Allergen-specific IgG and IgA in serum and bronchoalveolar lavage fluid in a model of experimental feline asthma.

Allergic asthma, a Th2 cell driven response to inhaled allergens, has classically been thought of as predominantly mediated by IgE antibodies. To investigate the role of other immunoglobulin classes (e.g., IgG and IgA) in the immunopathogenesis of allergic asthma, levels of these allergen-specific immunoglobulins were measured in serum and mucosal fluids. Bermuda grass allergen (BGA)-specific IgG and IgA ELISAs in serum and bronchoalveolar lavage fluid (BALF) were developed and optimized in an experimental model of BGA-induced feline asthma. Levels of BGA-specific IgG and IgA significantly increased over time in serum and BALF after allergen sensitization. Additionally, these elevated levels of BGA-specific IgG and IgA were seen in conjunction with the development of an asthmatic phenotype indicated by positive intradermal skin tests, enhanced airways hyperreactivity, and increased eosinophil percentages in the BALF.

Production of polyclonal antisera against feline immunoglobulin E and its use in an ELISA in cats with experimentally induced asthma.

Serum samples from six cats with experimentally induced asthma were used to purify feline IgE using gel filtration and affinity chromatography. The resultant IgE, evaluated for purity by immunoelectrophoresis (IEP) and reactivity by Prausnitz-Kustner (PK) testing, was used to develop polyclonal rabbit anti-feline IgE antisera. Using reverse cutaneous anaphylaxis (RCA), the antisera were determined to be specific for feline IgE. The polyclonal rabbit anti-feline IgE antiserum was then validated in an allergen-specific ELISA. Serum samples from an additional five asthmatic cats sensitized with Bermuda grass allergen (BGA) were evaluated prior to sensitization, after parenteral sensitization, and after aerosol sensitization and challenge. A significant increase in serum BGA-specific IgE was noted over time.

Interrelations of organism prevalence, specimen collection method, and host age, sex, and breed among 8,354 canine urinary tract infections (1969-1995).

Selected information was compiled from canine urinalyses and urine cultures conducted between January 1969 and December 1995. Eight thousand three hundred fifty-four microbial isolates (bacteria and fungi) included 4,873 isolates from females and 3,481 from males. Ten bacterial genera accounted for 96.3% of the urinary isolates, including Escherichia coli (44.1%), Staphylococcus spp. (11.6%), Proteus spp. (9.3%), Klebsiella spp. (9.1%), Enterococcus spp. (8.0%), and Streptococcus spp. (5.4%) as the 6 most common isolates in both genders of dogs. Among these 6 genera, female dogs were generally predisposed over males, although males had more urinary tract infections (UTIs) caused by Klebsiella spp. Distributions of ages at UTI diagnosis tended to be similar between genders. Infection with a single microbial species was responsible for >72% of UTIs in both genders. Among females, 40 breeds and a mixed-breed group represented 90.2% of all positive urine cultures, 88.4% of the individual dogs with UTIs. and 88.2% of the microbial isolations. Among males, these same 41 breed groups represented 87.9% of all positive urine cultures, 87.6% of the individual dogs, and 88.2% of the microbial isolations.

Comparison of results of thoracic radiography, cytologic evaluation of bronchoalveolar lavage fluid, and histologic evaluation of lung specimens in dogs with respiratory tract disease: 16 cases (1996-2000).

OBJECTIVE: To compare results of thoracic radiography, cytologic evaluation of bronchoalveolar lavage (BAL) fluid, and histologic evaluation of biopsy and necropsy specimens in dogs with respiratory tract disease and to determine whether histologic evaluation provides important diagnostic information not attainable by the other methods. DESIGN: Retrospective study. ANIMALS: 16 dogs. PROCEDURE: BAL fluid was classified as normal, neutrophilic, eosinophilic, mononuclear, mixed, neoplastic, or nondiagnostic. Radiographic abnormalities were classified as interstitial, bronchial, bronchointerstitial, or alveolar. Histologic lesions were classified as inflammatory, fibrotic, or neoplastic, and the predominant site of histologic lesions was classified as the alveoli, interstitium, or airway. RESULTS: The predominant radiographic location of lesions correlated with the histologic location in 8 dogs. Of 11 dogs with histologic evidence of inflammatory disease, 8 had inflammatory BAL fluid. Of the 2 dogs with histologic evidence of neoplasia, 1 had BAL fluid suggestive of neoplasia, and the other had BAL fluid consistent with septic purulent inflammation. Two dogs without any histologic abnormalities had mononuclear or nondiagnostic BAL fluid. Two dogs with histologic evidence of fibrosis had mononuclear or mixed inflammatory BAL fluid. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that although thoracic radiography, cytologic evaluation of BAL fluid, and histologic evaluation of lung specimens are complementary, each method has limitations in regard to how well results reflect the underlying disease process in dogs with respiratory tract disease. Lung biopsy should be considered in cases where results of radiography and cytology are nondiagnostic.

Recurrent and persistent urinary tract infections in dogs: 383 cases (1969-1995).

Laboratory records of bacterial urine cultures from 383 dogs with recurrent or persistent urinary tract infections (UTI) diagnosed at the University of California Veterinary Medical Teaching Hospital (VMTH) between 1969 and 1995 were reviewed retrospectively to characterize the bacteria involved and their association with age, gender, and breed of dogs affected. Sixty-eight breeds and a mixed-breed group were represented. Escherichia coli was the most common isolate, although mixed-bacterial infections were seen in 58% of the female and 55% of the male dogs. Recurrent and persistent UTI were most prevalent in middle-aged to older German shepherd dogs, miniature/toy poodles, and Labrador retrievers, with no apparent sex predilection. Criteria fitting recurrent and persistent UTI were present in 0.3% of all dogs seen at the VMTH during this 26-year period.

Evaluation of serum feline trypsin-like immunoreactivity for the diagnosis of pancreatitis in cats.

OBJECTIVE: To evaluate serum feline trypsin-like immunoreactivity (fTLI) concentration and results of abdominal ultrasonography, CBC, and serum biochemical analyses for diagnosis of pancreatitis in cats. DESIGN: Prospective study. ANIMALS: 28 cats with clinical signs compatible with pancreatitis. PROCEDURE: Serum fTLI concentrations were determined, and abdominal ultrasonography, CBC, and serum biochemical analyses were performed prior to histologic evaluation of pancreatic, hepatic, and intestinal specimens. On the basis of histologic results, cats were categorized as having a normal pancreas (n = 10), pancreatic fibrosis with ongoing inflammation (9), pancreatic fibrosis without inflammation (4), and acute necrotizing pancreatitis (5). Serum fTLI concentrations and results of CBC, serum biochemical analyses, and histologic evaluation of hepatic and intestinal specimens were compared among groups. RESULTS: Significant differences in serum fTLI concentrations or any hematologic or biochemical variable were not detected among the 4 groups of cats. Median serum fTLI concentrations were 51 micrograms/L (range, 18 to 200 micrograms/L) in cats with a normal pancreas, 32 micrograms/L (range, 12 to > 200 micrograms/L) in cats with pancreatic fibrosis and ongoing inflammation, 124 micrograms/L (range, 36 to > 200 micrograms/L) in cats with pancreatic fibrosis without ongoing inflammation, and 30 micrograms/L (range, 24 to 84 micrograms/L) in cats with acute necrotizing pancreatitis. We detected a high prevalence of concurrent hepatic and intestinal tract disease in cats with pancreatitis. CONCLUSIONS AND CLINICAL RELEVANCE: In cats with clinical signs of pancreatitis, serum fTLI concentration is poorly associated with histopathologic diagnosis.

Endogenous lipid pneumonia in cats: 24 cases (1985-1998).

OBJECTIVE: To determine clinical signs, radiographic and histologic abnormalities, and concurrent diseases in cats with endogenous lipid pneumonia (EnLP) and to determine the pathologic importance of EnLP in cats. DESIGN: Retrospective study. ANIMALS: 24 cats. PROCEDURE: Medical records of cats in which EnLP was confirmed by histologic examination of necropsy specimens were reviewed. Information collected from the medical records included signalment, body weight, clinical signs, and results of clinicopathologic tests. Thoracic radiographs were reviewed by a radiologist; histologic specimens were reviewed by a pathologist. RESULTS: All cats had nonspecific clinical abnormalities, such as lethargy, anorexia, or weight loss; 16 had signs of respiratory tract disease. All cats had concurrent systemic diseases, and clinicopathologic abnormalities were reflective of these conditions. Nonspecific abnormalities were detected on thoracic radiographs from 9 of 11 cats. Most cats had macroscopic, multifocal, subpleural lesions; inflammatory infiltrates, cholesterol clefts, and multinucleated giant cells were common. Ten cats had an underlying obstructive pulmonary disease that was the likely cause of EnLP. Lesions of EnLP were not considered to be severe enough or extensive enough to be the cause of death in any of these cats. CONCLUSIONS AND CLINICAL RELEVANCE: EnLP is an uncommon respiratory tract disorder of cats with no pathognomonic clinical, laboratory, or radiographic findings. Although EnLP was not the cause of death in any of these cats, results of the present study do suggest that EnLP may be a marker for potentially severe underlying obstructive pulmonary disease.

Laryngeal paralysis in cats: 16 cases (1990-1999).

OBJECTIVE: To determine clinical signs, physical examination findings, radiographic features, and concurrent diseases in cats with laryngeal paralysis, as well as evaluate the outcome of medical or surgical management. DESIGN: Retrospective study. ANIMALS: 16 cats. PROCEDURE: Medical records from January 1990 to April 1999 were examined for cats with laryngeal paralysis. Signalment, clinical signs, physical examination findings, cervical and thoracic radiographic findings, laryngeal examination results, and clinical outcome were reviewed. RESULTS: No breed or sex predilection was identified in 16 cats with laryngeal paralysis. The most common clinical signs included tachypnea or dyspnea, dysphagia, weight loss, change in vocalization, coughing, and lethargy. Clinical signs were evident for a median of 245 days. Airway obstruction was apparent on cervical and thoracic radiographic views in 9 cats. Examination of the larynx revealed bilateral laryngeal paralysis in 12 cats and unilateral laryngeal paralysis in 4 cats. The 4 cats with unilateral disease were managed with medical treatment, and 3 of these had acceptable long-term outcomes. Seven of 12 cats with bilateral paralysis underwent surgery; procedures performed included left arytenoid tie back, bilateral arytenoid tie back and ventriculo-cordectomy, and partial left arytenoidectomy. One cat was euthanatized as a result of complications from surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Laryngeal paralysis is an uncommon cause of airway obstruction in cats. Cats with less severe clinical signs (often with unilateral paralysis) may be successfully managed with medical treatment, whereas cats with severe airway obstruction (often with bilateral paralysis) may benefit from surgical intervention.

Clinical, radiographic, and pathologic features of bronchiectasis in cats: 12 cases (1987-1999).

OBJECTIVE: To determine clinical, radiographic, and pathologic features of bronchiectasis in cats. DESIGN: Retrospective study. ANIMALS: 12 cats with histologic evidence of bronchiectasis. PROCEDURE: Information on signalment, body weight, clinical signs of respiratory disease, concurrent diseases, method by which lung tissue specimens were obtained (surgical biopsy or necropsy), and histopathologic findings was obtained by reviewing medical records from January 1987 to June 1999 for cats with confirmation of bronchiectasis by histologic examination. Available thoracic radiographs were reviewed by a board-certified radiologist. RESULTS: Bronchiectasis was most commonly identified in older male cats. Clinical signs referable to the lower portion of the respiratory tract were detected in only 5 cats but, when evident, were usually chronic (duration > 1 year). Radiographic pattern of bronchiectasis was cylindrical in 4 cats, and in 1 of these cats, a saccular pattern was also identified. For most cats, bronchiectasis was detected in a single lung lobe. Radiographic evidence of bronchiectasis was not detected in 2 cats. Concurrent respiratory diseases included chronic bronchitis and bronchiolitis, neoplasia, bronchopneumonia, endogenous lipid pneumonia, and emphysema. CONCLUSIONS AND CLINICAL RELEVANCE: Bronchiectasis appears to be an uncommon respiratory tract disorder that predominantly affects older male cats. Thoracic radiography may not be sensitive for the diagnosis of bronchiectasis in cats. Bronchiectasis in cats appears to be a sequela of chronic inflammatory bronchopulmonary diseases, especially chronic bronchitis, neoplasia, and bronchopneumonia.

Conservation and novelty in the evolution of cell adhesion and extracellular matrix genes.

New proteins and modules have been invented throughout evolution. Gene "birth dates" in Caenorhabditis elegans range from the origins of cellular life through adaptation to a soil habitat. Possibly half are "metazoan" genes, having arisen sometime between the yeast-metazoan and nematode-chordate separations. These include basement membrane and cell adhesion molecules implicated in tissue organization. By contrast, epithelial surfaces facing the environment have specialized components invented within the nematode lineage. Moreover, interstitial matrices were likely elaborated within the vertebrate lineage. A strategy for concerted evolution of new gene families, as well as conservation of adaptive genes, may underlie the differences between heterochromatin and euchromatin.

Serum total and ionized magnesium concentrations and urinary fractional excretion of magnesium in cats with diabetes mellitus and diabetic ketoacidosis.

OBJECTIVE: To determine magnesium (Mg) status in cats with naturally acquired diabetes mellitus (DM) and diabetic ketoacidosis (DKA), evaluate changes in Mg status after treatment for DKA, and correlate Mg status with systemic blood pressure and degree of glycemic control. DESIGN: Case series and cohort study. ANIMALS: 12 healthy cats (controls), 21 cats with DM, and 7 cats with DKA. PROCEDURE: Serum total magnesium (tMg) and ionized magnesium (iMg) concentrations and spot urinary fractional excretion of magnesium (FEmg) were determined, using serum and urine samples obtained from all cats when they were entered in the study and from cats with DKA 12, 24, and 48 hours after initiating treatment. Indirect blood pressure and degree of glycemic control were determined in 10 and 21 cats with DM, respectively. RESULTS: Initially, 2 and 13 cats with DM and 1 and 4 cats with DKA had serum tMg and iMg concentrations, respectively, less than the low reference limit (mean-2 SD) determined for controls. In cats with DKA, serum tMg concentration decreased significantly over time after initiating treatment. Urinary FEmg was significantly higher in cats with DM or DKA, compared with controls. Systemic hypertension was not detected nor was there a correlation between Mg status and degree of glycemic control in cats with DM. CONCLUSIONS AND CLINICAL RELEVANCE: Hypomagnesemia was a common finding in cats with DM and DKA and was more readily identified by measuring serum iMg concentration than tMg concentration. The clinical ramifications of hypomagnesemia in such cats remain to be determined.

Effect of magnesium-deficient diet on serum and urine magnesium concentrations in healthy cats.

OBJECTIVE: To evaluate the efficacy of using serum total and ionized magnesium (Mg) concentrations and urine Mg concentrations to identify Mg deficiency in cats. ANIMALS: 6 healthy castrated male cats. PROCEDURE: A Mg-replete diet was fed for 37 days, followed by a Mg-deficient diet for 37 days. On days 1, 3, and 7 of the last week of each diet, serum ionized and total Mg concentrations were determined; in addition, urine Mg concentration was determined each day of the last week. Serum total and ionized Mg concentrations were compared with urine Mg concentration, amount of Mg excreted during 24 hours (24-hour urine Mg excretion), ratio of urine Mg concentration to urine creatinine concentration (Umg:Ucr), and urinary fractional excretion of Mg (FEmg) to determine which variable best predicted Mg status. RESULTS: Cats fed Mg-deficient diets had significantly lower serum total and ionized Mg concentrations and 24-hour urine Mg excretion values, compared with cats fed Mg-replete diets. Serum total Mg concentration was the best predictor of Mg status. Twenty-four-hour urine Mg excretion was a repeatable, reliable measurement and had the best correlation with serum total Mg concentration. Serum total Mg concentration also correlated with urine Mg concentration, Umg:Ucr, and FEmg. CONCLUSIONS AND CLINICAL RELEVANCE: Serum total and ionized Mg concentrations can be used to identify cats with dietary-induced Mg deficiencies. Twenty-four-hour urine Mg excretion and urine Mg concentration correlated best with serum total Mg concentration and, therefore, may be the most useful urine variables for identifying Mg deficiency.

Healthy cats are commonly colonized with "Helicobacter heilmannii" that is associated with minimal gastritis.

Gastric Helicobacter infection in healthy pet cats is not well characterized. We performed endoscopy with gastric biopsy on 15 healthy pet cats that were rigorously screened to exclude underlying or concurrent diseases that might affect Helicobacter colonization. Gastric mucosa biopsy specimens were examined by histology, culture, and PCR for the presence of Helicobacter infection and by histology for the presence of gastritis. Of 15 cats, all but 1 had gastric Helicobacter-like organisms (GHLOs) on examination by light microscopy, and in the one histologically negative cat, GHLOs were detected by PCR. Gastric inflammation was mild or was absent for all cats. No Helicobacter species were identified by culture. Analysis of the 16S rRNA sequence from Helicobacter strains from 10 cats showed that all bacteria were closely related to Helicobacter felis, although there was heterogeneity among the sequences. These results suggest that the gastric mucosa of healthy pet cats is commonly colonized with an uncultivated Helicobacter that is closely related to H. felis, is associated with little or no gastritis, and shows heterogeneity in its 16S rRNA sequence. The epithet "Helicobacter heilmannii" continues to be an appropriate working designation for these bacteria.

Pulmonary thromboembolism in cats: 29 cases (1987-1997).

OBJECTIVE: To determine clinical signs, clinicopathologic abnormalities, radiographic findings, histologic abnormalities, and predisposing factors or diseases in cats with pulmonary thromboembolism (PTE). DESIGN: Retrospective study. ANIMALS: 29 cats in which PTE was confirmed at necropsy. PROCEDURE: Information on signalment, body weight, history, results of physical examination, results of CBC and serum biochemical analyses, whether PTE was suspected prior to death, type of indwelling venous catheter and duration of venous catheterization, results of thoracic radiography, and whether cats had any concurrent diseases was obtained from medical records. RESULTS: PTE was identified in cats of various ages (median, 8.7 years), weights (median, 4.1 kg [9 lb]), and breeds. The most common owner-reported problems included lethargy (17 cats), anorexia (14), weight loss (10), and difficulty breathing (8); physical abnormalities included lethargy (21), tachypnea or dyspnea (16), and dehydration (13). Clinicopathologic abnormalities reflected concurrent or underlying diseases. Common radiographic abnormalities included pulmonary vessel abnormalities (11), pleural effusion (8), and peripheral noncircumscribed consolidations (6). Underlying or predisposing conditions, including cardiac disease (12), neoplasia (10), corticosteroid administration (8), disseminated intravascular coagulation (5), protein-losing nephropathy (4) or enteropathy (4), immune-mediated hemolytic anemia (2), and sepsis (2) were identified in all cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that PTE can develop in cats of any age, sex, or breed. Because PTE is a serious, potentially life-threatening disease, it should be suspected in cats with thoracic radiographic changes suggestive of uneven distribution of blood flow between lung lobes, especially in cats that have predisposing factors or diseases.

Disposition of cyproheptadine in cats after intravenous or oral administration of a single dose.

OBJECTIVE: To determine disposition of cyproheptadine hydrochloride in cats after intravenous or oral administration of a single dose. ANIMALS: 6 healthy cats. PROCEDURE: A randomized crossover design was used, and each cat was studied after intravenous (2 mg) and oral (8 mg) administration of cyproheptadine. Blood samples were collected at fixed time intervals after drug administration, and serum cyproheptadine concentration was determined by means of polarized immunofluorescence. RESULTS: Mean (+/- SD) residence time was significantly longer after oral (823 +/- 191 minutes) than after intravenous (339 +/- 217 minutes) administration, but no significant differences were detected between other pharmacokinetic parameters after oral and intravenous administration. Mean +/- SD oral bioavailability was 1.01 +/- 0.36. Mean elimination half-life after oral administration was 12.8 +/- 9.9 hours. Peak extrapolated cyproheptadine concentration was 669 +/- 206 ng/ml. Only 1 cat developed adverse effects (transient vocalization). CONCLUSIONS: Cyproheptadine appeared to be well tolerated in cats and had high bioavailability after oral administration. The mean elimination half-life of 12 hours indicated that approximately 2.5 days must elapse to achieve steady-state concentrations of cyproheptadine after oral administration of multiple doses. A 12-hour dosing interval is acceptable, but an 8-hour interval may be indicated for some cats. CLINICAL RELEVANCE: On the basis of pharmacokinetic parameters determined in this study, the oral form of cyproheptadine appears to be suitable for use in clinical trials to treat anorexia in cats. Its half-life is compatible with once or twice daily dosing.

Understanding Workers' Compensation Law.

"Understanding Workers' Compensation Law" is a primer on workers' compensation, intended to give physicians a basic understanding of how workers' compensation systems function. With this background, it is hoped that those physicians who treat patients suffering from work-related injuries will more fully appreciate their role in the system. The article also outlines a few helpful hints to assist the physician when she or he is treating workers' compensation patients so that the physician can streamline his or her practice and involvement in this area and make interaction with all parties less burdensome.

Development of callosal connections in the sensorimotor cortex of the hamster.

To investigate the development of corpus callosal connectivity in the hamster sensorimotor cortex, we have used the sensitive axonal tracer 1,1 dioctadecyl-3,3,3',3', tetramethylindocarbocyanine perchlorate (DiI), which was injected either in vivo or in fixed brains of animals 3-6 days postnatal. First, to study changes in the overall distribution of developing callosal afferents we made large injections of DiI into the corpus callosal tract. We found that the anterogradely labeled callosal axons formed a patchy distribution in the contralateral sensorimotor cortex, which was similar to the pattern of adult connectivity described in earlier studies of the rodent corpus callosum. This result stands in contrast to previous retrograde studies of developing callosal connectivity which showed that the distribution of callosal neurons early in development is homogeneous and that the mature, patchy distribution arises later, primarily as a result of the retraction of exuberant axons. The initial patchy distribution of callosal axon growth into the sensorimotor cortex described in the present study suggests that exuberant axons destined to be eliminated do not enter the cortex. In addition, small injections of DiI into developing cortex resulted in homotopic patterns of callosal topography in which reciprocal regions of sensorimotor cortex are connected, as has been shown in the adult. Second, to study the radial growth of callosal afferents we followed the extension of individual callosal axons into the developing cortex. We found that callosal axons began to invade the contralateral cortex on about postnatal day 3, with little or no waiting period in the callosal tract. Callosal afferents then advanced steadily through the cortex, never actually invading the cortical plate but extending into layers on the first day that they could be distinguished from the cortical plate. The majority of callosal axons grew radially through the cortex and did not exhibit substantial branching until postnatal day 8, the age when the cortical plate disappears and callosal afferents reach the outer layer of cortex. This mode of radial growth through cortex prior to axon branching could serve to align callosal afferents with their radial or columnar targets before arborizing laterally.

Guidance of callosal axons by radial glia in the developing cerebral cortex.

During development, columns of the mammalian cerebral cortex are formed by migration of neurons along fascicles of radial glia. Subsequently, axons of the corpus callosum connect reciprocal regions of each cerebral hemisphere. To determine whether the radial growth of callosal afferents through the developing cortex may be guided by particular cellular elements, we examined the ultrastructural relationship between callosal afferents and radial fibers in the early postnatal hamster sensorimotor cortex. Developing callosal axons and their growth cones were labeled with HRP injected into the cortex at 3 d postnatal when the growth cones have extended across the callosum and are just entering the contralateral cortex. An EM analysis of 30 HRP-labeled axons and their growth cones revealed that they extended upon fascicles of radial processes associated with migrating neurons. Reconstruction of seven of these growth cones, serially sectioned in their entirety, showed that growth cones were associated with the same radial fascicle as their axon. Growth cones also touched other cellular elements such as axons. However, the finding that callosal afferents, from the point at which they enter the cortex to their growth cones, were apposed to a continuous fascicle of radial fibers suggests that callosal axons are tracking along radial processes. We conclude that the majority of the radial processes within fascicles are likely to be glial, based on their relatively large diameters, electron-lucent cytoplasm with a regular array of microtubules, the presence of glycogen granules, occasional cytoplasmic protrusions lacking microtubules, and their consistent association with migrating neurons. We propose therefore that radial glia may serve a guidance function for growing callosal axons in their radial trajectory through the developing cerebral cortex.

Morphology and cellular interactions of growth cones in the developing corpus callosum.

Previous studies of growth cones in invertebrates have shown that they become larger and more complex when changing direction in response to cell-specific contacts (Bentley and Caudy, '83; Raper et al., '83b; Caudy and Bentley, '86). In pathways of the vertebrate nervous system, analogous regions, termed "decision regions," have been identified in which axons change direction and their growth cones become more elaborate than when tracking along straight trajectories (Tosney and Landmesser, '85a; Bovolenta and Mason, '87). In order to assess the generality of these principles to the mammalian CNS, we studied the morphology of growth cones and their interactions with the environment in the developing corpus callosum. Given the straight pathway that callosal axons could use to navigate across the callosum, one might predict that later arriving axons would extend on those growing out earlier and that therefore, by analogy with previous studies, many growth cones would have simple tapered morphologies. Surprisingly, however, virtually all growth cones in the callosal white matter, regardless of age or position, were complex with broad lamellipodial veils and/or numerous, often lengthy filopodia. Only growth cones entering the cortical target were consistently smaller. As seen in the EM, the predominant elements in the callosal pathway are other axons and growth cones; we found no evidence for specialized contacts. These results suggest that there is no specific decision region for the fiber population as a whole; rather it is possible that in this mammalian CNS pathway individual growth cones respond independently to molecular cues broadly distributed in the callosum.