Teriparatide increases bone formation in modeling and remodeling osteons and enhances IGF-II immunoreactivity in postmenopausal women with osteoporosis.

Transiliac bone biopsies were obtained from 55 women treated with teriparatide or placebo for 12-24 months. We report direct evidence that modeling bone formation at quiescent surfaces was present only in teriparatide-treated patients and bone formation at remodeling sites was higher with teriparatide than placebo. INTRODUCTION: Recombinant teriparatide [human PTH(1-34)], a bone formation agent for the treatment of osteoporosis when given once daily subcutaneously, increases biochemical markers of bone turnover and activation frequency in histomorphometry studies. MATERIALS AND METHODS: We studied the mechanisms underlying this bone-forming action of teriparatide at the basic multicellular unit by the appearance of cement lines, a method used to directly classify surfaces as modeling or remodeling osteons, and by the immunolocalization of IGF-I and IGF-II. Transiliac bone biopsies were obtained from 55 postmenopausal women treated with teriparatide 20 or 40 microg or placebo for 12-24 months (median, 19.8 months) in the Fracture Prevention Trial. RESULTS: A dose-dependent relationship was observed in modeling and mixed remodeling/modeling trabecular hemiosteons. Trabecular and endosteal hemiosteon mean wall thicknesses were significantly higher in both teriparatide groups than in placebo. There was a dose-dependent relationship in IGF-II immunoreactive staining at all bone envelopes studied. The greater local IGF-II presence after treatment with teriparatide may play a key role in stimulating bone formation. CONCLUSIONS: Direct evidence is presented that 12-24 months of teriparatide treatment induced modeling bone formation at quiescent surfaces and resulted in greater bone formation at remodeling sites, relative to placebo.     

Facial Nerve Neuroma: Surgical Concept and Functional Results

This study reviewed the management and outcomes of 11 facial nerve neuromas treated in our institution during the past two decades with particular emphasis on surgical concepts and functional outcomes. All patients underwent complete surgical resection of their tumor. Eight patients (73%) were followed on an outpatient basis. A retrospective chart review for pre- and postoperative clinical and radiological data was performed. All facial neuromas were multi-segment tumors. All segments of the facial nerve were represented, but 54% involved the geniculate ganglion and 45% involved the labyrinthine or tympanic portions of the nerve, or both. Depending on the extent of sensorineural hearing loss, surgical removal was performed through the middle cranial fossa or translabyrinthine approach. To obtain adequate nerve reconstruction, we combined intra- and extracranial approaches (e.g., the transmastoidal and transtemporal routes). Regardless of the type of nerve reconstruction, the best recovery achieved was moderate facial weakness (House-Brackmann Grade III) in 75% of the patients, even in a patient who was Grade IV preoperatively. The choice of treatment for facial neuromas and surgical approach depends on the extent of tumor, grade of facial palsy, and hearing function. When facial palsy is present, complete resection is clearly indicated. In patients without facial dysfunction, a conservative strategy consisting of clinical and radiological observation should be considered as a treatment option.     

Fat absorption in premature infants: medium-chain triglycerides and long-chain triglycerides are absorbed from formula at similar rates

Fat absorption from two different premature infant formulas and one full-term formula containing three different fat blends was investigated in two groups of premature infants. The first group of nine infants (gestational age, 29.1 +/- 0.88 weeks; postnatal age, 3.13 +/- 0.71 weeks) was fed alternately for 1 week each SMA preterm formula containing either high levels (50%) of medium-chain triglycerides (MCT) (6:0, 8:0, and 10:0) or high levels (86%) of long-chain triglycerides (LCT) (greater than or equal to C12). Except for fat blends, the formulas were otherwise identical. The second group of 11 infants (gestational age, 30.5 +/- 0.77 weeks, studied at a postnatal age of 4.33 +/- 0.91 weeks) was fed for 1 week a full-term infant formula, S-26, containing 98% LCT. Fat absorption (studied during a 3-day fat balance period) was similar irrespective of fat blend: 89.08 +/- 2.37% during feeding of preterm SMA, 50% MCT; 87.0 +/- 3.81% during feeding of preterm SMA, 86% LCT; and 83.00 +/- 2.89% during feeding of S-26, 98% LCT. Weight gain (grams per day) and increase in length (centimeters per day) were 23.2 +/- 1.7, 21.20 +/- 1.7, and 14.28 +/- 2.9, and 0.17 +/- 0.06, 0.16 +/- 0.04, and 0.22 +/- 0.07 during feeding of the three fat blends, respectively. Lipase activity levels in fasting gastric aspirates were higher during feeding of the LCT than the MCT formula. The possible stimulation of gastric lipase secretion secondary to long-chain fatty acid stimulation of cholecystokinin secretion might be related to the efficient digestion of formula fat, irrespective of triglyceride-fatty acid chain length.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human Aldehyde Dehydrogenase: Kinetic Identification of the Isozyme for Which Biogenic Aldehydes and Acetaldehyde Compete

Michaelis constants and maximal velocities for phenylacetaldehyde (a metabolite of phenylethylamine), 3,4-dihydroxyphenylacetaldehyde (a metabolite of dopamine), 5-hydroxyindole acetaldehyde (a metabolite of serotonin), and 3,4-dihydroxyphenylglycolaldehyde (a metabolite of epinephrine and norepinephrine) have been determined for both cytoplasmic (E1) and mitochondrial (E2) isozymes of human liver aldehyde dehydrogenase (EC 1.2.1.3). Kinetic constants with biogenic aldehydes have never been previously determined for individual homogeneous isozymes of aldehyde dehydrogenase from any species. Mathematical treatment of these constants suggests that competition with acetaldehyde during alcohol metabolism would severely inhibit dehydrogenation of biogenic aldehydes with the mitochondrial and not the cytoplasmic isozyme of human liver aldehyde dehydrogenase.     

Metabolic mapping of functional activity in the olfactory system of normal and hypogonadal (hpg) mice

The hypogonadal mouse, which lacks gonadotropin-releasing hormone, has been suggested as an animal model of Kallmann's syndrome, one symptom of which is hyposmia. We have determined the metabolic activity of the olfactory system, in normal and hypogonadal mice, using [14C]-2-deoxyglucose quantitative autoradiography. In the olfactory lobes, deoxyglucose uptake was greatest in the glomerular and granule cell layers and low in the olfactory nerve layer and bulb core. The pattern of uptake was similar in both hypogonadal and normal mice breathing filtered air. Exposure of normal mice to ethyl acetoacetate significantly increased deoxyglucose uptake in the olfactory nerve layer and glomerular layer, but not in the granule cell layer. Several foci of intense metabolic activity were produced, apparently corresponding to small groups of activated glomeruli. There were no changes in the secondary or tertiary projections of the olfactory system. In hypogonadal mice, ethyl acetoacetate failed to increase the number of foci and the density of labelling in the olfactory nerve layer and glomerular layer. These data show that the functional activity of the olfactory system in hypogonadal mice breathing air is apparently normal. However, the olfactory response to ethyl acetoacetate is significantly less in hypogonadal mice. Whether this is due to their lack of gonadotropin-releasing hormone requires further experimentation.     

Corticosterone controls the developmental emergence of fear and amygdala function to predator odors in infant rat pups

In many altricial species, fear responses such as freezing do not emerge until sometime later in development. In infant rats, fear to natural predator odors emerges around postnatal day (PN) 10 when infant rats begin walking. The behavioral emergence of fear is correlated with two physiological events: functional emergence of the amygdala and increasing corticosterone (CORT) levels. Here, we hypothesize that increasing corticosterone levels influence amygdala activity to permit the emergence of fear expression. We assessed the relationship between fear expression (immobility similar to freezing), amygdala function (c-fos) and the level of corticosterone in pups in response to presentation of novel male odor (predator), littermate odor and no odor. CORT levels were increased in PN8 pups (no fear, normally low CORT) by exogenous CORT (3 mg/kg) and decreased in PN12 pups (express fear, CORT levels higher) through adrenalectomy and CORT replacement. Results showed that PN8 expression of fear to a predator odor and basolateral/lateral amygdala activity could be prematurely evoked with exogenous CORT, while adrenalectomy in PN12 pups prevented both fear expression and amygdala activation. These results suggest that low neonatal CORT level serves to protect pups from responding to fear inducing stimuli and attenuate amygdala activation. This suggests that alteration of the neonatal CORT system by environmental insults such as alcohol, stress and illegal drugs, may also alter the neonatal fear system and its underlying neural control.     

L-Dopa-responsive Parkinson's syndrome in association with phenylketonuria: In vivo dopamine transporter and D2 receptor findings.

Reports of parkinsonism in phenylketonuria are exceedingly rare. We report on a patient who had received a delayed diagnosis of phenylketonuria as an infant and subsequently developed levodopa-responsive parkinsonism at the age of 33. Single-photon emission computed tomography (SPECT) using (123)I-FP-CIT ([(123))I]-2 beta-carbomethoxy-3beta-(-4-iodophenyl)-N-(3-fluoropropyl)-nortropane) used to measure dopamine transporter levels on two occasions, 7 and 9 years after the onset of neurological symptoms, were normal. Iodine-123-iodo-lisuride SPECT (IBZM) imaging, however, showed reduced caudate over putamen binding. This combination of imaging findings indicates a possible upregulation of postsynaptic D2 receptors in the context of intact presynaptic dopamine nerve terminal density.