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Tapetal changes in beagle dogs. II. Ocular changes after intravenous administration of a macrolide antibiotic--rosaramicin.

Two studies were conducted to assess the toxicity of rosaramicin (a macrolide antibiotic) when given intravenously for 30 consecutive days to beagle dogs with and without a tapetum lucidum (a light reflecting structure within the choroid of the eye). In the initial study, groups of three tapetal dogs/sex were given 20, 40, or 80 mg of rosaramicin/kg, twice daily. Ophthalmoscopic examination during Week 4 revealed dose-related, bilateral ocular changes characterized by a brown-tan discoloration and general pallor or loss of reflectivity of the normally blue-purple or yellow-green, highly reflective tapetum lucidum. These findings were restricted to the tapetal fundus; recovery occurred between Weeks 4 and 10 of the postdose period. To further investigate these changes, a second study was conducted in which groups of three tapetal dogs were given rosaramicin or erythromycin lactobionate (comparative macrolide antibiotic) at 80 mg/kg, twice daily. A third group of atapetal dogs was given 80 mg of rosaramicin/kg, twice daily. A similar change was observed in tapetal dogs given 80 mg of rosaramicin/kg, twice daily, in the follow-up study, but not in the other two groups. No other compound-related changes were observed in either study. The ocular changes observed in dogs given rosaramicin were reversible and structure-specific, occurring only in animals possessing a tapetum lucidum.

Animals↗

Heterogeneity of metachromatic cells in human nose: significance of mucosal mast cells.

The distribution and abundance of histochemically and morphologically distinct subpopulations of metachromatic cells were investigated in nasal secretions and scrapings from patients with allergic rhinitis, as well as in nasal biopsy specimens from other patients. These analyses of the metachromatic cells demonstrate that basophils and two distinct mast cell populations are present in nasal specimens. One mast cell subpopulation was analogous to the atypical mucosal mast cell of the rat and human intestine, whereas the other cell population was similar to the typical connective tissue mast cell type. In nasal scrapings greater than 80% of the metachromatic cells was mast cells, almost exclusively of the atypical "mucosal" type. However, basophils were the predominant metachromatic cell type in nasal secretions, and atypical mast cells were more abundant than typical mast cells. Few basophils were observed in biopsy specimens, but mast cells were widely distributed in various anatomic compartments. Atypical mast cells outnumbered the typical type in the epithelium and lamina propria, whereas the reverse was true in the submucosa. When the number and type of metachromatic cell in scrapings were analyzed in relation to clinical findings, there was a significant correlation with severity of symptomatology and nasal swelling and pallor. Atypical "mucosal" mast cells were the major cell type in all specimens, from those with mild to those with severe clinical findings. When the distinct spectrum of responsiveness to antiallergic compounds of atypical mast cells is considered, these observations have important therapeutic implications.

Adolescent↗

Necrolytic migratory erythema without glucagonoma in patients with liver disease.

BACKGROUND: Necrolytic migratory erythema (NME) is an uncommon inflammatory dermatosis with a distinct clinical and histologic appearance. NME is usually associated with glucagonoma. Only a few cases of NME in the absence of glucagonoma have been previously reported. OBJECTIVE: We sought to understand further the pathogenesis of NME by analyzing data from three patients. METHODS: Three patients were examined both clinically and histopathologically. RESULTS: Each patient had an extensive erythematous scaling eruption in intertriginous, perioral, and acral areas, and a markedly red, smooth tongue. Skin biopsy specimens showed confluent parakeratosis, epidermal pallor, papillary edema, and a lymphohistiocytic infiltrate. Two patients had alcoholic liver disease and one had liver dysfunction as a result of hemochromatosis. Serum albumin level was depressed, and liver enzyme values were increased in all three patients. Glucagonoma was undetectable in these patients. CONCLUSION: In the absence of glucagonoma, hepatocellular dysfunction and hypoalbuminemia appear to be the most common factors associated with NME.

Adult↗

Regional synaptic pathology in Alzheimer's disease.

Synaptic pathology in Alzheimer's disease (AD) may occur diffusely or may have regional predilections. A new antibody called EP10 which detects synaptophysin-like immunoreactivity was used to study synapses in postmortem brain tissue. Four brain regions from cases of AD and controls were studied. Controls with a wide range of ages were used to investigate the possibility of age-related changes in synaptophysin-like immunoreactivity. A significant reduction in the EP10 antigen was observed to occur with age in the control caudate but not in the hippocampus or temporal or occipital cortices. Antigen levels were significantly reduced in the hippocampus (77%) and the temporal cortex (54%) in AD. The expected abnormal pallor of the outer two-thirds of the dentate gyrus molecular layer was observed with immunocytochemistry. In the temporal cortex, the reduction in synaptophysin-like immunoreactivity was inversely correlated with the neurofibrillary tangle count. No such relationship existed in the hippocampus. These results suggest that at least certain components of the synaptic loss in AD occur regionally and are disproportionately large in the hippocampus.

Alzheimer Disease↗

Acute and subchronic toxicity studies with detirelix, a luteinizing hormone-releasing hormone antagonist, in the rat and monkey.

Acute (single dose), 2-week, and 3-month toxicology studies were conducted with detirelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, in rats and cynomolgus monkeys. Acute studies were conducted by intravenous and subcutaneous injection. Subchronic studies were conducted by daily subcutaneous injection. Clinical signs after a single intravenous dose included lethargy, edema, cyanosis, pallor, and red ears in rats at greater than or equal to 0.3 mg/kg and lethargy and facial flushing in monkeys at greater than or equal to 0.5 mg/kg. In subchronic studies, detirelix at greater than or equal to 0.4 mg/kg/day (rats) and at greater than or equal to 0.2 mg/kg/day (monkeys) produced atrophy of the reproductive organs, inhibition of ovulation and spermatogenesis, decreased body weight gain in male rats and monkeys, and increased body weight gain in female rats. In the rat, morbidity and/or mortality occurred throughout the treatment phase at a subcutaneous dose of greater than or equal to 2.0 mg/kg/day. In both species, the time to recovery of normal reproductive organ morphology and function was directly related to dose. Exogenous testosterone decreased the severity of reproductive and body weight effects in male rats. In conclusion, the acute effects of detirelix were consistent with peripheral vasodilation. Subchronic effects were associated with inhibition of pituitary gonadotropic and gonadal hormone secretion.

Animals↗

Rubratoxin B mycotoxicosis in the Mongolian gerbil.

The LD50 for rubratoxin B dissolved in dimethylsulphoxide and administered to Mongolian gerbils by ip injection was 2.0 (2.26-1.77) mg/kg body weight. The gross alterations observed at autopsy were pallor and mottling of the kidneys and liver and congestion of the spleen. The histopathological alterations seen were renal tubular degeneration and necrosis, degenerative changes in hepatocytes, and congestion of the spleen. The morphopathogenesis of lesions after a single ip LD50 dose was evaluated in a second study. The histopathological alterations that were observed were focal degeneration and necrosis of hepatocytes and renal tubular degeneration and necrosis. Hepatic lesions were observed in gerbils killed between 2 and 12 hr after dosing and included multifocal cytoplasmic vacuolation and coagulative necrosis of hepatocytes. The renal lesions were first observed 2 hr after dosing and increased to maximum severity at 40 hr after dosing. Tubular regeneration accompanied ongoing tubular necrosis at the end of the test period. The activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were increased 4 hr after dosing, peaked at 24 hr and remained elevated to the end of the test period. Serum K+ concentration was increased 16 hr after dosing and remained elevated to the end of the test period. In a third study, rubratoxin B was administered ip once daily for 7 days at doses of 25, 50 or 75% of the ip LD50. Toxicity was dose related and cumulative with multiple doses. Histopathological alterations included renal tubular degeneration and necrosis, mild tubular dilation and focal necrosis of hepatocytes. In a fourth study, rubratoxin B was administered ip at a dose of 25% of the ip LD50 once daily for 7 days. Histopathological alterations included renal tubular degeneration, mild renal tubular dilation and focal necrosis of hepatocytes. Activities of AST and ALT in serum were slightly increased after multiple doses of rubratoxin B. Results of urinalysis indicated hepatic and renal tubular damage.

Adenosine Triphosphatases↗

Rubratoxin B mycotoxicosis in the Swiss ICR mouse.

The LD50 for rubratoxin B dissolved in dimethylsulphoxide and administered to ICR mice by ip injection was 0.31 (0.22-0.43) mg/kg body weight. Gross alterations consisted of congestion of the liver and spleen and pallor and mottling of the kidneys. The histopathological alterations seen were hepatic and splenic congestion and renal tubular degeneration. The morphopathogenesis of lesions following a single ip LD50 dose was evaluated in a second study. Hepatic lesions were observed in mice killed between 8 and 40 hr after dosing and included diffuse sinusoidal congestion with mild sinusoidal ectasia, leucostasis, multifocal cytoplasmic vacuolation and necrosis of individual hepatocytes. Renal lesions were mild, not time-dependent, and consisted of mild degenerative changes in tubular epithelial cells of the outer stripe of the outer zone of the medulla. The activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were increased 2 hr after dosing, peaked at 4 hr and returned to control values by the end of the test period. In a third study, rubratoxin B was administered ip daily for 1 wk at doses of 25, 50 and 75% of the ip LD50. Toxicity was dose related and cumulative with multiple doses at the highest dose. In a fourth study, rubratoxin B was administered ip at a dose of 75% of the ip LD50 daily for 1 wk. Histopathological alterations included hepatic congestion and mild sinusoidal ectasia, multifocal necrosis of hepatocytes, splenic congestion and mild renal tubular degeneration. Serum activities of AST and ALT were increased after multiple doses of rubratoxin B.

Alanine Transaminase↗

Clinical features of Balkan endemic nephropathy.

This paper describes the clinical symptoms and signs of Balkan endemic nephropathy (BEN). The initial asymptomatic period followed by weakness and lassitude during renal insufficiency is emphasized. Non-characteristic lumbar pain may be present and episodes of macrohaematuria may occur. There is no fever, no severe dysuria, and no general disease preceding the symptoms. No oedema of the nephrotic type is recognized. Working capacity is unaffected until the late stage of the disease. In the advanced stages pallor of the skin and xantochromia of palms and soles are noticeable. Blood pressure is normal, but in the advanced phase may be elevated. In the uraemic phase a full uraemic syndrome is found. Urothelial tumours are frequent, occurring in 2-47% of cases; tumour cells may be found in the urine. Proteinuria of tubular type may be found early; in the uraemic phase it is constant. In the urinary sediment there are scarce white and red blood cells (the latter episodically abundant). Bacteriuria is present in about 20% of women patients. Glucosuria (less than 10%) and aminoaciduria (less than 10%) have been reported. In the early stages of BEN the urine concentration capacity is impaired earlier than renal blood flow and glomerular filtration rate. Enzymuria is present in the early phases. Tamm-Horsfall protein may be increased in the urine. Normo- or hypochromic normocytic hyporegenerative anaemia is a frequent finding. Bone marrow and leucocytes are normal. Serum proteins and immunoglobulins are not altered. Complement is normal; anti-glomerular basal membrane and anti-tubular basal membrane are negative. On radiography, kidney size varies from normal to the size of a small contracted kidney. The clinical picture of the disease is that of a slowly progressing tubulo-interstitial chronic nephritis.

Balkan Nephropathy↗

Differential behavioral outcomes in the sciatic cryoneurolysis model of neuropathic pain in rats.

We have previously introduced a novel animal model of neuropathic pain in rats following a peripheral mononeuropathy produced by freezing the common sciatic nerve, a technique termed sciatic cryoneurolysis (SCN). In this study, we have further characterized the temporal pattern of behavioral changes following SCN, including thermal hyperalgesia and mechanical allodynia. These behaviors were assessed using noxious thermal (radiant heat) and non-noxious tactile (von Frey filament) stimuli, respectively. Following unilateral SCN, animals exhibited significant (P < 0.001) bilateral tactile hypersensitivity (allodynia) that persisted at least 10 weeks. However, this lesion did not result in thermal hypersensitivity (hyperalgesia). In fact, thermal sensitivity in the operated limb remained significantly suppressed throughout the 10 weeks (P < 0.001). Furthermore, we observed autotomy in 76% of SCN-lesioned animals as well as transient weight loss and pale eye syndrome (PES), a phenomenon previously unreported in other neuropathic pain models. PES is a sustained, visibly distinct pallor of the normally pink eye color of the albino rat. We believe PES is a putative marker of heightened sympathetic efferent activity. The severity of autotomy following SCN correlated significantly with both weight loss (P < 0.001) and the expression of PES (P < 0.001). Autotomy behavior preceded the onset of allodynia; however, there was no correlation between the severity of expression of these behaviors. These behavioral sequelae are comparable to those seen in other animal models of neuropathic pain, but differ in respect to the increased frequency of autotomy and the lack of thermal hyperalgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Clinical and pathologic features of experimental Schistosoma japonicum infection in pigs.

Nine piglets, 2-5 months old and weighing 12-15 kg were infected percutaneously with 5000 to 6000 cercariae of Schistosoma japonicum. Three similar piglets which were not infected served as controls. Infected animals were necropsied at 5, 10, 30, 40, 59, 90, 120, 150 and 180 days post-infection (PI) and the controls at 5, 60 and 180 days PI. The prepatent period varied from 27 to 33 days after infection. Clinical signs observed, coincident with egg production, were loss of appetite, lethargy, pallor of mucous membranes, diarrhea, progressive emaciation and dehydration. One piglet was moribund when killed for necropsy at 40 days and another piglet died 59 days PI. Pathological changes induced by S. japonicum included erythematous papules on the site of inoculation, petechial hemorrhages in the lungs, catarrhal to hemorrhagic enteritis, bluish-gray discoloration of the liver, and egg granulomas in the liver, lungs, spleen, intestines, pancreas and mesenteric lymph nodes. Endophlebitis with intimal hyperplasia was occasionally observed in veins harboring adult schistosomes.

Animals↗

Toxicity of amphotericins on chronic administration to mongrel dogs.

Conditioned mongrel dogs were given 30 i.v. injections of either AMB (amphotericin B, 0.75 mg/kg body weight), AME (amphotericin B methyl ester, 10 mg/kg body weight), or 5% glucose solution without antimicrobic. Severe loss of body weight and nephrotoxicity occurred with AMB; hepatic dysfunction resulted with AME; astrogliosis and pallor of the myelin were found in dogs given AME and 5% glucose solution.

Amphotericin B↗

Characterization of subcutaneous microvascular blood flow during tilt table-induced neurally mediated syncope.

OBJECTIVES: This study aimed to characterize subcutaneous blood flow changes during neurally mediated syncope and to determine whether microvasculature oscillation (vasomotion) is characteristically altered in conjunction with syncopal events. BACKGROUND: Marked pallor is commonly associated with neurally mediated syncope. However, little attention has been paid to the evaluation of subcutaneous blood flow and vasomotion in this setting. METHODS: This study utilized laser Doppler flowmetry to assess changes in subcutaneous microvascular blood flow during head-up tilt table testing in 13 patients with syncope and 6 control subjects. Blood flow and vasomotion frequency were measured continuously before, during and after completion of 80 degrees head-up tilt testing (< or = 25-min duration). RESULTS: Among the 13 patients with syncope, tilt testing reproduced syncopal symptoms in 9 (tilt-positive group) but not in 4 (tilt-negative group). None of the six control subjects developed symptoms during testing. Baseline mean subcutaneous blood flow did not differ significantly among the three groups. However, during upright tilt, blood flow gradually diminished in the tilt-positive group, reaching a nadir of 0.8 +/- 0.33 ml/min per 100 g of tissue (mean +/- SD), but remained relatively constant in the tilt-negative group and control subjects. The difference in mean blood flow response to tilt was statistically significant when the tilt-positive group was compared with either the tilt-negative group or control subjects (p < 0.001). Similarly, baseline blood flow oscillation frequency did not differ significantly in the three subgroups (tilt-positive group 0.2 +/- 0.11 Hz; tilt-negative group 0.2 +/- 0.02 Hz; control subjects 0.2 +/- 0.11 Hz). Subsequently, during tilt testing only the tilt-positive group exhibited increased oscillation frequency; oscillation frequency remained essentially constant throughout the tilt test in the tilt-negative group and control subjects (p < 0.001, tilt-positive group vs. either the tilt-negative group or control subjects). CONCLUSIONS: These findings document an expected diminution of subcutaneous blood flow in association with neurally mediated syncope and indicate that characteristic changes in microvasculature oscillation frequency occur in conjunction with syncopal symptoms. To the extent that microvasculature vasomotion is influenced by neural control, the changes in vasomotion frequency are consistent with relative diminution of peripheral sympathetic neural influence during neurally mediated syncopal episodes.

Adolescent↗

Pathological aspects of transcutaneous cardiac pacing.

Although electrical energy has the potential to produce myocardial injury, the risk of tissue damage from transcutaneous cardiac pacing is largely unknown. This study reports the anatomical findings of a canine transcutaneous stimulation study. Ten dogs had 100-mA, 20-msec (pulse duration), transcutaneous impulses delivered across the thorax for 30 minutes at a rate of 80 stimuli per minute. Seventy-two hours later the animals were sacrificed, and the heart, lungs, and tissues of the chest wall were examined for pathological changes. Gross and microscopic lesions consistent with electrically induced myocardial damage were found in all hearts examined. These lesions included myocardial pallor and focal myofibril coagulation necrosis in the right ventricular outflow tract and perivascular microinfarcts in the posterior left ventricular myocardium. These lesions were not extensive; less than 5% of the right ventricular free wall and less than 1% of the left ventricular posterior wall were involved. Lesions of this extent would not be expected to cause clinically detectable changes in cardiovascular status. Short-term use of transcutaneous pacing appears to be safe. Determination of the potential for clinically significant injury with long-term use requires further study.

Animals↗

Human ivermectin exposure.

Ivermectin is a veterinary antiparasitic medication for domestic animals. Two cases of human exposure to veterinary preparations of ivermectin are reported. Patient number one accidentally self-injected ivermectin and developed nausea, pallor, and transient pain and numbness in the affected extremity. Patient number two, a 4-year-old child, ingested an unknown amount of the paste preparation and remained asymptomatic. As ivermectin is being used with increasing frequency in veterinary medicine, more human exposures may be anticipated.

Adult↗

Electromotive administration of guanethidine for treatment of reflex sympathetic dystrophy: a pilot study in eight patients.

Persistent neuropathic pain is associated with diagnostic and therapeutic challenges that may be very difficult to resolve. This report describes eight patients with incapacitating, posttraumatic neuropathic pain characteristic of reflex sympathetic dystrophy (RSD) who were treated by electromotive administration of guanethidine into affected areas of skin. Following 1-5 treatments, six patients experienced complete resolution of all superficial symptoms of hyperalgesia, pain, pallor, coolness, and sweating of the affected areas. One patient demonstrated partial relief of these symptoms, and one patient failed to respond. The results of this preliminary study suggest that electromotive administration of the the sympatholytic agent, guanethidine, may be useful in the treatment of some types of neuropathic pain. These findings justify the implementation of further controlled studies.

Adult↗

Dysmyelinogenesis in animal model of GM1 gangliosidosis.

Magnetic resonance imaging (MRI), pathologic examinations, and biochemical analyses were performed on 2 different canine mutants with GM1 gangliosidosis (i.e., English Springer Spaniel and Portuguese Water Dog) and on age- and sex-matched controls. Serial MRI studies were also performed on a child with infantile-onset GM1 gangliosidosis. The affected dogs had abnormalities on MRI, including a relative increase in gray matter and an abnormal signal intensity of cerebral and cerebellar white matter observed on T2-weighted MRI. White matter changes on MRI were similar to white matter abnormalities observed in a 15-month-old boy with GM1 gangliosidosis. The weight ratio of white to gray matter from the frontal lobe was markedly reduced. Microscopic examination revealed characteristic ballooned neurons which stained lightly with Luxol-fast blue. The central cerebral and cerebellar folia white matter exhibited pallor and gliosis, while the corpus callosum and fornix stained normally with Luxol-fast blue. Axons appeared intact on Bodian staining. Ultrastructural studies revealed fewer myelinated axons in affected puppies. Total gangliosides in gray matter were elevated. Thin-layer chromatography demonstrated GM1 ganglioside as the predominant ganglioside. The amount of cerebrosides and sulfatides was reduced in the gray and white matter when compared to controls but the ratio in gray and white matter remained unchanged. Immunostaining of neutral glycolipids disclosed increased amounts of stage-specific embryonic antigen-1 glycolipid in gray matter. These findings suggest that canine models for GM1 gangliosidosis are associated with abnormal myelin development which may be similar to the human disease.

Animals↗

Visual system electrodiagnosis in neurologic disease of childhood.

Electrodiagnostic examination of the visual system includes visual evoked potentials and electroretinography. These tests can be applied to all ages. Pitfalls in the clinical ophthalmologic examination of children, such as optic nerve pallor and pigmentary retinopathy, can be clarified by these tests. Investigation of neurodegenerative disease may be directed to the most likely defect by results of visual evoked potential testing and electroretinography. The child who is unable to meaningfully communicate sensory experience can be objectively evaluated by these studies. Familiarity with the applications and limitations of these tests will allow the examiner to choose the appropriate setting and time to apply each of them.

Brain Diseases↗

[Cystic retroperitoneal lymphangioma: a tumor of polymorphic clinical manifestations. Apropos of three cases].

BACKGROUND: Cystic retroperitoneal lymphangioma is a rare benign tumor with varied clinical presentation. CASE REPORTS: Case 1. A girl was born at term after ultrasonography had shown a cystic abdominal mass by 31 weeks of GA. This mass, clinically palpable at birth, was found again by ultrasonography. Surgical excision on day 3 was incomplete, requiring a second excision at the age of 2 months, followed by persistence of the cyst near the bladder; the patient was asymptomatic at the age of 2 years. Case 2. This full-term female newborn was admitted because of jaundice and pallor. Examination showed a firm mass of the left flank that was confirmed by X-rays and ultrasonography. Despite blood transfusion, anemia persisted, requiring surgery that showed a cystic hemorrhagic mass that was voided. A second partial excision was performed a few weeks later and, at the age of 7 months, ultrasonography showed a few small cystic masses behind the left kidney. Case 3. A 16-month-old boy was operated on for right inguinal hernia. The hernial sac contained fluid and its wall was thick. Ultrasonography and CT scan performed 3 days later were normal. The child was examined again 28 months later because he suffered from abdominal pain; a large mass was palpable in the right flank that appeared cystic at ultrasonography and CT scan. A retroperitoneal lymphangioma was completely excised. CONCLUSION: Because the risk of complications is apparently high, surgical treatment is always necessary. In the newborn period, complete excision is difficult, requiring delayed surgery.

Female↗