Ocular manifestations of Donohue's syndrome.

INTRODUCTION: Donohue's syndrome, also known as Leprechaunism, is a rare autosomal recessive disease that manifests at birth with symptoms of endocrine dysfunction. Metabolic characteristics of the disease include postprandial hyperglycemia, fasting hypoglycemia, insulin resistance, hyperinsulinemia, and failure to thrive. The physical features most often associated with this condition include hypertrichosis, pachyderma, acanthosis nigricans, prominent genitalia, and elfin-like facial characteristics of prominent eyes, wide nostrils, thick lips, and large, low-set ears. Not only is this syndrome rare, but it often results in infant and early childhood mortality. The literature regarding ocular manifestations is limited. CASE REPORT: We present a case of a 29-year-old male with Donohue's syndrome and significant ocular findings including a subluxated mature cataract, retinal detachment, high myopia, and optic atrophy. DISCUSSION: These ocular sequelae are discussed with regard to the noted endocrine dysfunction and its effects on tissue development and growth.     

A behavioral group procedure for parents of severely troubled and troubling youth in out-of-home care: Alternative to conventional parent training

Many youth, their parents, and social services regard the unification of the family as the most desirable outcome for youth in out-of-home placements. This goal is often difficult to achieve because the families of these troubled/troubling youths are often severely dysfunctional, with multiple problems. A group process model for serving natural parents of youth in placement is described which, in conjunction with one-on-one interactions with professionals, appears to have a positive impact on these families and on youths' return home. Group components that seem particularly important are described, including attendance by invitation only, public commitment to attend and participate, reminder prompts, transportation support, babysitting support, refreshments, opportunity to visit with their child, defined staff roles, an empowering approach, and starting where the parent is. The group process maintained a relatively high level of both attendance and participation by the targeted parents. Participants tended to achieve most goals that they set in the group. Our experience indicates that interventions with natural parents of troubled youth can enable even a very dysfunctional family to improve enough to receive youth back into their home.The authors are grateful for the assistance of Sharon Estill, Jim Bernardo, Anita Mentzer, Dave Walker, and Suni Dague-Lyman for assistance in collecting the data reported here. Debbie Buchanan and others have been a great assistance in transporting families.     

Mechanical characterization of collagen fibers and scaffolds for tissue engineering

Engineered tissues must utilize scaffolding biomaterials that support desired cellular functions and possess or can develop appropriate mechanical characteristics. This study assessed properties of collagen as a scaffolding biomaterial for ligament replacements. Mechanical properties of extruded bovine achilles tendon collagen fibers were significantly affected by fiber diameter, with smaller fibers displaying higher tangent moduli and peak stresses. Mechanical properties of 125 micrometer-diameter extruded fibers (tangent modulus of 359.6+/-28.4MPa; peak stress of 36.0+/-5.4MPa) were similar to properties reported for human ligaments. Scaffolds of extruded fibers did not exhibit viscoelastic creep properties similar to natural ligaments. Collagen fibers from rat tail tendon (a well-studied comparison material) displayed characteristic strain-softening behavior, and scaffolds of rat tail fibers demonstrated a non-intuitive relationship between tangent modulus and specimen length. Composite scaffolds (extruded collagen fibers cast within a gel of Type I rat tail tendon collagen) were maintained with and without fibroblasts under standard culture conditions for 25 days; cell-incorporated scaffolds displayed significantly higher tangent moduli and peak stresses than those without cells. Because tissue-engineered products must possess appropriate mechanical as well as biological/chemical properties, data from this study should help enable the development of improved tissue analogues.     

Long-term wear of ceramic matrix composite materials for hip prostheses under severe swing phase microseparation

The purpose of this study was to evaluate the long-term wear performance of alumina matrix composite (AMC) heads against alumina matrix composite inserts and alumina matrix composite heads against alumina (Al) inserts with the use of a hip-joint simulator incorporating severe swing phase joint microseparation. The wear of AMC on Al produced an average wear rate of 0.61 mm3/million cycles over the 5-million-cycle test duration. The wear of AMC on AMC produced an average wear rate of 0.16 mm3/million cycles over the 5-million-cycle test duration. Both the AMC on alumina and AMC on AMC produced significantly lower wear than previously tested HIPed alumina, where an average wear rate of 1.84 mm3/million cycles was reported over 5 million cycles. The wear mechanisms and wear debris of AMC on AMC and AMC on Al were similar to those observed in previous alumina retrieval studies with stripe wear caused by intragranular fracture and wear debris consisting of predominantly uniform 10-20-nm-sized particles and a few irregular particles up to 3 microm in size.     

Mast cell tryptase and proteinase-activated receptor 2 induce hyperexcitability of guinea-pig submucosal neurons

Mast cells that are in close proximity to autonomic and enteric nerves release several mediators that cause neuronal hyperexcitability. This study examined whether mast cell tryptase evokes acute and long-term hyperexcitability in submucosal neurons from the guinea-pig ileum by activating proteinase-activated receptor 2 (PAR2) on these neurons. We detected the expression of PAR2 in the submucosal plexus using RT-PCR. Most submucosal neurons displayed PAR2 immunoreactivity, including those colocalizing VIP. Brief (minutes) application of selective PAR2 agonists, including trypsin, the activating peptide SL-NH₂ and mast cell tryptase, evoked depolarizations of the submucosal neurons, as measured with intracellular recording techniques. The membrane potential returned to resting values following washout of agonists, but most neurons were hyperexcitable for the duration of recordings (> 30 min–hours) and exhibited an increased input resistance and amplitude of fast EPSPs. Trypsin, in the presence of soybean trypsin inhibitor, and the reverse sequence of the activating peptide (LR-NH₂) had no effect on neuronal membrane potential or long-term excitability. Degranulation of mast cells in the presence of antagonists of established excitatory mast cell mediators (histamine, 5-HT, prostaglandins) also caused depolarization, and following washout of antigen, long-term excitation was observed. Mast cell degranulation resulted in the release of proteases, which desensitized neurons to other agonists of PAR2. Our results suggest that proteases from degranulated mast cells cleave PAR2 on submucosal neurons to cause acute and long-term hyperexcitability. This signalling pathway between immune cells and neurons is a previously unrecognized mechanism that could contribute to chronic alterations in visceral function.     

Autoradiographic evidence of primary projections to the caudal cochlear nucleus in cats

Six adult cats received unilateral cochlear injections of 30–70 μCi ³H-leucine (³-H-leu) in saline. After 20–48 hours, their brains were prepared for autoradiography. The octopus cell area (OCA) and the dorsal region (DCN) of the cochlear nucleus of both the injected and uninjected sides were studied in detail. Grain counts of autoradiographs always showed much greater label in the injected side. Autoradiography confirmed uniform distribution of primary afferents in the OCA, as seen in grain counts over the whole area (both somata and neuropil); however, grains were more densely packed over somata than neuropil of the OCA. In DCN, grain counts showed a gradient of label from the deep to superficial layers, a greater density of label over somata than neuropil of the deep DCN, and uniform distribution of label over the whole fusiform cell layer of the DCN. These results showed (1) best resolution and localization in cats that survived 24 hours and with exposures of two weeks, (2) no significant diffusion of label to other CNS regions than the auditory nuclei,and (3) transneuronal transport of label after 48-hour survival times. Liquid scintillation counts (LSC) of cochlear nerve roots ipsilateral and contralateral to the injection showed at least a 10:1 ratio in all cats. This report not only gives new autoradiographic evidence of the distribution of primary afferents within the caudal cochlear nucleus, but also provides a useful approach to the study of distribution of specific amino acids implicated in central neurotransmission by cochlear terminals.     

The pelvic epithelium of the rat kidney: A scanning and transmission electron microscopic study

The renal pelvis of the rat is characterized by extensions called specialized fornices that penetrate into the outer zone of the outer medulla (a type II as classified by Pfeiffer, 1968, 1970). The renal pelvic epithelium, therefore, covers areas of the kidney from the inner medulla, the inner and outer stripe of the outer medulla, and the cortex. The renal pelves of seven rats were studied by transmission and scanning electron microscopy. The transitional epithelium on the nonparenchymal surface of the pelvis was three to four cell layers thick (zone 0–1). This epithelium became thinner where it covered the renal cortex (zone 1–2) or the outer medulla. Although the apical cells of the epithelium retained the asymmetric luminal unit-membrane plaques, the number of cytoplasmic fusiform vesicles decreased as one studied the epithelium progressing over the zones from cortex toward papilla. Scanning electron microscopy demonstrated a small number of surface cells of a different morphology that were characterized by apical microvilli. The number of these microvillous lining cells increased as the epithelium covering the outer (zone 2–3) and inner (zone 3–4) stripe regions of the outer medulla was viewed, until the inner medulla was entirely covered by this cell type. In a reciprocal manner, the cells with the asymmetric apical plaques decreased in numbers and in their morphologic specialization in each successive region. The epithelium surrounding the inner medulla (zone 6–7) was completely devoid of this transitional cell type. Judging from the morphologic characteristics of the epithelia, one could surmise that little exchange of urea, water, and salts would occur with the extrarenal connective tissue or the cortical parenchyma. Recycling of urea might become more important physiologically with the outer stripe parenchyma, and even more so with the increased surfaces of the inner stripe parenchyma that lined the secondary pyramid, as well as with the epithelium lining the inner medulla.     

Inhibition of phospholipase A2 (PLA2) activity by nifedipine and nisoldipine is independent of their calcium-channel-blocking activity

The effects of several calcium antagonists on phospholipase A₂ (PLA₂) activity were examined. Nifedipine and nisoldipine inhibited a cell-free preparation of PLA₂ in a dose-dependent manner with maximal inhibition of 71–77% observed at 100M. More potent or equipotent dihydropyridine calcium antagonists such as nitrendipine and felodipine did not inhibit PLA₂ activity. In addition, nondihydropyridine calcium antagonists such as diltiazem, verapamil, and cinnarazine failed to reduce PLA₂ activity markedly. Nifedipine and nisoldipine also reduced PLA₂ activity in intact mouse peritoneal macrophages where PLA₂ activity was monitored by free [¹⁴C]arachidonic acid release from [¹⁴C]arachidonic acid-prelabeled cells. When levels of PGE₂ and LTC₄ were measured by radioimmunoassay, it was found that the synthesis of these two metabolites was concomitantly inhibited by nifedipine and nisoldipine. In vivo, nifedipine and nisoldipine inhibited tetradecanoylphorbol acetate (TPA) induced ear edema. UV irradiation of nifedipine and nisoldipine (which destroys the slow caicium-channel-blocking activity of these compounds) did not result in a loss of PLA₂ inhibitory activity. In fact, in both instances the UV-irradiated forms of nifedipine and nisoldipine were slightly more potent PLA₂ inhibitors than the parent compound alone. We therefore conclude that the ability of nifedipine and nisoldipine to inhibit PLA₂ was direct and unrelated to their actions on slow calcium channels.     

Early experience influences adult retention of aversively motivated tasks in normal,but not DSP4-treated rats

Sprague-Dawley rat pups were injected with DSP4 or water within 48 hr of birth and tested as adults in an inhibitory avoidance task and in a Y-maze discrimination reversal task. Half of the animals were also tested as juveniles during postnatal weeks 4–5, in tasks assessing odor preferences and general investigatory behavior. Controls, but not drug-treated adults, which received the juvenile testing, showed significantly better retention on both tasks than either controls or drug-treated animals not tested as juveniles. Neonatal DSP4 significantly reduced norepinephrine concentrations in the hippocampus and frontal cortex, but not the heart. The results suggest that central norepinephrine may modulate the effects of early experience on adult learning.