Prolonged mechanical ventilation and intracranial hemorrhage: impact on developmental progress through 18 months in infants weighing 1,200 grams or less at birth.

In this prospective, longitudinal study, the relative impact of intracranial hemorrhage and prolonged mechanical ventilation on developmental progress during the first 18 months of life of infants weighing 1,200 g or less at birth was examined. A total of 159 surviving infants were divided into two groups: infants with and those without intracranial hemorrhage. These groups were then subdivided into groups of infants receiving prolonged mechanical ventilation (greater than 21 days) and those mechanically ventilated for 21 days or less, thus creating four subgroups. Group 1 (intracranial hemorrhage and prolonged mechanical ventilation) and group 3 (intracranial hemorrhage and no prolonged mechanical ventilation) showed no statistically significant differences for severity of intracranial hemorrhage, persistence of ventriculomegaly, or presence of periventricular leukomalacia. A repeated-measures analysis of variance demonstrated a main effect for prolonged mechanical ventilation on outcome as measured by the Bayley Mental Development Index and Bayley Psychomotor Development Index at 4, 8, 12, and 18 months of age (corrected for prematurity). Forward stepwise regression revealed prolonged mechanical ventilation to the best predictor of Bayley indexes at all ages except 4 months of age, for which the Psychomotor Development Index was best predicted by length of hospitalization. No main effect for intracranial hemorrhage was demonstrated, but the motor performance of infants with intracranial hemorrhage declined significantly with age. By contrast prolonged mechanical ventilation was associated with uniformly poor performance at every age and serves as a powerful marker for poor developmental progress during the first 18 months of life in infants weighing 1,200 g or less at birth.

Insulin growth factor-I inhibits apoptosis in hematopoietic progenitor cells. Implications in thymic aging.

A decline in plasma concentrations of both growth hormone and IGF-I occurs during aging of humans and rodents, and this is accompanied by involution of the thymus gland. Exogenous growth hormone induces the synthesis of IGF-I, which acts on bone marrow-derived hematopoietic progenitors of the myeloid and lymphoid lineages to promote their replication and survival. The increase in survival of these cells is caused by the ability of IGF-I to inhibit their apoptotic death. In contrast to the multipotential colony-stimulating-factor IL-3, inhibition of apoptosis by IGF-I requires the activation of the critical intracellular effector PI 3-kinase. These data establish that hematopoietic progenitors can use more than one intracellular signaling pathway in order to maintain their survival. The data also extend the original hypothesis that IGF-I shares with the colony-stimulating factors the properties of promoting DNA synthesis and inhibiting programmed cell death. Collectively, these data establish that hematopoietic progenitor cells are important targets for IGF-I, and this is likely to be important in understanding thymic aging.

Clinical and immunohistochemical characterization of thymic lymphosarcoma in a heifer.

A 2-year-old Holstein heifer with a swollen brisket, jugular vein distention, muffled heart sounds, tachycardia, and free gas bloat was examined. Thymic lymphosarcoma was suspected based on a negative agar gel immunodiffusion test for bovine leukemia virus, presence of atypical lymphocytes in pleural fluid, and detection of a mass in the thoracic inlet. Right-sided cardiac catheterization was performed, and markedly increased jugular venous pressures (41 mm Hg) with a pressure gradient of 29 mm Hg immediately cranial to the heart indicated constriction of the cranial vena cava. Immunohistochemical staining of formalin fixed, paraffin-embedded tissue sections of the tumor using a rabbit antihuman T cell, CD3 polyclonal antibody confirmed that the neoplastic lymphocytes were of thymic origin.

Granulomatous and eosinophilic rhinitis in a cow caused by Pseudallescheria boydii species complex (Anamorph Scedosporium apiospermum).

A 2-year-old Hereford cow was presented to the teaching hospital for increased respiratory noise and bilateral bloody nasal discharge. A nodular rhinitis was detected clinically, and the nasal biopsy revealed a granulomatous and eosinophilic rhinitis with intralesional fungi. The cow was euthanized due to financial constraints. Grossly multifocal-to-coalescing, raised, ulcerated firm nodules were present in both nares. Histologically, the lamina propria was expanded by intense infiltrates of eosinophils, epithelioid macrophages, multinucleate giant cells, lymphocytes, and plasma cells. Associated with the inflammatory cells were variably sized, septate hyphae, 5-8 microm in diameter, admixed with numerous, terminal conidia, 6-30 microm in diameter, with a discrete outer wall identified by culture as Pseudallescheria boydii species complex (anamorph Scedosporium apiospermum). The infection was localized to the nasal cavity with no gross or microscopic evidence of a systemic dissemination.

Eosinophilic colitis and hepatitis in a horse with colonic intramucosal ciliated protozoa.

Tissues from a 9-year-old American Standardbred gelding with a history of anorexia, mild colic, and unexpected death were submitted to the Laboratories of Veterinary Diagnostic Medicine at the University of Illinois for histopathologic examination. Microscopic diagnoses were severe subacute, diffuse eosinophilic colitis with intralesional protozoa and a subacute to chronic eosinophilic portal hepatitis with granuloma formation. Two tissue-invading, ciliated protozoa were identified in large numbers within the colonic mucosa. The ciliates were Polymorphella ampulla and Cycloposthium sp., Phylum:Ciliophora. The eosinophilic colitis and portal hepatitis in association with the overpopulation and invasion by the ciliated protozoa suggests a causal etiology.

Cavitary periventricular leukomalacia: incidence and short-term outcome in infants weighing less than or equal to 1200 grams at birth.

One hundred surviving infants with birthweights less than or equal to 1200 g were examined longitudinally, using real-time ultrasonography of the brain. Five infants were diagnosed as having cavitary periventricular leukomalacia (PVL). One infant expired within a month following discharge; the remaining four entered a follow-up program and received developmental assessments. Three infants had moderate-severe spastic diplegia and the fourth had spastic quadriplegia. Cavitary PVL can be diagnosed in vivo and predicts future motor delay or cerebral palsy. Since the typical site of PVL involves the optic radiations, and the incidence of visual-perceptual disturbances is high in premature infants, further research is needed to explore the possible relationship between these two abnormalities.

Neuronal vacuolation and spinocerebellar degeneration in young Rottweiler dogs.

With the recent epizootic of bovine spongiform encephalopathy in Europe, the differential diagnosis of neuronal vacuolation and spongiform change in other species has become critically important. Four Rottweiler puppies of both sexes, presented at 3-8 months of age, had clinical signs of generalized weakness and ataxia that started at 6 weeks of age. In all pups, neurologic examination detected an ataxia and tetraparesis, most severe in the pelvic limbs, and slowed proprioceptive placing reactions. Subsequently, there was rapid progressive neurologic deterioration, with severe placing deficits, knuckling, severe ataxia, and quadraparesis by 8 months of age. At necropsy, no gross lesions were observed. Microscopic lesions were restricted to the nervous system. The major lesion in all dogs was an intracytoplasmic neuronal vacuolation that was most prominent in the cerebellar roof nuclei and in nuclei of the extrapyramidal system. Similar vacuolation was found in neurons in both dorsal nerve root ganglia, myenteric plexus, and other ganglia of the autonomic nervous system. The single or multiple empty vacuoles were between 1 and 45 microm in diameter. A mild spongiform change was seen in the adjacent neuropil. Purkinje cell vacuolation and degeneration with segmental cell loss was seen in the oldest dog. In ventromedial and dorsolateral areas of the spinal cord white matter, there was mild bilaterally symmetrical axonal degeneration. Immunoblotting and immunocytochemical staining of the brain for protease-resistant scrapie prion protein was negative. All forms of vacuoles were negative for immunohistochemical staining with a variety of lectins. Ultrastructurally, the vacuoles were bound by a single membrane and contained granular material and sometimes membranous profiles. There was mild distension of the cytocavitary network but no unequivocal connection with the vacuoles was found. Axosomatic and axodendritic synapses in affected neurons were intact both ultrastructurally and with synaptophysin immunostaining. The clinicopathologic findings were different from those seen in the other neurologic diseases of Rottweilers. The age of the dogs, distribution and type of the lesions, ultrastructural findings, and negative immunoblotting most likely rule out the possibility of a scrapie agent-associated spongiform encephalopathy. However, the etiology of this new disease was not determined.

Intracranial hemorrhage and neurodevelopmental outcome at one year in infants weighing 1200 grams or less. Prognostic significance of ventriculomegaly at term gestational age.

Seventy-five surviving infants weighting 1200 g or less at birth were followed up longitudinally, employing real-time ultrasonographic examination of the brain from birth to term corrected gestational age. Evaluations using the Milani-Comparetti Motor Developmental Screening Test and developmental testing using the Bayley Scales of Infant Development were performed at 4, 8, and 12 months corrected age. Thirty-five (46.7%) of the infants were diagnosed to have intracranial hemorrhage (ICH). These infants were significantly smaller and lighter and were mechanically ventilated close to five times longer than infants without ICH. ICH was predictive of poorer developmental outcome through the first postnatal year. ICH infants had significantly lower Bayley motor scores at both 4 and 12 months. Sixteen of the 20 who scored less than 84 on one or both of the Bayley Scales at one year had a history of ICH. When infants with hemorrhage and normal ventricles at term (ICH-no VM) were compared to infants with hemorrhage and ventriculomegaly at term (ICH-VM), the poorest motor outcome was seen in the ICH-VM group. Only the ICH-VM group showed motor performance significantly poorer than the non-ICH group at 12 months of age. Regardless of severity of hemorrhage, the data suggested an added risk for poorer developmental outcome in ICH survivors who had ventriculomegaly or abnormal periventricular morphology at term. Thus, intracranial hemorrhage per se indicates significantly greater risk of short-term motor sequelae continuing through the first four postnatal months, but persistently abnormal ventricles serve as a more significant "marker" of risk for longer term neuromotor delays at one year corrected age.(ABSTRACT TRUNCATED AT 250 WORDS)