is a rare pseudo-neoplastic disorder of the cerebellum with typical MRI findings. A 25-year-old man presenting with progressive neck pain, dizziness, and impaired vision is reported. CT and MRI revealed a left cerebellar haemispheric mass and obstructive hydrocephalus. Lhermitte-Duclos disease was histologically confirmed after surgical removal of the lesion. The typical MRI appearance of a nonenhancing haemispheric cerebellar mass with preservation and exaggeration of the normal gyral pattern allows pre-operative diagnosis of this condition. The literature is reviewed and clinical presentation, radiology and histopathology are discussed.     

Is there a role for laparoscopic appendectomy in pediatric surgery?

Although laparoscopic procedures are currently in vogue in general surgery, the role of this approach in children has not been prospectively evaluated in the United States using the new instrumentation now available to us. To assess the value of laparoscopic appendectomy (LA) in childhood, we prospectively compared 14 LAs with 50 open appendectomies (OA) over 6 months in a single children's hospital. Antibiotic usage was at the discretion of the surgeon regardless of the procedure performed and was not different between groups. LA was performed under the direction of a single laparoscopy-trained surgeon and patient selection was based on parental consent. A three-puncture LA technique was used; children from this group were allowed to return to full activities as soon as they were comfortable. There were no significant differences between groups for severity of disease, age, weight, hospital cost, or complications. The types of complications that developed were comparable in both groups. The percent of complicated appendicitis (gangrene or perforation) was 32% in the OA group and 36% in the LA group. Patients in the LA group spent significantly fewer days in the hospital and returned to unrestricted activities (school, athletics, etc) faster than patients in the OA group. LA is approximately $1,000 more expensive than OA, the differences being easily explainable by the cost of the disposable supplies necessary for the procedure (laser fibers, trocars, etc), but because of the shorter hospital stay in the LA group the mean total cost for each group was comparable. These data suggest that although there appears to be no cost advantage, LA shortens the hospital stay and allows children to return to unrestricted activity sooner than OA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sevelamer hydrochloride with or without alphacalcidol or higher dialysate calcium vs calcium carbonate in dialysis patients: an open-label, randomized study.

BACKGROUND: Sevelamer hydrochloride was recently proposed as a phosphate binder to prevent hypercalcaemia in place of calcium alkaline salts in dialysis patients. So far, it has been evaluated only in patients receiving calcitriol, without comparison with CaCO(3) alone, although the latter was found to be as effective as the combination of calcitriol and Al(OH)(3) in suppressing parathyroid hormone (PTH) without inducing hypercalcaemia and to have a better lowering effect on serum phosphate. Moreover, this bile salt binder may decrease serum 25-OH vitamin D. Therefore, we compared for 5 months two strategies for controlling moderate hyperparathyroidism: CaCO(3) alone vs sevelamer in conjunction with measures to increase calcium balance. METHODS: Forty-two patients were randomized: 21 continued their treatment with 4.8 g/day CaCO(3) and 21 were switched to sevelamer (initial dose: 2.4 g/day, increased to 4.4 g/day). Each month, when serum-corrected calcium decreased below 2.30 mmol/l, dialysate calcium was increased or alphacalcidol was given at each dialysis session, according to serum PO(4) levels. The following parameters were monitored: serum Ca, PO(4), bicarbonate and protein, weekly; and serum PTH, 25-OH vitamin D and total, LDL and HDL cholesterol monthly. RESULTS: Except for higher serum phosphate at month 1, lower serum bicarbonate at month 2 and lower LDL cholesterol at month 5 in the sevelamer group, no difference was found between the two groups. Compared with baseline levels, PTH increased and 25-OH vitamin D decreased significantly in both groups, these two parameters being inversely correlated. CONCLUSIONS: Given comparable control of plasma calcium, phosphate and 25-OH vitamin D, PTH control is comparable in both strategies. Sevelamer does not induce greater vitamin D depletion than CaCO(3). The transient decrease of serum bicarbonate after discontinuation of CaCO(3) in the sevelamer group suggests a less optimal prevention of acidosis. The sevelamer-induced decrease in LDL cholesterol gives this drug a potential advantage in cardiovascular prevention.     

Self-perception and action in infancy

By 2–3 months, infants engage in exploration of their own body as it moves and acts in the environment. They babble and touch their own body, attracted and actively involved in investigating the rich intermodal redundancies, temporal contingencies, and spatial congruence of self-perception. Recent research is presented, which investigats the spatial and temporal determinants of self-perception and action infancy. This research shows that, in the course of the first weeks of life, infants develop an ability to detect intermodal invariants and regularities in their sensorimotor experience, which specify themselves as separate entities agent in the environment. Recent observations on the detection of intermodal invariants regarding self-produced leg movements and auditory feedback of sucking by young infants are reported. These observations demonstrate that, early in development and long before mirror self-recognition, infants develop a perceptual ability to specify themselves. It is tentatively proposed that young infants’ propensity to engage in self-perception and systematic exploration of the perceptual consequences of their own action plays an important role in the intermodal calibration of the body and is probably at the origin of an early sense of self: the ecological self.     

Substance P-like-immunoreactive sensory neurons in dorsal root ganglia of the chick embryo: ontogenesis and influence of peripheral targets.

The expression of substance P (SP) was studied in sensory neurons of developing chick lumbosacral dorsal root ganglia (DRG) by using a mixture of periodic acid, lysine and paraformaldehyde as fixative and a monoclonal antibody for SP-like immunostaining. The first SP-like-immunoreactive DRG cells appeared first at E5, then rapidly increased in number to reach a peak (88% of ganglion cells) at E8, and finally declined (59% at E12, 51% after hatching). The fall of the SP-like-positive DRG cells resulted from two concomitant events affecting a subset of small B-neurons: a loss of neuronal SP-like immunoreactivity and cell death. After one hindlimb resection at an early (E6) or late (E12) stage of development (that is before or after establishment of peripheral connections), the DRG were examined 6 days later. In both cases, a drastic neuronal death occurred in the ispilateral DRG. However, the resection at E6 did not change the percentage of SP-like-positive neurons, while the resection at E12 severely reduced the proportion of SP-like-immunoreactive DRG cells (25%). In conclusion, connections established between DRG and peripheral target tissues not only promote the survival of sensory neurons, but also control the maintenance of SP-like-expression. Factors issued from innervated targets such as NGF would support the survival of SP-expressing DRG cells and enhance their SP content while other factors present in skeletal muscle or skin would hinder SP expression and therefore lower SP levels in a subset of primary sensory neurons.