Children with acute lymphoblastic leukemia (ALL) often develop bone pain, abnormal gait, and unusual fractures while in remission and receiving continuing chemotherapy. A prospective longitudinal cohort study was undertaken of bone mass and biochemical mineral status in 40 consecutive children (27 male, 13 female, aged 0.3-17.0 years) receiving therapy on the Dana-Farber Cancer Institute protocol 87-01. Radiography, lumbar spine dual-photon absorptiometry, and biochemical measurements of mineral status were performed at diagnosis and at 6-month intervals throughout 24 months of chemotherapy. Eleven patients were not completely evaluated (4 deaths and 7 off study). Radiographic evidence of osteopenia was observed in 10, 64, and 76% at diagnosis, 12 and 24 months, respectively. Fractures occurred in 39% of children during treatment. Reduction in bone mineral content (BMC), as measured by Z scores, occurred in 64% of patients and was most severe in those greater than 11 years of age at diagnosis. Reduction in BMC during the first 6 months of therapy had a positive predictive value of 64%, while an increase in BMC had a negative predictive value of 82% for subsequent fracture. By 6 months of therapy, 31/37 (84%) children were hypomagnesemic, of whom 16 (52%) were hypermagnesuric. Plasma osteocalcin was subnormal at diagnosis in 29/40 (73%) but increased to normal by 6 months of treatment. Vitamin D status was normal throughout, but plasma 1,25-dihydroxyvitamin D remained subnormal in greater than 70% of children. Urinary cross-link N-telopeptide was normal at diagnosis and became elevated in 58% of children by the end of therapy. Suppressed bone mineralization is evident at diagnosis in a minority of children with ALL. Skeletal morbidity and a reduction in bone mineral mass become more prevalent during treatment, with increased bone resorption, perhaps mainly as a consequence of corticosteroid administration.

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Cetaceans (whales, dolphins, and porpoises) have a soft tissue flipper that encases most of the forelimb, and elongated digits with an increased number of phalanges (hyperphalangy). In addition, some cetaceans exhibit a reduction in digit number. Although toothed cetaceans (odontocetes) are pentadactylous, most baleen whales (mysticetes) are tetradactylous and also lack a metacarpal. This study conducts a survey of cetacean metacarpal and phalangeal morphologies, traces the evolution of hyperphalangy in a phylogenetic context, optimizes characters onto previously published cetacean phylogenies, and tests various digit loss hypotheses. Dissections were performed on 16 cetacean flippers representing 10 species (8 mysticetes, 2 odontocetes). Phalangeal count data were derived from forelimb radiographs (36 odontocetes, 5 mysticetes), osteological specimens of articulated forelimbs (8 mysticetes), and were supplemented with published counts. Modal phalangeal counts were coded as ordered and unpolarized characters and optimized onto two known cetacean phylogenies. Results indicate that digital ray I is reduced in many cetaceans (except Globicephala) and all elements of digital ray I were lost in tetradactylous mysticetes. Fossil evidence indicates this ray may have been lost approximately 14 Ma. Most odontocetes also reduce the number of phalangeal elements in digit V, while mysticetes typically retain the plesiomorphic condition of three phalanges. Results from modal phalangeal counts show the greatest degree of hyperphalangy in digits II and III in odontocetes and digits III and IV in mysticetes. Fossil evidence indicates cetacean hyperphalangy evolved by at least 7-8 Ma. Digit loss and digit positioning may underlie disparate flipper shapes, with narrow, elongate flippers facilitating fast swimming and broad flippers aiding slow turns. Hyperphalangy may help distribute leading edge forces, and multiple interphalangeal joints may smooth leading edge flipper contour. Anat Rec, 290:654-672, 2007. 2007 Wiley-Liss, Inc.

The forelimb of cetaceans (whales, dolphins, and porpoises) has been radically modified during the limb-to-flipper transition. Extant cetaceans have a soft tissue flipper encasing the manus and acting as a hydrofoil to generate lift. The neuromuscular anatomy that controls flipper movement, however, is poorly understood. This study documents flipper neuromuscular anatomy and tests the hypothesis that antebrachial muscle robustness is related to body size. Data were gathered during dissections of 22 flippers, representing 15 species (7 odontocetes, 15 mysticetes). Results were compared with published descriptions of both artiodactyls and secondarily aquatic vertebrates. Results indicate muscle robustness is best predicted by taxonomic distribution and is not a function of body size. All cetaceans have atrophied triceps muscles, an immobile cubital joint, and lack most connective tissue structures and manus muscles. Forelimbs retain only three muscle groups: triceps (only the scapular head is functional as the humeral heads are vestigal), and antebrachial extensors and flexors. Well-developed flexor and extensor muscles were found in mysticetes and basal odontocetes (i.e., physeterids, kogiids, and ziphiids), whereas later diverging odontocetes (i.e., monodontids, phocoenids, and delphinids) lack or reduce these muscles. Balaenopterid mysticetes (e.g., fin and minke whales) may actively change flipper curvature, while basal odontocetes (e.g., sperm and beaked whales) probably stiffen the flipper through isometric contraction. Later diverging odontocetes lack musculature supporting digital movements and are unable to manipulate flipper curvature. Cetacean forelimbs are unique in that they have lost agility and several soft tissue structures, but retain sensory innervations.

Physostigmine (an anticholinesterase agent that increases acetylcholine at the synapse), in a dose of 0.5 milligram, was given intravenously to seven normal human volunteers. When injected during rapid eye movement (REM) sleep, physostigmine woke the subjects, and when injected during non-REM sleep, it induced REM sleep. This result suggests that cholinergic mechanisms play a role in the induction of REM sleep and in modulating cortical arousal mechanisms.