Coexisting endogenous lipoid pneumonia, cholesterol granulomas, and pulmonary alveolar proteinosis in a pediatric population: a clinical, radiographic, and pathologic correlation.

Benign pulmonary diseases that have been associated with the accumulation of endogenous lipids within the alveoli, bronchioles, and interstitial tissues include endogenous lipoid pneumonia (ELP), pulmonary alveolar proteinosis (PAP), pulmonary interstitial and intra-alveolar cholesterol granulomas (PICG), various xanthomatous lesions, and malakoplakia. In ELP, fat-filled finely vacuolated macrophages fill the alveoli. In PAP, the aveoli become filled with cholesterol and periodic acid-Schiff (PAS)-positive acellular debris. In PICG, cholesterol esters are released from degenerating macrophages and, as organization occurs, the cholesterol is deposited in the form of acicular clefts within the interstitium. These morphologically distinct presentations of endogenous lipid deposition within the lung have long been thought to represent unique disease processes but several authors now postulate a possible relationship between these entities. We report here on the clinical, radiographic, and morphologic findings in eight pediatric patients with diverse primary disease processes who were subsequently found to have varying and often coexisting degrees of ELP, PAP, and PICG.


Microdissection study of the myenteric plexus in acardia, ataxia-telangiectasia, cystic fibrosis, extrahepatic biliary atresia, pediatric AIDS and Werdnig-Hoffmann disease.

Microdissection-point count morphometric study of the myenteric (Auerbach) plexus or esophagus, small intestine, and colon was done for infants and children with acardia (2), ataxia-telangiectasia (5), cystic fibrosis of the pancreas (CFP) (25), extrahepatic biliary atresia (EBA) (17), pediatric AIDS (10), and Werdnig-Hoffmann disease (WHD) (8). Values for fractional area of neural tissue in the plane of the plexus were compared to those of control patients in same age range as those in each disease category by t-test. Statistically abnormal values included low values for small intestine and colon in Werdnig-Hoffmann disease, high values for small intestine and colon in biliary atresia, and high value for colon but a low value for small intestine in cystic fibrosis. Values for all three loci were within the normal range for ataxia telangiectasia and pediatric AIDS. The mechanisms of the low value for small and large intestines in WHD, which causes chronic constipation as a result of skeletal muscle weakness, and of the high values for colon in CFP and EBA, both causing malabsorption with bulky stools, are unclear. The value for small intestine in acardia was normal for term but lower than expected for fetal bowel of the same size, possibly because of reduced neural crest inflow to the fetal bowel.


Osteogenesis imperfecta and Ebstein's anomaly: a case report with autopsy findings.

Osteogenesis imperfecta is an inherited disorder of collagen synthesis. It has a wide range of phenotypic expressions, but cardiovascular anomalies tend to be rare. When they do occur, they usually consist of aortic or mitral valve disease. We report an autopsy case of a 36-week gestation infant with coexisting osteogenesis imperfecta and Ebstein's anomaly. The simultaneous occurrence of two relatively rare entities may reflect a generalized expression of an underlying collagen synthesis defect.


Transthoracic herniation of the fetal lung: bagpipe lung.

We describe a case of subtotal herniation of a lung through an intercostal space into an extrathoracic (axillary) position that occurred in a 16-week-old fetus. There was no malformation of the thoracic wall other than the hiatus at the site of herniation. The left and the right lungs were of similar size and weights and the lung/body weight ratio was normal. Histology revealed no difference between the normal and the abnormally positioned lung. We were unable to find a report of a similar case of the condition, which has implications for concepts of lung development.


Fetal rhabdomyoma and nevoid basal cell carcinoma syndrome.

A 6-year-old white female presented with a fetal rhabdomyoma of the posterior mediastinum and retroperitoneum. Radiologic evaluation and family history revealed features of the nevoid basal cell carcinoma syndrome (NBS). Literature review disclosed two other children with NBS and fetal rhabdomyoma, which should be regarded as one of the soft tissue tumors associated with NBS.


Pulmonary hypertension with coexisting portal hypertension.

A 10-year-old boy who had portal hypertension secondary to portal fibrosis/intrahepatic biliary atresia developed syncopal episodes related to strenuous activity. A work-up excluded a metabolic or neurologic etiology and cardiac catheterization demonstrated significant pulmonary hypertension. Six months later he died and an autopsy revealed pulmonary plexogenic arteriopathy without microemboli. Previous reported cases of this symptom complex are reviewed. In addition, he had a history of nonspecific colitis, ulcerative stomatitis, and conjunctivitis responsive to steroid therapy. The possible relationship of these manifestations to the portal pulmonary pathology is discussed.


Angiosarcoma of the liver in childhood: a clinicopathologic and follow-up study of 10 cases.

The clinical, morphologic, and follow-up findings in 10 cases of childhood hepatic angiosarcoma are reported. Six patients were female and four were male. The age range was 18 months to 7 years, with a mean of 3.7 years. The usual presenting feature was an abdominal mass, with or without associated symptoms. The histologic pattern of childhood hepatic angiosarcoma typically consists of large hypercellular whorls of spindled sarcoma cells intermingled with bile ducts, vessels, and collagen. Factor VIII staining of tumor cells is focal, cytoplasmic, and weak in character. Intracellular eosinophilic, PAS-positive globules are present in most cases and may be abundant. The prognosis is poor; follow-up available in seven cases showed only one to be alive 32 months after diagnosis. The remaining six patients had died 0-27 months (mean 10 months) after diagnosis.


Fetal distribution of cocaine: case analysis.

The implications of gestational cocaine use are widely documented. There is evidence that cocaine crosses the placenta in animals and humans; however, the fetal distribution of the drug and its metabolites has not been documented. We describe the distribution of cocaine and benzoylecgonine (BE) in the fetus of a cocaine user mother. Cocaine and BE were detected in brain, scalp, liver, kidney, heart, placenta, blood, and hair. The liver contained substantially more cocaine than other tissues, whereas the brain had more BE than any other sample.


Brain stem and cervical cord dysraphic lesions in iniencephaly.

Iniencephaly is a rare, lethal, axial dysraphic malformation complex diagnosed on the basis of three cardinal features: deficiency of the occipital bone, cervicothoracic spinal retroflexion, and rachischisis. The majority of the patients also have various associated viscerae malformations. An iniencephalic female fetus delivered at 35 5/7 weeks of gestation revealed severe anomalies of the central nervous system and the spine: the cerebellar vermis was hypoplastic, the medulla oblongata was flattened and broadened, and the cervical canal was widely patent dorsally. The thoracolumbar spinal cord had a duplicated central canal and lacked a dorsal fissure, representing a minor degree of diastematomyelia. The cervicothoracic spine showed severe bony anomalies including aplasia and fusion of vertebral bodies.


Digestive tract involvement with exudative enteropathy in Langerhans cell histiocytosis.

Protein-losing enteropathy was observed in two children with Langerhans' cell histiocytosis (LCH). One patient was an infant with congenital cutaneous lesions; the second child had sigmoid and lymph node infiltration. Electron microscopy and immunohistochemistry confirmed, in both, infiltration of duodenum, skin, and liver by LCH. Gastrointestinal involvement by LCH seldom produces prominent clinical manifestations but indicates widespread multisystem disease. Immunohistochemical and/or ultrastructural features allow definitive diagnosis from mucosal biopsy specimens. Review of the literature of gastrointestinal infiltration by LCH emphasizes its poor prognosis, especially when associated with organ dysfunction.


Persistent pulmonary hypertension of the newborn due to alveolar capillary dysplasia.

Three unrelated female term infants died when less than 1 month old from intractable pulmonary hypertension associated with deficient capillaries in airspace walls, anomalous small pulmonary veins in bronchiolar-arterial rays, and medial thickening in small pulmonary arteries together with peripheral muscularization. This complex vascular abnormality in the lungs has been termed alveolar capillary dysplasia and/or misalignment of lung vessels in seven previously reported cases. Each infant also showed abnormally immature parenchymal development in the lungs, as was noted in four of the seven prior cases. One had phocomelia; four of the seven prior cases had a variety of congenital anomalies. The primary pulmonary vascular anomaly is likely to be a failure of fetal lung vascularization dating from the second trimester and to be due to action of an unknown teratogen. Centroacinar veins may represent bronchial veins that do not normally develop beyond the ends of cartilaginous bronchi. Pulmonary arterial occlusive changes are interpreted as reactive to obstruction at the level of pulmonary arterioles.


Mesenchymal hamartoma of the chest wall: a cooperative study with review of the literature.

The clinicopathologic features of three examples of mesenchymal hamartoma of the chest wall are described. The entity has been recorded under a number of names including osteochondroma, osteochondrosarcoma, benign chondroblastoma, mesenchymoma, and chondromatous hamartoma. The condition is manifest at birth or shortly thereafter with deformity of the chest wall and respiratory distress. Radiographic examination reveals a well-defined, partly calcified mass involving one or more ribs. The tumor is composed predominantly of chondroid tissue with large endothelium-lined blood spaces and immature mesenchyme with osteoclastic giant cells and osteoid. We review the literature and suggest that the lesion should be distinguished from aneurysmal bone cyst, chondroma, and other mesenchymal neoplasms. In order to avoid local recurrence the recommended treatment is complete surgical resection.


Fetal and placental pathology in two cases of maternal varicella infection.

We describe the fetal and placental pathology in two cases of maternal varicella infection. Varicella in pregnancy is uncommon, and although sporadic cases of fetal involvement are described very little regard has been paid to placental features. Only one previous report describes the changes in both the fetus and its associated placenta. In both our cases the placenta showed chronic villitis with with granuloma formation, and occasional cells with nuclear viral-like inclusions were detected. Cells with similar inclusions were found in the lung interstitium, and foci of dystrophic calcification were present in the liver.


X-linked myotubular myopathy: a case report of prenatal and perinatal aspects.

Nine families have been reported in which male newborns presented with X-linked myotubular (centronuclear) myopathy. Little is known about the biochemical basis of this disorder or about its natural history in utero. We report a family in which an infant with myotubular myopathy presented in utero with polyhydramnios, poor fetal movement, and fetal cardiac arrhythmias. Shortly after birth the infant died from severe respiratory insufficiency. Gas chromatography-mass spectrophotometry for serum organic acids showed a large octanoic acid peak, but total acyl-CoA dehydrogenase activities in liver were normal. The maternal family history was significant for two perinatal male deaths. Postmortem examination revealed generalized muscle wasting, cardiac enlargement, cryptorchidism, and flexion contractures. Examination of muscle showed numerous fibers that had enlarged, centrally located nuclei and perinuclear clear zones. The muscle fibers were hypotrophic and predominantly of type I. Biopsy specimens of the muscles of the mother and maternal aunt had increased numbers of centrally located nuclei. Neurologic examination was normal. The case demonstrates the typical clinical course, pathology, and family history of severe X-linked myotubular myopathy. In addition, it confirms the reported detection of fetal cardiac arrhythmias and documents what may be an abnormality in fatty acid oxidation.


Inflammatory pseudotumor of the kidney with extensive metaplastic bone.

Inflammatory pseudotumor (IPT) of the kidney is a very rare lesion. We describe an 8-year-old boy with IPT of the kidney presenting as a single episode of hematuria. The case highlights a new feature, metaplastic bone, not previously described in IPT. This new feature may be helpful in establishing the correct preoperative and histopathologic diagnosis of IPT of kidney and avoiding inappropriately aggressive therapy. Despite its rarity, IPT of the kidney should be kept in mind in the differential diagnosis of a solitary renal mass.


Studies of vertebral coronal cleft in rhizomelic chondrodysplasia punctata.

Dissection and serial section-reconstruction preparations from vertebrae with coronal cleft of a 2 5/12-year-old girl with rhizomelic chondrodysplasia punctata are described. The cartilage plate between the dorsal and ventral vertebral ossification centers, abnormal thickness of which is the explanation of the radiologic coronal cleft, shows differences in thickness, with dorsal and ventral midline extensions and with small foci of communication of the cancellous bone of the dorsal and ventral ossification centers of the vertebral body bilaterally. Although the process in coronal cleft is in some ways similar to that of radiologic "retarded epiphyseal closure," the explanation of the coronal clefts in rhizomelic chondrodysplasia punctata appears to be overproduction of cartilage in the zone between the dorsal and ventral vertebral body ossification centers, plus reduced removal of cartilage cells from this zone. No evidences of persistence of notochord cells were seen microscopically in sections of the coronal clefts.


Prenatal diagnosis.

The enormous progress witnessed in the field of prenatal diagnosis during the past two decades is likely to continue into the future. Improved imaging techniques are likely to enhance the resolution of noninvasively obtained fetal images considerably over their current excellent quality. Although this undoubtedly will be true for ultrasonography, the increased speed of magnetic resonance equipment may offer a new realm of imaging possibilities. Computerized image processing, analysis, and three-dimensional reconstructions all should make interpretation of fetal images easier and more understandable to the nonspecialist. Advances in molecular genetics will continue to accelerate, greatly expanding the range and accuracy of prenatal diagnosis. The alert pediatrician who is sensitive to genetic issues may, by early detection of pediatric disorders and careful family history assessment, be in a position to identify families at risk for serious genetic conditions and provide the opportunity to make informed decisions on reproductive options that avert a major tragedy. The pediatrician, working with obstetric colleagues, should be part of a team effort to support families going through prenatal testing. Familiarity with these rapidly changing technologies will make it far easier to support the family needing additional explanation about prenatal diagnosis issues.


In situ choriocarcinoma arising in partial hydatidiform mole: implications for the risk of persistent trophoblastic disease.

The risk of persistent trophoblastic disease following partial hydatidiform mole is controversial. In spite of claims that 4 to 11% of cases require chemotherapy, there is a paucity of affected patients in the literature. A critical review of those patients suggests an alternative or unproven diagnosis in the majority. An instance of placental in situ choriocarcinoma arising in a partial mole is reported. Because in situ choriocarcinoma may represent the incipient lesion in the majority of the one-third of cases of gestational choriocarcinoma that follow a normal pregnancy, we postulate that the presence of the in situ lesion in a partial mole supports the view that the risk of persistent trophoblastic disease may be no greater after partial mole than after a normal gestation.


Neurofibromatosis cerebral vasculopathy in an infant: clinical, neuroradiographic, and neuropathologic studies.

An infant with neurofibromatosis developed recurrent cerebrovascular accidents beginning at 3 months of life. Cerebral arteriography demonstrated large-vessel occlusive disease and bilateral severe moyamoya. At autopsy these lesions were apparent on gross examination, and advanced intimal and medial dysplasia was seen on microscopic examination of both the anterior and posterior circulations. Although rare, neurofibromatosis cerebrovasculopathy may occur in young infants and may account for some strokes in this age group.


Hyperplasia of lymphoglandular complexes in colon segments in Hirschsprung's disease: a form of diversion colitis.

This is a study of the size and number of lymphoglandular complexes (LGDs) in the resected segment of aganglionic left colon of 20 children (mean age 26 months) obtained several months to years after being defunctionalized by proximal colostomy, compared with 5 controls (mean age 20 months). All the resected aganglionic segments had a nodular mucosa. The number of LGCs/mm of muscularis mucosae was 0.58 +/- 0.2; in controls the number was 0.24 +/- 0.12 (P less than .0025). The mean size of LGCs in aganglionic colon was 1.23 +/- 0.27 mm, and in controls it was 0.57 +/- 0.21 (P less than .0005). Because LGCs have been related to antigen processing, hyperplasia of LGCs in defunctionalized colonic segments of Hirschsprung's disease may represent a reaction to stagnant contents. Its combination with cryptitis (present in six cases) may represent a form of diversion colitis, a condition recognized in adults in bypassed colonic segments after surgical diversion of the fecal stream.


Legal issues in managing breast disease.

The impact of legal issues in breast cancer care reflects the significance of breast cancer as a health concern of women. Breast cancer has emerged as a leading liability risk for primary care physicians, with most cases focusing on delayed diagnosis. Although the clinical impact of delayed diagnosis of breast cancer is often controversial, physicians should strive to diagnose breast cancer as early as possible in the natural history of the disease. No currently available data suggest that a delay of less than 2 months between the onset of symptoms and diagnosis or treatment adversely influences outcome. Techniques that help physicians reduce the liability risks associated with breast cancer care include patient education, adequate documentation and follow-up, and referral or consultation in high-risk situations.


Breast imaging. A practical look at its capabilities and its limitations.

The film-screen technique is evolving as the standard for mammography. Sonography is the only other method that currently has a defined role in breast imaging. Mammography should be performed at facilities that have received American College of Radiology accreditation or its equivalent, because technical quality assurance is an important part of mammographic practice. Interpretive quality may be assured by outcome audits performed by mammography facilities. Primary care physicians are best suited to encouraging eligible women to undergo screening studies and should consider these recommendations: Refer patients for screening mammography to accredited facilities according to established guidelines. Educate patients about the need for regular screening. Provide annual breast physical examination. Refresh your knowledge on breast health and the techniques of physical examination if necessary. Teach patients breast self-examination techniques. Demand low-cost, high-quality screening mammography; be aware of local variability of charges and quality.


Intestinal ganglioneuroblastoma in a 22-week fetus.

The clinical history and autopsy findings of a 22-week fetus with intestinal ganglioneuroblastoma, cardiac anomalies, omphalocele, and ileal atresia are presented. Ganglioneuroblastoma was confined to the large intestine and was not suspected prenatally despite ultrasonographic examination. Although enteric ganglia share neural crest lineage with other sites of congenital neuroblastoma, this is the first report of a primary intestinal ganglioneuroblastoma in a fetus or child. Various hypotheses are discussed to explain the coexistence of cardiac malformation and congenital neuroblastoma in this fetus and other cases in the literature. It is hypothesized that other malformations evident in this fetus were caused by the tumor, possibly as teratogenic effects of neuroblastoma-derived catecholamines during embryogenesis.


Asymptomatic HIV infection. A primary care disease.

Asymptomatic human immunodeficiency virus infection is a disease entering the primary care arena more and more frequently. Patients may be monitored in this setting until complications and clinical deterioration develop (typically after several years). As the disease progresses, referral to consultants who specialize in AIDS may be appropriate. However, many patients do not live near a major healthcare center and do not have the financial, physical, or emotional capability to travel to one as they become sicker. In these cases, primary care physicians, with the aid of a personally chosen network of specialized consultants, should offer care as the disease progresses to its terminal stage.


Acne vulgaris. Topical and systemic therapies.

Acne vulgaris is a condition commonly treated by primary care physicians. An understanding of the causes of the disease and methods of clinical evaluation allows selection of appropriate therapy. Effective treatment is available for all types of acne, including severe, nodulocystic forms. Regardless of the regimen chosen, patients should receive encouragement and instructions about the necessity of regular ongoing treatment for a successful outcome.


Fever of unknown origin in the elderly. A sequential approach to diagnosis.

Elderly patients with persistent unexplained fever require a diagnostic evaluation that focuses on specific infections (eg, occult abdominal abscess, bacterial endocarditis, miliary tuberculosis), rheumatic disorders (eg, temporal arteritis, polyarteritis nodosa), and neoplasms (eg, lymphoma, nephroma). Assessment is directed by the subtle clues elicited from meticulous, repeated history taking and physical examination. Therapeutic trials or exploratory laparotomy may be appropriate but should not be attempted out of a sense of frustration.


Magnesium deficiency and diabetes mellitus. Causes and effects.

A large body of evidence demonstrates the prevalence and adverse clinical consequences of magnesium deficiency in patients with diabetes mellitus. It would be prudent for physicians who treat these patients to consider magnesium deficiency as a contributing factor in many diabetic complications and in exacerbation of the disease itself. Repletion of the deficiency or prophylactic supplementation with oral magnesium may help avoid or ameliorate such complications as arrhythmias, hypertension, and sudden cardiac death and may even improve the course of the diabetic condition.


Stress and the heart. Mechanisms, measurement, and management.

Unrelieved physical or mental stress and repeated episodic stress are ultimately harmful to the cardiovascular system and thus can be life-threatening. In this article, Dr Eliot describes efforts to quantify the psychophysiologic responses to stress and to identify the components of stress and its clinical consequences. He also explains the importance of controlling the real-life episodic fluctuations in blood pressure that occur daily in response to stress.


Coronary artery disease in surgical patients. Preoperative evaluation.

Primary care physicians play a major role in the risk stratification of patients with coronary artery disease (CAD) preparing for noncardiac surgery. Preoperative risk assessment takes into account the type and urgency of surgery and the extent of underlying CAD. With this approach, patients can be categorized as being at high, intermediate, or low risk for postoperative cardiac complications. Judicious use of preoperative noninvasive cardiac testing may help identify those patients at particularly high risk for such complications.


Coronary artery disease in surgical patients. Perioperative management.

With effective communication, optimal use of perioperative therapeutic techniques, and postoperative follow-up, the medical, surgical, and anesthetic teams can prevent or minimize cardiac complications that occur during the postoperative period. Up to 50% of postoperative myocardial infarctions may be silent, or they may present as congestive heart failure, hypotension, or arrhythmia. Dyspnea is a common finding. All high-risk patients should be monitored in the intensive care unit during the first 7 days after surgery, when adverse cardiac events are most common.


Anaphylaxis. How to manage and prevent this medical emergency.

Anaphylaxis is a dramatic, major medical emergency. Understanding of the pathogenesis, emergency treatment, and subsequent prophylaxis can reduce both morbidity and mortality. Treatment of anaphylaxis should begin with a high degree of suspicion. Taking a wait-and-see attitude in hopes that the reaction will be mild may have serious results.


Delirium and acute psychosis. Mental states calling for clear diagnostic thinking and careful management.

Management of a delirious or acutely psychotic patient calls for rapid but well-considered decision making by the treating physician. Clear diagnostic thinking is vitally important in making a presumptive diagnosis and forming a treatment plan. Appropriate treatment usually returns patients to a less agitated state and allows for definitive treatment of any underlying illness.


Gastrointestinal foreign bodies. When to remove them, when to watch and wait.

By being aware of which patients are at high risk for ingestion or insertion of foreign bodies, physicians can be on the lookout for objects in the gastrointestinal tract and ready to institute initial care. Esophageal foreign bodies and other objects that increase the chance of perforation or obstruction may require urgent endoscopic or surgical removal. Other objects may be expelled on their own. Identification of those that require early intervention is the key to successful management.


'Halloween diarrhea'. An unexpected trick of sorbitol-containing candy.

When a patient with severe diarrhea and flatulence is afebrile and the results of physical examination are negative, a food source should be suspected as the cause of the problem. Careful scrutiny of the patient's diet and a high index of suspicion may implicate the artificial sweetener sorbitol. Exclusion of sorbitol from the patient's diet is recommended in these cases before embarking on an extensive clinical investigation.


Lead poisoning in children. The ramifications and the road to prevention.

Environmental lead poisoning is easier to prevent than to treat, and it can be destructive or deadly if ignored. Dr Schlenker, medical director of the Milwaukee Health Department, shares his approach to screening young children for potentially dangerous blood lead levels, educating the community about prevention of lead poisoning, and eradicating environmental sources of lead.


Evaluation of common breast masses.

Most breast lesions, including those that are malignant, are found by women themselves, which emphasizes the importance of breast self-examination. Comprehensive knowledge of breast anatomy and the characteristics that suggest that a mass is benign or suspicious aids primary care physicians in choosing the proper sequence of action. Drs Bland and Love discuss the common breast lesions and provide a detailed algorithm for management.


Autoimmunity and glomerulonephritis.

Autoimmunity is now unequivocally regarded as the predominant pathogenic process underlying most forms of primary and secondary glomerulonephritis in humans. Most of the investigations so far have been focused upon humoral mechanisms. Consequently, the role of cell-mediated immunity in nephritis is still incompletely understood. Nonetheless, as a result of contemporary studies, a number of previously unidentified auto-antibodies in association with glomerulonephritis have been discovered. However, apart from anti-NC1 antibodies in the classical Goodpasture syndrome, the exact role of these auto-antibodies in the pathogenesis of glomerulonephritis yet remains undefined. This fact, however, does not undermine the relevance of exploring these auto-antibodies. They have been of immense help in sub-classifying glomerulonephritis previously thought homogeneous (Figure 3). Besides, analysis of auto-antibodies has assisted tremendously in the early diagnosis of rapidly progressive glomerulonephritis. This, in turn, has aided in early commencement of therapy thus contributing to regression in morbidity and mortality resulting from these disorders. Moreover, investigation of these auto-antibodies is of enormous value for future studies aimed at understanding the pathogenic mechanisms involved in glomerulonephritis.


Treatment of Raynaud's phenomenon with triiodothyronine corrects co-existent autonomic dysfunction: preliminary findings.

Cardiovascular autonomic function was assessed in 9 subjects with Raynaud's phenomenon. The underlying diseases were systemic lupus erythematosus (n = 5), systemic sclerosis (n = 3) and rheumatoid arthritis (n = 1). Five standard non-invasive tests, 3 of heart rate and 2 of blood pressure, were employed. Compared with age and sex matched controls (n = 25), the number of values abnormal was 24 of 45 (53%) overall and between one and 4 (median, 2) individually. Significant differences were present for 3 tests, two of heart rate and one of blood pressure. The subjects were given triiodothyronine, 60 to 80 micrograms per day, for vasospastic attacks. Autonomic function was reassessed between weeks 4 and 9 (9 subjects) and between weeks 12 and 18 (8 subjects) after introduction of triiodothyronine. Test results showed a considerable improvement. At the second reassessment, the number of values abnormal was now 5 of 40 (12.5%) overall and nil (n = 4) or one (n = 4) individually. Significant differences remained for one heart rate test only. Adverse side effects to triiodothyronine occurred in a single subject and were readily controlled. Evidence of somatic neuropathy was present electrophysiologically in all 9 subjects and clinically in 8. Triiodothyronine may have corrected autonomic dysfunction by increasing blood flow to ischaemic peripheral nerves or by acting on the autonomic system more directly. Further study of triiodothyronine in autonomic insufficiency appears merited.


Lymphocytic adenosine deaminase activity in typhoid fevers.

Lymphocyte adenosine deaminase (L-ADA) activity, a measure of lymphocyte activity, was estimated in 10 healthy controls and 30 patients with typhoid fever (20 uncomplicated and 10 complicated) at the time of admission, at onset of complications and weekly until recovery. Mean L-ADA activity in healthy controls was 20.49 +/- 3.62 mU/10(6) cells. In uncomplicated patients L-ADA activity was 36.33 +/- 5.09 mU/10(6) cells at time of admission, which is significantly raised as compared to controls. It remained high at the height of the fever and at defervescence. In complicated patients L-ADA activity was significantly low at admission (15.33 +/- 2.35 mU/10(6) cells) and fell further with development of complications (7.86 +/- 4.07 mU/10(6) cells). At defervescence L-ADA activity increased significantly above the control activity (31.24 +/- 5.37). Serial L-ADA activity can be of prognostic significance. A cut-off value of 24 mU/10(6) cells is suggested to predict prognosis and severity of disease. Activity below this indicates a probability of a severe, prolonged course and may help in instituting early and energetic treatment.


Use of the SeHCAT test in the investigation of diarrhoea.

The SeHCAT test was used to investigate possible bile acid malabsorption in 166 patients presenting to a district general hospital with chronic diarrhoea of uncertain cause. Eighty-four (51%) patients had impaired SeHCAT retention. These included 23 of 28 patients with a possible type I abnormality (terminal ileal resection or disease, previous pelvic radiotherapy), 20 of 74 with a possible type II abnormality (idiopathic diarrhoea), 32 of 45 with a possible type III abnormality (post-cholecystectomy, post-vagotomy), and 9 of 19 with diarrhoea associated with diabetes. Patients with severe bile acid malabsorption demonstrated a good response to cholestyramine whereas the response in patients with a mildly abnormal SeHCAT retention was variable. Bile acid malabsorption is an important cause of diarrhoea in patients presenting with unexplained chronic diarrhoea.


Vocal cord paralysis and oesophago-broncho-aortic fistula complicating foreign body-induced oesophageal perforation.

A 61 year old man died after presenting with a 24 h history of haematemesis and haemoptysis, and one year history of hoarseness of voice. Post-mortem examination showed a dental plate eroding through the mid-oesophagus into a bronchus and into the descending arch of the aorta, with scarring suggestive of old perforation. An organized haematoma also involved the left recurrent laryngeal nerve. Vocal cord paralysis may be a manifestation of foreign body-induced oesophageal perforation, which can lead to death from an oesophago-broncho-aortic fistula. Both complications of oesophageal perforation from a foreign body have not to our knowledge been previously reported.


Horner's syndrome in severe tetanus.

A 66 year old man was admitted with a left Horner's syndrome, and trismus due to tetanus. Three days later he had respiratory arrests, classical tetanic spasms and was ventilated. He had associated severe autonomic dysfunction, tachyarrhythmias, hypotension, sweating and constipation. There was complete resolution of the left Horner's syndrome with recovery from tetanus.


Falciparum malaria-induced hypoglycaemia in a diabetic patient.

We report a patient with diabetes mellitus who suffered severe falciparum malaria complicated by profound and persistent hypoglycaemia. The hypoglycaemia evolved before therapy with quinine was begun and resolved with eradication of the parasitaemia. The patient reverted to her baseline hyperglycaemia despite continuation of quinine. This case illustrates the critical role of falciparum malaria in the pathogenesis of malaria-associated hypoglycaemia, rather than quinine-mediated mechanisms. Anticipation of hypoglycaemia in falciparum malaria and its vigorous treatment may improve the poor prognosis associated with this complication.


Life threatening hypophosphataemia in a patient with Philadelphia chromosome-positive chronic myelogenous leukaemia in acute blastic crisis.

Life-threatening hypophosphataemia developed in a 47 year old woman with blastic crisis of chronic myelogenous leukaemia. The patient's hospitalization was characterized by reciprocal relationship between her white cell count and the serum phosphorus levels. The patient did not demonstrate any of the usual causes of profound hypophosphataemia. The postulated mechanism of this patient's hypophosphataemia is uptake by the rapidly dividing leukaemic cells. To the best of our knowledge this is the first case in the English literature of hypophosphataemia associated with blast crisis of Philadelphia chromosome-positive chronic myelogenous leukaemia.


Mitral stenosis in the Maroteaux-Lamy syndrome: a treatable cause of dyspnoea.

The case is reported of a young woman with the Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI) who presented with rapidly progressive dyspnoea due to mitral stenosis. Mitral valve replacement was performed and the appearance of the valve was typical of mucopolysaccharide infiltration. Dyspnoea in patients with the Maroteaux-Lamy syndrome may be due primarily to cardiac valve involvement, and in this setting, valve surgery is safe and effective.


Sotalol-induced torsade de pointes: management with magnesium infusion.

A 69 year old woman was treated with sotalol (320 mg daily) for intermittent atrial fibrillation. Sotalol was initially well tolerated and reversion to sinus rhythm with sinus bradycardia occurred 4 weeks after initiation of therapy. Shortly thereafter, the patient developed recurrent syncope due to torsade de pointes. This was treated successfully with intravenous magnesium infusion and withdrawal of sotalol. Subsequently, the atrial fibrillation was adequately managed using amiodarone, with no recurrence of torsade de pointes. Development of bradycardia associated with reversion to sinus rhythm represents a potential cause of 'late' pro-arrhythmic effects of sotalol.


Portal vein thrombosis in a complicated case of Crohn's disease.

Portal vein thrombosis is a rare complication of ulcerative colitis and is invariably fatal. This report describes a patient with severe Crohn's disease who underwent elective surgery complicated by an anastomotic disruption with faecal peritonitis. Following emergency laparotomy he developed left hypochondrial pain which was a manifestation of splenomegaly consequent upon portal vein thrombosis. Anticoagulation was successful in preventing further spread of the thrombosis as monitored by colour Doppler ultrasound. Severe active disease, surgery and sepsis have been recognized as predisposing factors for thromboembolic complications in inflammatory bowel disease and this patient was exposed to all three. It is conceivable that portal vein thromboses occur more commonly than suspected and ultrasound scanning could ascertain the prevalence if performed prospectively.


Pancreatic abscess due to Salmonella typhi.

Isolated involvement of the pancreas in Salmonella typhi bacteraemia is rare. A case of pancreatic abscess due to S. typhi is reported which was managed conservatively.


Late presentation of a congenital gastric diverticulum causing pyloric obstruction.

We report a case of adult pyloric obstruction caused by the delayed presentation of a congenital gastric diverticulum. The derivation, classification and treatment of these abnormalities are discussed.


Inguinal bladder hernia associated with vesico-ureteric reflux.

The urinary bladder is frequently found as a component of inguinal herniae. This report describes a case of 'bladder hernia' associated with vesico-ureteric reflux. The current methods of investigation and subsequent treatment for this condition are reviewed along with the possible underlying cause of vesico-ureteric reflux in this case.


Cytolytic anticardiac membrane antibodies in the pathogenesis of myopericarditis.

Antisarcolemmal (ASAs) and antimyolemmal antibodies (AMLAs) are serological hallmarks of inflammatory heart muscle disease. They occur in a similar incidence in postcardiac injury syndromes, sarcoid heart disease or in dilated and hypertrophic cardiomyopathy. Rarely but still notably they are found with increasing age or in coronary artery disease. We therefore examined whether they are truly pathogenetic or whether they also possess properties of 'natural antibodies'. AMLAs and ASAs, like natural antibodies, have specificity for preserved structures on the membrane; they possess cross-reactivity and increase with age. In contrast to natural antibodies, however, they occur frequently after viral stimulation or other forms of trauma, are more often of the IgG and IgA than of the IgM isotype and fix complement in the acute stage of the disease. They also possess cytolytic and cytotoxic properties when incubated in vitro with isolated heart muscle cells. Antigenic mimicry has been demonstrated to be operative, since they are cross-reactive to viral proteins.


The carditis/cardiomyopathy of rheumatic fever: relationship to pathogenesis.

Although the relationship between group A streptococcal upper respiratory tract infection and the development of acute rheumatic fever has been known for many years, the pathogenetic mechanism(s) have never been defined. Thus, the mechanism of damage to the valves and to the myocardium in patients with rheumatic fever remains unexplained. Traditionally, emphasis has been placed on the valvular damage in rheumatic heart disease, but there is considerable evidence for myocardial involvement. An abnormal immune response to some as yet unrecognized somatic or extracellular antigen of the group A streptococcus is probably related to the cardiomyopathy. This abnormal immune response is supported by considerable clinical and experimental evidence. Recent studies have suggested other mechanism to explain the myocardial damage including the influx of lymphocytes into the area as well as the possibility of damage relating to generation of oxygen-free radicals. As more sophisticated molecular biological studies of the group A streptococcus become available, perhaps the mystery of this very unique and common cardiomyopathy can be resolved.


Positron-emission tomography and cardiomyopathy.

Because of its quantitative power and capacity to image biochemically unaltered tracers of physiological substrates, cardiac positron-emission tomography has emerged as a promising diagnostic modality and a powerful clinical research tool. It has enhanced characterization of the efficacy of diverse interventions designed to improve myocardial perfusion, differentiation of reversibly from irreversibly injured ischaemic myocardium, and detection of cardiomyopathic states. Progress in high rates of data acquisition, improved spatial and temporal resolution, accelerated image processing, and 3-dimensional display of images of myocardium offer promise for widespread applications to early detection of cardiac allograft rejection, graft atherosclerosis, and the efficacy of pharmacological interventions designed to protect recipients of cardiac allografts.


Anticardiac antibodies in hypertrophic cardiomyopathy as a marker of severity.

Twenty-three patients (mean age 27 years, 15 male, 8 female) with hypertrophic cardiomyopathy (10 'obstructive', 13 'non-obstructive') mostly of the sporadic type were examined for anticardiac antibodies circulating in the peripheral blood or bound in the endomyocardial biopsy. Immunoglobulin deposition in the biopsies was found in 41% of cases of the IgG isotype. IgM and complement fixation occurred less frequently. Predominant findings in the patients sera were antimyolemmal (78%) and antifibril antibodies (43%). The patients' sera were not cytolytic except for one case indicating that neither a toxic serum factor nor antibody-mediated cardiocytolysis were operative to a significant degree in hypertrophic cardiomyopathy. The patient's lymphocytes did not demonstrate a cytotoxic effect either alone or in the presence of the autologous serum.


Cardiomyopathies and specific heart muscle diseases. Definitions, terminology, classifications and new and old approaches.

Cardiomyopathies are defined as 'heart muscle diseases of unknown cause' and classified into hypertrophic, dilated and restrictive types, respectively. Hypertrophic cardiomyopathy is notable for massive ventricular hypertrophy without obvious cause, impaired diastolic and systolic function, a tendency for sudden death and a familial propensity. Dilated cardiomyopathy by contrast, demonstrates severe systolic failure progressing to congestive heart failure, with usually no familial tendency. Restrictive cardiomyopathy and diastolic heart disease represent syndromes with restriction to ventricular filling due to restrictive forces in the endomyocardium (and in constrictive pericarditis in the pericardium). The commonest cause of restrictive cardiomyopathy is endomyocardial fibrosis now usually known as hypereosinophilic endomyocardial disease. Specific heart muscle diseases are those conditions in which myocardial disease is due to a known cause: they usually produce systolic failure though occasionally a restrictive syndrome is evident. Amyloid heart disease occupies a place intermediate between cardiomyopathies and specific heart muscle diseases. The major features of the above conditions are described and current and future advances noted. Examples are the identification of the gene probably responsible for hypertrophic cardiomyopathy located on chromosome 14, and the identification of virus RNA particles in the myocardium in both myocarditis and in dilated cardiomyopathy, which strengthens the growing evidence suggesting that some cases of dilated cardiomyopathy may be due to previous myocarditis.


Left ventricular involvement in right ventricular cardiomyopathy.

Right ventricular cardiomyopathy is generally considered a disease with isolated right ventricular involvement, although there are some case reports of concomitant abnormalities of the left ventricle. In order to evaluate the prevalence, characteristics and natural history of left ventricular involvement in this disease, 39 patients with right ventricular cardiomyopathy were studied by 2-dimensional echocardiography. At first evaluation 25 patients (group 1) showed right ventricular abnormalities and a normal left ventricle. In the remaining 14 patients (group 2) the right ventricular abnormalities were associated with left ventricular involvement (asynergic areas and/or mild diffuse hypokinesia). During the follow-up, left ventricular involvement appeared in 6 patients of group 1 and worsened in 4 patients of group 2. Five patients died. Pathological examination (available in 4 cases) showed, at the level of the right ventricle, marked atrophy of myocytes and fibro-fatty replacement, and predominant fibrosis at left ventricular level. Left ventricular involvement is thus frequent in right ventricular cardiomyopathy. At least in some cases the disease appears to be progressive.


Controversial issues in restrictive cardiomyopathy.

The topic of restrictive cardiomyopathy remains controversial for many reasons. The term cardiomyopathy is unfortunately sometimes used interchangeably with diastolic heart failure. Furthermore, diastolic heart failure is sometimes linked with other causes of diastolic dysfunction such as hypertrophic cardiomyopathy and mitral valve disease. Restrictive cardiomyopathy is a clinical entity of primary or secondary myocardial disease presenting a picture that closely simulates that of constrictive pericarditis. In the majority of cases the correct diagnosis can be arrived at following a careful paradigm that begins with history and may end with endomyocardial biopsy. Many of the old teachings about how to distinguish restrictive cardiomyopathy from constrictive pericarditis have not held up with time and clinical experience: in particular equal diastolic pressures on both sides of the heart are compatible with either restrictive cardiomyopathy or constrictive pericarditis.


Doppler echocardiographic evaluation of left ventricular diastolic function in patients with systemic sarcoidosis.

In order to estimate left ventricular diastolic function in systemic sarcoidosis, Doppler echocardiography was utilized in 10 normal female subjects (aged 45 +/- 13 years) and in 10 female patients (aged 48 +/- 14 years), with biopsy proven sarcoidosis and without any clinical evidence of other cardiac disease or hypertension. Left ventricular systolic function assessed by two-dimensional echocardiography was normal in both groups (ejection fraction greater than 60%). The following Doppler echocardiographic parameters were measured: peak early diastolic flow velocity (E), peak late atrial diastolic flow velocity (A), the ratio (E/A) and deceleration of the flow velocity in early diastole (E-F slope). The results showed that 5 patients had two or more abnormal Doppler diastolic indexes, indicating impaired left ventricular relaxation, while the remaining 5 patients had values within or just outside normal limits. The mean values for the patients as a whole showed increased A velocity (0.77 +/- 0.11 m/s versus 0.61 +/- 0.10 m/s; P + 0.05), decreased E/A ratio (1.05 +/- 0.32 versus 1.4 +/- 0.30; P + 0.01), normal E velocity and normal E-F slope, compared with the mean values of the normal group. We concluded that a large percentage (50%) of patients with systemic sarcoidosis, had reduced diastolic performance of the left ventricle, at a stage of the disease when systolic dysfunction is not yet evident.


Anticoagulant treatment of atrial fibrillation in the elderly.

There is now adequate clinical evidence that the most appropriate treatment of elderly patients with non-valvular atrial fibrillation is with low dose warfarin. Patients may have contraindications to therapy with this agent, but should not be denied treatment based on age alone. Withholding treatment based on age places patients at unwarranted risk for severely disabling thromboembolic complications.


Venous thromboembolism.

Pulmonary embolism is a complication of venous thrombosis. It is a major cause of morbidity and mortality, but a condition that is highly preventable and, when diagnosed, very effectively treated. Yet in the United States, more people die of pulmonary embolism each year than of AIDS. The clinician must maintain a high index of suspicion at all times in the patient at risk for this entity, keeping in mind that overall only about one-third of the patients suspected of having pulmonary embolism actually turn out to have it. A strong suspicion alone is not enough to warrant initiation of treatment, as a clinician must confirm with appropriate studies that venous thrombosis or pulmonary embolism is present. If studies of the lower extremities are negative, then a high probability ventilation perfusion scan (V/Q) or a positive pulmonary angiogram must be obtained before therapy should be considered. However, a high probability V/Q scan occurs in only 40% of patients with angiographically proven pulmonary embolism. Thus, if suspicion is high enough, do not accept a V/Q scan of 'indeterminate probability' as negative for pulmonary embolism. Even more important, though, is prevention of the disease with appropriate measures and that every individual who is at medium to high risk for development of deep venous thrombosis must have some kind of prophylaxis.


The pathogenesis of dilated cardiomyopathy.

Using the WHO/ISFC definition and recommendations of nomenclature for cardiomyopathies, the aetiology is unknown. Over many years research has concentrated on defining pathogenetic mechanisms and owing to the widespread use of the bioptome-permitting recovery of fresh endomyocardial tissue-myocarditis has emerged as being intimately involved in the pathogenesis of dilated cardiomyopathy. In approximately 2,000 patients with a presumed diagnosis of dilated cardiomyopathy, myocarditis was found in 28% of these cases. The morphological diagnosis of myocarditis has been fraught with difficulties and, in attempt to establish criteria for its recognition, a group of cardiovascular pathologists (the author among them) met in Dallas in 1984. These criteria are detailed and categorization into acute, resolving (healing) and resolved (healed) has been emphasized because of important therapeutic implications. The cause of myocarditis has been established as being due to coxsackie B viruses. Up to recent times such findings could only be surmised by investigations such as micro-neutralization tests. It was not until the hydridization probe was employed that direct proof was provided. These studies together with immunological consequences continue to be investigated in the hope of providing a rational approach to therapy.


Effect of pyridoxine deficiency on immunological phenomena.

Measurements of serine hydroxymethyltransferase (SHMT) in resting lymphocyte cultures showed that the level of activity of this enzyme was very low. Under the influence of mitogenic stimuli serine hydroxymethyl-transferase activity was induced 5-20-fold. Addition in the cultures of 4-deoxypyridoxine, a potent antagonist of vitamin B6 coenzymes, concurrently with the mitogen, inhibits the induction of serine hydroxymethyltransferase. Thus deoxypyridoxine exerts its effects not only at the level of the enzyme itself by antagonizing the coenzyme but also at the level of its biosynthesis. Synchronous addition of vitamin B6 with deoxypyridoxine effectively reverses the inhibitory effects. The T helper cells of the lymphocyte culture are very sensitive to deoxypyridoxine action in contrast to T suppressor cells. The effect of phytohaemagglutinin or concanavalin A on the production of interleukin-1b, interleukin-2 and interleukin-2 receptors is profoundly affected by deoxypyridoxine. These results give a deeper insight of the mechanisms by which pyridoxine deficiency causes significant reduction of humoral and cellular immune responses to antigenic stimuli. On the basis of the data of this report a detailed illustration of the events that follow the T cell activation is presented. From this investigation the enzyme serine hydroxymethyltransferase emerges as a key element in the processes of immune responses and cell proliferation. Based on this finding we advance the following two propositions for possible future medical application: (i) combination of deoxypyridoxine with immunosuppressive drugs in case of immunosuppressive therapy or organ transplantation. (ii) the enzyme presents an excellent target for chemotherapy and therefore development of special agents directed against its apoprotein may prove to be a very valuable medical tool.


Heart and heart-lung transplantation in the 1990s.

After 22 years of clinical application in our unit, heart transplantation is now an accepted therapeutic method. Its indications are well established, its surgical technique and post-operative control and treatment well defined, mostly due to better diagnosis of the rejection episodes with the aid of echocardiography and endomyocardial biopsy and the use of cyclosporin. The results are remarkable with a survival rate of 70% at 5 years, and a full rehabilitation into family, social and often professional life for almost all the survivors. Its use has dramatically changed the prognosis of patients with irreversible cardiac failure but underlines the lack of a sufficient number of donors' hearts. The heart-lung transplantation, making use of the progress of heart transplantation, has been used successfully since 1982 and for the first time in Europe by our group. Improvement in the selection of recipients, lung preservation, surgical technique and post-operative management have brought a new and real hope to patients not only irreversible cardiopulmonary lesions but also terminal pulmonary disease.


Classification of turkeys as low or high volume semen producers using discriminant analysis.

Medium White turkeys in Generation 10 of divergent selection for semen ejaculate volume (SEV) were classified into lines that produce either low or high volumes of semen using a multivariate statistical technique, discriminant analysis. The discriminant function was based on records of hen fertility, embryonic mortality in the early and late incubation periods, and the incidence of pipped eggs. A hit ratio, the proportion of birds correctly categorized as low or high, of .60 was obtained. The discriminant function was subsequently used to classify birds in Generation 12. A misclassification rate of .28 and .48 was obtained for birds in the low and high lines, respectively. It was concluded that the relatively low rates of misclassification indicate a potential method for identifying male and female turkeys as belonging to low or high SEV lines, based on fertility and incubation records.


Effects of photoschedule and strain cross on broiler performance and carcass yield.

The purpose of the present experiment was to examine possible interactions of strain cross and age with photoschedule for broiler performance and carcass yield. Day-old male broiler chicks from strain crosses of either Peterson x Arbor Acres (PA) or Ross x Arbor Acres (RA) were placed in light-controlled chambers (5.6 lx) with either 23 h light (L):1 h dark (D) from 1 to 56 days (Treatment E) or 6L:18D from 1 to 14 days and 1L:3D repeated from 15 to 56 days of age (Treatment BI). There were age by light treatment and age by strain cross interactions for BW; Treatment E had greater BW than Treatment BI from 7 to 42 days, and the PA cross BW was greater than the RA cross BW from 1 to 42 days of age. Cumulative feed efficiency was improved by Treatment BI compared with Treatment E up to 49 days. There were no differences among main effects for mortality, and the incidence of leg problems increased with age. Fillet and tender yields (per lean carcass weight) were higher for Treatment E than BI and opposite responses were seen for drumstick and thigh yields. The RA cross showed higher fillet and tender yields than the PA cross and the opposite relationship was found for drumstick and wing yields.


Live performance and carcass yield of broiler strain crosses provided either sixteen or twenty-three hours of light per day.

The purpose of the present study was to compare a restricted (R) lighting program [16 h light (L):8 h dark (D)] with a standard extended (E) lighting schedule (23L:1D) for broilers. Experiment 1 was carried out during March and April (mean temperature of 23.3 C). Light treatments were 1) E; 2) R; 3) 16L:8D Days 1 to 21 and 23L:1D thereafter to 49 days (R3E); and 4) 16L:8D Days 1 to 14 and 23L:1D thereafter to 49 days (R2E). Treatments were factorially arranged with two strain crosses [Indian River x Arbor Acres (IA) and Peterson x Arbor Acres (PA)]. Experiment 2 was carried out during the summer (mean temperature of 27.0 C). Light Treatments E and R were factorially arranged with two strain crosses [Cobb x Arbor Acres (CA) and PA]. In Experiment 1, BW of Cross PA was greater than BW of Cross IA at 1, 14, 35, and 49 days of age. The percentage of birds with breast blisters was greater in Cross PA than IA. The incidence of broken clavicles was lower in Treatments R and R3E than in Treatments E or R2E. In Experiment 2, Treatment E had greater BW than R from 7 to 42 days of age, and BW of Cross CA was greater than that of PA from 1 to 48 days. Yield (percentage of lean carcass weight) of breast meat at 49 days of age was higher for Treatment E than R, and the percentage of birds with breast blisters was greater in Treatment R than E.(ABSTRACT TRUNCATED AT 250 WORDS)


Dietary supplementation with xanthophyll as an effective way of identifying low-producing broiler breeder hens.

The relationship between dietary levels of xanthophyll, the degree of pigmentation in the hen, and egg production rate was studied in commercial broiler breeders (Anak 2000). In the first study, the degree of shank and beak coloration, measured with a 15-grade Roche yolk color fan, was determined in broiler breeder pullets until 34 wk of age. Although overall body coloration decreased with age following initiation of egg production, the degree of shank coloration was two- to threefold higher than that of the beak. In the second study, Roche Carophyll-red (canthaxanthin, 10%) was supplemented at levels of 0, 10, and 20 mg/kg in a corn and soybean diet containing xanthophyll, and given to hens for a period of 4 wk beginning at 55 wk of age. Increasing dietary canthaxanthin levels increased pigmentation of beak and egg yolk in a quadratic manner, whereas pigmentation increased linearly in the shank. The production rate was inversely related to the degree of shank and beak pigmentation. In a third study, the relationship between hen pigmentation (using Carophyll-red, 30 mg/kg of diet) and production rate was examined in a commercial flock of broiler breeder hens. Hens were sampled according to shank coloration (Grades 1 to 3) and egg production was monitored. The production rate of hens with high coloration was significantly lower (by approximately 33%) than the flock average. At peak production, shank pigmentation was too low to differentiate visually between degrees of coloration. Dietary supplementation of 5% corn gluten meal increased shank pigmentation and enabled efficient identification of the nonlaying hens.


The effect of feed restriction and Eimeria maxima infection with or without medication on growth and feed intake in broilers.

Day-old male broiler chicks were raised in floor pens. At 4 days of age, birds in 75% of the pens were inoculated with Eimeria maxima via the feed. There were four dietary treatments: uninoculated, unmedicated control (UUC), infected, unmedicated control (IUC), infected, halofuginone-medicated (3 ppm, HM), or infected, salinomycin-medicated (66 ppm, SM). At 6 days of age, birds in 50% of the pens of each treatment were restricted for 5 days to their maintenance energy intake level. The remainder consumed feed ad libitum. Medication reduced growth from 0 to 6 days of age and feed intake was depressed, irrespective of medication, in infected birds from 0 to 21 days of age. Growth, however, was improved with intake of coccidiostat over IUC from 6 to 11 days of age but did not match UUC until 28 days of age. At 42 and 49 days of age, infected birds were lighter than UUC birds. Dressing percentage for HM and SM birds was greater than that of UUC birds at 49 days of age but HM birds also had a greater percentage of abdominal fat at both 42 and 49 days of age. Feed restriction resulted in some compensatory growth immediately following refeeding. Experimental feed:gain ratio was improved in restricted birds (1.98 versus 2.03 g:g). At 42 and 49 days of age, restricted birds were lighter than birds eating ad libitum and also had a significantly greater percentage abdominal fat. A lower breast yield was observed at 42 days of age in restricted birds.


Effects of two nipple drinker types with different flow rates on the productive performance of broiler chickens during summerlike growing conditions.

Three trials were conducted to study the effects of a high flow volume (2.3 mL/s) nipple waterer (HFN) versus a low flow volume (.4 mL/s) nipple waterer (LFN) on the productive performance of broiler chickens as measured by average body weight (kilograms), average feed conversion (kilograms:kilogram), and percentage mortality rate. Equal numbers of male and female birds were used during Trial 1; only male birds were used during Trials 2 and 3. All trials were conducted during the summer months. An attempt was made during Trial 2 to expose the birds to artificial heat stress. No differences were seen during any of the trials in feed conversion between the two treatments. In Trial 1 the only significant difference (P less than or equal to .05) exhibited was in average male body weight (1.87 kg HFN; 1.84 kg LFN). A highly significant difference (P less than or equal to .01) was seen in average body weight (1.75 kg HFN; 1.64 kg LFN) during Trial 2. Average body weight difference during Trial 3 was highly significant at 42 days of age but not at Day 49. Mortality rate figures during Trial 2 indicate a highly significant difference during the 38-day period prior to heat stress (2.2% LFN; .4% HFN), and significant difference during the heat stress period (38 to 44 days; 2.9% LFN; 1.5% HFN). During Trial 3 mortality rate differences were significant by 49 days (20.6% LFN; 11.4% HFN) although there was no difference at 42 days.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of coccidiosis on the distribution of dietary lutein in the chick.

A series of experiments was run to determine whether the distribution of dietary carotenoids in chick plasma and tissue was dependent upon a saturable carrier, and to observe how infection with Eimeria acervulina affected this distribution. Broiler (Hubbard x Hubbard) and Sex Sal (Rhode Island Red x White Rock) chicks were fed a white corn and soybean meal-based diet supplemented with varying levels of a commercial lutein concentrate. Plasma, small intestine, and liver were analyzed for lutein. In the first experiment, mean plasma values in control broiler chicks increased linearly from 0 to 200 ppm supplementation. Mean plasma values of infected chicks were decreased an average of 71% as compared with controls, and reached a plateau between 100 and 200 ppm dietary lutein. In the second experiment, plasma, small intestinal, and liver lutein levels in broiler chicks reached a plateau between 200 and 500 ppm. In the third experiment, plasma and liver values in Sex Sal chicks leveled off between 250 and 500 ppm whereas levels in the small intestine increased linearly. Infection of the Sex Sal chicks at 3 wk of age with E. acervulina caused plasma lutein levels to be reduced about 88%, small intestinal levels 76%, and liver levels 72%. Supplementation with 500 ppm resulted in higher proportions of lutein in tissues. Infection with E. acervulina shifted the ratios to even higher proportions in the tissues at all supplementation levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Fermentation of [14C]lactose in broiler chicks by cecal anaerobes.

Volatile fatty acids and lactic acid were products of [14C]lactose metabolism in 10-day-old broiler chicks. The [14C]lactose and unlabeled lactose were given to chicks in combination with cultures of cecal anaerobes (direct fed microbials) from adult broiler chickens. Aliquots of these cecal anaerobes had been used previously to reduce Salmonella typhimurium colonization in broiler chicks. In the current study, chicks were treated with anaerobes and anaerobes plus lactose on the day of hatch. Chicks given lactose plus anaerobes also received unlabeled lactose in the drinking water. Chicks in all treatment groups received [14C]lactose on Day 10 posthatch. After 5 h, most of the radiolabel was detected in the foregut and intestine. Significantly lower concentrations of [14C]lactic acid were detected in the serum and foregut of chicks given anaerobes and anaerobes plus lactose than in the similar samples from control chicks. Additionally, significantly less [14C]lactic acid was detected in the feces of chicks treated with anaerobes plus lactose than in feces from control chicks and chicks receiving only anaerobes. Significant differences in the total content of volatile fatty acids and lactic acid were detected in the serum, liver, intestine, and ceca of chicks treated with anaerobes or anaerobes plus lactose. These data indicate that cecal flora utilize lactose to produce volatile fatty acids and lactic acid.


Influence of increasing photoperiod and toe clipping on breast buttons of turkeys.

Two 17-wk experiments compared the effects of an increasing photoperiod treatment (INC) versus a constant photoperiod treatment (23H), and intact toes versus clipped toes, on the breast button incidence and performance of heavy tom turkeys. Under INC, the photoperiod was increased gradually from 8 to 23 h between 4 and 16 wk. Under 23H, the photoperiod remained constant at 23 h. Use of INC versus 23H resulted in a significant reduction in breast button incidence at 17 wk in both experiments (P less than .05). Toe clipping had no effect on breast button incidence. The presence of breast buttons was positively correlated with body weight at 12 wk, and area of unfeathered skin over the keel at 17 wk. In Experiment 1, the photoperiod treatments had no significant effect on 17-wk body weight or mortality, but the INC treatment had an adverse effect on feed efficiency (P less than .05). In Experiment 2, turkeys reared under INC were heavier at 17 wk (P less than .05), with similar feed efficiencies. Mortality was significantly lower on INC than 23H up to 12 wk in Experiment 2 (P less than .05). Turkeys with intact toes were .44 kg heavier than turkeys with clipped toes at 17 wk in both experiments (P less than .05) and had similar feed efficiencies. Mortality to 4 wk was lower for turkeys with intact than clipped toes in Experiment 2 (P less than .05). Increasing photoperiod treatments have potential for improving turkey performance, survival, and carcass quality.(ABSTRACT TRUNCATED AT 250 WORDS)


Evidence that bacteria are not causative agents of stunting syndrome in poults.

Two experiments were conducted to determine the effect of removing bacteria, including long segmented filamentous organisms (LSFO), from inoculum known to induce stunting syndrome (SS) in poults. Experiment 1 consisted of two identically designed trials. In each trial, each of four treatments was assigned to an isolator. Three treatments consisted of dosing, by crop intubation, groups of 1-day-old poults with unfiltered SS inoculum or filtrate of inoculum passed through .45- or .20-micron microfilters. Uninoculated poults were dosed with inoculum carrier, saline. Experiment 2 was done in battery facilities. Three rooms were used and each room housed one of three treatment groups. Triplicate pens of 10 poults each within each room were dosed by crop intubation with saline (uninoculated), unfiltered inoculum, or filtrate from .20-micron filtration. As compared with uninoculated poults, weight gain through 7 days was reduced 20% (P less than .05) by unfiltered and filtered inocula in both experiments. Jejunal maltase activity also was decreased (P less than .01) by unfiltered and filtered inocula. Feed efficiency (FE) was not determined in Experiment 1, but in Experiment 2, FE from 1 to 14 days of age was impaired by inoculum, irrespective of filtration. This effect was not evident during the 14- to 20-day period. The observation that the adverse effects of giving filtered inoculum to poults were the same as those caused by unfiltered inoculum indicated that bacteria, including LSFO, were not primary causative agents of the SS experimentally induced in poults.


Effect of age and sex on true digestibility of amino acids of rapeseed and soybean meals in growing broilers.

Studies were conducted to evaluate the influence of age and sex of birds on true digestibilities of protein (TDP) and amino acids (TDAA) of two rapeseed meals and a soybean meal. Sixty-four broilers (50% of each sex) were used both in the first (at 3 wk of age) and the second trials (on the same animals at 6 wk of age). At the end of 3 and 6 wk of age, the birds were fasted for 24 h and then force-fed with moistened diets (diet:water: 50:50) approximately 40 and 90 g, respectively. Excreta were collected during the two 24-h periods after force-feeding. The TDP and TDAA of rapeseed and soybean meals decreased significantly as the age of broilers increased from 3 to 6 wk. At 3 wk of age, the TDP and TDAA were not influenced by the sex of the animals. At 6 wk of age, the TDAA of the two rapeseed meals was higher in males than in females. The TDAA of soybean meal did not vary with sex. Sex had no effect on the TDP values of the three raw materials tested.


Measurement of metabolizable energy in poultry feeds by an in vitro system.

A two-stage in vitro system (IVDE) for estimating AMEn in poultry feeds was investigated. For 71 diets ranging from 2.2 to 3.4 kcal/g, the average AMEn was 2.889 kcal/g and the mean IVDE value was 3.005 kcal/g. From the 71 diets, 30 (42.2%) showed differences between AMEn and IVDE of less than .100 kcal/g and represented diets across the AMEn range of values. The statistical analysis of the data showed a standard error of the estimate (SEE) of .152 kcal/g for the 71 diets assayed. No clear differences in accuracy of AMEn among the diets, as related to the composition and proportion of ingredients, were observed. Thus, the IVDE method gave different AMEn for diets of similar composition. The application of the IVDE system to selected ingredients showed that the AMEn of corn was underestimated by the method. However the AMEn of roasted, extruded soybeans and oats was estimated accurately by the IVDE method. Other ingredients were greatly overestimated by the in vitro technique (soybean meal, corn gluten meal, and barley). The results of applying the IVDE method for estimating AMEn showed the limitations of this technique with regard to the universality of its application. Although the method was successful in estimating AMEn values of diets and ingredients, for many samples the IVDE technique did not give acceptable results.


Effect of dietary polyunsaturated fatty acid concentration on performance, fat deposition, and carcass fatty acid composition in broiler chickens.

The effect of dietary polyunsaturated fatty acid (PUFA) concentration on body fat deposition and composition in broiler chickens was studied. Twenty-day-old birds were fed five isocaloric diets supplemented with different combinations of tallow and vegetable oils. Contents of abdominal adipose tissue (AAT) as well as body fat were determined at 40 days of age. A significant linear effect was observed between dietary PUFA and feed utilization. Fatty acid (FA) profiles in AAT and total body fat were correlated to dietary PUFA content, with the main effect of higher dietary PUFA being a reduction in monoenoic FA (C16:1 and C18:1) and an increase in C18:2. The effect of dietary PUFA on the saturated FA (C16:0 and C18:0) was small and not statistically significant. Increased dietary PUFA modified FA composition such that C18:2, rather than C18:1 became the dominant FA in AAT. In that respect, greater changes were observed in FA composition of AAT, as compared with that on the whole carcass. The deposition of saturated and monoenoic FA in the whole carcass during the experimental period was related to dietary PUFA content in a quadratic manner. However, deposition of C18:2 and C18:3 was not affected by intake and their utilization (deposition:intake ratio) was reduced in a manner parallel to their dietary levels.


Influence of dietary n-6 and n-3 polyunsaturates on lipids in chickens divergently selected for body weight.

The effects of dietary lipid sources rich in n-6 (soybean oil) or n-3 (menhaden oil) polyunsaturated fatty acids (PUFA) on blood triacylglycerol levels and tissue fatty acid compositions in female chickens from two genetic lines were examined. Triacylglycerol concentrations in the plasma very low density and low density lipoprotein fractions were elevated in the low-weight (LW) chickens compared with the high-weight (HW) group. Chicken heterophil to lymphocyte ratios and total antibody titers to sheep red blood cells at 84 days were not influenced by genetic line or by the dietary lipid fed. Concentrations of C18:1 fatty acid isomers and total monounsaturates were highest in liver and heart tissues of HW chickens. Feeding menhaden oil enriched the plasma, liver, and heart with n-3 PUFA in both genetic lines. The data indicate a difference in hepatic fatty acid metabolism between the HW and LW lines that is unaffected by dietary n-6 or n-3 PUFA.


Morphological study of the dove spleen.

The spleen and vascular resin cast from doves were observed by a light and a scanning electron microscope for the purpose of studying the histological structure and the mode of the splenic blood microcirculation. The trabeculae of the dove spleen were poorly developed and the white and red pulps could not be distinguished from each other as is also the case of the chicken spleen. The luminal surface of the sinus was covered by continuous endothelial cells that had nuclear protrusion into the lumen. The blood cells passed to the sinus via the small gap of the luminal surface of the sinus. Irregular resin masses that connected the terminal portion of the artery with the venous sinus were observed. The direct connection between the arterial terminalis and venous sinus could not be recognized. When the resin was injected retrograde to blood flow from the vein, the sinus ended blindly.


A method of analysis of the electrical activity of the proximal gastrointestinal tract of the chicken.

The present paper describes a method of recording and analyzing electromyographical (EMG) signals from the digestive tract of the chicken. The EMG signals from the proventriculus, gizzard, and duodenum were recorded after implantation of Ni and Cr electrodes. The amplified EMG signals were digitized using a sampling frequency of 50 samples per second, and numerical data was stored immediately on the hard disk (1 datum = 1 byte). The software designed allowed: 1) detection of spike-bursts with a high accuracy; 2) analysis of maximum amplitude (with a maximum error of 6.7%), mean amplitude, duration, and frequency of the spike-bursts; the time of interval between spike-bursts, and the percentage of activity; 3) integration of the recorded data with a variable time set; and 4) a wave analysis by means of the Fourier algorithm. These methods, already used in EMG studies in mammals, are assembled and adapted for its application in birds.


A quantitative chemical study of the comb and wattle galactosaminoglycans from single comb White Leghorn roosters.

Galactosaminoglycans from mature rooster comb and wattle tissues were separated into five fractions by ethanol precipitation. An average of 90% total uronic acid was recovered in Fractions I to III. Fractions I and II were dermatan sulfate with relatively high proportions of L-iduronic acid (61 to 80%), but this uronic acid was a minor component (30%) in Fraction III, in which D-glucuronic acid was the major uronic acid. Digestion with testicular hyaluronidase suggested that most if not all of the galactosaminoglycans in Fractions I to III were copolymers containing both L-iduronic acid and D-glucuronic acid. Fractions IV and V contained much lower proportions of L-iduronic acid and showed broader electrophoresis bands than did Fraction III.


Research note: age-dependent changes in 3-oxy-methyl-D-glucose and leucine intestinal absorption in chickens.

Intestinal absorption of 3-oxy-methyl-D-glucose (3-OMG) and leucine were studied in intestinal slices from fasted 1-, 2-, and 3-wk-old chickens. The intestinal segments studied were the duodenum, jejunum, ileum, and cecum, with the latter divided into proximal and medial regions. There was a decrease in the intestinal absorption of 3-OMG and leucine in the duodenal, jejunal, and proximal cecal segments with increasing age of the chicken. The medial cecum did not show age-dependent differences in the uptake of substrates. In the ileum, there was a decrease in intestinal absorption of 3-OMG and leucine between Weeks 1 and 2, but thereafter the uptake was similar to that of the 2nd wk.


Research note: eggshell quality in Japanese quail fed different fatty acids.

The purpose of the present study was to determine the effects of diets containing 3% palmitic acid (Diet PA), oleic acid (Diet OA), or linoleic acid (Diet LA) on the shell quality of eggs of Japanese quail. Each diet was fed to 10 hens maintained individually in wire quail laying cages. There was no difference (P greater than .05) in feed consumption between hens fed Diets OA and LA, but hens of both groups consumed less (P less than .05) feed than those fed Diet PA. Egg weight, shell weight, and thickness of shell plus membrane were not influenced by dietary treatment (P greater than .05). However, specific gravity of eggs from hens fed Diet OA was significantly higher (P less than .05) than that of eggs from those fed either Diet PA or Diet LA. Comparison of these data with hatchability data obtained in a previous experiment conducted under similar conditions suggests that the differences in hatchability would not be explained by differences in eggshell quality.


Research note: efficacy of various flavonoids and simple phenolics in prevention of nutritional myopathy in the chick.

A 33-day feeding experiment was conducted with 3-day-old broiler chicks to assess the efficacy of various flavonoid and simple phenolic antioxidants in preventing nutritional muscular dystrophy (NMD) resulting from vitamin E deficiency. None of the flavonoids or simple phenolics at a dietary concentration of 1,000 ppm completely prevented NMD but quercetin reduced (P less than .05) its incidence and quercetin, morin, and ferulic acid reduced (P less than .05) the severity of the disorder. The low-selenium, low-vitamin E diet also promoted the development of a mild exudative diathesis (ED) in many of the birds, which was inhibited (P less than .05) by the rutin and silymarin treatments, but exacerbated (P less than .05) by quercetin, morin, and ferulic acid. Changes in concentrations of vitamin E in plasma, liver, or muscle, caused by the various treatments (other than vitamin E), were not related to protection against NMD or ED.


Effects of intranasal neostigmine on oesophageal motility in man.

The effects of intranasally administered neostigmine on oesophageal peristalsis and lower oesophageal sphincter tone were investigated in 21 healthy volunteers. After 30 min of basal recording of oesophageal tracings, neostigmine (3 or 5.4 mg) or the inert vehicle were given. The oesophageal recording was continued for 45-60 min after administration. Neostigmine increased the amplitude and duration of the peristaltic waves without significantly affecting conduction. Lower oesophageal sphincter tone was also increased but post-swallowing relaxation was normal. At the highest dose, the effects of neostigmine lasted 45 min or more. There were no side effects and the heart rate was only slightly slowed. The results suggest that intranasal administration of neostigmine might be clinically useful for stimulation of upper gastrointestinal tract peristalsis.


Pteroylpolyglutamate pool modifications in rat liver after chronic administration of phenobarbitone and valproate.

Chronic intraperitoneal administration of low doses of phenobarbitone and valproate caused different alterations in hepatic percentage distribution of pteroylpolyglutamate derivatives without modification of total folate content. Phenobarbitone treatment caused a significant decrease of the percentage content of reduced unsubstituted and methylene-substituted derivatives, while valproate produced an increase of the percentage content of methenyl-, formyl- and formimino-substituted derivatives and a concomitant percent increase of hexaglutamates. The modified ratios of various pteroylpolyglutamates, both in phenobarbitone- and in valproate-treated animals, probably contribute to influencing the partitioning of the one-carbon pool through the various areas of one-carbon metabolism.


Graphical analysis of data from pharmacology experiments.

Dose-response curves are often used in the study of the interaction of hormones and receptors. From these plots, IC50 or EC50 values are calculated. In these pharmacological assays it is implicitly assumed that a single receptor predominates in a tissue. In this paper the interaction of a ligand with two receptors is studied from a theoretical point of view. It is assumed that the responses mediated by these receptors are qualitatively or quantitatively different. The theoretical direct and Scatchard plots display a high variety of shapes depending upon the difference in potency of the effect of the drug acting in both receptors and upon the magnitude and sign of the individual response. When dose-response curves taken from the literature have been transformed into direct or Scatchard plots new information has become available. With respect to this, it is shown that agonists of purinergic receptors seem to interact with two different populations of receptors. We claim that carefully designed experiments must provide valuable information concerning the number of subtypes of receptors present in a given system and the kind of response mediated by them.


Lack of inhibition of ornithine decarboxylase activity by ibuprofen.

The influence of the anti-inflammatory drug ibuprofen on the activity of ornithine decarboxylase (ODC, EC 4.1.1.17), the key enzyme of polyamine synthesis, was studied using a 20,000 g supernatant of rat testis and regenerating liver homogenates as sources of the enzyme. Ibuprofen, in all concentrations studied (10(-6) to 2 x 10(-3) M), did not influence either testicular or hepatic ODC activity in vitro. The role of ODC in inflammatory processes and the lack of ODC inhibition by ibuprofen are discussed in view of the controversial findings of other authors.


Activation of the Langendorff perfused rat heart depolarized by increased external potassium concentration.

Myocardial activation under depolarized conditions was studied in spontaneously beating Langendorff perfused hearts from albino rats. Depolarization was obtained by increasing external potassium concentration in steps (5.4, 7.4, 10, 10.5, 11 and 11.5 mM) in the perfusing solution with or without adrenaline (Adr). Left ventricle isovolumic systolic pressure and coronary flow did not change as external potassium increased, albeit being larger with Adr in the perfusing solution. Atrial and ventricular rates decreased, the latter showing a larger decline. The same behaviour was displayed by perfused hearts, with higher rates being developed by the group with Adr. PR interval and QRS complex duration increased as a function of external potassium. PR intervals were the same in both groups but QRS duration was larger in the Adr group, indicating that AV conduction was not changed in presence of Adr but intraventricular conduction was delayed in that situation. It was also observed that in the great majority of perfused hearts, differing from isolated preparations, ventricular mechanical activity ceased at around 11.5 mM external potassium.


Neuropsychopharmacological study of 2,4-dihydro[1,2,4]triazolo[3,4-c][1,4]benzothiazine-1-one (IDPH-791).

The neuropsychopharmacological profile of a new centrally acting skeletal muscle relaxant, 2,4-dihydro[1,2,4]triazolo[3,4-c][1,4]benzothiazine-1-one (IDPH-791), an analogue of triazolobenzothiazine, has been described and compared to mephenesin, a well known centrally-acting muscle relaxant. IDPH-791 was found to be safer and of longer duration of action than mephenesin in all the tests conducted in this study. Both IDPH-791 and mephenesin caused ataxia, decrease in spontaneous activity and inhibition of pinnal reflex. IDPH-791 was 1.5 to 2.0 times more potent in exhibiting motor inco-ordination and anticonvulsant activity than mephenesin in mice and rats. IDPH-791 was twice as active in inhibiting various spinal polysynaptic reflexes, crossed extensor, flexor, and linguomandibular reflexes; however, both did not affect the typical monosynaptic reflex, patellar reflex. IDPH-791 and mephenesin did not have sedative activity. Although mephenesin exhibited haemolytic activity, IDPH-791 was devoid of this activity. It is concluded that IDPH-791 is a safe and effective centrally-acting muscle relaxant having a longer duration of action than mephenesin. IDPH-791 is also devoid of sedative and haemolytic activity.


Cardiotoxicity induced by doxorubicin in vivo: protective activity of the spin trap alpha-phenyl-tert-butyl nitrone.

The role of free radical generation in the development of the acute cardiotoxicity induced by doxorubicin (DXR) in the rat and the protective activity of anti-radical drugs were investigated in in vivo experiments by evaluating the body weight curve, ECG, contractile performance and coronary flow up to 10 days after DXR. A lipophilic spin trap (alpha-phenyl-tert-butyl nitrone, PBN) was continuously administered at a dose of 0.65 mg/kg every hour for 2 weeks by an intraperitoneal osmotic pump. DXR was administered i.v. at a dose of 9 mg/kg 3 days after beginning the PBN infusion. DXR impaired ECG and body weight gain after 3 days (partly reversible at later times), while contractility and coronary flow were significantly impaired throughout the experimental time. PBN was shown to prevent the DXR-induced alterations of contractility and coronary flow, while ECG was non-significantly improved. The body weight curve was not affected. Since the dose of PBN used does not produce pharmacological effects, the protective activity in rats receiving DXR indicates that free radicals may play a causal role in the acute cardiotoxicity in vivo. The use of suitable spin traps and administration schedules seems to be an interesting approach for the prevention of radical-dependent pathologies.


In vitro activity of sulphimidazole alone and in association with trimethoprim against enteric pathogens.

Sulphimidazole is a new sulphonamide belonging to the class of intestinal sulphonamides and characterized by the fact that it is active even in vitro. It has the heterocyclic ring of 5-nitroimidazoles on amidic nitrogen. Its antibacterial activity is similar to that of the classical sulphonamides but differs in that it also combats certain anaerobic bacteria such as Clostridium botulinum. This effect is completely absent in the case of sulphadiazine and sulphamethoxazole. Also, since p-amino-benzene-sulphonamide is present in the molecule, the drug acts in synergism with trimethoprim against certain aerobic or facultative strains of enteric pathogens.


A study of the neuronal and non-neuronal stores of dopamine in rat and rabbit kidney.

The present study has examined the effects of 6-hydroxydopamine (6-OHDA) alone and in combination with pargyline, desipramine and GBR 12909 and denervation as induced by occlusion of the renal artery (RAO) on the endogenous dopamine (DA) and noradrenaline (NA) contents in rat and rabbit renal tissues; the effects of chemical denervation on catecholamine levels in the left ventricle were also studied. In rat and rabbit renal medulla and rat renal cortex, 6-OHDA and pargyline plus 6-OHDA selectively reduced NA (85-92% reduction) without a parallel decrease in DA tissue content (19-27% reduction). This 6-OHDA- and pargyline plus 6-OHDA-insensitive DA pool was found to be resistant to denervation as induced by RAO. The NA-depleting effect of 6-OHDA in these renal areas was found to be prevented by the previous administration of desipramine, but not with that of GBR 12909. In the rabbit renal cortex, 6-OHDA selectively reduced NA (90% reduction) without a parallel depletion of DA (20% reduction); previous treatment with pargyline abolished this selectivity. Again, only desipramine, but not GBR 12909, was found to prevent the NA and DA depleting effect of 6-OHDA in the rabbit renal cortex. Denervation induced by RAO was also found to produce a parallel depletion of DA and NA tissue levels in this renal area. In the left ventricle, 6-OHDA alone or in combination with pargyline produced a parallel depletion of DA and NA tissue levels (79-88% reduction) in both species. These results provide evidence against the presence of independent dopaminergic neurones in rat and rabbit kidney and suggest that in rat and rabbit renal medulla and rat renal cortex most of DA is stored in a non-neuronal compartment; in rabbit renal cortex some of the DA appears to be located in noradrenergic neurones, in a store different from that which contains NA.


Release of atrial natriuretic factor induced by the A1 adenosine receptor agonist 2-chloro-N6-cyclopentyl-adenosine in the rat.

The effect of the adenosine receptor agonists, 2-chloro-N6-cyclopentyladenosine (CCPA) and 2-hexynyl-adenosine-5'-N-ethylcarboxamide (HENECA) on atrial natriuretic factor (ANF) release was investigated. The A1 adenosine receptor agonist CCPA markedly increased plasma ANF levels, following subcutaneous (s.c.), but not intracerebroventricular injection. ANF release evoked by the s.c. injection of CCPA was completely abolished by s.c. pretreatment with the selective A1 adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine. The A2 adenosine receptor agonist HENECA did not produce ANF release. The results of the present study suggest that peripheral adenosine mechanisms might be involved in the control of ANF secretion, through the activation of A1 adenosine receptors. Preliminary results show that CCPA produces ANF release also from isolated atria, thus suggesting that its action on ANF release is, at least in part, direct, and not only a consequence of cardiovascular modifications.


Role of aldehyde dehydrogenase in the biological activity of spermine dialdehyde, a novel immunosuppressive/purging agent.

The antitumour and immunosuppressive activities of spermine dialdehyde (SDA), a synthetic, oxidized form of spermine, were examined using L1210 cell lines and murine bone marrow cells. SDA acted as a high affinity substrate for aldehyde dehydrogenase (ADH) derived from different sources, with kinetic profiles similar to other aldehyde substrates. The murine leukaemic, cyclophosphamide-resistant L1210/CPA cells, having high levels of intracellular ADH activity, were less sensitive to SDA compared to ADH deficient L1210/O cells as measured by [3H]-thymidine incorporation in proliferation studies. Furthermore, pretreatment of L1210/CPA cells with the ADH inhibitor, diethyl aminobenzaldehyde (DEAB), resulted in potentiation of the SDA response. Murine bone marrow cells were more resistant to SDA than splenic T cells. However, addition of DEAB to bone marrow cultures potentiated the sensitivity of progenitor cells to SDA, as measured by colony formation. The results indicate that levels of ADH in the target tissues would determine the potency of SDA and subsequently offer selectivity and specificity to the therapeutic potentials of this putative purging agent.


Splanchnic haemodynamic effects of ketanserin in anaesthetized cirrhotic rats.

The effects of ketanserin, atenolol and their association on portal vein pressure (PVP), portal and caval bile acid concentrations (PBA and CBA), and extraction ratio of bile acids (ER) after oral loading with chenodeoxycholic acid were investigated in anaesthetized cirrhotic rats. PVP was significantly reduced by ketanserin and by the association ketanserin plus atenolol; PBA was significantly decreased in all the treated groups, whereas the reduction of CBA was significant only in the rats treated with ketanserin and atenolol alone. ER was increased by atenolol and ketanserin, but it was not modified by their association. Moreover, a significant correlation was observed between PBA and CBA and between PVP and ER. These results suggest that, in anaesthetized cirrhotic rats, ketanserin reduces PVP probably through more complex mechanisms than the simple indirect reduction of portal flow, and that the association of ketanserin plus atenolol has no additive effect in reducing PVP.


The effects of S(-) and R(+) sulpiride, metoclopramide, cisapride and domperidone on the small intestine suggest DA2-receptors are involved in the control of small intestinal transit time in rats.

To study the effect of intraperitoneal S(-)sulpiride (1-15 mg/kg), R(+)sulpiride (5-10 mg/kg), metoclopramide (1-15 mg/kg), cisapride (10 mg/kg) and domperidone (5-10 mg/kg) on intestinal progression, rats were given the test drug followed by oral lactulose. Their hydrogen excretion was used to calculate the small bowel transit time (SBTT) and maximum peak time (MPT). Metoclopramide (7.5 mg/kg) had the greatest effect on SBTT (-25%), followed by S(-)sulpiride and domperidone. S(-)sulpiride (10 mg/kg) had the greatest activity on the MPT (-35.2%) followed by metoclopramide. R(+)sulpiride and cisapride did not modify SBTT and MPT. In conclusion S(-)sulpiride is the isomer active on intestinal transit and DA2-receptors seem important targets in the modulation of intestinal progression, since S(-)sulpiride, metoclopramide and domperidone are DA2-receptor antagonists, and R(+)sulpiride and cisapride are not. The H2 breath test proved a valid method for measuring the effect of drugs on the small intestine in animals.


Non-serotonergic 3H-ketanserin binding sites in human platelets: characteristics and interaction with calcium antagonists.

Here we report the identification of binding sites for 3H-ketanserin in human platelet membranes. At 4 degrees C, 3H-ketanserin binding is saturable (Bmax = 0.58 pmol/mg protein), rapid (equilibrium being attained within 20 min) and reversible. The kinetics of the association and dissociation curves are consistent with the existence of a single class of binding sites, as confirmed also by computer-assisted analysis of the saturation curve. Specific binding is increased by Ca2+ and Mg2+. 3H-ketanserin binding is inhibited by serotonin (Ki = 48.5 microM), unlabeled ketanserin (Ki = 3-15 nM), as well as by another antiserotonergic drug, methysergide (Ki = 32.6 microM). However, other selective 5-HT2 ligands, such as ritanserin, spiperone and cyproheptadine fail to interact with 3H-ketanserin binding. On the contrary, tetrabenzine, a monoamine depleting agent, when preincubated at 30 degrees C, did inhibit the specific binding completely. 3H-ketanserin specific binding is inhibited in a dose-dependent fashion by some calcium blocking agents, with different potencies: verapamil (Ki = 2.25 microM), diltiazem (Ki = 139 microM) and SIM6080, a new Ca(2+)-antagonist related to the phenylalkylamines (Ki = 5.22 microM). Flunarizine inhibited 3H-ketanserin specific binding only at relatively high concentrations (IC50 greater than 100 microM), while nitrendipine did not show any inhibitory effect up to 20 microM. The present evidence indicates that all the sites labeled by 3H-ketanserin at 4 degrees C might be coincident with the monoamino transporter identified in other systems, and that they might play a role in the modulation of platelet aggregation exerted by some calcium blocking agents.


Vigabatrin does not affect the intestinal absorption of phenytoin in rat duodeno-jejunal loops in situ.

The antiepileptic drug vigabatrin (GVG) is known to decrease significantly the serum concentration of concurrently administered phenytoin (PHT) in epileptic patients. To assess a possible mechanism for this interaction, the effect of GVG on the intestinal absorption of PHT was investigated by means of circulation experiments in an in situ rat duodeno-jejunal loop. GVG did not affect the rate of disappearance of PHT from the loop perfusing medium, providing evidence against occurrence of GVG-induced impairment of PHT absorption.