Early pharmacokinetics and clinical effects of oral D-amphetamine in normal subjects

Seven normal subjects received 0.25 mg/kg D-amphetamine orally, both after an overnight fast and again after a standard breakfast. Plasma levels, subjective and cardiovascular effects, and observer-rated activation were assessed hourly for 5 hr. Food did not affect amphetamine levels. Plasma levels peaked at 2-3 hr. Maximum cardiovascular effects generally occurred at 1 hr, whereas maximum behavioral and subjective effects occurred at 2 hr. Subjective and behavioral effects declined thereafter, in spite of substantial amphetamine levels. A separate group of 8 subjects received 0.5 mg/kg D-amphetamine orally. Plasma levels, subjective and cardiovascular effects, and activation ratings were assessed hourly for 4 hr. Maximum plasma levels were approximately twice those seen in the first group. In this case, plasma levels peaked at 3-4 hr; blood pressure and subjective and behavioral effects were all maximal at 2-3 hr and were declining by 4 hr, in spite of stable or rising plasma levels.     

Repair of large midline incisional hernias with polypropylene mesh: Comparison of three operative techniques

Polypropylene mesh is widely used for the reconstruction of incisional hernias that cannot be closed primarily. Several techniques have been advocated to implant the mesh. The objective of this study was to evaluate, retrospectively, early and late results of three different techniques, onlay, inlay, and underlay. The records of 53 consecutive patients with a large midline incisional hernia — 25 women and 28 men, mean age 60.4 (range 28–94) — were reviewed. Polypropylene mesh was implanted using the onlay technique in 13 patients, inlay in 23 patients, and underlay in 17 patients. Either the greater omentum or a polyglactin mesh was interponated between the mesh and the viscera. The records of these 53 patients were reviewed with respect to: size and cause of the hernia, pre- and postoperative mortality and morbidity, with special attention to wound complications. Patients were invited to attend the outpatient clinic at least 12 months after implantation of the mesh for physical examination of the abdominal wall. Postoperative complications occurred in 14 (26.4%) patients. The onlay technique had significantly more complications, as compared to both other techniques. Reherniation occurred in 15 (28.3%) patients. The reherniation rate of the inlay technique was significantly higher than after the underlay technique (44% vs 12%, P=0.03) and tended to be higher than the onlay technique (44% vs 23%, P=0.22). Repair of large midline incisional hernias with the use of a polypropylene mesh carries a high risk of complications and has a high reherniation rate. The underlay technique seems to be the better technique.     

Lupus optic neuritis with negative serology

A 56-year-old woman with a 12-year history of systemic lupus erythematosus presented with severe optic-disc swelling and blepharitis. At the same time, she developed acute pancreatitis and ultimately died of gram-negative sepsis. Although it appeared that the ocular and systemic disorders were manifestations of lupus, her serum antinuclear antibody and complement levels remained normal throughout her hospital course. Optic neuritis may be secondary to lupus, but the diagnosis is difficult to make when the serology is negative.     

Characterization of antibody and selection of alternative drug therapy in hydrochlorothiazide-induced immune hemolytic anemia

The authors report the clinical and laboratory findings of a patient who had severe immune hemolytic anemia due to hydrochlorothiazide (HCTZ). In this case, the HCTZ antibody reacted not only with other thiazide and thiazide-like drugs, but also with a chemically unrelated diuretic, ethacrynic acid. These results indicate that HCTZ antibody activity is not restricted solely to the thiazides and imply that therapy with any of the reactive drugs would be contraindicated for this patient. The serologic screening for drug reactivity may be useful for selecting alternative therapy for patients with drug-induced immune hemolytic anemia.     

Rat posterior parietal cortex: topography of corticocortical and thalamic connections

Anatomical and functional findings support the contention that there is a distinct posterior parietal cortical area (PPC) in the rat, situated between the rostrally adjacent hindlimb sensorimotor area and the caudally adjacent secondary visual areas. The PPC is distinguished from these areas by receiving thalamic afferents from the lateral dorsal (LD), lateral posterior (LP), and posterior (Po) nuclei, in the absence of input from the ventrobasal complex (VB) or dorsal lateral geniculate (DLG) nuclei. Behavioral studies have demonstrated that PPC is involved in spatial orientation and directed attention. In the present study we used fluorescent retrograde axonal tracers primarily to investigate the cortical connections of PPC, in order to determine the organization of the circuitry by which PPC is likely to participate in these functions, and also to determine how the topography of its thalamic connections differs from that of neighboring cortical areas. The cortical connections of PPC involve the ventrolateral (VLO) and medial (MO) orbital areas, medial agranular cortex (area Fr2), portions of somatic sensory areas Par1 and Par2, secondary visual areas Oc2M and Oc2L, auditory area Tel, and retrosplenial cortex. The secondary visual areas Oc2L and Oc2M have cortical connections which are similar to those of PPC, but are restricted within orbital cortex to area VLO, and within area Fr2 to its caudal portion, and do not involve auditory area Te1. The cortical connections of hindlimb cortex are largely restricted to somatic sensory and motor areas. Retrosplenial cortex, which is medially adjacent to PPC, has cortical connections that are prominent with visual cortex, do not involve somatic sensory or auditory cortex, and include the presubiculum. We conclude that PPC is distinguished by its pattern of cortical connections with the somatic sensory, auditory and visual areas, and with areas Fr2, and VLO/MO, in addition to its exclusive thalamic connectivity with LD, LP and Po. Because recent behavioral studies indicate that PPC, Fr2 and VLO are involved in directed attention and spatial learning, we suggest that the interconnections among these three cortical areas represent a major component of the circuitry for these functions in rats.     

Selective labeling of sensory hair cells and neurons in auditory, vestibular, and lateral line systems by a monoclonal antibody

This study reports that zn-1, a monoclonal antibody, labels hair cells but not supporting cells in the inner ear and the lateral line of the axolotl salamander, Ambystoma mexicanum. Zn-1 immunocytochemically labels the cytoplasm and stereocilia of mature hair cells in the sacculus, in the utriculus, and in the mechanoreceptive neuromast organs of the lateral line. Lower levels of labeling mark newly formed hair cells in the periphery of the sacculus and in regenerating neuromasts. Zn-1 also selectively labels neuronal processes and perikarya in the lateral line nerves and ganglia and the VIIIth cranial nerve and ganglion. Processes and perikarya are labeled by zn-1 in the dorsolateral medulla oblongata, at sites of termination of the afferent octaval and lateral line neurons. Western blot analysis revealed that zn-1 labels one or more proteins with molecular weights of 80 and 160 kDa. The identity of these protein bands remains to be determined. The presence of a specific epitope expressed in both hair cells and neurons, but not in supporting cells, in the vestibular and auditory epithelia of the ear and in the mechanoreceptive neuromasts of the lateral line suggests shared cytogenetic heritages. These findings are consistent with a close evolutionary relationship between otic and lateral line senses, such as that inherent to the theoretical evolutionary scheme outlined in van Bergeijk's "acousticolateralis hypothesis." The protein recognized by zn-1 is as yet unidentified, but its conservative evolution suggests that it may serve an important function in the statoacoustic and lateral line systems.     

SCREENING PROCEDURES IN PEDIATRICS

Pediatric health screening procedures, both prenatal and postnatal, have a tremendous potential in improving the health status of children and in turn reducing the resource burden on the parents and the State. The existing recommendations, inherent problems and different screening procedures are discussed. The need for suitable mass screening pediatric procedures in the Indian context is stressed.KEY WORDS: Pediatric screening procedures     

Acute effects of the selective cholinergic channel activator (nicotinic agonist) ABT-418 in Alzheimer’s disease

To explore further the potential for cognitive enhancement utilizing nicotinic stimulation in Alzheimer’s disease (AD), six otherwise healthy subjects with moderate AD received placebo and three doses (6, 12, and 23 mg) of the novel selective cholinergic channel activator (ChCA) (nicotinic agonist) ABT-418 over 6 h in a double-blind, within-subjects, repeated-measures design. Subjects showed significant improvements in total recall and a decline in recall failure on a verbal learning task. Qualitatively similar improvements were seen in non-verbal learning tasks such as spatial learning and memory, and repeated acquisition. No significant behavioral, vital sign, or physical side effects were seen. These results confirm that stimulating central nicotinic receptors has acute cognitive benefit in AD patients. These findings suggest that selective ChCAs have a potential therapeutic role in dementing disorders, and that further studies with this or similar agents in AD and/or Parkinson’s disease are warranted. Received: 27 February 1998/Final version: 9 September 1998